FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Leker, RR McKay, RDG AF Leker, RR McKay, RDG TI Using endogenous neural stem cells to enhance recovery from ischemic brain injury SO CURRENT NEUROVASCULAR RESEARCH LA English DT Review DE neural stem cells; neurogenesis; stroke; ischemia; growth-factors ID CENTRAL-NERVOUS-SYSTEM; LEUKEMIA INHIBITORY FACTOR; FIBROBLAST-GROWTH-FACTOR; MIDDLE CEREBRAL-ARTERY; ADULT-RAT HIPPOCAMPUS; PROGENITOR CELLS; DENTATE GYRUS; CORTICAL NEUROGENESIS; NEURONAL PROGENITORS; MAMMALIAN FOREBRAIN AB The use of cell-based therapy may be a valid therapeutic approach to ischemic brain injury. Stem cells have been proposed as a new form of cell based therapy in a variety of disorders, including acute and degenerative brain diseases. Up to date most efforts have concentrated on transplantation of embryonic stem cells (ESC) or neural stem cells (NSCs) obtained from immortalized cell lines into the diseased brain. These procedures require harvesting the appropriate stem cell, expansion in vitro and transplantation. Endogenous NSCs have been identified in the central nervous system where they reside largely in the subventricular zone and in the subgranular zone of the hippocarnpus. Endogenous NSCs may be capable of self-renewal and differentiation into functional glia and neurons. Manipulation of endogenous NSCs may bypass the need to use ESC as a form of therapy thus avoiding the complex ethical and biological issues involved with ES cells or immortalized cell lines. This review summarizes the evidence recently gathered in support of a therapeutic role for endogenous NSCs in acute experimental stroke. C1 NINDS, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. RP Leker, RR (reprint author), NINDS, Lab Mol Biol, NIH, Bldg 36,Room 3c12,36 Convent Dr,MSC 4092, Bethesda, MD 20892 USA. EM lekerr@nih.ninds.gov NR 81 TC 19 Z9 23 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PD DEC PY 2004 VL 1 IS 5 BP 421 EP 427 DI 10.2174/1567202043361938 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 916LM UT WOS:000228386400004 PM 16181090 ER PT J AU Senderowicz, AM AF Senderowicz, AM TI Targeting cell cycle and apoptosis for the treatment of human malignancies SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID DEPENDENT KINASE INHIBITOR; GROWTH-FACTOR RECEPTOR; METASTATIC COLORECTAL-CANCER; CYC202 R-ROSCOVITINE; PHASE-I TRIAL; LUNG-CANCER; REFRACTORY NEOPLASMS; SPINDLE CHECKPOINT; ANTICANCER DRUGS; CLINICAL-TRIALS AB Oncogenic transformation leads to cell cycle aberration and apoptosis dysregulation. Targeting cell cycle and apoptosis pathways has emerged as an attractive approach for the treatment of cancer. The activity of cdks can be modulated by targeting these kinases with small molecules that bind to the ATP binding pocket of cdks, or by altering the composition of the cdk/endogenous cdk inhibitor complexes by different mechanisms. Apoptosis can be modulated by targeting pro-apoptotic or pro-survival pathways. Several proteins relevant to oncogenic and proliferative processes, such as p53, bcl-2, AKT, ras and epidermal growth factor receptor, are also important in blocking apoptosis. Several small molecules that modulate cell cycle control and apoptosis have been approved recently and many will be approved in the near future. Several challenges remain, including finding ways of targeting these agents specifically to tumors (sparing normal cells), and the development of rationales for combining these new agents with standard therapies and for prioritizing the development of an overwhelming number of novel small molecules targeting cell cycle and apoptosis. Novel technologies such as genomics and proteomics will be instrumental in designing combinatorial regimens tailored to patients on the basis of the genetic makeup of tumors. Irrespective of all shortcomings, the future of modulation of apoptosis and cell cycle machinery for oncology therapy is quite exciting. C1 NIDCR, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Senderowicz, AM (reprint author), NIDCR, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sendero@helix.nih.gov NR 77 TC 69 Z9 75 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2004 VL 16 IS 6 BP 670 EP 678 DI 10.1016/j.ceb.2004.09.014 PG 9 WC Cell Biology SC Cell Biology GA 874YY UT WOS:000225387800011 PM 15530779 ER PT J AU Wahl, SM Vazquez, N Chen, WJ AF Wahl, SM Vazquez, N Chen, WJ TI Regulatory T cells and transcription factors: gatekeepers in allerrgic inflammation SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID TGF-BETA; AIRWAY HYPERREACTIVITY; HYGIENE HYPOTHESIS; ALLERGIC DISEASE; CUTTING EDGE; FACTOR FOXP3; NKT CELLS; RESPONSES; ASTHMA; GATA-3 AB Antigen-provoked polarization of CD4(+) T cells along the Th1 pathway is often associated with autoimmune and chronic inflammatory diseases, whereas extreme skewing of the response toward a Th2 phenotype has been linked to atopy and allergic diseases. Intense interest in the underlying molecular mechanisms that control polarization has revealed a contingent of regulatory transcription factors, which not only help to define these pathways but also suggest potential sites for interventional tactics. Moreover, the recent identification of transcription factors specifically associated with CD4(+)CD25(+) regulatory T-cells provides new clues regarding manipulation of this population in pursuit of directed immune regulation. Continued unraveling of the pathways underlying the development of deleterious immune responses and their control will guide new avenues of investigation and intervention. C1 NIDCR, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDCR, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov NR 47 TC 24 Z9 27 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2004 VL 16 IS 6 BP 768 EP 774 DI 10.1016/j.coi.2004.09.006 PG 7 WC Immunology SC Immunology GA 871AY UT WOS:000225102800014 PM 15511671 ER PT J AU Merrick, BA Bruno, ME AF Merrick, BA Bruno, ME TI Genomic and proteomic profiling for biomarkers and signature profiles of toxicity SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE biomarkers; DNA microarray; proteomics; signature profile; toxicity; toxicogenomics ID CDNA MICROARRAY ANALYSIS; GENE-EXPRESSION; EPITHELIAL-CELLS; END-POINTS; RAT-LIVER; IDENTIFICATION; TOXICOGENOMICS; BINDING; HEPATOTOXICANTS; PATHWAY AB Toxicity profiling measures and compares all gene expression changes among biological samples after toxicant exposure. Toxicity profiling with DNA microarrays to measure all mRNA transcripts (transcriptomics), or by global separation and identification of proteins (proteomics), has led to the discovery of better descriptors of toxicity. toxicant classification and exposure monitoring than current indicators. A shared goal in transcript and proteomic profiling is the development of biomarkers and signatures of chemical toxicity. In this review, biomarkers and signature profiles are described for specific chemical toxicants that affect target organs such as liver, kidney, neural tissues, gastrointestinal tract and skeletal muscle. for specific disease models such as cancer and inflammation, and for unique chemical-protein adducts underlying cell injury. The recent introduction of toxicogenomics databases support researchers in sharing, analyzing, visualizing and mining expression data, assist the integration of transcriptomics, proteomics and toxicology datasets, and eventually will permit in silico biomarker and signature pattern discovery. C1 NIEHS, Natl Ctr Toxicogenomics, Res Triangle Pk, NC 27709 USA. RP Merrick, BA (reprint author), NIEHS, Natl Ctr Toxicogenomics, POB 12233, Res Triangle Pk, NC 27709 USA. EM merrick@niehs.nih.gov NR 46 TC 49 Z9 52 U1 0 U2 8 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD DEC PY 2004 VL 6 IS 6 BP 600 EP 607 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 885ZW UT WOS:000226196900004 PM 15663324 ER PT J AU Sarafianos, SG Das, K Hughes, SH Arnold, E AF Sarafianos, SG Das, K Hughes, SH Arnold, E TI Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT PRIMER UNBLOCKING; POLYMERASE ACTIVE-SITE; DOUBLE-STRANDED DNA; NONNUCLEOSIDE INHIBITORS; CRYSTAL-STRUCTURES; CONFORMATIONAL-CHANGES; ANGSTROM RESOLUTION; ANALOG RESISTANCE; TEMPLATE-PRIMER AB HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites. C1 CABM, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA. NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Sarafianos, SG (reprint author), CABM, Piscataway, NJ 08854 USA. EM arnold@cabm.rutgers.edu OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [R37 AI 27690]; NIGMS NIH HHS [P01 GM 66671] NR 101 TC 97 Z9 102 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD DEC PY 2004 VL 14 IS 6 BP 716 EP 730 DI 10.1016/j.sbi.2004.10.013 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 883WE UT WOS:000226045600012 PM 15582396 ER PT J AU Lee, JH Koretsky, AP AF Lee, JH Koretsky, AP TI Manganese enhanced magnetic resonance imaging SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review ID IN-VIVO; CONTRAST AGENTS; INFARCTED MYOCARDIUM; BASAL GANGLIA; MOUSE-BRAIN; CA CHANNELS; 3D MRI; MICE; ION; ACTIVATION AB Manganese is an essential metal that participates as a co-factor in a number of critical biological functions such as electron transport, detoxification of free radicals, and synthesis of neurotransmitters. Like other heavy metals, high concentrations of manganese are toxic. For example, chronic overexposure to manganese leads to movement disorders. In order to maintain this balance between being an essential participant in enzyme function and being a toxic heavy metal, a rich biology has evolved to transport and store manganese. Paramagnetic forms of manganese ions are potent MRI relaxation agents. Indeed, Mn2+ was the first contrast agent proposed for use in MRI. Recently, there is renewed interest in combining the strong MRI relaxation effects of Mn2+ with its unique biology in order to expand the range of information that can be measured by MRI. Manganese Enhanced MRI is being developed to give unique tissue contrast, assess tissue viability, act as a surrogate marker of calcium influx into cells and trace neuronal connections. In this article we review recent work and point out prospects for the future uses of manganese enhanced MRI. C1 NINDS, LFMI, NIH, Bethesda, MD 20812 USA. RP Koretsky, AP (reprint author), NINDS, LFMI, NIH, Bldg 10,B1D118,10 Ctr Dr, Bethesda, MD 20812 USA. EM koretskya@ninds.nih.gov RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 60 TC 37 Z9 37 U1 1 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 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD DEC PY 2004 VL 5 IS 6 BP 529 EP 537 DI 10.2174/1389201043376607 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 877EP UT WOS:000225550900006 PM 15579042 ER PT J AU Kobayashi, H Brechbiel, MW AF Kobayashi, H Brechbiel, MW TI Dendrimer-based nanosized MRI contrast agents SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review ID MAGNETIC-RESONANCE LYMPHOGRAPHY; IRON-OXIDE PARTICLES; AFFINITY FOLATE RECEPTOR; NEUTRON-CAPTURE THERAPY; BREAST-CANCER XENOGRAFT; NON-HODGKINS-LYMPHOMA; GD-DTPA-POLYLYSINE; MONOCLONAL-ANTIBODY; POLYAMIDOAMINE DENDRIMER; IN-VIVO AB Paramagnetic metals can induce T1 shortening by interaction with free water molecules. Two metal ions, Gadolinium and Manganese, arc currently available for human use. Gadolinium-based MRI contrast agents (CAs) can operate using a similar to100-fold lower concentration of Gadolinium ions in comparison to the necessary concentration of Iodine atoms employed in CT imaging in the tissues. Therefore, numerous macromolecular MRI CAs prepared employing relatively simple chemistry are readily available that can provide sufficient enhancement for multiple applications. Herein, we describe the synthesis, characteristics, and potential applications of dendrimer-based macromolecular MRI CAs in our recently reported libraries. This entire series of dendrimer-based macromolecular MRI CAs have a spherical shape and possess similar surface charges. Changes in molecular size altered the route of excretion. Smaller sized contrast agents, of less than 60 kD molecular weight, were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Less hydrophilic and larger sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants of CAs formed with polypropylenimine diaminobutane dendrimer cores quickly accumulated in the liver and can function as liver contrast agents. Larger hydrophilic agents are also useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents and might also be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy. C1 NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room B3B69,MCS 1002,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov NR 78 TC 109 Z9 112 U1 2 U2 38 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD DEC PY 2004 VL 5 IS 6 BP 539 EP 549 DI 10.2174/1389201043376571 PG 11 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 877EP UT WOS:000225550900007 PM 15579043 ER PT J AU Barrett, J AF Barrett, J TI Are stem cells and T cells best transplanted separately? SO CYTOTHERAPY LA English DT Editorial Material ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC MYELOID-LEUKEMIA; LOW-DOSE CYCLOSPORINE; ADD-BACK; SELECTIVE DEPLETION; ACUTE GVHD; LYMPHOCYTES; MALIGNANCIES; PROPHYLAXIS C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 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 PD DEC PY 2004 VL 6 IS 6 BP 529 EP 532 DI 10.1080/14653240410011927 PG 4 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700001 PM 15764019 ER PT J AU Dunbar, C Nabel, EG McKay, R AF Dunbar, C Nabel, EG McKay, R TI Introduction to Clinical applications of stem cells at the National Institutes of Health: a meeting held on 24 May 2004 at the Cinical Center of the National Institutes of Health, Bethesda, Maryland, USA SO CYTOTHERAPY LA English DT Editorial Material C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Dunbar, C (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 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 PD DEC PY 2004 VL 6 IS 6 BP 585 EP 585 DI 10.1080/14653240410011945 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 890JY UT WOS:000226508700007 ER PT J AU Dunbar, CE AF Dunbar, CE TI Stem and progenitor cell therapies: insights from non-human primate models SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID MOBILIZATION; AMD3100; CXCR4; BLOOD AB Genetic marking strategies in the non-human primate model have elucidated a number of principles relevant to implementation of clinical stem cell therapies, including the lineage potential, number and lifespan of hematopoietic stem and progenitor cells, and differences in the functional properties of marrow cells mobilized into the peripheral blood utilizing different regimens. C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 3 Z9 3 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 PD DEC PY 2004 VL 6 IS 6 BP 586 EP 588 DI 10.1080/14653240410005320 PG 3 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700008 PM 15764024 ER PT J AU Walshe, J Bishop, MR AF Walshe, J Bishop, MR TI Factors affecting engraftment of allogeneic hematopoietic stem cells after reduced-intensity conditioning SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST DISEASE; HEMATOLOGIC MALIGNANCIES; LYMPHOCYTE DEPLETION; DONOR ENGRAFTMENT; GRAFT-REJECTION; THERAPY; CHEMOTHERAPY; CHIMERISM; REGIMEN AB Several factors influence the engraftment of allogeneic hematopoietic stem cells (HSC). Recently, there has been increased utilization of transplant-conditioning regimens that use reduced doses of chemotherapy and radiation that are considered to be non-myeloablative. These non-myeloablative (or reduced-intensity) allogeneic HSC transplants (RIST) decrease early post-transplant complications, but they are associated with higher incidences of mixed chimerism and graft rejection compared with transplantation after myeloablative conditioning. RIST provides a unique opportunity to study allogeneic HSC engraftment. In particular, host immune status and stem cell graft composition have emerged as important factors affecting engraftment after RIST. Based on these observations, it has been hypothesized that conditioning regimens and allograft composition can be tailored to an individual patient's immune and disease status prior to transplant. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Ctr Canc Res, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 23 TC 8 Z9 8 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 PD DEC PY 2004 VL 6 IS 6 BP 589 EP 592 DI 10.1080/14653240410005285 PG 4 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700009 PM 15773022 ER PT J AU Barrett, J Solomon, S AF Barrett, J Solomon, S TI The transition from bench to bedside: lessons learned in the creation of a new T-cell product for the clinic SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID GRAFT-VERSUS-HOST; BONE-MARROW TRANSPLANTATION; MYELOID-LEUKEMIA CELLS; SELECTIVE DEPLETION; DISEASE PROPHYLAXIS; LYMPHOCYTES; MODEL; GVHD AB While the technology of translational research is sometimes considered a poor relation to 'basic science', it has become a central focus of work to turn exciting new concepts into practical therapies. Here we use the example of selective T-cell depletion of allografted lymphocytes to illustrate the problems of scale-up, reproducibility, sterility, safety and regulatory concerns encountered during the bench to bedside process. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 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 PD DEC PY 2004 VL 6 IS 6 BP 593 EP 595 DI 10.1080/14653240410011936 PG 3 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700010 PM 15764025 ER PT J AU Song, L Baksh, D Tuan, RS AF Song, L Baksh, D Tuan, RS TI Mesenchymal stem cell-based cartilage tissue engineering: cells, scaffold and biology SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID HUMAN TRABECULAR BONE; PROGENITOR CELLS AB Cartilage repair and regeneration by stem cell-based tissue engineering could be of enormous therapeutic and economic potential benefit for an aging population. However, to use stem cells effectively, their natural environment must be understood in order to expand them in vitro without compromising their multilineage potential and their specific differentiation program. Collaboration between diverse academic disciplines and between research and regulatory government agencies and industry is crucial before cell-based cartilage tissue engineering can achieve its full therapeutic potential. C1 NIAMSD, Cartilage Biol & Orthoped Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthoped Branch, NIH, US Dept HHS, 50 South Dr,Room 1503,MSC 8022, Bethesda, MD 20892 USA. NR 10 TC 60 Z9 67 U1 0 U2 10 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD DEC PY 2004 VL 6 IS 6 BP 596 EP 601 DI 10.1080/14653240410005276 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700011 PM 15773023 ER PT J AU Cannon, RO AF Cannon, RO TI Cardiovascular potential of BM-derived stem and progenitor cells SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID CORONARY-ARTERY-DISEASE; BONE-MARROW CELLS; COLONY-STIMULATING FACTOR; MYOCARDIAL-INFARCTION; ENDOTHELIAL-CELLS; S-NITROSYLATION; CLINICAL-TRIAL; LIMB ISCHEMIA; TRANSPLANTATION; ANGIOGENESIS AB Observational and experimental studies suggest that BM-derived stem and progenitor cells may have the capacity to repair damaged cardiovascular tissue and initiate blood vessel growth in regions of ischemia. Despite controversies regarding transdifferentiation potential of adult stem cells, clinical trials are underway testing the hypothesis that BM cell-based approaches to a broad spectrum of cardiovascular diseases and disease presentations will be safe and effective strategies for patient management. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10 Room 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 35 TC 5 Z9 5 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 PD DEC PY 2004 VL 6 IS 6 BP 602 EP 607 DI 10.1080/14653240410005294 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700012 PM 15764026 ER PT J AU de Silva, R Lederman, RJ AF de Silva, R Lederman, RJ TI Delivery and tracking of therapeutic cell preparations for clinical cardiovascular applications SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID MESENCHYMAL STEM-CELLS; ACUTE MYOCARDIAL-INFARCTION; BONE-MARROW-CELLS; ISCHEMIC-HEART FAILURE; PROGENITOR CELLS; TOPCARE-AMI; TRANSPLANTATION; REGENERATION; IMPLANTATION; DIFFERENTIATION AB Experimental observations suggesting adult stem cell plasticity and cross-lineage transdifferentiation have underpinned the investigation of cell therapy for cardiovascular disease. Many challenges still face the full realization of cardiovascular regenerative medicine. This brief review will highlight some of these, with emphasis on the choice of cell preparation, route of cell delivery and tracking of delivered cells. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10,Room 2C713,10 Ctr Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [Z01 HL005062-03] NR 36 TC 4 Z9 4 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 PD DEC PY 2004 VL 6 IS 6 BP 608 EP 614 DI 10.1080/14653240410005339 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700013 PM 15764027 ER PT J AU Muraro, PA Cassiani-Ingoni, R Martin, R AF Muraro, PA Cassiani-Ingoni, R Martin, R TI Using stem cells in multiple sclerosis therapies SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID SPINAL-CORD-INJURY; NEURAL STEM; AXONAL GROWTH; FOLLOW-UP; TRANSPLANTATION; DISEASE; RESCUE; MRI AB Stem cell transplantation approaches offer for the first time the opportunity to design therapeutic approaches for multiple sclerosis ( MS) with curative intent. Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS and from studies of myelin/neural repair in experimental models of demyelinating disorders. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B16,10 Ctr Dr,MSC1400, Bethesda, MD 20892 USA. OI Muraro, Paolo/0000-0002-3822-1218 NR 23 TC 4 Z9 5 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 PD DEC PY 2004 VL 6 IS 6 BP 615 EP 620 DI 10.1080/14653240410005311 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700014 PM 15764028 ER PT J AU Frank, JA Anderson, SA Kalsih, H Jordan, EK Lewis, BK Yocum, GT Arbab, AS AF Frank, JA Anderson, SA Kalsih, H Jordan, EK Lewis, BK Yocum, GT Arbab, AS TI Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID TRANSFECTION AGENTS; TRACKING; NANOPARTICLES; FERUMOXIDES; TRAFFICKING; PROGENITOR; MIGRATION AB Superparamagnetic iron oxide (SPIO) nanoparticles are being used for intracellular magnetic labeling of stem cells and other cells in order to monitor cell trafficking by magnetic resonance imaging (MRI) as part of cellular-based repair, replacement and treatment strategies. This review focuses on the various methods for magnetic labeling of stem cells and other mammalian cells and on how to translate experimental results from bench to bedside. C1 NINDS, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Clin Ctr,NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Frank, JA (reprint author), NINDS, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Clin Ctr,NIH, Bldg 10,Room B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA. NR 16 TC 92 Z9 97 U1 1 U2 7 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD DEC PY 2004 VL 6 IS 6 BP 621 EP 625 DI 10.1080/14653240410005267 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700015 PM 15773025 ER PT J AU Read, EJ AF Read, EJ TI Innovation meets quality: moving cellular therapies at the National Institutes for Health from bench to bedside SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT Meeting no Clinical Applications of Stem Cells CY MAY 24, 2004 CL Natl Inst Hlth, Clin Ctr, Bethesda, MD HO Natl Inst Hlth, Clin Ctr ID CHRONIC GRANULOMATOUS-DISEASE; PERIPHERAL-BLOOD; CLOSED-SYSTEM; GENE-THERAPY; CELLS; TRANSPLANTATION; IMMUNOTHERAPY; ENGRAFTMENT; GENERATION; CANCER AB The National Institutes of Health (NIH) Department of Transfusion Medicine has supported clinical investigation in cellular therapies over the past 20 years. This experience, which encompasses product development research, quality system design and product manufacturing for a wide range of early phase clinical trials, provides a firm basis for future work with novel stem cell therapies. C1 NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20814 USA. RP Read, EJ (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711,10 Ctr Dr, Bethesda, MD 20814 USA. NR 21 TC 1 Z9 1 U1 0 U2 4 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD DEC PY 2004 VL 6 IS 6 BP 626 EP 628 DI 10.1080/14653240410005302 PG 3 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 890JY UT WOS:000226508700016 PM 15764029 ER PT J AU Yu, Q Shen, Y Chatterjee, B Siegfried, BH Leatherbury, L Rosenthal, J Lucas, JF Wessels, A Spurney, CF Wu, YJ Kirby, ML Svenson, K Lo, CW AF Yu, Q Shen, Y Chatterjee, B Siegfried, BH Leatherbury, L Rosenthal, J Lucas, JF Wessels, A Spurney, CF Wu, YJ Kirby, ML Svenson, K Lo, CW TI ENU induced mutations causing congenital cardiovascular anomalies SO DEVELOPMENT LA English DT Article DE congenital heart defects; cardiovascular anomalies; ENU mutagenesis; mouse mutants; ultrasound imaging ID HOLT-ORAM-SYNDROME; JUNCTION PROTEIN CONNEXIN-43; CELL-CELL COMMUNICATION; NEURAL CREST MIGRATION; DIGEORGE-SYNDROME; HEART-DISEASE; CARDIAC MALFORMATION; DELETION SYNDROME; ALAGILLE-SYNDROME; CANDIDATE GENE AB We used non-invasive high frequency ultrasound to screen N-ethyl-N-nitrosourea mutagenized mouse fetuses for congenital cardiovascular anomalies. We ultrasound scanned 7546 mouse fetuses from 262 mutagenized families, and identified 124 families with cardiovascular defects. Represented were most of the major congenital cardiovascular anomalies seen clinically. The ENU-induced mutations in several families were mapped using polymorphic microsatellite DNA markers. One family with forelimb anomalies and ventricular septal defects, phenotypes similar to Holt-Oram syndrome, and one family with transposition of the great arteries and heart situs anomalies were mapped to different regions of mouse chromosome 4. A third mutation causing persistent truncus arteriosus and craniofacial defects, phenotypes reminiscent of DiGeorge syndrome, was mapped to mouse chromosome 2. We note that mouse chromosomes 4 and 2 do not contain Tbx5 or Tbx1, genes previously linked to Holt-Oram and DiGeorge syndromes, respectively. In two other families, the ENU-induced mutation was identified - Sema3C(L605P) was associated with persistent truncus arteriosus with interrupted aortic arch, and the Gja1(W45X) connexin43 mutation caused conotruncal malformation and coronary aneurysms. Although our screen was designed as a recessive screen, a number of the mutations showed cardiovascular phenotypes in both heterozygote and homozygote animals. These studies show the efficacy of ENU mutagenesis and high-throughput ultrasound phenotyping in recovering mutations causing a wide spectrum of congenital heart defects. These ENU-induced mutations hold promise in yielding new insights into the genetic basis for human congenital heart disease. C1 NHLBI, NIH, Lab Dev Biol, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Dept Pediat, Bethesda, MD 20814 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Med Univ S Carolina, Dept Anat & Cell Biol, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Lo, CW (reprint author), NHLBI, NIH, Lab Dev Biol, Bldg 10, Bethesda, MD 20892 USA. EM loc@nhlbi.nih.gov FU NHLBI NIH HHS [HL36059, HL66611, HL70140, P01-HL52813, T32-HL07710, ZO1-HL005701]; NICHD NIH HHS [P01-HD39946, HD39946] NR 66 TC 69 Z9 72 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 2004 VL 131 IS 24 BP 6211 EP 6223 DI 10.1242/dev.01543 PG 13 WC Developmental Biology SC Developmental Biology GA 887RW UT WOS:000226324200018 PM 15548583 ER PT J AU Allhusen V Belsky, J Booth, CL Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Payne, C Phillips, D Pianta, R Robeson, W Spieker, S Vandell, DL Weinraub, M AF Allhusen, V Belsky, J Booth, CL Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Payne, C Phillips, D Pianta, R Robeson, W Spieker, S Vandell, DL Weinraub, M CA NICHD Early Child Care Res Net TI Affect dysregulation in the mother-child relationship in the toddler years: Antecedents and consequences SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID EXTERNALIZING BEHAVIOR PROBLEMS; AGE 3 YEARS; DEVELOPMENTAL PERSPECTIVE; INDIVIDUAL-DIFFERENCES; EMOTION REGULATION; FAMILY-INTERACTION; ATTACHMENT; INFANCY; TEMPERAMENT; PREDICTORS AB The purpose of this study was to examine child, maternal, and family antecedents of children's early affect dysregulation within the mother-child relationship and later cognitive and socioemotional correlates of affect dysregulation. Children's affect dysregulation at 24 and 36 months was defined in the context of mother-child interactions in semistructured play and toy cleanup. Dyads were classified as dysregulated at each age based on high negative affect. Affect dysregulation was associated with less maternal sensitivity and stimulation, more maternal depressive symptoms, and lower family income over the first 36 months of life. Children with early negative mood, lower Bayley Mental Development Index scores and insecure-avoidant (15 months) or insecure-resistant attachment classifications (36 months) were more likely to be in an affect-dysregulated group. Controlling for family and child variables, affect-dysregulated children had more problematic cognitive, social, and behavioral outcomes at 54 months, kindergarten, and first grade. The findings are discussed in terms of the early role played by parents in assisting children with affect regulation, the reciprocal nature of parent-child interactions, and the contribution of affect regulation to children's later cognitive, social, and behavioral competence. C1 NICHD Early Child Care Res Network, Rockville, MD 20852 USA. RP Allhusen V (reprint author), NICHD Early Child Care Res Network, 6100 Execut Blvd,4A01, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012; Nguyen, Linh/H-3611-2012; OI Marshall, Nancy L/0000-0002-4799-2030; Belsky, Jay/0000-0003-2191-2503; Pianta, Robert/0000-0002-6280-8051 NR 81 TC 69 Z9 69 U1 5 U2 27 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 2004 VL 16 IS 1 BP 43 EP 68 DI 10.1017/S0954579404040404 PG 26 WC Psychology, Developmental SC Psychology GA 805GY UT WOS:000220356000003 ER PT J AU Liu, Y Han, SSW Wu, YY Tuohy, TMF Xue, HP Cai, JL Back, SA Sherman, LS Fischer, I Rao, MS AF Liu, Y Han, SSW Wu, YY Tuohy, TMF Xue, HP Cai, JL Back, SA Sherman, LS Fischer, I Rao, MS TI CD44 expression identifies astrocyte-restricted precursor cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE stem cells; neuroepithelial cells; glial-restricted precursors; differentiation; extracellular matrix protein ID NEUROEPITHELIAL STEM-CELLS; FIBROBLAST-GROWTH-FACTOR; DEVELOPING SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; NEURONAL PRECURSORS; SUBVENTRICULAR ZONE; OLIGODENDROCYTE; DIFFERENTIATION; RAT AB The precise lineage between neural stem cells and mature astrocytes remains poorly defined. To examine astrocyte development, we have characterized glial precursors from neural tissue derived from early embryonic ages. We show that CD44 identifies an astrocyte-restricted precursor cell (ARP) that is committed to generating astrocytes in vitro and in vivo in both rodent and human tissue. CD44+ cells arise later in development than neuronal-restricted precursors (NRPs) or tripotential glial-restricted precursors (GRPs). ARPs are distinguished from GRP and NRP cells by their antigenic profile and differentiation ability. ARPs can be generated from GRP cells in mass or clonal cultures and in vivo after transplantation, suggesting a sequential differentiation of neuroepithelial stem cells (NEPs) to GRPs to ARPs and then to astrocytes. The properties of ARPs are different from other astrocyte precursors described previously in their expression of CD44 and S-100beta and absence of other lineage markers. Using a CD44 misexpression transgenic mouse model (CNP-CD44 mouse), we show that CD44 overexpression in vivo and in vitro decreases the number of mature glia and increases the number of O4+/GFAP+ cells tenfold. Misexpression of CD44 in culture inhibits oligodendrocytes and arrests cells at the precursor state. In summary, our data provide strong evidence for the existence of a CD44+ ARP in the developing nervous system. (C) Published by Elsevier Inc. C1 NIA, Neurosci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. Oregon Hlth Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Sch Med, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Med, Dept Pediat, Portland, OR 97201 USA. RP Liu, Y (reprint author), NIA, Neurosci Lab, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM liuyi@grc.nia.nih.gov; raomah@grc.nia.nih.gov RI Tuohy, Therese/A-8665-2009; Fischer, Itzhak/D-1080-2012 OI Fischer, Itzhak/0000-0003-3187-8740 NR 53 TC 103 Z9 105 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2004 VL 276 IS 1 BP 31 EP 46 DI 10.1016/j.ydbio.2004.08.018 PG 16 WC Developmental Biology SC Developmental Biology GA 872WV UT WOS:000225240800003 PM 15531362 ER PT J AU Hu, J Chen, YX Wang, D Qi, XX Li, TG Hao, J Mishina, Y Garbers, DL Zhao, GQ AF Hu, J Chen, YX Wang, D Qi, XX Li, TG Hao, J Mishina, Y Garbers, DL Zhao, GQ TI Developmental expression and function of Bmp4 in spermatogenesis and in maintaining epididymal integrity SO DEVELOPMENTAL BIOLOGY LA English DT Article DE BMPs; Bmp4; spermatogenesis; mouse; genetics; male germ cells; epididymis ID PRIMORDIAL GERM-CELLS; MORPHOGENETIC PROTEIN-RECEPTOR; THREONINE KINASE RECEPTOR; FIBROBLAST-GROWTH-FACTOR; MOUSE EMBRYOGENESIS; TESTICULAR FACTORS; SIGNALING PATHWAYS; MURINE EPIDIDYMIS; GENE-EXPRESSION; SPERM MOTILITY AB Bone morphogenetic, proteins (BMPs) play essential roles in many aspects of developmental biology. We have previously shown that Bmp7, Bmp8a, and Bmp8b of the 60A class of Bmp genes have additive effects in spermatogenesis and in maintaining the epididymal integrity of the caput and caudal regions. Here we report that Bmp4 of the Dpp class has a unique expression pattern in the developing testis and epididymis. Bmp4 heterozygous males on a largely C57BL/6 background show compromised fertility due to degeneration of germ cells, reduced sperm counts, and decreased sperm motility. More interestingly, some of these males show extensive degeneration of the epididymal epithelium in the corpus region, rather than in the caput and cauda regions as for Bmp7 and Bmp8 mutants. Thus, these genetic data reveal a region-specific requirement of different classes of BMPs for epididymal epithelium to survive and have significant implications on male reproductive health and perhaps birth control. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Pharmacol, Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA. Univ Missouri, Coll Vet Med, Dept Pathobiol, Columbia, MO 65211 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX USA. RP Zhao, GQ (reprint author), Univ Texas, SW Med Ctr, Dept Pharmacol, Green Ctr Reprod Biol Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM guang.zhao@utsouthwestem.edu FU BHP HRSA HHS [DH36218]; NICHD NIH HHS [HD39154] NR 69 TC 48 Z9 52 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2004 VL 276 IS 1 BP 158 EP 171 DI 10.1016/j.ydbio.2004.08.034 PG 14 WC Developmental Biology SC Developmental Biology GA 872WV UT WOS:000225240800012 PM 15531371 ER PT J AU Kishigami, S Yoshikawa, SI Castranio, T Okazaki, K Furuta, Y Mishina, Y AF Kishigami, S Yoshikawa, SI Castranio, T Okazaki, K Furuta, Y Mishina, Y TI BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo SO DEVELOPMENTAL BIOLOGY LA English DT Article DE BMP signaling; midline; perinode; left-right asymmetry ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; LEFT-RIGHT SPECIFICATION; NODAL EXPRESSION; CRANIOFACIAL DEVELOPMENT; PRIMITIVE STREAK; PATHWAYS; GENE; RECEPTOR; PITX2 AB Vertebrate organisms are characterized by dorsal-ventral and left-right asymmetry. The process that establishes left-right asymmetry during vertebrate development involves bone morphogenetic protein (BMP)-dependent signaling, but the molecular details of this signaling pathway remain poorly defined. This study tests the role of the BMP type I receptor ACVRI in establishing left-right asymmetry in chimeric mouse embryos. Mouse embryonic stem (ES) cells with a homozygous deletion at Acvr1 were used to generate chimeric embryos. Chimeric embryos were rescued from the gastrulation defect of Acvr1 null embryos but exhibited abnormal heart looping and embryonic turning. High mutant contribution chimeras expressed left-side markers such as nodal bilaterally in the lateral plate mesoderm (LPM), indicating that loss of ACVRI signaling leads to left isomerism. Expression of lefty1 was absent in the midline of chimeric embryos, but shh, a midline marker, was expressed normally, suggesting that, despite formation of midline, its barrier function was abolished. High-contribution chimeras also lacked asymmetric expression of nodal in the node. These data suggest that ACVRI signaling negatively regulates left-side determinants such as nodal and positively regulates lefty1. These functions maintain the midline, restrict expression of left-side markers, and are required for left-right pattern formation during embryogenesis in the mouse. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Mol Dev Biol Grp, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Biomol Engn Res Inst, Dept Mol Biol, Suita, Osaka 5650874, Japan. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Mishina, Y (reprint author), NIEHS, Mol Dev Biol Grp, Reprod & Dev Toxicol Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM mishina@niehs.nih.gov RI Okazaki, Kenji/H-4393-2012 NR 39 TC 38 Z9 40 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2004 VL 276 IS 1 BP 185 EP 193 DI 10.1016/j.ydbio.2004.08.042 PG 9 WC Developmental Biology SC Developmental Biology GA 872WV UT WOS:000225240800014 PM 15531373 ER PT J AU Ebert, SN Rong, Q Boe, S Thompson, RP Grinberg, A Pfeifer, K AF Ebert, SN Rong, Q Boe, S Thompson, RP Grinberg, A Pfeifer, K TI Targeted insertion of the Cre-recombinase gene at the phenylethanolamine n-methyltransferase locus: A new model for studying the developmental distribution of adrenergic cells SO DEVELOPMENTAL DYNAMICS LA English DT Article DE epinephrine; catecholamines; pacemaking; heart development ID CARDIAC CONDUCTION SYSTEM; NEURAL CREST; ARTERIAL POLE; CHANNEL HCN4; RAT-HEART; EXPRESSION; MOUSE; DIFFERENTIATION; GLUCOCORTICOIDS; NORADRENALINE AB To evaluate the developmental distribution of adrenergic cells in vivo, we inserted the Cre-recombinase gene into the locus encoding for the epinephrine biosynthetic enzyme phenylethanolamine n-methyltransferase (Pnmt) and crossed these Pnmt-Cre mice with ROSA26 reporter (R26R) mice to activate LacZ (encoding P-galactosidase) expression in cells that were selectively derived from the adrenergic lineage. Our data show the following: (1) Insertion of Cre-recombinase into the Pnmt locus created a functional knockout of Pnmt expression with concomitant loss of epinephrine in homozygous Pnmt(Cre/Cre) mice; (2) Despite the reduction in Pnmt expression and epinephrine production in Pnmt(Cre/Cre) mice, these mice were viable and fertile, with no apparent developmental defects; (3) When crossed with R26R mice, Pnmt-Cre activation of LacZ expression faithfully recapitulated Pnmt expression in vivo; and (4) LacZ expression was activated in substantial numbers of pacemaking, conduction, and working cardiomyocytes. (C) 2004 Wiley-Liss, Inc. C1 Georgetown Univ, Ctr Med, Dept Pharmacol, Washington, DC 20057 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC USA. RP Ebert, SN (reprint author), Georgetown Univ, Ctr Med, Dept Pharmacol, 3900 Reservoir Rd,NW, Washington, DC 20057 USA. EM eberts@georgetown.edu OI Pfeifer, Karl/0000-0002-0254-682X NR 32 TC 36 Z9 36 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2004 VL 231 IS 4 BP 849 EP 858 DI 10.1002/dvdy.20188 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 874DM UT WOS:000225331100020 PM 15517585 ER PT J AU Pipe, ME Lamb, ME Orbach, Y Esplin, PW AF Pipe, ME Lamb, ME Orbach, Y Esplin, PW TI Recent research on children's testimony about experienced and witnessed events SO DEVELOPMENTAL REVIEW LA English DT Article; Proceedings Paper CT 3rd Biennial Meeting of the Cognitive-Development-Society CY OCT, 2003 CL Park City, UT SP Cognit Dev Soc ID LONG-TERM RETENTION; INVESTIGATIVE UTTERANCE TYPES; ANATOMICALLY DETAILED DOLLS; NARRATIVE ELABORATION; YOUNG-CHILDREN; SEXUAL-ABUSE; EYEWITNESS TESTIMONY; CONTEXT REINSTATEMENT; INTERVIEWING PRESCHOOLERS; TRAUMATIC EXPERIENCES AB Research on memory development has increasingly moved out of the laboratory and into the real world. Whereas early researchers asked whether confusion and susceptibility to suggestion made children unreliable witnesses, furthermore, contemporary researchers are addressing a much broader range of questions about children's memory, focusing not only on children's frailties but also on their competencies. In this review, we emphasize work on factors that promote the retrieval and accurate recounting of experienced or witnessed events and the implications of these findings for forensic interview practices. Research shows that children are capable of providing accurate information about their experiences, although their ability to convey the information is affected not only by the qualities of their memories, but also by the types of retrieval mechanisms employed and the quality of the communication between them and their interlocutors. We thus discuss several characteristics of to-be-remembered events that affect memory and are relevant to children's recall in applied settings; retrieval conditions and their effects on the amount and accuracy of the information that children report; and research on investigative interviews conducted in forensic contexts. Because many of the variables that influence memory are age-related, developmental changes in children's ability to accurately report, and recount their experiences are highlighted. Published by Elsevier Inc. C1 Univ Cambridge, Dept Social & Dev Psychol, Cambridge CB2 3RQ, England. NICHHD, Bethesda, MD USA. RP Lamb, ME (reprint author), Univ Cambridge, Dept Social & Dev Psychol, Free Sch Lane, Cambridge CB2 3RQ, England. EM mel37@cam.ac.uk NR 242 TC 57 Z9 58 U1 6 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2297 EI 1090-2406 J9 DEV REV JI Dev. Rev. PD DEC PY 2004 VL 24 IS 4 BP 440 EP 468 DI 10.1016/j.dr.2004.08.006 PG 29 WC Psychology, Developmental SC Psychology GA 876BF UT WOS:000225469800005 ER PT J AU Koska, J DelParigi, A de Courten, B Weyer, C Tataranni, PA AF Koska, J DelParigi, A de Courten, B Weyer, C Tataranni, PA TI Pancreatic polypeptide is involved in the regulation of body weight in pima Indian male subjects SO DIABETES LA English DT Article ID PRADER-WILLI SYNDROME; FOOD-INTAKE; Y4 RECEPTOR; ANOREXIA-NERVOSA; GUT HORMONE; SECRETION; OBESITY; MICE; CHILDREN; RELEASE AB Pancreatic polypeptide (PP) is released from the pancreas in response to a meal. In humans, low-circulating PP levels have been observed in obesity, and administration of pharmacological doses of PP has been shown to decrease food intake. The aim of the present study was to investigate whether low circulating PP is associated with weight gain in Pima Indians. Plasma PP concentrations were measured after an overnight fast and 30 min after a standardized mixed meal in 33 nondiabetic male subjects who had a follow-up visit 4.9 +/- 2.5 years later. Cross-sectionally, fasting and postprandial PP levels were negatively associated with body size and adiposity. Prospectively, the change in PP response to the meal was negatively associated with the change in body weight (r = -0.53, P = 0.002). In contrast, a high fasting PP level was positively associated with change in body weight (r = 0.45, P = 0.009). In conclusion, our results provide evidence that, even within the physiological range, PP contributes to the regulation of energy balance in humans. However this contribution appears to be more complex than anticipated because of the opposite effect of fasting and postprandial. PP on the risk of future weight gain. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Baker Heart Res Inst, Melbourne, Vic, Australia. RP Koska, J (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. EM jkoska@mail.nih.gov OI de Courten, Barbora/0000-0001-8760-2511 NR 31 TC 18 Z9 19 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 IS 12 BP 3091 EP 3096 DI 10.2337/diabetes.53.12.3091 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874CI UT WOS:000225328100008 PM 15561938 ER PT J AU Lu, YR Herrera, PL Guo, YB Sun, D Tang, ZY LeRoith, D Liu, JL AF Lu, YR Herrera, PL Guo, YB Sun, D Tang, ZY LeRoith, D Liu, JL TI Pancreatic-specific inactivation of IGF-I gene causes enlarged pancreatic islets and significant resistance to diabetes SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; BETA-CELL GROWTH; INSULIN-RESISTANCE; TRANSGENIC MICE; SIGNAL-TRANSDUCTION; ENDOCRINE PANCREAS; C57BL/6J MICE; RAT ISLETS; NOD MICE; RECEPTOR AB The dogma that IGF-I stimulates pancreatic islet growth has been challenged by combinational targeting of IGF or IGF-IR (IGF receptor) genes as well as beta-cell-specific IGF-IR gene deficiency, which caused no defect in islet cell growth. To assess the physiological role of locally produced IGF-I, we have developed pancreatic-specific IGF-I gene deficiency (PID) by crossing Pdx1-Cre and IGF-I/loxP mice. PID mice are normal except for decreased blood glucose level and a 2.3-fold enlarged islet cell mass. When challenged with low doses of streptozotocin, control mice developed hyperglycemia after 6 days that was maintained at high levels for at least 2 months. In contrast, PID mice only exhibited marginal hyperglycemia after 12 days, maintained throughout the experiment. Fifteen days after streptozotocin, PID mice demonstrated significantly higher levels of insulin production. Furthermore, streptozotocin-induced P-cell apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL] assay) was significantly prevented in PID mice. Finally, PID mice exhibited a delayed onset of type 2 diabetes induced by a high-fat diet, accompanied by super enlarged pancreatic islets, increased insulin mRNA levels, and preserved sensitivity to insulin. Our results suggest that locally produced IGF-I within the pancreas inhibits islet cell growth; its deficiency provides a protective environment to the beta-cells and potential in combating diabetes. C1 McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ H3A 2T5, Canada. Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. Shanghai Univ, E Inst, Shanghai Clin Ctr Endocrine & Metab Dis, Div Endocrine & Metab, Shanghai, Peoples R China. RP Liu, JL (reprint author), Royal Victoria Hosp, Fraser Labs, Room M3-15,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM jun-li.liu@mcgill.ca NR 50 TC 49 Z9 52 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 IS 12 BP 3131 EP 3141 DI 10.2337/diabetes.53.12.3131 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874CI UT WOS:000225328100013 PM 15561943 ER PT J AU Gregg, EW Cadwell, BL Cheng, YJ Cowie, CC Williams, DE Geiss, L Engelgau, MM Vinicor, F AF Gregg, EW Cadwell, BL Cheng, YJ Cowie, CC Williams, DE Geiss, L Engelgau, MM Vinicor, F TI Trends in the prevalence and ratio of diagnosed to undiagnosed diabetes according to obesity levels in the U.S SO DIABETES CARE LA English DT Article ID NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE; US ADULTS; COFFEE CONSUMPTION; NATIONAL-HEALTH; MALE PHYSICIANS; RISK-FACTOR; MELLITUS; WOMEN AB OBJECTIVE - To examine trends in the prevalence of diagnosed and undiagnosed diabetes and the proportion of total cases previously diagnosed, according to obesity status in the U.S. over the past 40 years. RESEARCH DESIGN AND METHODS - We assembled data from five consecutive cross-sectional national surveys: National Health Examination Survey I (1960-1962), National Health and Nutrition Examination Survey (NHANES) I (1971-1974), NHANES II (1976-1980), NHANES III (1988-1994), and NHANES 1999-2000. Diagnosed diabetes was ascertained, and height and weight were measured in adults aged 20-74 years in all surveys. In NHANES II, NHANES III, and NHANES 1999-2000, a fasting glucose level greater than or equal to126 mg/dl was used to identify cases among individuals not reporting diabetes. Design-based analyses and Bayesian models estimate the probability that prevalence of diabetes increased within four BMI groups (<25, 25-29, 30-34, and greater than or equal to35 kg/m(2)). RESULTS - In the U.S. population aged 20-74 years between 1976-1980 and 1999-2000,, significant increases in the prevalence of diagnosed diabetes (3.3-5.8%, probability >99.9%) were accompanied by nonsignificant increases in undiagnosed diabetes (2.0-2.4%, 66.6%). This resulted in an increase in total diabetes (5.3 8.2%, >99.9%) and a modest nonsignificant increase in the proportion of cases that were diagnosed (62-70%, 62.4%). However, these trends varied considerably by BMI level. In individuals with BMI greater than or equal to35 kg/m(2), diagnosed diabetes increased markedly (from 4.9% in 1960, to 8.6% during 1976-1980, to 15.1% in 1999-2000; probability >99.9%), whereas undiagnosed diabetes declined considerably (12.5% during 1976-1980 to 3.2% in 1999-2000, probability of increase 4.5%) Therefore, the proportion of total diabetes cases that were diagnosed increased from 41 to 83% (probability 99.9%) among individuals with BMI greater than or equal to35 kg/m(2). By comparison, changes in prevalence within BMI strata <35 kg/m(2) were modest and there was no increase in the percent of total cases that were diagnosed. CONCLUSIONS - National surveys over the last several decades have found large increases in diagnosed diabetes, particularly in overweight and obese individuals, but this has been accompanied by large decreases in undiagnosed diabetes only among individuals with BMI greater than or equal to35 kg/m(2). This suggests that improvements in diabetes awareness and detection are most prominent among this subgroup. C1 CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA 30341 USA. Northrop Grumman, Div Informat Technol, Atlanta, GA USA. NIDDK, NIH, Bethesda, MD USA. RP Gregg, EW (reprint author), CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, 4770 Buford Hwy,NE Mailstop K-10, Atlanta, GA 30341 USA. EM edg7@cdc.gov NR 38 TC 190 Z9 199 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2004 VL 27 IS 12 BP 2806 EP 2812 DI 10.2337/diacare.27.12.2806 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874DU UT WOS:000225331900006 PM 15562189 ER PT J AU Kim, H Haluzik, M Gavrilova, O Yakar, S Portas, J Sun, H Pajvani, UB Scherer, PE LeRoith, D AF Kim, H Haluzik, M Gavrilova, O Yakar, S Portas, J Sun, H Pajvani, UB Scherer, PE LeRoith, D TI Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE adiponectin; adipose tissue; hyperinsulinaemic-euglycaemic clamp; insulin sensitivity; muscle insulin action; thiazolidinediones ID PPAR-GAMMA AGONISTS; SKELETAL-MUSCLE; GENE-EXPRESSION; TROGLITAZONE ACTION; GLUCOSE-UPTAKE; RESISTANCE; MICE; ROSIGLITAZONE; RECEPTOR; LIVER AB Aim/hypothesis. The aim of this study was to examine the effects of thiazolidinediones on the MKR mouse model of type 2 diabetes. Methods. Six-week-old wild-type (WT) and MKR mice were fed with or without rosiglitazone or pioglitazone for 3 weeks. Blood was collected from the tail vein for serum biochemistry analysis. Hyperinsulinaemic - euglycaemic clamp analysis was performed to study effects of thiazolidinediones on insulin sensitivity of tissues in MKR mice. Northern blot analysis was performed to measure levels of target genes of PPAR. agonists in white adipose tissue and hepatic gluconeogenic genes. Results. Thiazolidinedione treatment of MKR mice significantly lowered serum lipid levels and increased serum adiponectin levels but did not affect levels of blood glucose and serum insulin. Hyperinsulinaemic - euglycaemic clamp showed that whole-body insulin sensitivity and glucose homeostasis failed to improve in MKR mice after rosiglitazone treatment. Insulin suppression of hepatic endogenous glucose production failed to improve in MKR mice following rosiglitazone treatment. This lack of change in hepatic insulin insensitivity was associated with no change in the ratio of HMW : total adiponectin, hepatic triglyceride content, and sustained hepatic expression of PPAR. and stearoyl-CoA desaturase 1 mRNA. Interestingly, rosiglitazone markedly enhanced glucose uptake by white adipose tissue with a parallel increase in CD36, aP2 and GLUT4 gene expression. Conclusions/ interpretation. These data suggest that potentiation of insulin action on tissues other than adipose tissue is required to mediate the antidiabetic effects of thiazolidinediones in our MKR diabetic mice. C1 NIDDK, Mol & Cellular Physiol Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. Charles Univ, Fac Med 1, Dept Med 3, Prague, Czech Republic. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. RP LeRoith, D (reprint author), NIDDK, Mol & Cellular Physiol Sect, Diabet Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 8D12, Bethesda, MD 20892 USA. EM Derek@helix.nih.gov NR 49 TC 22 Z9 26 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2004 VL 47 IS 12 BP 2215 EP 2225 DI 10.1007/s00125-004-1581-6 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 889UK UT WOS:000226468000019 PM 15662559 ER PT J AU Tangrea, MA Chuaqui, RF Gillespie, JW Ahram, M Gannot, G Wallis, BS Best, CJM Linehan, WM Liotta, LA Pohida, TJ Bonner, RF Emmert-Buck, MR AF Tangrea, MA Chuaqui, RF Gillespie, JW Ahram, M Gannot, G Wallis, BS Best, CJM Linehan, WM Liotta, LA Pohida, TJ Bonner, RF Emmert-Buck, MR TI Expression microdissection - Operator-independent retrieval of cells for molecular profiling SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE expression microdissection; immunohistochemistry; genomics; proteomics ID LASER CAPTURE MICRODISSECTION; POLYMERASE CHAIN-REACTION; SINGLE CELLS; TISSUE; IDENTIFICATION; CARCINOMA; CANCER; DNA AB Tissue microdissection is an important method for the study of disease states. However, it is difficult to perform high-throughput molecular analysis with current techniques. We describe here a prototype version of a novel technique (expression microdissection) that allows for the procurement of desired cells via molecular targeting. Expression microdissection (xMD) offers significant advantages over available methods, including an increase in dissection speed of several orders of magnitude. xMD may become a valuable tool for investigators studying cancer or other disease states in patient specimens and animal models. C1 NCI, Pathogenet Unit, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Sci Applicat Intl Corp, Frederick, MD USA. Natl Canc Inst, Signal Proc & Instrumentat Sect, Computat Biosci & Engn Lab, Bethesda, MD USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Adv Technol Ctr, 8717 Grovemont Circle, Gaithersburg, MD 20878 USA. EM buckm@mail.nih.gov RI Bonner, Robert/C-6783-2015 NR 20 TC 30 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD DEC PY 2004 VL 13 IS 4 BP 207 EP 212 DI 10.1097/01.pdm.0000135964.31459.bb PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 874CG UT WOS:000225327900002 PM 15538110 ER PT J AU Brantley, E Trapani, V Alley, MC Hose, CD Bradshaw, TD Stevens, MFG Sausville, EA Stinson, SF AF Brantley, E Trapani, V Alley, MC Hose, CD Bradshaw, TD Stevens, MFG Sausville, EA Stinson, SF TI Fluorinated 2-(4-amino-3-methylphenyl) benzothiazoles induce CYP1A1 expression, become metabolized, and bind to macromolecules in sensitive human cancer cells SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT 14th World Congress of Pharmacology CY JUL 07-12, 2002 CL SAN FRANCISCO, CA SP Int Union Pharmacol ID AMINO-ACID PRODRUGS; ANTICANCER DRUG SCREEN; ANTITUMOR BENZOTHIAZOLES; IN-VITRO; BIOLOGICAL-PROPERTIES; CYTOCHROME P4501A1; TUMOR-CELLS; 2-(4-AMINOPHENYL)BENZOTHIAZOLES; AGENT; LINES AB Fluorinated 2-(4-amino-3-methylphenyl) benzothiazoles possess potent antiproliferative activity against certain cancer cells, similar to the unfluorinated 2-(4-amino-3-methylphenyl) benzothiazole (DF 203, NSC 674495). In "sensitive" cancer cells, DF 203 is metabolized by, can induce expression of, and binds covalently to CYP1A1. Metabolism appears to be essential for its antiproliferative activity through DNA adduct formation. However, a biphasic dose-response relationship compromises its straightforward development as a chemotherapeutic agent. We investigated whether fluorinated benzothiazoles inhibit cancer cell growth without the biphasic dose-response, and whether the fluorinated benzothiazoles are also metabolized into reactive species, with binding to macromolecules in sensitive cancer cells. One fluorinated benzothiazole, 2-(4-amino-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) did exhibit potent, antiproliferative activity without a biphasic dose-response. The fluorinated benzothiazoles were also metabolized only in cells, which subsequently showed evidence of cell death. We used microsomes from genetically engineered human B-lymphoblastoid cells expressing cytochromes P450 (CYP1A1, CYP1A2, or CYP1B1) to clarify the basis for fluorinated benzothiazole metabolism. 5F 203 induced CYP1A1 and CYP1B1 mRNA expression in sensitive breast and renal cancer cells, whereas 5F 203 induced CYP1A1 mRNA but not CYP1B1 mRNA expression in sensitive ovarian cancer cells. 5F 203 did not induce CYP1A1 or CYP1B1 mRNA expression in any "resistant" cancer cells. The fluorinated benzothiazoles induced CYP1A1 protein expression exclusively in sensitive cells. [C-14] 5F 203 bound substantially to subcellular fractions in sensitive cells but only minimally in resistant cells. These data are concordant with the antiproliferative activity of fluorinated benzothiazoles deriving from their ability to become metabolized and bind to macromolecules within sensitive cells. C1 NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA. Univ Nottingham, Sch Pharmaceut Sci, Canc Res Labs, Nottingham NG7 2RD, England. Sci Applicat Int Corp, Screening Technol Branch, Dev Therapeut Program, Frederick, MD USA. RP Stinson, SF (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, POB B,Bldg 1047,Room 6, Frederick, MD 21701 USA. EM stinson@dtpax2.ncifcrf.gov OI Trapani, Valentina/0000-0002-0259-6624 NR 39 TC 34 Z9 35 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2004 VL 32 IS 12 BP 1392 EP 1401 DI 10.1124/dmd.104.001057 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 872ID UT WOS:000225200000010 PM 15355884 ER PT J AU Basu, NK Kole, L Kubota, S Owens, IS AF Basu, NK Kole, L Kubota, S Owens, IS TI Response to the letter to the editor by Drs. N. Picard and P. Marquet regarding a publication: Basu et al., Drug Metabolism and Disposition 32:768-773 (2004) SO DRUG METABOLISM AND DISPOSITION LA English DT Letter ID MYCOPHENOLIC-ACID; IDENTIFICATION C1 NIH, Bethesda, MD 20892 USA. RP Basu, NK (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2004 VL 32 IS 12 BP 1525 EP 1525 DI 10.1124/dmd.104.002345 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 872ID UT WOS:000225200000029 ER PT J AU Liotta, LA Petricoin, EF Veenstra, TD Conrads, TP AF Liotta, LA Petricoin, EF Veenstra, TD Conrads, TP TI High-resolution serum proteomic patterns for ovarian cancer detection SO ENDOCRINE-RELATED CANCER LA English DT Letter C1 NCI, Biomed Proteom Program, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. US FDA, Natl Canc Inst, Clin Proteom Program, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. Natl Canc Inst, Pathol Lab, Clin Proteom Program, Canc Res Ctr, Bethesda, MD 20892 USA. RP Veenstra, TD (reprint author), NCI, Biomed Proteom Program, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. EM Veenstra@ncifcrf.gov NR 6 TC 3 Z9 4 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2004 VL 11 IS 4 BP 585 EP 587 DI 10.1677/erc.1.00873 PG 3 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 890JW UT WOS:000226508500002 ER PT J AU Eisenhofer, G Huynh, TT Pacak, K Brouwers, FM Walther, MM Linehan, WM Munson, PJ Mannelli, M Goldstein, DS Elkahloun, AG AF Eisenhofer, G Huynh, TT Pacak, K Brouwers, FM Walther, MM Linehan, WM Munson, PJ Mannelli, M Goldstein, DS Elkahloun, AG TI Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome SO ENDOCRINE-RELATED CANCER LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TRANSCRIPTION FACTOR ETS-1; ENDOCRINE NEOPLASIA TYPE-2; INDUCIBLE FACTOR-I; CELL MIGRATION; ALPHA(2)BETA(1) INTEGRINS; TUMOR ANGIOGENESIS; GELATINASE-A; FACTOR VEGF; RECEPTORS AB Pheochromocytomas in von Hippel-Lindau (VHL) syndrome produce exclusively norepinephrine, whereas those in multiple endocrine neoplasia type 2 (MEN 2) produce epinephrine. This study examined the pathways activated in VHL-associated pheochromocytomas by comparing gene expression profiles in VHL and MEN 2 tumors in relationship to profiles in sporadic norepinephrine-and epinephrine-producing tumors. Larger and more distinct differences in gene expression among hereditary than sporadic tumors indicated the importance of the underlying mutation to gene expression profiles. Many of the genes over-expressed in VHL compared with MEN 2 tumors were clearly linked to the hypoxia-driven angiogenic pathways that are activated in VHL-associated tumorigenesis. Such genes included those for the glucose transporter, vascular endothelial growth factor (VEGF), placental growth factor, angiopoietin 2, tie-1, VEGF receptor 2 and its coreceptor, neuropilin-1. Other up-regulated genes, such as connective tissue growth factor, cysteine-rich 61, matrix metalloproteinase 1, vascular endothelial cadherin, tenascin C, stanniocalcin 1, and cyclooxygenases 1 and 2 are known to be involved in VEGF-regulated angiogenesis. Shared differences in expression of subsets of genes in norepinephrine- versus epinephrine-producing hereditary and sporadic pheochromocytomas indicated other differences in gene expression that may underlie the biochemical phenotype. Over-expression of the hypoxia-inducible transcription factor, HIF-2alpha, in norepinephrine-predominant sporadic and VHL tumors compared with epinephrine-producing tumors indicates that expression of this gene depends on the noradrenergic biochemical phenotype. The findings fit with the known expression of HIF-2a in norepinephrine-producing cells of the sympathetic nervous system and might explain both the development and noradrenergic biochemical phenotype of pheochromocytomas in VHL syndrom. C1 NIH, NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NIH, NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Florence, Dept Clin Physiopathol, Florence, Italy. Natl Inst Hlth, NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Elkahloun, AG (reprint author), NIH, NINDS, Clin Neurocardiol Sect, Bldg 50,Room 5231 & 5232,10 Ctr Dr, Bethesda, MD 20892 USA. EM abdel@nhgri.nih.gov OI Mannelli, Massimo/0000-0002-8001-9857 NR 78 TC 111 Z9 113 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2004 VL 11 IS 4 BP 897 EP 911 DI 10.1677/erc.1.00838 PG 15 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 890JW UT WOS:000226508500024 PM 15613462 ER PT J AU Bossis, I Stratakis, CA AF Bossis, I Stratakis, CA TI Minireview: PRKAR1A: Normal and abnormal functions SO ENDOCRINOLOGY LA English DT Review ID PROTEIN-KINASE-A; RI-ALPHA-SUBUNIT; NODULAR ADRENOCORTICAL DISEASE; RII(BETA) REGULATORY SUBUNIT; MAMMARY EPITHELIAL-CELLS; CARNEY COMPLEX; CYCLIC-AMP; BETA SUBUNIT; TARGETED DISRUPTION; TUMOR-SUPPRESSOR AB The type 1alpha regulatory subunit (RIalpha) of cAMP-dependent protein kinase (PKA) (coded by the PRKAR1A gene) is the main component of type I PKA, which regulates most of the serine-threonine kinase activity catalyzed by the PKA holoenzyme in response to cAMP. Carney complex (CNC), or the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, is a multiple endocrine (and not only) neoplasia syndrome that is due to PRKAR1A-inactivating mutations. The R1alpha protein and PRKAR1A mRNA have been found to be upregulated in a series of cell lines and human and rodent neoplasms, suggesting this molecule's involvement in tumorigenesis and its potential role in cell cycle regulation, growth, and/or proliferation. Alterations in PKA activity elicit a variety of effects depending on the tissue, developmental stage, degree of differentiation, and cAMP levels. In addition, RIalpha may have functions independent of PKA. The presence of inactivating germline mutations and the loss of its wild-type allele in some CNC lesions indicate that PRKAR1A might function as a tumor suppressor gene in these tissues, but could PRKAR1A be a classic tumor suppressor gene? Probably not, and this review explains why. C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 98 TC 117 Z9 123 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2004 VL 145 IS 12 BP 5452 EP 5458 DI 10.1210/en.2004-0900 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871DL UT WOS:000225109400007 PM 15331577 ER PT J AU Weinstein, LS Liu, J Sakamoto, A Xie, T Chen, M AF Weinstein, LS Liu, J Sakamoto, A Xie, T Chen, M TI Minireview: GNAS: Normal and abnormal functions SO ENDOCRINOLOGY LA English DT Review ID STIMULATORY G-PROTEIN; MCCUNE-ALBRIGHT-SYNDROME; XL-ALPHA-S; PSEUDOHYPOPARATHYROIDISM TYPE IB; INCREASED INSULIN SENSITIVITY; G(S)ALPHA KNOCKOUT MICE; ADENYLYL-CYCLASE; GS-ALPHA; FIBROUS DYSPLASIA; HEREDITARY OSTEODYSTROPHY AB GNAS is a complex imprinted gene that uses multiple promoters to generate several gene products, including the G protein alpha-subunit (G(s)alpha) that couples seven-transmembrane receptors to the cAMP-generating enzyme adenylyl cyclase. Somatic activating G(s)alpha mutations, which alter key residues required for the GTPase turn-off reaction, are present in various endocrine tumors and fibrous dysplasia of bone, and in a more widespread distribution in patients with McCune-Albright syndrome. Heterozygous inactivating G(s)alpha mutations lead to Albright hereditary osteodystrophy. G(s)alpha is imprinted in a tissue-specific manner, being primarily expressed from the maternal allele in renal proximal tubules, thyroid, pituitary, and ovary. Maternally inherited mutations lead to Albright hereditary osteodystrophy (AHO) plus PTH, TSH, and gonadotropin resistance (pseudohypoparathyroidism type 1A), whereas paternally inherited mutations lead to AHO alone. Pseudohypoparathyroidism type 1B, in which patients develop PTH resistance without AHO, is almost always associated with a GNAS imprinting defect in which both alleles have a paternal-specific imprinting pattern on both parental alleles. Familial forms of the disease are associated with a mutation within a closely linked gene that deletes a region that is presumably required for establishing the maternal imprint, and therefore maternal inheritance of the mutation results in the GNAS imprinting defect. Imprinting of one differentially methylated region within GNAS is virtually always lost in pseudohypoparathyroidism type 1B, and this region is probably responsible for tissue-specific Gs(alpha) imprinting. Mouse knockout models show that Gs(alpha) and the alternative Gs(alpha) isoform XLalphas that is expressed from the paternal GNAS allele may have opposite effects on energy metabolism in mice. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 NR 78 TC 155 Z9 165 U1 0 U2 10 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 DEC PY 2004 VL 145 IS 12 BP 5459 EP 5464 DI 10.1210/en.2004-0865 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871DL UT WOS:000225109400008 PM 15331575 ER PT J AU Deroo, BJ Hewitt, SC Peddada, SD Korach, KS AF Deroo, BJ Hewitt, SC Peddada, SD Korach, KS TI Estradiol regulates the thioredoxin antioxidant system in the mouse uterus SO ENDOCRINOLOGY LA English DT Article ID LEUKEMIA-DERIVED FACTOR; EARLY EMBRYONIC LETHALITY; AUTOCRINE GROWTH-FACTOR; MAMMALIAN THIOREDOXIN; TARGETED DISRUPTION; HUMAN ENDOMETRIUM; OXIDATIVE STRESS; MESSENGER-RNA; RAT UTERUS; FACTOR ADF AB The rodent uterus responds to acute estradiol (E2) treatment with a series of well characterized physiological responses. In a recent screen for genes involved in this response, we found that several genes in the thioredoxin (Txn) pathway were rapidly modified after E2 treatment in the mouse uterus. Txn is a 12-kDa protein with multiple roles in the cell, including protection against oxidative stress and apoptosis, regulation of transcription factor activity, and regulation of cellular proliferation. Txn in combination with Txn reductase (Txnrd) and Txn-interacting protein (Txnip) constitute the mammalian Txn pathway. This pathway exists in multiple locations in the cell, including the cytosol and mitochondria. To analyze the levels of Txn, Txnrd, and Txnip in the uterus, we treated ovariectomized adult mice with a time course of E2 and analyzed mRNA levels by real-time PCR. E2 rapidly decreased the expression of Txnip, but increased the levels of cytosolic Txn1 and Txnrd1 as well as mitochondrial Txn2. Using the ER antagonist, ICI 182,780, and mice lacking functional estrogen receptor alpha (ERalpha), we demonstrate that these E2-mediated changes require ERalpha, but not ERalpha. The repression of Txnip by E2 was also demonstrated in vitro in MCF-7 human breast cancer cells. This repression was blocked by treatment with the histone deacetylase inhibitor, trichostatin A, suggesting that repression by E2 may involve regulation of histone acetylation. We conclude that the rapid E2-mediated activation of the Txn pathway is an important step in the response of the mammalian uterus to estrogen. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Environm Dis & Med Program, NIH, Res Triangle Pk, NC 27709 USA. RP Deroo, BJ (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, MD E4-01,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM deroo@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 49 Z9 52 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 DEC PY 2004 VL 145 IS 12 BP 5485 EP 5492 DI 10.1210/en.2004-0471 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871DL UT WOS:000225109400012 PM 15345672 ER PT J AU Cawley, NX Zhou, JC Hill, JM Abebe, D Romboz, S Yanik, T Rodriguiz, RM Wetsel, WC Loh, YP AF Cawley, NX Zhou, JC Hill, JM Abebe, D Romboz, S Yanik, T Rodriguiz, RM Wetsel, WC Loh, YP TI The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits SO ENDOCRINOLOGY LA English DT Article ID PATHWAY SORTING RECEPTOR; SECRETORY GRANULES; ENZYME-ACTIVITY; CPE(FAT) MICE; REQUIRES INTERACTION; INSULIN SENSITIVITY; HUMAN PROINSULIN; FAT MUTATION; CELL-LINE; RAT AB A carboxypeptidase E (CPE) knockout ( KO) mouse was generated by deletion of exons 4 and 5 from the CPE gene, and its phenotype was characterized. KO mice became obese by 10 - 12 wk of age and reached 60 - 80 g by 40 wk. At this age, body fat content was more than double that in the wild-type (WT) controls. The null animals consumed more food overall, were less physically active during the light phase of the light-dark cycle, and burned fewer calories as fat than WT littermates. Fasting levels of glucose and insulin-like immunoreactivity in plasma were elevated in both male and female KO mice at approximately 20 wk; males recovered fully and females partially from this state by 32 wk. At this time, insulin-like immunoreactivity in the plasma, identified as proinsulin, was 50 - 100 times higher than that of the WT animals. The KO mice showed impaired glucose clearance and were insulin resistant. High levels of leptin and no circulating fully processed cocaine- and amphetamine-related transcript, a peptide that is responsive to leptin-induced feedback inhibition of feeding, were found in serum. The KO mice were subfertile and showed deficits in GnRH processing in the hypothalamus. Behavioral analyses revealed that KO animals showed diminished reactivity to stimuli and had reduced muscle strength and coordination, as well as visual placing and toe-pinch reflexes. These data demonstrate that CPE KO mice display a wide range of neural and endocrine abnormalities and suggest that CPE may have additional physiological roles beyond those ascribed to peptide processing and sorting of prohormones in cells. C1 NICHHD, Sect Cellular Neurobiol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol & Med, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC 27710 USA. Xenogen Biosci Corp, Cranbury, NJ 08512 USA. RP Loh, YP (reprint author), NICHHD, Sect Cellular Neurobiol, Dev Neurobiol Lab, NIH, MSC 4480,Bldg 49,Room 5A22,49 Convent Dr, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU NICHD NIH HHS [HD-36015] NR 43 TC 55 Z9 58 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2004 VL 145 IS 12 BP 5807 EP 5819 DI 10.1210/en.2004-0847 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871DL UT WOS:000225109400047 PM 15358678 ER PT J AU Lubin, JH Colt, JS Camann, D Davis, S Cerhan, JR Severson, RK Bernstein, L Hartge, P AF Lubin, JH Colt, JS Camann, D Davis, S Cerhan, JR Severson, RK Bernstein, L Hartge, P TI Epidemiologic evaluation of measurement data in the presence of detection limits SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE dust; environmental exposure; imputation; missing data; non-Hodgkin lymphoma; pesticides ID FAGERSTROM TOLERANCE QUESTIONNAIRE; CENSORED REGRESSION-MODELS; DATA SETS; NICOTINE DEPENDENCE; TOBIT-MODEL; CHLORPYRIFOS; ESTIMATORS; PESTICIDES; EXPOSURES; RESIDENCE AB Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of "fill-in" values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5-10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case-control study of non-Hodgkin lymphoma. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. SW Res Inst, San Antonio, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Coll Med, Rochester, MN USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Univ So Calif, Dept Prevent Med, Norris Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA USA. RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8042, Rockville, MD 20852 USA. EM lubinj@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105] NR 39 TC 324 Z9 327 U1 6 U2 31 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 DEC PY 2004 VL 112 IS 17 BP 1691 EP 1696 DI 10.1289/ehp.7199 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 880ID UT WOS:000225781300046 PM 15579415 ER PT J AU McCurdy, LE Roberts, J Rogers, B Love, R Etzel, R Paulson, J Witherspoon, NO Dearry, A AF McCurdy, LE Roberts, J Rogers, B Love, R Etzel, R Paulson, J Witherspoon, NO Dearry, A TI Incorporating environmental health into pediatric medical and nursing education SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE education; environmental health; medical student; nursing; nursing student; pediatrics; resident ID CURRICULA; RESIDENTS; STUDENTS; ASTHMA AB Pediatric medical and nursing education currently lacks the environmental health content necessary to appropriately prepare pediatric health care professionals to prevent, recognize, manage, and treat environmental-exposure-related disease. Leading health institutions have recognized the need for improvements in health professionals' environmental health education. Parents are seeking answers about the impact of environmental toxicants on their children. Given the biologic, psychological, and social differences between children and adults, there is a need for environmental health education specific to children. The National Environmental Education and Training Foundation, in partnership with the Children's Environmental Health Network, created two working groups, one with expertise in medical education and one with expertise in nursing education. The working groups reviewed the transition from undergraduate student to professional to assess where in those processes pediatric environmental health could be emphasized. The medical education working group recommended increasing education about children's environmental health in the medical school curricula, in residency training, and in continuing medical education. The group also recommended the expansion of fellowship training in children's environmental health. Similarly, the nursing working group recommended increasing children's environmental health content at the undergraduate, graduate, and continuing nursing education levels. Working groups also identified the key medical and nursing organizations that would be important in leveraging these changes. A concerted effort to prioritize pediatric environmental health by governmental organizations and foundations is essential in providing the resources and expertise to set policy and provide the tools for teaching pediatric environmental health to health care providers. C1 Natl Environm Educ & Training Fdn, Washington, DC 20006 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Childrens Environm Hlth Network, Washington, DC USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP McCurdy, LE (reprint author), Natl Environm Educ & Training Fdn, 1707 H St NW,Suite 900, Washington, DC 20006 USA. EM mccurdy@neetf.org NR 28 TC 23 Z9 25 U1 1 U2 7 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 DEC PY 2004 VL 112 IS 17 BP 1755 EP 1760 DI 10.1289/ehp.7166 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 880ID UT WOS:000225781300054 PM 15579423 ER PT J AU Gladen, BC Klebanoff, MA Hediger, ML Katz, SH Barr, DB Davis, MD Longnecker, MP AF Gladen, BC Klebanoff, MA Hediger, ML Katz, SH Barr, DB Davis, MD Longnecker, MP TI Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE child development; DDE; DDT; growth; prenatal exposure delayed effects; puberty ID POLYCHLORINATED-BIPHENYLS PCBS; DICHLORODIPHENYL DICHLOROETHENE DDE; HUMAN-MILK; ORGANOCHLORINE COMPOUNDS; CHILDHOOD GROWTH; MATERNAL SMOKING; MALARIA CONTROL; HUMAN-SERUM; IN-UTERO; BIRTH AB DDT (dichlorodiphenyltrichloroethane), a pesticide once used widely in agriculture and now limited to public health use, remains a controversial chemical because of a combination of benefits and risks. DDT or its breakdown products are ubiquitous in the environment and in humans. Compounds in the DDT family have endocrine actions and have been associated with reproductive toxicity. A previous study reported associations between prenatal exposure to p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene] and increased height and weight in adolescent boys. We examined a group with higher exposures to see whether similar associations would occur. Our study group was 304 males born in Philadelphia in the early 1960s who had participated in a previous study. Anthropometric and pubertal measures from one to six visits during their adolescent years were available, as were stored maternal serum samples from pregnancy. We measured p,p'-DDE, p,p'-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], and o,p'-DDT [1,1,1-trichloro-2(o-chlorophenyl)-2-(p-chlorophenyl)-ethane] in the maternal serum. Outcomes examined in the boys were height, ratio of sitting height to height, body mass index, triceps skinfold thickness, ratio of subscapular to the sum of triceps and subscapular skinfold thicknesses, skeletal age, serum testosterone, and serum dehydroepiandrosterone sulfate. No associations between prenatal exposure to any of the DDT compounds and any outcome measure were seen. C1 NIEHS, Biostat Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Univ Penn, Krogman Ctr Res Child Growth & Dev, Philadelphia, PA USA. Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Dept Hlth & Human Serv, Atlanta, GA USA. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, Dept Hlth & Human Serv, NIH, POB 12233,Mail Drop A3-03, Res Triangle Pk, NC 27709 USA. EM gladen@niehs.nih.gov RI katz, solomon/B-3426-2012; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Longnecker, Matthew/0000-0001-6073-5322 NR 63 TC 48 Z9 48 U1 0 U2 3 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 DEC PY 2004 VL 112 IS 17 BP 1761 EP 1767 DI 10.1289/ehp.7287 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 880ID UT WOS:000225781300055 PM 15579424 ER PT J AU Galperin, MY AF Galperin, MY TI Genomes back-to-back: when sequencing race is a good thing SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BACILLUS-LICHENIFORMIS; LEGIONELLA-PNEUMOPHILA; SYMBIOBACTERIUM-THERMOPHILUM; BIOFILM FORMATION; YERSINIA-PESTIS; BACTERIUM; PLASTICITY; EVOLUTION C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 24 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD DEC PY 2004 VL 6 IS 12 BP 1205 EP 1209 DI 10.1111/j.1462-2920.2004.00737.x PG 5 WC Microbiology SC Microbiology GA 873FE UT WOS:000225264500001 PM 15560818 ER PT J AU Ilias, I Tselebis, A Theotoka, I Hatzimichelakis, E AF Ilias, I Tselebis, A Theotoka, I Hatzimichelakis, E TI Association of perceived family support through glycemic control in native Greek patients managing diabetes with diet alone SO ETHNICITY & DISEASE LA English DT Letter ID CARE C1 Klimax Support Fdn, Athens, Greece. Sotiria Hosp, Dept Psychiat, Athens, Greece. Univ Athens, Sch Med, Dept Psychiat, Eginit Hosp, GR-10679 Athens, Greece. Alexandra Hosp, Endocrine Sect 1, Ctr Diabet, Athens, Greece. RP Ilias, I (reprint author), NICHD, PREB, NIH, Bldg 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM iiliasmd@yahoo.com NR 10 TC 3 Z9 3 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2004 VL 14 IS 1 BP 2 EP 2 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 803OE UT WOS:000220239600002 PM 15002916 ER PT J AU Fouts, HN AF Fouts, HN TI Social and emotional contexts of weaning among Bofi farmers and foragers SO ETHNOLOGY LA English DT Article DE tropical farmers and foragers; Central Africa; parent-child relations; weaning ID COMPARATIVE PERSPECTIVE; EARLY-CHILDHOOD; CHILDREN; SUBSISTENCE; EXPERIENCE; INFANTS; GROWTH; KENYA; LIFE; AGE AB Weaning is a topic of much theoretical interest in anthropology, psychology, and public health. Several specific images about weaning are ubiquitous throughout the scholarly literature, but these are inadequate for describing the full spectrum of social and emotional factors involved in weaning. The images are evaluated in the context of comparative data collected among the Bofi farmers and foragers. While most studies of weaning have focused on health issues, this analysis identifies social and emotional factors related to caregiving practices, children's responses to weaning, and social transitions that accompany weaning. The Bofi farmers and foragers provide an interesting comparison of weaning because, although they live in the same natural ecology and speak the same language, they have distinct patterns of child-rearing and weaning. The comparison of Bofi weaning practices leads to a discussion of weaning patterns among other farmers and foragers and weaning patterns predicted by region and subsistence. C1 NICHHD, Bethesda, MD 20892 USA. RP Fouts, HN (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 45 TC 9 Z9 9 U1 0 U2 0 PU UNIV PITTSBURGH PI PITTSBURGH PA DEPT ANTHROPOLOGY, PITTSBURGH, PA 15260 USA SN 0014-1828 J9 ETHNOLOGY JI Ethnology PD WIN PY 2004 VL 43 IS 1 BP 65 EP 81 PG 17 WC Anthropology SC Anthropology GA 815HZ UT WOS:000221034700005 ER PT J AU Moyrand, F Chang, YC Himmelreich, U Kwon-Chung, KJ Janbon, G AF Moyrand, F Chang, YC Himmelreich, U Kwon-Chung, KJ Janbon, G TI Cas3p belongs to a seven-member family of capsule structure designer proteins SO EUKARYOTIC CELL LA English DT Article ID CRYPTOCOCCUS-NEOFORMANS SEROTYPE; O-DEACETYLATED GLUCURONOXYLOMANNAN; 2D NMR-SPECTROSCOPY; SACCHAROMYCES-CEREVISIAE; MONOCLONAL-ANTIBODY; GENE DISRUPTION; MUTANT STRAINS; POLYSACCHARIDE; VIRULENCE; COMPLEX AB The polysaccharide capsule is the main virulence factor of the basidiomycetous yeast Cryptococcus neoformans. Four genes (CAP10, CAP59, CAP60, and CAP64) essential for capsule formation have been previously identified, although their roles in the biosynthetic pathway remain unclear. A genetic and bioinformatics approach allowed the identification of six CAP64-homologous genes, named CAS3, CAS31, CAS32, CAS33, CAS34, and CAS35, in the C. neoformans genome. This gene family is apparently specific in a subclass of the basidiomycete fungi. Single as well as double deletions of these genes in all possible combinations demonstrated that none of the CAP64-homologous genes were essential for capsule formation, although the cas35Delta strains displayed a hypocapsular phenotype. The chemical structure of the glucuronomannan (GXM) produced by the CAS family deletants revealed that these genes determined the position and the linkage of the xylose and/or O-acetyl residues on the mannose backbone. Hence, these genes are all involved in assembly of the GXM structure in C. neoformans. C1 Inst Pasteur, Unite Mycol Mol, F-75724 Paris 15, France. Max Planck Inst Neurol Res, Cologne, Germany. NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Janbon, G (reprint author), Inst Pasteur, Unite Mycol Mol, 25 Rue Dr Roux, F-75724 Paris 15, France. EM janbon@pasteur.fr OI Janbon, Guilhem/0000-0002-4788-1154 FU NIAID NIH HHS [AI47079, R01 AI047079] NR 53 TC 37 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD DEC PY 2004 VL 3 IS 6 BP 1513 EP 1524 DI 10.1128/EC.3.6.1513-1524.2004 PG 12 WC Microbiology; Mycology SC Microbiology; Mycology GA 880XU UT WOS:000225824400015 PM 15590825 ER PT J AU Banerjee, S Myung, K AF Banerjee, S Myung, K TI Increased genome instability and telomere length in the elg1-deficient Saccharomyces cerevisiae mutant are regulated by S-phase checkpoints SO EUKARYOTIC CELL LA English DT Article ID STRAND BREAK REPAIR; GROSS CHROMOSOMAL REARRANGEMENTS; DNA-REPLICATION CHECKPOINT; SYNDROME GENE; CELL-CYCLE; MAINTENANCE; STABILITY; COMPLEX; YEAST; SUPPRESSION AB Gross chromosomal rearrangements (GCRs) are frequently observed in cancer cells. Abnormalities in different DNA metabolism including DNA replication, cell cycle checkpoints, chromatin remodeling, telomere maintenance, and DNA recombination and repair cause GCRs in Saccharomyces cerevisiae. Recently, we used genome-wide screening to identify several genes the deletion of which increases GCRs in S. cerevisiae. Elg1, which was discovered during this screening, functions in DNA replication by participating in an alternative replication factor complex. Here we further characterize the GCR suppression mechanisms observed in the elg1Delta mutant strain in conjunction with the telomere maintenance role of Elg1. The elg1Delta mutation enhanced spontaneous DNA damage and resulted in GCR formation. However, DNA damage due to inactivation of Elg1 activates the intra-S checkpoints, which suppress further GCR formation. The intra-S checkpoints activated by the elg1Delta mutation also suppress GCR formation in strains defective in the DNA replication checkpoint. Lastly, the elg1Delta mutation increases telomere size independently of other previously known telomere maintenance proteins such as the telomerase inhibitor Pif1 or the telomere size regulator Rif1. The increase in telomere length caused by the elg1Delta mutation was suppressed by a defect in the DNA replication checkpoint, which suggests that DNA replication surveillance by Dpb11-Mec1/Tel1-Dun1 also has an important role in telomere length regulation. C1 NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A22, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov NR 50 TC 34 Z9 35 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD DEC PY 2004 VL 3 IS 6 BP 1557 EP 1566 DI 10.1128/EC.3.6.1557-1566.2004 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 880XU UT WOS:000225824400019 PM 15590829 ER PT J AU Hansen, AL Johnsen, BH Sollers, JJ Stenvik, K Thayer, JF AF Hansen, AL Johnsen, BH Sollers, JJ Stenvik, K Thayer, JF TI Heart rate variability and its relation to prefrontal cognitive function: the effects of training and detraining SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE physical fitness; detraining; training; heart rate variability; cognitive function ID NEUROCOGNITIVE FUNCTION; CARDIOVASCULAR FITNESS; PERSONALITY DIMENSIONS; WORKING-MEMORY; OLDER-ADULTS; EXERCISE; NEUROBIOLOGY; PERSPECTIVE; MODULATION; INHIBITION AB The aim of the present study was to investigate the relationship between physical fitness, heart rate variability (HRV) and cognitive function in 37 male sailors from the Royal Norwegian Navy. All subjects participated in an 8-week training program, after which the subjects completed the initial cognitive testing (pre-test). The subjects were assigned into a detrained group (DG) and a trained group (TG) based on their application for further duty. The DG withdrew from the training program for 4 weeks after which all subjects then completed the cognitive testing again (post-test). Physical fitness, measured as maximum oxygen consumption ((V) over dot O-2max), resting HRV, and cognitive function, measured using a continuous performance task (CPT) and a working memory test (WMT), were recorded during the pre-test and the post-test, and the data presented as the means and standard deviations. The results showed no between-group differences in (V) over dot O-2max or HRV at the pre-test. The DG showed a significant decrease in (V) over dot O-2max from the pre- to the post-test and a lower resting HRV than the TG on the post-test. Whereas there were no between-group differences on the CPT or WMT at the pre-test, the TG had faster reaction times and more true positive responses on tests of executive function at the post-test compared to the pre-test. The DG showed faster reaction times on non-executive tasks at the post-test compared to the pre-test. The results are discussed within a neurovisceral integration framework linking parasympathetic outflow to the heart to prefrontal neural functions. C1 Univ Bergen, Dept Psychosocial Sci, N-5015 Bergen, Norway. NIA, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. Headquarters Def Command Norway, N-0016 Oslo, Norway. RP Hansen, AL (reprint author), Univ Bergen, Dept Psychosocial Sci, Christiesgate 12, N-5015 Bergen, Norway. EM anitalill5@yahoo.no NR 46 TC 117 Z9 117 U1 5 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD DEC PY 2004 VL 93 IS 3 BP 263 EP 272 DI 10.1007/s00421-004-1208-0 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 872RZ UT WOS:000225227400002 PM 15338220 ER PT J AU Rotanova, TV Melnikov, EE Khalatova, AG Makhovskaya, OV Botos, I Wlodawer, A Gustchina, A AF Rotanova, TV Melnikov, EE Khalatova, AG Makhovskaya, OV Botos, I Wlodawer, A Gustchina, A TI Classification of ATP-dependent proteases Lon and comparison of the active sites of their proteolytic domains SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE AAA(+) proteins; Lon proteases; proteolytic site; LonA and LonB subfamilies; Ser-Lys dyad ID AAA PLUS PROTEINS; ESCHERICHIA-COLI; DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; SUBSTRATE; ATPASES; LA; HYDROLYSIS; EXPRESSION; CHAPERONE AB ATP-dependent Lon proteases belong to the superfamily of AAA(+) proteins. Until recently, the identity of the residues involved in their proteolytic active sites was not elucidated. However, the putative catalytic Ser-Lys dyad was recently suggested through sequence comparison of more than 100 Lon proteases from various sources. The presence of the catalytic dyad was experimentally confirmed by site-directed mutagenesis of the Escherichia coli Lon protease and by determination of the crystal structure of its proteolytic domain. Furthermore, this extensive sequence analysis allowed the definition of two subfamilies of Lon proteases, LonA and LonB, based on the consensus sequences in the active sites of their proteolytic domains. These differences strictly associate with the specific characteristics of their AAA(+) modules, as well as with the presence or absence of an N-terminal domain. C1 Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Miklukho Maklaya St 16-10,GSP-7, Moscow 117997, Russia. EM rotanova@enzyme.siobc.ras.ru; alla@ncifcrf.gov NR 47 TC 55 Z9 58 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD DEC PY 2004 VL 271 IS 23-24 BP 4865 EP 4871 DI 10.1111/j.1432-1033.2004.04452.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 879WV UT WOS:000225750800029 PM 15606774 ER PT J AU Mayer, AMS Gustafson, KR AF Mayer, AMS Gustafson, KR TI Marine pharmacology in 2001-2: antitumour and cytotoxic compounds SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE marine; antitumour; cytotoxicity; anticancer; antineoplastic; agents; preclinical; clinical; pharmacology; review ID AGENT KAHALALIDE-F; HUMAN BONE-MARROW; PHASE-II TRIAL; CYANOBACTERIUM LYNGBYA-MAJUSCULA; GORGONIAN BRIAREUM-EXCAVATUM/; MULTIDRUG-RESISTANCE PROTEIN; NON-HODGKINS-LYMPHOMA; CYTOCHROME-C RELEASE; IN-VITRO TOXICITY; ANTICANCER AGENT AB During 2001 and 2002, marine antitumour pharmacology research aimed at the discovery of novel antitumour agents was published in 175 peer-reviewed articles. The purpose of this paper is to present a structured Review of the antitumour and cytotoxic properties of 97 marine natural products, many of them novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids, and peptides. The organisms yielding these bioactive compounds comprise a taxonomically diverse group of marine invertebrate animals, algae, fungi and bacteria. Antitumour pharmacological studies were conducted with 30 structurally characterised natural marine products in a number of experimental and clinical models which further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human turnout cell lines was reported for 67 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy, is the fact that marine anticancer research was sustained by a collaborative effort, involving researchers from Australia, Brazil, Canada, Denmark, Egypt, France, Germany, Italy, Japan, Netherlands, New Zealand, the Phillipines, Russia, Singapore, South Korea, Thailand, Taiwan, Turkey, Spain, Switzerland, Taiwan, Thailand, Turkey, and the United States. Finally, this 2001-2 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine antitumour agents has continued at the same pace as during 1998, 1999 and 2000. (C) 2004 Elsevier Ltd. All rights reserved. C1 Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, Downers Grove, IL 60515 USA. NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. RP Mayer, AMS (reprint author), Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, 555 31st St, Downers Grove, IL 60515 USA. EM amayer@midwestem.edu OI Mayer, Alejandro /0000-0002-8358-4528 FU NIEHS NIH HHS [1 R15 ES12654-01] NR 176 TC 84 Z9 85 U1 2 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2004 VL 40 IS 18 BP 2676 EP 2704 DI 10.1016/j.ejca.2004.09.005 PG 29 WC Oncology SC Oncology GA 883EN UT WOS:000225993400016 PM 15571951 ER PT J AU Dimitrakakis, C Gosselink, L Gaki, V Bredakis, N Keramopoulos, A AF Dimitrakakis, C Gosselink, L Gaki, V Bredakis, N Keramopoulos, A TI Phytoestrogen supplementation: a case report of male breast cancer SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE breast cancer; male; phytoestrogens ID CELLS IN-VITRO; POSTMENOPAUSAL WOMEN; DIETARY; GENISTEIN; PREMENOPAUSAL; ADVENTISTS; GROWTH AB Patients seeking alternatives to hormone replacement are increasingly using non-prescription phytoestrogen supplements. The potential of these herbal remedies to prevent bone loss, heart disease, menopausal symptoms or breast cancer has been a focus of attention in scientific and lay literature. It is important to understand the effects of phytoestrogens, particularly whether excess exposure can promote hyperplasia or neoplasia of breast tissue. We report the case of a man diagnosed with breast cancer whose history was notable for extensive use of supplemental phytoestrogens and the absence of family history of breast cancer or BRCA1/BRCA2 mutation.. In conclusion, breast tissue effects of phytoestrogens remain unclear. The increasing popularity and availability of phytoestrogen dietary supplements necessitates additional research in order to counsel patients regarding their safety and efficacy. (C) 2004 Lippincott Williams Wilkins. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Iaso Womans Hlth Hosp, Breast Ctr, Athens, Greece. RP Dimitrakakis, C (reprint author), 8 Niriidon St, Athens 16673, Greece. EM dimitrac@mail.nih.gov NR 20 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD DEC PY 2004 VL 13 IS 6 BP 481 EP 484 DI 10.1097/00008469-200412000-00003 PG 4 WC Oncology SC Oncology GA 878WC UT WOS:000225677000003 PM 15548940 ER PT J AU Mantzoros, C Petridou, E Alexe, DM Skalkidou, A Dessypris, N Papathoma, E Salvanos, H Shetty, G Gavrila, A Kedikoglou, S Chrousos, G Trichopoulos, D AF Mantzoros, C Petridou, E Alexe, DM Skalkidou, A Dessypris, N Papathoma, E Salvanos, H Shetty, G Gavrila, A Kedikoglou, S Chrousos, G Trichopoulos, D TI Serum adiponectin concentrations in relation to maternal and perinatal characteristics in newborns SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BIRTH-WEIGHT; PLASMA ADIPONECTIN; GROWTH-FACTORS; CARDIOVASCULAR-DISEASE; ENDOMETRIAL CANCER; INSULIN-RESISTANCE; BINDING-PROTEINS; GESTATIONAL-AGE; ADIPOSE-TISSUE; CORD BLOOD AB Objective: To assess serum adiponectin levels of neonates in relation to ponderal index and birth length with and without adjustment for potential confounding factors including maternal factors and perinatal characteristics. Design: A cross-sectional study. Methods: Three hundred and three newborns (Caucasian, singleton, full term, with a birth weight of greater than or equal to2500 g, and apparently healthy) were included in the study. Blood samples were collected from the newborns no later than the fifth day of life for measurements of adiponectin and major IGF system components (IGF-I, IGF-II, IGF binding protem-3 (IGFBP-3)). The data were analyzed using simple and multiple regression analyses. Results: Adiponectin is substantially higher in neonates than in adults, with no evidence of the gender dimorphism observed among adults. We found an inverse association between neonatal adiponectin levels and newborn ponderal index and a positive association with newborn length by univariate analysis. We also found it statistically significant inverse association of adiponectin with jaundice/bilirubin, and a marginally significant positive association of this hormone with IGFBP-3 but no significant association with any maternal factors. In multivariate analysis, the inverse association between serum adiponectin and ponderal index does not remain significant after adjustment for potential confounding factors. In contrast, neonatal adiponectin levels correlate inversely significantly and independently with liver maturity and IGF-II and tend to remain positively associated with IGFBP-3 and increased birth length. Conclusions: An inverse association of adiponectin with ponderal index by univariate analysis is not independent from confounding factors. In contrast, the positive association between serum adiponectin and birth length may reflect either a direct effect of adiponectin or an adiponectin-mediated increase in the sensitivity of tissues to insulin and components of the IGF system, and needs to be explored further. C1 Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Dept Internal Med,Beth Israel Deaconess Med Ctr, Boston, MA USA. Univ Athens, Dept Hyg & Epidemiol, Sch Med, Athens 11527, Greece. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Alexandra Matern Hosp, Dept Neonatol, Athens, Greece. Elena Venizelou Matern Hosp, Dept Neonatol, Athens, Greece. NICHHD, Paediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Paediat 1, Ag Sophia Childrens Hosp, Athens 11527, Greece. RP Petridou, E (reprint author), Univ Athens, Dept Hyg & Epidemiol, Sch Med, 75 Mikras Asias Str, Athens 11527, Greece. EM epetrid@med.uoa.gr FU NIDDK NIH HHS [DK 58785, 5T32DK07816-18] NR 46 TC 33 Z9 35 U1 0 U2 1 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD DEC PY 2004 VL 151 IS 6 BP 741 EP 746 DI 10.1530/eje.0.1510741 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 882VY UT WOS:000225969200010 PM 15588241 ER PT J AU Ogino, S Wilson, RB Gold, B AF Ogino, S Wilson, RB Gold, B TI New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE SMN1; SMN; spinal muscular atrophy; copy number; genetic counseling; risk assessment ID SPINAL MUSCULAR-ATROPHY; GENE DOSAGE ANALYSIS; MOTOR-NEURON GENE; SINGLE NUCLEOTIDE; COPY NUMBER; MOLECULAR ANALYSIS; RISK ASSESSMENT; MUTATION-RATE; HUMAN GENOME; SMA CARRIER AB Most spinal muscular atrophy patients lack both copies of SMN1. Loss of SMN1 ('0-copy alleles') can occur by gene deletion or SMN1-to-SMN2 gene conversion. Despite worldwide efforts to map the segmental duplications within the SMN region, most assemblies do not correctly delineate these genes. A near pericentromeric location provides impetus for the strong evidence that SMN1 and SMN2 arose from a primate-specific paralogous gene duplication. Here we meta-analyzed our recent laboratory results together with available published data, in order to calculate new mutation rates and allele/haplotype frequencies in this recalcitrant and highly unstable region of the human genome. Based on our tested assumption of compliance with Hardy-Weinberg equilibrium, we conclude that the SMN1 allele frequencies are: '0-copy disease alleles,' 0.013; '1-copy normal alleles,' 0.95; '2-copy normal alleles (ie, two copies of SMN1 on one chromosome),' 0.038; and '1 D disease alleles (SMN1 with a small intragenic mutation),' 0.00024. The SMN1 haplotype ['(SMN1 copy number)-(SMN2 copy number)'] frequencies are: '0-0,' 0.00048; '0-1,' 0.0086; '0-2,' 0.0042; '1-0,' 0.27; '1-1,' 0.66; '1-2,' 0.015; '2-0,' 0.027; and '2-1,' 0.012. Paternal and maternal de novo mutation rates are 2.1x10(-4) and 4.2x10(-5), respectively. Our data provide the basis for the most accurate genetic risk calculations, as well as new insights on the evolution of the SMN region, with evidence that nucleotide position 840 ( where a transition 840C>T functionally distinguishes SMN2 from SMN1) constitutes a mutation hotspot. Our data also suggest selection of the 1-1 haplotype and the presence of rare chromosomes with three copies of SMN1. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Natl Canc Inst, Human Genet Sect, Lab Gen Divers, Frederick, MD USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu NR 45 TC 46 Z9 53 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD DEC PY 2004 VL 12 IS 12 BP 1015 EP 1023 DI 10.1038/sj.ejhg.5201288 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 871VR UT WOS:000225165200006 PM 15470363 ER PT J AU Avidan, H Kipnis, J Butovsky, O Caspi, RR Schwartz, M AF Avidan, H Kipnis, J Butovsky, O Caspi, RR Schwartz, M TI Vaccination with autoantigen protects against aggregated beta-amyloid and glutamate toxicity by controlling microglia: effect of CD4(+)CD25(+) T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE neuroprotection; T cell-based vaccination; protective autoimmunity; CNS injury; Alzheimer's disease ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; SPINAL-CORD-INJURY; ALZHEIMERS-DISEASE; NEUROPROTECTIVE AUTOIMMUNITY; THERAPEUTIC VACCINATION; NEURONAL SURVIVAL; SELF-ANTIGEN; B-CELLS; IMMUNIZATION AB Neurodegenerative diseases differ in etiology but are propagated similarly. We show that neuronal loss caused by intraocular injection of aggregated beta-amyloid was significantly greater in immunodeficient mice than in normal mice. The neurodegeneration was attenuated or augmented by elimination or addition, respectively, of naturally occurring CD4(+)CD25(+) regulatory T cells (Treg). Vaccination with retina-derived antigens or with the synthetic copolymer glatiramer acetate (Copolymer-1, Cop-1), but not with beta-amyloid, reduced the ocular neuronal loss. In mouse hippocampal slices, microglia encountering activated T cells overcame the cytotoxicity of aggregated beta-amyloid. These findings support the concept of "protective autoimmunity", show that a given T cell-based vaccination is protective at a particular site irrespective of toxicity type, and suggest that locally activated T cells induce a microglial phenotype that helps neurons withstand the insult. Alzheimer's and other neurodegenerative diseases might be arrested or retarded by vaccination with Cop-1 or related compounds or by treatment with compounds that weaken Treg suppression. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, M (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. EM michal.schwartz@weizmann.ac.il NR 48 TC 52 Z9 53 U1 1 U2 3 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 DEC PY 2004 VL 34 IS 12 BP 3434 EP 3445 DI 10.1002/eji.200424883 PG 12 WC Immunology SC Immunology GA 878WE UT WOS:000225677200015 PM 15549735 ER PT J AU Yanaba, K Mukaida, N Matsushima, K Murphy, PM Takehara, K Sato, S AF Yanaba, K Mukaida, N Matsushima, K Murphy, PM Takehara, K Sato, S TI Role of C-C chemokine receptors 1 and 5 and CCL3/macrophage inflammatory protein-1 alpha in the cutaneous Arthus reaction: possible attenuation of their inhibitory effects by compensatory chemokine production SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CCR1; CCR5; CCL3; Arthus reaction; inflammation ID MAST-CELL RECRUITMENT; INTERCELLULAR-ADHESION MOLECULE-1; MICE LACKING; CUTTING EDGE; PROTEIN 1-ALPHA; DENDRITIC CELLS; INNATE IMMUNITY; HOST-DEFENSE; L-SELECTIN; RANTES AB The deposition of immune complexes induces an acute inflammatory response with tissue injury. Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple chemokines. To assess the role of the chemokine receptors CCR1 and CCR5, and a ligand for these receptors CCL3/macrophage inflammatory protein-1alpha, in this pathogenic process, the reverse passive cutaneous Arthus reaction was induced in mice lacking CCR1, CCR5, or CCL3. Edema was significantly attenuated in CCR1-deficient (CCR1(-/-)) and CCL3(-/-) mice but not CCR5(-/-) mice, compared with wild-type mice. Numbers of infiltrating neutrophils and mast cells were reduced in CCL3(-/-) and CCR1(-/-) mice, respectively, compared with wild-type mice. CCR1 and CCR5 were expressed on neutrophils and mast cells. Remarkably, the intradermal mRNA expression of CCL5/RANTES, another ligand for CCR1 and CCR5, was increased in CCR5(-/-) and CCL3(-/-) mice, compared with wild-type mice, while the cutaneous CCL3 mRNA expression was augmented in CCR1(-/-) and CCR5(-/-) mice. These results indicate that CCR1, CCR5, and CCL3 cooperatively contribute to the cutaneous Arthus reaction, and also suggest that enhanced expression of CCL3 and CCL5 compensates for the loss of CCR1, CCR5, and CCL3 in the reaction. C1 Kanazawa Univ, Dept Dermatol, Grad Sch Med Sci, Kanazawa, Ishikawa 9208641, Japan. Jikei Univ, Dept Dermatol, Sch Med, Tokyo, Japan. Kanazawa Univ, Canc Res Inst, Div Mol Bioregulat, Kanazawa, Ishikawa 920, Japan. Univ Tokyo, Sch Med, Dept Mol Prevent Med, Tokyo 113, Japan. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Sato, S (reprint author), Kanazawa Univ, Dept Dermatol, Grad Sch Med Sci, 13-1 Takaramachi, Kanazawa, Ishikawa 9208641, Japan. EM s-sato@med.kanazawa-u.ac.jp RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 NR 58 TC 8 Z9 9 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 DEC PY 2004 VL 34 IS 12 BP 3553 EP 3561 DI 10.1002/eji.200425426 PG 9 WC Immunology SC Immunology GA 878WE UT WOS:000225677200027 PM 15517609 ER PT J AU Joseph, EK Levine, JD AF Joseph, EK Levine, JD TI Caspase signalling in neuropathic and inflammatory pain in the rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; chemotherapy; death receptor; HIV/AIDS; tumour necrosis factor ID TUMOR-NECROSIS-FACTOR; CISPLATIN-INDUCED APOPTOSIS; SPINAL NERVE LIGATION; CYTOCHROME-C RELEASE; SENSORY NEURONS; PERIPHERAL NEUROPATHY; FACTOR-ALPHA; CELL-DEATH; RHEUMATOID-ARTHRITIS; TNF-ALPHA AB Whereas small-fibre sensory neuropathies might ultimately lead to cell death and loss of sensation, they first progress through a phase, which might last for years, characterized by the presence of analgesia-resistant neuropathic dysesthesias and pain. Much previous research has addressed these two phases as separate phenomena mediated by presumably discrete biochemical mechanisms. We hypothesized that activity in signalling pathways that ultimately lead to apoptosis plays a critical role in the generation of neuropathic pain, before death of sensory neurons becomes apparent. We have tested the hypothesis that activator and effector caspases, defining components of programmed cell death (apoptosis) signalling pathways, also contribute to pain-related behaviour in animals with small-fibre peripheral neuropathies and that the death receptor ligand, tumour necrosis factor-alpha, and its downstream second messenger, ceramide, also produce pain-related behaviour via this mechanism. In two models of painful peripheral neuropathy, HIV/AIDS therapy (induced by the nucleoside reverse transcriptase inhibitor, dideoxycytidine), and cancer chemotherapy (induced by vincristine) peripheral neuropathy, and for pain-related behaviour induced by tumour necrosis factor-alpha and its second messenger, ceramide, inhibition of both activator (1, 2, 8 and 9) and effector (3) caspases attenuates neuropathic pain-related behaviour, although has no effect in streptozotocin-diabetic neuropathy and control rats. We conclude that during a latent phase, before apoptotic cell death is manifest, the caspase signalling pathway can contribute to pain in small-fibre peripheral neuropathies, and that inflammatory/immune mediators also activate these pathways. This suggests that these pathways are potential targets for novel pharmacological agents for the treatment of inflammatory as well as neuropathic pain. C1 Univ Calif San Francisco, Dept Med, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Program Biomed Sci, San Francisco, CA 94143 USA. RP Joseph, EK (reprint author), Univ Calif San Francisco, Dept Med, Div Neurosci, Box 0440-C522, San Francisco, CA 94143 USA. EM aley@itsa.ucsf.edu NR 72 TC 104 Z9 122 U1 1 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 2004 VL 20 IS 11 BP 2896 EP 2902 DI 10.1111/j.1460-9568.2004.03750.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 876HQ UT WOS:000225487800007 PM 15579143 ER PT J AU Vahratian, A Buekens, P Del Vaux, T Boutsen, M Wang, Y Kupper, LL AF Vahratian, A Buekens, P Del Vaux, T Boutsen, M Wang, Y Kupper, LL TI Birthweight differences among infants of North African immigrants and Belgians in Belgium SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; BORN AB Background: Infants of North African immigrants are reported to have higher birthweights than their Belgian counterparts. It is unclear what mechanism contributes to this difference. Methods: Analyses were based on a hospital-based cohort of 1, 162 women. Results: Infants of North African immigrants were less likely to be born preterm, compared to infants of Belgian women. After adjusting for sociodemographic and maternal factors, the estimated difference in mean birthweight was 74 g (p=0.05). When limited to term births, this difference was 28 g (p=0.42). Conclusion: The difference in mean birthweight between North African and Belgian infants was explained by differences in preterm birth and other risk factors. C1 Univ N Carolina, Sch Publ Hlth, Dept Maternal & Child Hlth, Chapel Hill, NC 27515 USA. Inst Trop Med, STO HIV Res & Intervent Unit, B-2000 Antwerp, Belgium. Free Univ Brussels, Sch Publ Hlth, Dept Epidemiol & Social Med, Brussels, Belgium. Cook Cty Hosp, Collaborat Res Unit, Chicago, IL 60612 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27515 USA. RP Vahratian, A (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM vahratia@mail.nih.gov RI Vahratian, Anjel/A-1182-2011 NR 12 TC 19 Z9 20 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD DEC PY 2004 VL 14 IS 4 BP 381 EP 383 DI 10.1093/eurpub/14.4.381 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 894RL UT WOS:000226809200010 PM 15542873 ER PT J AU Elliott, L Yeatts, K Loomis, D AF Elliott, L Yeatts, K Loomis, D TI Ecological associations between asthma prevalence and potential exposure to farming SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE agriculture; asthma; ecological study; farming; livestock ID ALLERGIC DISEASES; EARLY-LIFE; CHILDREN; ADOLESCENTS; ENDOTOXIN; HEALTH; ATOPY; RISK AB Farming and exposure to livestock have been proposed as protective against the development of asthma in children. An ecological study was conducted to examine the support for these relationships in the USA. County-specific aggregate measures were used to examine the relationship between the prevalence of asthma and wheeze in 7th and 8th grade school children (aged 12-14 yrs) and selected measures of potential exposure to farming in the state of North Carolina. Binomial regression models were fitted to quantify these relationships, with adjustments for parental smoking, socioeconomic status, sex and race. Regression coefficients were reported for an increment of one interquartile range (IQR) in each indicator of exposure. The prevalence of asthma showed decreasing trends for most indicators of farm exposure. Regression results suggested that the largest decreases ill asthma prevalence were associated with the number of farms (-5.0% per IQR increment), acreage of hay (-7.2% per IQR increment) and beef cattle (-7.8% per IQR increment). The pattern of results was similar for wheezing. In conclusion, the findings of this study are consistent with the hypothesis that certain farm exposures are protective against childhood asthma. Further research with individual-level data is needed to identify the specific protective exposures. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Environm Sci, Chapel Hill, NC USA. RP Elliott, L (reprint author), Natl Inst Environm Hlth Sci, POB 12233, Res Triangle Pk, NC 27709 USA. EM elliott1@nichs.nih.gov NR 20 TC 12 Z9 13 U1 0 U2 2 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 DEC PY 2004 VL 24 IS 6 BP 938 EP 941 DI 10.1183/09031936.04.0006404 PG 4 WC Respiratory System SC Respiratory System GA 878EX UT WOS:000225630500010 PM 15572535 ER PT J AU Bettelheim, FA AF Bettelheim, FA TI Light scattering in lens research: an essay on accomplishments and promises SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Abraham Spector International Symposium CY OCT 11-13, 2003 CL Long Isl, NY DE diffusion coefficient; lens; light scattering; molecular size; polarized/depolarized ID PHOTON-CORRELATION SPECTROSCOPY; ALPHA-CRYSTALLIN; ROTATIONAL DIFFUSION; FLUCTUATION THEORY; INTERNAL MOTIONS; CIRCULAR DNA; OPACITIES; CATARACT; AGE; PARAMETERS AB This paper briefly reviews light scattering methodologies in lens research. In the phenomenological sense cataract formation (lens opacities or turbidities) in its early stages can be described by enhanced scattering of light. In the analytical sense information is obtained on the molecular entities involved in light scattering. In Section 2, different methodologies (mainly static and dynamic) of light scattering experiments are described, which had been used successfully in lens research. In Section 3 the problem of interpretation of light scattering data in condensed phase is considered. It is pointed out that due to interparticle interactions the concentration dependence of the data must be considered. If dilution or thin sectioning of samples is not ail option, it is better to report molecular parameters in terms of diffusion coefficients or decay times. In Section 4, a case is made to encourage light scattering experiments in the polarized/depolarized modes both in static and dynamic light scatterings. Preliminary data obtained with polarized/depolarized dynamic light scattering measurements on a-crystallin and interpreted in view of model systems and literature data imply that the molecule is a compact sphere with somewhat restricted segment mobility. The preliminary nature of this information is due to the unavailability of high power lasers and efficient polarizers in my lab at the time of these experiments. (C) 2004 Published by Elsevier Ltd. C1 Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. NEI, Lab Mechanism Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Bettelheim, FA (reprint author), Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. EM ziglers@nei.nih.gov NR 37 TC 7 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2004 VL 79 IS 6 BP 747 EP 752 DI 10.1016/j.exer.2004.06.004 PG 6 WC Ophthalmology SC Ophthalmology GA 883EZ UT WOS:000225994600003 PM 15642311 ER PT J AU John, M Jaworski, C Chen, ZG Subramanian, S Ma, WC Sun, F Li, DY Spector, A Carper, D AF John, M Jaworski, C Chen, ZG Subramanian, S Ma, WC Sun, F Li, DY Spector, A Carper, D TI Matrix metalloproteinases are down-regulated in rat lenses exposed to oxidative stress SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Abraham Spector International Symposium CY OCT 11-13, 2003 CL Long Isl, NY DE MMPs; MT-MMPs; TIMPs; beta-actin; oxidative stress; cataract ID PEROXIDASE-1 KNOCKOUT MICE; EPITHELIAL-CELLS; GENE-EXPRESSION; ACTIN; CATARACT; MECHANISM; DAMAGE; INHIBITORS; PATHWAY; COMPLEX AB Matrix metalloproteinases are important biological effectors of tissue remodelling. Increased MMP expression occurs during injury, inflammation, cellular transformation, and oxidative stress. Oxidative stress in the lens, a causal factor in cataractogenesis, has been shown to induce MMP secretion. The objective of this study was to assess the expression of MMPs and their regulators in an oxidative stress model of cataract, where epithelial cell death and cortical fibre cell swelling occurs in rat lenses after exposure to riboflavin, oxygen, and light. Two time points (4 and 7 hr of exposure) were chosen in order to compare transparent lenses with partially opaque lenses. MMP activity, protein, and mRNA levels were measured. The results show that MMP-2, MMP-9, MT1-MMP, and MT3-MMP are down-regulated by oxidative stress and that the down-regulation is most likely due to reduced gene transcription. In contrast, genes for catalase, glutathione peroxidase, and GAPDH are essentially unaffected, while beta-actin mRNA and protein levels are markedly increased at both time points. The down-regulation of MMPs occurs in lenses still seemingly transparent after 4 hr of exposure, indicating that reduced MMP activity is a relatively early response to the oxidative stress. Moreover, in our model system, MMIP inhibition, not induction, is associated with cataractogenesis. (C) 2004 Elsevier Ltd. All rights reserved. C1 NEI, Sect Mol Therapeut, NIH, Bethesda, MD 20892 USA. Univ Nacl Colombia, Coll Phys & Surg, Dept Ophthalmol, New York, NY 10032 USA. RP Carper, D (reprint author), NEI, Sect Mol Therapeut, NIH, Bldg 7,Room 202,9000 Rockville Pike, Bethesda, MD 20892 USA. EM carperd@nei.nih.gov NR 39 TC 13 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2004 VL 79 IS 6 BP 839 EP 846 DI 10.1016/j.exer.2004.08.025 PG 8 WC Ophthalmology SC Ophthalmology GA 883EZ UT WOS:000225994600017 PM 15642321 ER PT J AU Sun, G Ma, Y Gao, X Konig, S Fales, HM Kador, PF AF Sun, G Ma, Y Gao, X Konig, S Fales, HM Kador, PF TI Method for isolating tight-binding inhibitors of rat lens aldose reductase SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Abraham Spector International Symposium CY OCT 11-13, 2003 CL Long Isl, NY DE diabetic complications; aldose reductase; aldose reductase inhibitors; electrospray ionisation mass spectrometry ID ELECTROSPRAY MASS-SPECTROMETRY; TYPE-1 DIABETES-MELLITUS; GALACTOSE-FED DOGS; ESCHERICHIA-COLI; RETINAL CHANGES; GENE; NEPHROPATHY; SUSCEPTIBILITY; POLYMORPHISMS; RETINOPATHY AB Numerous animal studies indicate that aldose reductase inhibitors (ARIs) are beneficial for the prevention or amelioration of diabetic complications such as neuropathy, nephropathy and the ocular complications of cataract, retinopathy and keratopathy. To aid in the identification of novel potent ARIs, we have previously developed a screening method that is based on the formation of a non-covalent ternary tight-binding enzyme-inhibitor-nucleotide (AR-ARI-NADPH) complex that can be isolated using YM-10 filter units. Here, we report a modification of this method that permits us to rapidly identify tight binding ARIs that are isolated by denaturation from AR-ARI-NADPH complexes that are free of possible contamination resulting from the reaction of methanol with the YM-10 filter units. For the development of this procedure, nine structurally diverse ARIs were mixed with purified recombinant rat lens aldose reductase (RLAR) bound with NADPH to form tight-binding RLAR-ARI-NADPH complexes. These complexes were purified by high pressure Sephadex 75 size exclusion chromatography using ammonium acetate buffer and the formation of each complex was confirmed by electrospray ionisation mass spectrometry (ESI-MS). Each of the complexes was then denatured with methanol, rechromatographed on the size exclusion column, and the identity of the bound ARIs was confirmed by ESI-MS. The apparent ARI binding with aldose reductase to form a tight binding ARI complex appeared proportional to their IC50 values. This procedure allows for the rapid identification of tight binding ARIs with apparent IC(50)s < 0(.)1 mum. (C) 2004 Published by Elsevier Ltd. C1 NEI, Lab Ocular Therapeut, Bethesda, MD 20892 USA. Natl Heart Lung & Blood Inst, Lab Biophys Chem, NIH, Bethesda, MD 20892 USA. RP Kador, PF (reprint author), Univ Nebraska, Coll Med, Coll Pharm, Omaha, NE 68198 USA. EM pkador@unmc.edu RI Konig, Simone/B-6504-2008 OI Konig, Simone/0000-0003-0672-7246 NR 27 TC 2 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2004 VL 79 IS 6 BP 919 EP 926 DI 10.1016/j.exer.2004.05.011 PG 8 WC Ophthalmology SC Ophthalmology GA 883EZ UT WOS:000225994600026 PM 15642330 ER PT J AU Hawse, JR Hejtmancik, JF Horwitz, J Kantorow, M AF Hawse, JR Hejtmancik, JF Horwitz, J Kantorow, M TI Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Abraham Spector International Symposium CY OCT 11-13, 2003 CL Long Isl, NY DE age-related cataract; clear human lenses; gene expression ID ALPHA-CRYSTALLIN; PROTEIN; GLUTATHIONE; CELLS; PROLIFERATION; INHIBITION; CHAPERONE; DAMAGE; MOUSE AB We have examined the gene expression profiles of young, old and cataractous human lenses in order to differentiate those gene expression changes specific for cataract from those also associated with lens aging. Differentially expressed transcripts were identified by oligonucleotide microarray analysis and clustered according to their known functions. Four hundred and twelve transcripts that are increased and 919 transcripts that are decreased were identified at the 2-fold or greater level between epithelia isolated from cataract relative to clear lenses while 182 transcripts that are increased and 547 transcripts that are decreased were identified at the 2-fold or greater level between young and old lens epithelia. Comparison of the cataract gene expression changes with those detected in lens aging revealed that only 3 transcripts exhibited similar trends in gene expression. These data suggest that cataract- and age-specific changes in gene expression do not overlap and provide evidence for multiple cataract- and age-specific gene expression changes in the human lens. (C) 2004 Elsevier Ltd. All rights reserved. C1 Florida Atlantic Univ, Charles E Schmidt Coll Sci, Dept Biomed Sci, Boca Raton, FL 33431 USA. NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD USA. Los Alamos Natl Lab, Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA USA. RP Kantorow, M (reprint author), Florida Atlantic Univ, Charles E Schmidt Coll Sci, Dept Biomed Sci, 777 Glades Rd,POB 3091, Boca Raton, FL 33431 USA. EM mkantoro@fau.edu FU NEI NIH HHS [R01 EY013022] NR 44 TC 25 Z9 27 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 DEC PY 2004 VL 79 IS 6 BP 935 EP 940 DI 10.1016/j.exer.2004.04.007 PG 6 WC Ophthalmology SC Ophthalmology GA 883EZ UT WOS:000225994600028 PM 15642332 ER PT J AU Kanungo, J Swamynathan, SK Piatigorsky, J AF Kanungo, J Swamynathan, SK Piatigorsky, J TI Abundant corneal gelsolin in Zebrafish and the 'four-eyed' fish, Anableps anableps: possible analogy with multifunctional lens crystallins SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Abraham Spector International Symposium CY OCT 11-13, 2003 CL Long Isl, NY DE crystallin; cornea; gelsolin; zebrafish ID ALDEHYDE DEHYDROGENASE; EYE DEVELOPMENT; GENE; PROTEINS; EXPRESSION; EVOLUTION; TRANSPARENCY; WATER; IDENTIFICATION; TRANSKETOLASE AB The cornea accumulates high proportions (can be up to 50%) of taxon-specific, water-soluble, cytoplasmic proteins (often enzymes) that have been considered analogous to the multifunctional lens crystallins. We have shown that gelsolin (an actin-severing protein) is the major water-soluble corneal protein of the zebrafish (Danio rerio) and the 'four-eyed' fish (Anableps anableps). Each Anableps eye contains one lens, an aquatic ventral cornea with an epithelium comprising 5-7 cell layers, and an air-exposed flatter dorsal cornea with an epithelium comprising >20 cell layers and appreciably enriched with glycogen. Gelsolin accounts for 38 and 21% of the dorsal and ventral cornea, respectively, suggesting that the abundance of gelsolin in the cornea is not incompatible with its function in air. The thicker, glycogen-enriched, air-exposed dorsal cornea may protect against UV irradiation and desiccation. Gelsolin comprises similar to50% of the 5 cell-layer thick aquatic corneal epithelium of zebrafish. Reported zebrafish ESTs have indicated the presence of a second gelsolin gene in this species. We show by RT-PCR that the abundant corneal gelsolin (also expressed weakly in lens) (C/L-gelsolin) is also expressed in early development and differs from a ubiquitously expressed gelsolin (U-gelsolin) that is not specialized for cornea. Microinjection tests showed that overexpression of C/L-gelsolin dorsalizes the embryo and can lead to axis duplication, while interruption of C/L-gelsolin expression with a specific morpholino oligonucleotide ventralizes the embryo and interferes with brain and eye development. The evidence that C/L-gelsolin participates in the bone morphogenetic protein (BMP)/Smad dorsal-ventral signaling pathway is reviewed. Finally, we speculate that soluble C/L-gelsolin:actin complexes in the cornea may be analogous to Soluble alphaA:alphaB-crystallin complexes in the lens. Together, our data are consistent with an analogy between the abundance of gelsolin in fish corneas and taxon-specific multifunctional crystallins in lenses. (C) 2004 Elsevier Ltd. All rights reserved. C1 NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Lab Mol & Dev Biol, NIH, 7 Mem Dr,Bldg 7,Room 100A, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov OI Swamynathan, Shivalingappa/0000-0002-9158-1511 NR 49 TC 10 Z9 10 U1 0 U2 5 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 DEC PY 2004 VL 79 IS 6 BP 949 EP 956 DI 10.1016/j.exer.2004.04.002 PG 8 WC Ophthalmology SC Ophthalmology GA 883EZ UT WOS:000225994600030 PM 15642334 ER PT J AU Bloom, ML Wolk, AG Simon-Stoos, KL Bard, JS Chen, J Young, NS AF Bloom, ML Wolk, AG Simon-Stoos, KL Bard, JS Chen, J Young, NS TI A mouse model of lymphocyte infusion-induced bone marrow failure SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; HEMATOPOIETIC PROGENITOR CELLS; MEDIATED APLASTIC-ANEMIA; INTERFERON-GAMMA; DONOR CELLS; NODE CELLS; STEM-CELLS; MICE; TRANSPLANTATION; DESTRUCTION AB Objective. To develop a mouse model for the study of the pathophysiologic mechanism and treatment of human bone marrow (BM) failure. Materials and Methods. Unmanipulated B6D2F1 or CByB6F1 hybrid mice were infused with 10-40 x 10(6) lymph node (LN) cells from their C57BL/6 (B6) parent. Pancytopenia was monitored by cell counting, while marrow damage was assessed by histological staining. Destruction of BM hematopoietic progenitor/stem cells was measured by colony formation in vitro and irradiation protection in vivo. Serum interferon-gamma (IFN-gamma) concentration was measured by enzyme-linked immunosorbent assay. BM T cell Vbeta and Fas expressions were analyzed by flow cytometry. Treatment effects of immunosupressive agents cyclosporine, antithymocyte globulin (ATG), anti-IFN-gamma, and anti-tumor necrosis factor-alpha (anti-TNF-alpha) were tested. Results. Infusion of 30-40 x 10(6)B6 LN cells led to rapid development of severe pancytopenia, BM hypoplasia, and death. Affected mice had drastically reduced hematopoietic progenitor and stem cells. BM of affected mice showed lymphocyte infiltration, oligoclonal T cell expansion, and upregulated Fas expression. Serum IFN-gamma concentration increased two- to three-fold. Timed administration of cyclosporine or ATG abrogated pancytopenia. Treatment with anti-IFN-gamma antibody reliably rescued mice, and treatment with anti-TNF-alpha antibody extended animal survival significantly. Conclusion. This mouse model indicates that activated lymphocytes and type I cytokines play important roles in marrow destruction in lymphocyte infusion-induced BM failure. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngn@nhlbi.nih.gov NR 26 TC 45 Z9 54 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2004 VL 32 IS 12 BP 1163 EP 1172 DI 10.1016/j.exphem.2004.08.006 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 884KH UT WOS:000226083100005 PM 15588941 ER PT J AU Ma, W Fitzgerald, W Liu, QY O'Shaughnessy, TJ Maric, D Lin, HJ Alkon, DL Barker, JL AF Ma, W Fitzgerald, W Liu, QY O'Shaughnessy, TJ Maric, D Lin, HJ Alkon, DL Barker, JL TI CNS stem and progenitor cell differentiation into functional neuronal circuits in three-dimensional collagen gels SO EXPERIMENTAL NEUROLOGY LA English DT Article DE neural stem cells; proliferation; neurogenesis; 3D matrix; collagen; GABA; glutamate; acetylcholine; synapse formation; Ca2+ imaging ID CENTRAL-NERVOUS-SYSTEM; NEURAL PRECURSOR CELLS; RAT CORTICAL-NEURONS; IN-VITRO; EXPRESSION; ACTIVATION; MATRIX; EMERGE AB The mammalian central nervous system (CNS) has little capacity for self-repair after injury, and neurons are not capable of proliferating. Therefore, neural tissue engineering that combines neural stem and progenitor cells and biologically derived polymer scaffolds may revolutionize the medical approach to the treatment of damaged CNS tissues. Neural stem and progenitor cells isolated from embryonic rat cortical or subcortical neuroepithelium were dispersed within type I collagen, and the cell-collagen constructs were cultured in serum-free medium containing basic fibroblast growth factor. The collagen-entrapped stem and progenitors actively expanded and efficiently generated neurons, which developed neuronal polarity, neurotransmitters, ion channels/receptors, and excitability. Ca2+ imaging showed that differentiation from BrdU(+)/TuJ1(-) to BrdU(-)/TuJ1(+) cells was accompanied by a shift in expression of functional receptors for neurotransmitters from cholinergic and purinergic to predominantly GABAergic and glutamatergic. Spontaneous postsynaptic currents were recorded by patch-clamping from precursor cell-derived neurons and these currents were partially blocked by 10-muM bicuculline, and completely blocked by additional 10 muM of the kainate receptor antagonist CNQX, indicating an appearance of both GABAergic and glutamatergic synaptic activities. Staining with endocytotic marker FM1-43 demonstrated active synaptic vesicle recycling occurring among collagen-entrapped neurons. These results show that neural stem and progenitor cells cultured in 3D collagen gels recapitulate CNS stem cell development; this is the first demonstration of CNS stem and progenitor cell-derived functional synapse and neuronal network formation in a 3D matrix. The proliferative capacity and neuronal differentiating potential of neural progenitors in 3D collagen gels suggest their potential use in attempts to promote neuronal regeneration in vivo. (C) 2004 Elsevier Inc. All rights reserved. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NICHHD, NASA NIH Ctr 3D Tissue Culture, NIH, Bethesda, MD 20892 USA. Blancehette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Ma, W (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6900,4555 Overlook Ave SW, Washington, DC 20375 USA. EM wma@cbmse.nrl.navy.mil NR 31 TC 130 Z9 142 U1 1 U2 37 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 DEC PY 2004 VL 190 IS 2 BP 276 EP 288 DI 10.1016/j.expneurol.2003.10.016 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 873EB UT WOS:000225261200002 PM 15530869 ER PT J AU Levenson, CW Cutler, RG Ladenheim, B Cadet, JL Hare, J Mattson, MP AF Levenson, CW Cutler, RG Ladenheim, B Cadet, JL Hare, J Mattson, MP TI Role of dietary iron restriction in a mouse model of Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Parkinson's disease; apoptosis; striatum; p53; desferrioxiamine; iron deficiency; MPTP ID MPTP-INDUCED NEUROTOXICITY; AMYLOID BETA-PEPTIDE; SUBSTANTIA-NIGRA; OXIDATIVE STRESS; PIVOTAL ROLE; NEURONS; ACCUMULATION; DEFICIENCY; BRAIN; RISK AB There is a growing body of evidence suggesting that iron chelation may be a useful therapy in the treatment of Parkinson's Disease (PD). Experiments were designed to test the impact of dietary iron availability on the pathogenic process and functional outcome in a mouse model of PD. Mice were fed diets containing low (4 ppm) or adequate (48 ppm) amounts of iron for 6 weeks before the administration of MPTP, a mitochondrial toxin that damages nigrostriatal dopaminergic neurons and induces Parkinson-like symptoms. Low dietary iron increased serum total iron binding capacity (P<0.001). Consistent with neuronal protection, iron restriction increased sphingomyelin C16:0 and decreased ceramide C16:0. However, there was a 35% decrease in striatal dopamine (DA) in iron-restricted mice. Motor behavior was also impaired in these animals. In vitro studies suggested that severe iron restriction could lead to p53-mediated neuronal apoptosis. Administration of MPTP reduced striatal DA (P<0.01) and impaired motor behavior in iron-adequate mice. However, in iron-restricted mice, striatal dopamine levels and motor behavior were unchanged compared to saline-treated mice. Thus, while reduced iron may provide protection against PD-inducing insults such as MPTP, the role of iron in the synthesis of DA and neuronal survival should be considered, particularly in the development of iron-chelating agents to be used chronically in the clinical setting. (C) 2004 Elsevier Inc. All rights reserved. C1 Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. Florida State Univ, Dept Nutr Food & Exercise Sci, Tallahassee, FL 32306 USA. NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. NIDA, Intramural Res Program, Mol Neuropsychiat Sect, Baltimore, MD 21224 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. RP Levenson, CW (reprint author), Florida State Univ, Program Neurosci, 237 Biomed Res Facil, Tallahassee, FL 32306 USA. EM levenson@neuro.fsu.edu RI Mattson, Mark/F-6038-2012 NR 45 TC 35 Z9 36 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2004 VL 190 IS 2 BP 506 EP 514 DI 10.1016/j.expneurol.2004.08.014 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 873EB UT WOS:000225261200022 PM 15530889 ER PT J AU Acosta, CJ Galindo, CM Deen, JL Ochiai, RL Lee, HJ von Seidlein, L Carbis, R Clemens, JD AF Acosta, CJ Galindo, CM Deen, JL Ochiai, RL Lee, HJ von Seidlein, L Carbis, R Clemens, JD TI Vaccines against cholera, typhoid fever and shigellosis for developing countries SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE cholera; developing countries; enteric diseases; shigellosis; typhoid fever; vaccines ID VI-CAPSULAR POLYSACCHARIDE; ENTERIC-COATED CAPSULES; CONTROLLED FIELD TRIAL; O-SPECIFIC POLYSACCHARIDE; LIVE-VECTOR VACCINE; SALMONELLA-TYPHI; FLEXNERI 2A; BACILLARY DYSENTERY; ORAL IMMUNIZATION; PROTECTIVE EFFICACY AB Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant burden, especially among the poor in countries where these illnesses are endemic. Older-generation, parenteral, whole-cell vaccines against cholera and typhoid fever were abandoned in many countries as public health tools because of problems with insufficient protection and/or inadequate safety profiles. Modern-generation licensed vaccines are available for cholera and typhoid fever, but are not widely used by those in greatest need. A number of experimental candidates exist for all three diseases. Future research should focus on generating the evidence necessary to obtain a consensus on the deployment of existing vaccines against cholera and typhoid fever, and on clinical evaluation of pipeline vaccine candidates against all three diseases. C1 Seoul Natl Univ, Int Vaccine Inst, Kwanak Ku, Seoul 151818, South Korea. NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20895 USA. RP Acosta, CJ (reprint author), Seoul Natl Univ, Int Vaccine Inst, Kwanak Ku, Res Pk,San 4-8 Bongcheon 7 Dong, Seoul 151818, South Korea. EM camilo_acosta2003@yahoo.com OI Ochiai, Leon/0000-0002-5079-6786 NR 126 TC 9 Z9 9 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD DEC PY 2004 VL 4 IS 12 BP 1939 EP 1951 DI 10.1517/14712598.4.12.1939 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 878XI UT WOS:000225680300009 PM 15571456 ER PT J AU Gourgiotis, L Skarulis, MC AF Gourgiotis, L Skarulis, MC TI Clinical uses of recombinant human thyrotropin SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE multinodular goiter; recombinant human thyrotropin; thyroglobulin; thyroid cancer; thyroid reserve ID DIFFERENTIATED THYROID-CARCINOMA; NONTOXIC MULTINODULAR GOITER; RADIOACTIVE IODINE UPTAKE; ALLOWS DOSE REDUCTION; HUMAN TSH; RADIOIODINE THERAPY; STIMULATING HORMONE; SERUM THYROGLOBULIN; NODULAR GOITER; I-131 THERAPY AB Recombinant human thyroid-stimulating hormone (rhTSH), used to enhance diagnostic radioiodine whole body scanning and thyroglobulin testing, has dramatically altered the management of patients with thyroid cancer. Withdrawal from thyroid hormone suppression therapy and subsequent hypothyroidism is no longer the only safe and effective method for thyroid cancer surveillance. Currently, rhTSH is only approved for the monitoring of low-risk patients with well-differentiated thyroid cancer and radioactive iodine administration, in selected cases. Additional applications of rhTSH include enhancing the sensitivity of positron emission tomography in thyroid cancer, the management of multinodular goiter, and dynamic testing of thyroid reserve. The diagnostic and therapeutic role of rhTSH in these areas is discussed in this review. C1 NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Skarulis, MC (reprint author), NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH, 10 Ctr Dr MSC 1771,Bldg 10 Room 8S235B, Bethesda, MD 20892 USA. NR 84 TC 3 Z9 3 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD DEC PY 2004 VL 5 IS 12 BP 2503 EP 2514 DI 10.1517/14656566.5.12.2503 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 880II UT WOS:000225781800009 PM 15571468 ER PT J AU Mabley, JG Pacher, P Deb, A Wallace, R Elder, RH Szabo, C AF Mabley, JG Pacher, P Deb, A Wallace, R Elder, RH Szabo, C TI Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation SO FASEB JOURNAL LA English DT Article DE OGG-1; diabetes; shock; hypersensitivity; DNA repair ID ADP-RIBOSE SYNTHETASE; TUMOR-NECROSIS-FACTOR; PEROXYNITRITE DECOMPOSITION CATALYST; DEPENDENT DIABETES-MELLITUS; BASE EXCISION-REPAIR; NITRIC-OXIDE; POLY(ADP-RIBOSE) POLYMERASE; SACCHAROMYCES-CEREVISIAE; NEUTROPHIL RECRUITMENT; ISCHEMIA-REPERFUSION AB OGG-1 DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. It excises 7,8-dihydro-8-oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG-1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG-1(-/-) mice are resistant to endotoxin ( lipopolysaccharide, LPS)-induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild-type controls ( OGG(+/+)). Furthermore, the deletion of the OGG-1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low-dose streptozotocin treatment. OGG-1(-/-) mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG-1(+/+) mice. Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. In the contact hypersensitivity induced by oxazolone, the OGG-1(-/-) mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG-1 in the regulation of inflammation. C1 Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England. Inotek Pharmaceut Corp, Beverly, MA USA. NIAAA, NIH, Lab Physiol Studies, Rockville, MD 20852 USA. Christie Hosp NHS Trust, Paterson Inst Canc Res, CR UK Carcinogenesis Grp, Manchester M20 4BX, Lancs, England. Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1085 Budapest, Hungary. RP Univ Brighton, Sch Pharm & Biomol Sci, Cockcroft Bldg,Lewes Rd, Brighton BN2 4GJ, E Sussex, England. EM jgmabley@hotmail.com RI e-, a/F-9947-2012; OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z99 AA999999]; NHLBI NIH HHS [R-01-HL/DK-71246, R-01-HL59266] NR 60 TC 49 Z9 49 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2004 VL 18 IS 15 BP 290 EP + DI 10.1096/fj.04-2278fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 884MZ UT WOS:000226091000026 PM 15677345 ER PT J AU Zhang, W Qin, LY Wang, TG Wei, SJ Gao, HM Liu, J Wilson, B Liu, B Zhang, WQ Kim, HC Hong, JS AF Zhang, W Qin, LY Wang, TG Wei, SJ Gao, HM Liu, J Wilson, B Liu, B Zhang, WQ Kim, HC Hong, JS TI 3-Hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity SO FASEB JOURNAL LA English DT Article DE Parkinson's disease; inflammation; neuroprotection; microglia; astroglia ID NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE SYNTHASE; PARKINSONS-DISEASE; MICROGLIAL ACTIVATION; RAT MODEL; MESENCEPHALIC NEURONS; INTRANIGRAL INJECTION; PROMOTES RECOVERY; MOUSE MODEL; CELL-DEATH AB The purpose of this study was to develop a novel therapy for Parkinson's disease (PD). We recently reported that dextromethorphan (DM), an active ingredient in a variety of widely used anticough remedies, protected dopaminergic neurons in rat primary mesencephalic neuron-glia cultures against lipopolysaccharide (LPS)-mediated degeneration and provided potent protection for dopaminergic neurons in a MPTP mouse model. The underlying mechanism for the protective effect of DM was attributed to its anti-inflammatory activity through inhibition of microglia activation. In an effort to develop more potent compounds for the treatment of PD, we have screened a series of analogs of DM, and 3-hydroxymorphinan (3-HM) emerged as a promising candidate for this purpose. Our study using primary mesencephalic neuron-glia cultures showed that 3-HM provided more potent neuroprotection against LPS-induced dopaminergic neurotoxicity than its parent compound. The higher potency of 3-HM was attributed to its neurotrophic effect in addition to the anti-inflammatory effect shared by both DM and 3-HM. First, we showed that 3-HM exerted potent neuroprotective and neurotrophic effects on dopaminergic neurons in rat primary mesencephalic neuron-glia cultures treated with LPS. The neurotrophic effect of 3-HM was glia-dependent since 3-HM failed to show any protective effect in the neuron-enriched cultures. We subsequently demonstrated that it was the astroglia, not the microglia, that contributed to the neurotrophic effect of 3-HM. This conclusion was based on the reconstitution studies, in which we added different percentages of microglia ( 10 - 20%) or astroglia ( 40 - 50%) back to the neuron-enriched cultures and found that 3-HM was neurotrophic after the addition of astroglia, but not microglia. Furthermore, 3-HM-treated astroglia-derived conditioned media exerted a significant neurotrophic effect on dopaminergic neurons. It appeared likely that 3-HM caused the release of neurotrophic factor(s) from astroglia, which in turn was responsible for the neurotrophic effect. Second, the anti-inflammatory mechanism was also important for the neuroprotective activity of 3-HM because the more microglia were added back to the neuron-enriched cultures, the more significant neuroprotective effect was observed. The anti-inflammatory mechanism of 3-HM was attributed to its inhibition of LPS-induced production of an array of pro-inflammatory and neurotoxic factors, including nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E-2 (PGE(2)) and reactive oxygen species (ROS). In conclusion, this study showed that 3-HM exerted potent neuroprotection by acting on two different targets: a neurotrophic effect mediated by astroglia and an anti-inflammatory effect mediated by the inhibition of microglial activation. 3-HM thus possesses these two important features necessary for an effective neuroprotective agent. In view of the well-documented very low toxicity of DM and its analogs, this report may provide an important new direction for the development of therapeutic interventions for inflammation-related diseases such as PD. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenet, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA. Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. Dalian Med Univ, Clin Hosp 1, Dept Neurol, Dalian, Peoples R China. Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA. Kangwon Natl Univ, Coll Pharm, Chunchon, South Korea. RP Zhang, W (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM zhang11@niehs.nih.gov RI gao, huiming/C-8454-2012; liu, Bin/A-7695-2009 NR 64 TC 24 Z9 33 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2004 VL 18 IS 15 BP 395 EP + DI 10.1096/fj.04-1586fje PG 25 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 884MZ UT WOS:000226091000019 PM 15596482 ER PT J AU Leppert, PC AF Leppert, PC TI 21st century - Reproductive Medicine Network (RMN) SO FERTILITY AND STERILITY LA English DT Letter C1 NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Leppert, PC (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. OI Leppert, Phyllis/0000-0002-2724-6217 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2004 VL 82 IS 6 BP 1718 EP 1718 DI 10.1016/j.fertnstert.2004.10.015 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 880PS UT WOS:000225802300049 PM 15589895 ER PT J AU Lunemann, JD Prass, K Zschenderlein, R AF Lunemann, JD Prass, K Zschenderlein, R TI Immunotherapy of chronic inflammatory demyelinating polyneuropathy SO FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE LA German DT Article ID INTRAVENOUS IMMUNOGLOBULIN TREATMENT; RANDOMIZED CONTROLLED TRIAL; PLASMA-EXCHANGE; DOUBLE-BLIND; MULTIPLE-SCLEROSIS; INTERFERON BETA-1A; RESEARCH CRITERIA; CROSS-OVER; POLYRADICULONEUROPATHY; CIDP AB Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated disease of the peripheral nervous system with an estimated prevalence of 1 - 2/100000. The clinical presentation is heterogeneous, but the most common form causes symmetrical progressive or relapsing weakness affecting proximal and distal muscles. CIDP is among the most treatable peripheral nerve disorders and corticosteroids, plasmapheresis and intravenous immunoglobulin have been shown to be effective in short-term prospective, randomized controlled trials. Data however indicate that approximately one-third of patients do not respond to these treatment modalities, nor do they provide equivalent evidence for a durable clinical response. There is a lack of good quality controlled trials of any other immunosuppressive agent, but cyclophosphamide and cyclosporin may be of value in patients with poor response to first-line modalities. Alternatively, the use of combination therapy may increase the efficacy in unresponsive patients. This review highlights the current status of CIDP treatment trials and discusses the significance of any therapeutic option in terms of efficacy, tolerability and cost-effects. C1 Univ Med Berlin, Charite, Neurol Klin & Poliklin, D-10098 Berlin, Germany. NINDS, Natl Inst Hlth, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Lunemann, JD (reprint author), Univ Med Berlin, Charite, Neurol Klin & Poliklin, Campus Mitte,Schumannstr 20-21, D-10098 Berlin, Germany. EM jan.luenemann@charite.de RI Lunemann, Jan/G-8729-2011 OI Lunemann, Jan/0000-0002-3007-708X NR 44 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0720-4299 J9 FORTSCHR NEUROL PSYC JI Forschritte Neurol. Psychiatr. PD DEC PY 2004 VL 72 IS 12 BP 672 EP 678 DI 10.1055/s-2004-830039 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 880PJ UT WOS:000225801400002 PM 15580532 ER PT J AU Terunuma, A Ye, J Emmert, S Khan, SG Kraemer, KH Vogel, JC AF Terunuma, A Ye, J Emmert, S Khan, SG Kraemer, KH Vogel, JC TI Ultraviolet light selection assay to optimize oligonucleotide correction of mutations in endogenous xeroderma pigmentosum genes SO GENE THERAPY LA English DT Article DE point mutation repair; oligonucleotide therapy; skin; XP ID DNA EXCISION-REPAIR; A COMPLEMENTING PROTEIN; MISMATCH REPAIR; CELLS; DISEASE; EXPRESSION; MECHANISMS; CANCER; XPAC AB Various oligonucleotide (ODN)-based approaches have been proposed for their ability to correct mutated genes at the normal chromosomal locations. However, the reported gene correction frequencies of these approaches have varied markedly in different experimental settings, including when different tissues or cell types are targeted. In order to find the optimal ODN-based approach for a specific target tissue, an assay system that allows direct comparison of the different methods on that tissue is necessary. Herein, we describe an XP-UVC selection assay that can be used to evaluate and compare gene correction frequencies in different cell types obtained from a xeroderma pigmentosum (XP) patient, following treatment by different ODN-based approaches. As an experimental example, the XP-UVC selection assay was used to assess the ability of chimeric RNA/DNA ODN to correct point mutations in the XPA gene. This assay can be used to assess and evaluate other types of ODN-based approaches, and to further optimize them. C1 NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, DNA Repair Sect, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1908,Bldg 10 Room 12N260, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 31 TC 2 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 2004 VL 11 IS 23 BP 1729 EP 1734 DI 10.1038/sj.gt.3302344 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 869NU UT WOS:000224992100008 PM 15334113 ER PT J AU Mocellin, S Panelli, M Wang, E Rossi, CR Pilati, P Nitti, D Lise, M Marincola, FM AF Mocellin, S Panelli, M Wang, E Rossi, CR Pilati, P Nitti, D Lise, M Marincola, FM TI IL-10 stimulatory effects on human NK cells explored by gene profile analysis SO GENES AND IMMUNITY LA English DT Article DE human NK cell; IL-10; gene profile ID MEDIATED TUMOR REJECTION; CLASS-I EXPRESSION; T-CELLS; IMMUNE RESPONSIVENESS; PEPTIDE RECEPTORS; MELANOMA-CELLS; GROWTH-FACTOR; INTERLEUKIN-10; CYTOKINE; CANCER AB The molecular mechanisms underlying the increase of natural killer (NK) cell anticancer activity mediated by interleukin (IL)-10 have not been elucidated. The aim of this study was to identify potential molecular mediators of IL-10 stimulatory effects by exploring the NK cell gene display induced by this cytokine. Gene profile was determined by high-throughput cDNA microarray and quantitative real-time PCR. In vitro, NK cells resting or conditioned with IL-10 were tested for cytotoxicity, migration and proliferation. IL-10 enhanced mRNA levels of cell activation/cytotoxicity- related genes (eg secretogranin, TIA-1, HMG-1, interferon-inducible genes) not upregulated by IL-2. In line with these findings, IL-10 increased NK cell in vitro cytotoxicity against Daudi cells. Unlike IL-2, IL-10 did not show any significant effect on NK cell in vitro proliferation and migration. However, gene profile analysis showed that IL-10 increased the expression of cell migration-related genes ( eg L-selectin, vascular endothelium growth factor receptor-1, plasminogen activator, tissue; formyl peptide receptor, lipoxin A4 receptor), which might support a stimulatory effect not evident with the in vitro functional assay. Overall, gene profiling allowed us to formulate new hypotheses regarding the molecular pathways underlying the stimulatory effects of IL-10 on NK cells, supporting further investigation aimed at defining its role in cancer immune rejection. C1 Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Mocellin, S (reprint author), Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. EM mocellins@hotmail.com RI Rossi, Carlo Riccardo/A-7685-2010 OI Rossi, Carlo Riccardo/0000-0001-7875-5655 NR 56 TC 49 Z9 53 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2004 VL 5 IS 8 BP 621 EP 630 DI 10.1038/sj.gene.6364135 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 875JD UT WOS:000225415400004 PM 15573087 ER PT J AU Nitto, T Dyer, KD Mejia, RA Bystrom, J Wynn, TA Rosenberg, HF AF Nitto, T Dyer, KD Mejia, RA Bystrom, J Wynn, TA Rosenberg, HF TI Characterization of the divergent eosinophil ribonuclease, mEar 6, and its expression in response to Schistosoma mansoni infection in vivo SO GENES AND IMMUNITY LA English DT Article DE Schistosoma mansoni; ribonuclease; eosinophils; interleukin-5 ID RAPID EVOLUTION; A SUPERFAMILY; GENE; MICE; INTERLEUKIN-5; NEUROTOXIN; SELECTION; FAMILY AB The eosinophil-associated ribonucleases (Ears) are rapidly evolving proteins found in multigene clusters that are unique to each rodent species. Of the 15 independent genes in the Mus musculus cluster, only mEars 1 and 2 are expressed at significant levels at homeostasis. Here we characterize the expression of mEar 6 in the liver and spleen in mice in response to infection with the helminthic parasite, Schistosoma mansoni. Interestingly, expression of mEar 6 is not directly related to the elevated levels of serum IL-5 or tissue eosinophilia characteristic of this disease, as no mEar 6 transcripts were detected in the liver or the spleen from uninfected IL-5-transgenic mice. The coding sequence of mEar 6 has diverged under positive selection pressure (K(a)/K(s) >1.0) and has a unique unpaired cysteine near the carboxy-terminus of the protein. The high catalytic efficiency of recombinant mEar 6 (k(cat)/K(m) = 0.9 x 10(6)/M/s) is similar to that of the cluster's closest human ortholog, eosinophil-derived neurotoxin (EDN/RNase 2). In summary, we have identified mEar 6 as one of only two RNase A superfamily ribonucleases known to be expressed specifically in response to pathophysiologic stress in vivo. C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Nitto, T (reprint author), NIAID, NIH, Lab Allerg Dis, 9000 Rockville Pike,Bldg 10,Room 11N104, Bethesda, MD 20892 USA. EM tnitto@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 24 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 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2004 VL 5 IS 8 BP 668 EP 674 DI 10.1038/sj.gene.6364143 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 875JD UT WOS:000225415400010 PM 15526002 ER PT J AU Gastwirth, JL Freidlin, B AF Gastwirth, JL Freidlin, B TI A note on appropriate use of statistical tests of mutation rates from ordered groups SO GENETIC TESTING LA English DT Article AB Recently it was found that the frequency of familial dysautonomia (FD) carriers in Ashkenazi Jews (AJ) was higher in AJ of Polish descent compared to AJ of non-Polish descent. The study population was classified into groups ranging from no to full Polish origin. The statistical procedure used to compare the frequencies of FD carriers did not incorporate this intrinsic ordering of individuals by degree of Polish ancestry. In this paper we describe a test designed to utilize this information and show that it is more powerful than the standard test of equality of proportions. In particular, the p value of the trend test on their data is noticeably lower (0.003) than 0.012 found by the standard test, providing stronger evidence for a relationship between allele frequency and Polish descent. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20814 USA. NCI, Biometr Res Branch, Bethesda, MD 20814 USA. RP Gastwirth, JL (reprint author), George Washington Univ, Dept Stat, 315 Funger Hall, Washington, DC 20052 USA. EM jlgast@gwu.edu NR 10 TC 2 Z9 2 U1 1 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD DEC PY 2004 VL 8 IS 4 BP 437 EP 440 DI 10.1089/gte.2004.8.437 PG 4 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 888ZU UT WOS:000226413900014 PM 15684877 ER PT J AU Blanchette, M Green, ED Miller, W Haussler, D AF Blanchette, M Green, ED Miller, W Haussler, D TI Reconstructing large regions of an ancestral mammalian genome in silico SO GENOME RESEARCH LA English DT Article ID AMINO-ACID-SEQUENCES; CHARACTER STATES; MOLECULAR EVOLUTION; MOUSE GENOME; GENE; ALGORITHM; DNA; PHYLOGENIES; ELEMENTS; IDENTIFICATION AB It is believed that most modern mammalian lineages arose from a series of rapid speciation events near the Cretaceous-Tertiary boundary. It is shown that such a phylogeny makes the common ancestral genome sequence an ideal target for reconstruction. Simulations suggest that with methods currently available, we can expect to get 98% of the bases correct in reconstructing megabase-scale euchromatic regions of an eutherian ancestral genome from the genomes of similar to20 optimally chosen modern mammals. Using actual genomic sequences from 19 extant mammals, we reconstruct 1.1 Mb of ancient genome sequence around the CFTR locus. Detailed examination suggests the reconstruction is accurate and that it allows us to identify features in modern species, such as remnants of ancient transposon insertions, that were not identified by direct analysis. Tracing the predicted evolutionary history of the bases in the reconstructed region, estimates are made of the amount of DNA turnover due to insertion, deletion, and substitution in the different placental mammalian lineages since the common eutherian ancestor, showing considerable variation between lineages. In coming years, such reconstructions may help in identifying and understanding the genetic features common to eutherian mammals and may shed light on the evolution of human or primate-specific traits. C1 Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. RP Blanchette, M (reprint author), Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. EM blanchem@mcb.mcgill.ca; haussler@soe.ucsc.edu FU NHGRI NIH HHS [1P41HG02371, HG-02238, P41 HG002371, R01 HG002238] NR 77 TC 87 Z9 91 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2004 VL 14 IS 12 BP 2412 EP 2423 DI 10.1101/gr.2800104 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 877EK UT WOS:000225550400005 PM 15574820 ER PT J AU Martin, N Patel, S Segre, JA AF Martin, N Patel, S Segre, JA TI Long-range comparison of human and mouse Sprr loci to identify conserved noncoding sequences involved in coordinate regulation SO GENOME RESEARCH LA English DT Article ID EPIDERMAL DIFFERENTIATION COMPLEX; GENOMIC DNA-SEQUENCES; BETA-GLOBIN GENE; CORNIFIED ENVELOPE; SCL LOCI; BARRIER FUNCTION; IDENTIFICATION; EXPRESSION; ELEMENTS; ALIGNMENTS AB Mammalian epidermis provides a permeability barrier between an organism and its environment. Under homeostatic conditions, epidermal cells produce structural proteins, which are cross-linked in an orderly fashion to form a cornified envelope (CE). However, under genetic or environmental stress, specific genes are induced to rapidly build a temporary barrier. Small proline-rich (SPRR) proteins are the primary constituents of the CE. Under stress the entire family of 14 Sprr genes is upregulated. The Sprr genes are clustered within the larger epidermal differentiation complex on mouse chromosome 3, human chromosome 1q21. The clustering of the Sprr genes and their upregulation under stress suggest that these genes may be coordinately regulated. To identify enhancer elements that regulate this stress response activation of the Sprr locus, we utilized bioinformatic tools and classical biochemical dissection. Long-range comparative sequence analysis identified conserved noncoding sequences (CNSs). Clusters of epidermal-specific DNasel-hypersensitive sites (HSs) mapped to specific CNSs. Increased prevalence of these HSs in barrier-deficient epidermis provides in vivo evidence of the regulation of the Sprr locus by these conserved sequences. Individual components of these HSs were cloned, and one was shown to have strong enhancer activity specific to conditions when the Sprr genes are coordinately upregulated. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Segre, JA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM jsegre@nhgri.nlh.gov NR 31 TC 21 Z9 21 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2004 VL 14 IS 12 BP 2430 EP 2438 DI 10.1101/gr.2709404 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 877EK UT WOS:000225550400007 PM 15574822 ER PT J AU Wu, SM Baxendale, V Chen, YL Pang, ALY Stitely, T Munson, PJ Leung, MYK Ravindranath, N Dym, M Rennert, OM Chan, WY AF Wu, SM Baxendale, V Chen, YL Pang, ALY Stitely, T Munson, PJ Leung, MYK Ravindranath, N Dym, M Rennert, OM Chan, WY TI Analysis of mouse germ-cell transcriptome at different stages of spermatogenesis by SAGE: Biological significance SO GENOMICS LA English DT Article DE expression profiling; SAGE; spermatogonia; spermatocyte; spermatid; spermatogenesis ID GENE-EXPRESSION PROFILES; SERIAL ANALYSIS; BOVINE SPERMATOZOA; RAT TESTIS; PROTEIN; CDNA; IDENTIFICATION; LOCALIZATION; COMPLEX; MATURATION AB The transcriptomes of mouse type A spermatogonia (Spga), pachytene spermatocytes (Spcy), and round spermatids (Sptd) were determined by sequencing the respective SAGE (Serial Analysis of Gene Expression) libraries. A total of 444,015 tags derived from one Spga, two Spcy, and one Sptd library were analyzed, and 34,619 different species of transcripts were identified, 5279 of which were novel. Results indicated the germ-cell transcriptome comprises of more than 30,000 transcripts. Virtual subtraction showed that cell-specific transcripts constitute 12-19.5% of the transcriptome. Components of the protein biosynthetic machinery are highly expressed in Spga. In Spcy transcription factors are abundantly expressed while transcripts encoding proteins involved in chromosome remodeling and testis-specific transcripts are prominent in Sptd. The databases generated by this work provide very useful resources for cellular localization of genes in silico. They are also extremely useful as sources for identification of splice variants of genes in germ cells. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20057 USA. NICHD, NIH, Bethesda, MD 20892 USA. NIH, CIT, Math & Stat Comp Lab, Bethesda, MD 20892 USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. RP Chan, WY (reprint author), NICHD, Lab Clin Genom, NIH, Bldg 49,Room 2A08,49 Convent Dr,MSC 4429, Bethesda, MD 20892 USA. EM chanwy@mail.nih.gov FU NICHD NIH HHS [HD33728] NR 52 TC 43 Z9 48 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 2004 VL 84 IS 6 BP 971 EP 981 DI 10.1016/j.ygeno.2004.08.018 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 873UM UT WOS:000225306600008 PM 15533714 ER PT J AU Nesbit, MA Bowl, MR Harding, B Schlessinger, D Whyte, MP Thakker, RV AF Nesbit, MA Bowl, MR Harding, B Schlessinger, D Whyte, MP Thakker, RV TI X-linked hypoparathyroidism region on Xq27 is evolutionarily conserved with regions on 3q26 and 13q34 and contains a novel P-type ATPase SO GENOMICS LA English DT Article DE adenosinetriphosphatase; guanine nucleotide exchange factor; high-mobility group box protein; snRNA; phylogeny ID RECESSIVE IDIOPATHIC HYPOPARATHYROIDISM; GENE; DBL; SOX3; EXPRESSION; PROTOONCOGENE; DEFICIENCY; SEQUENCES; SUBFAMILY; XQ26-Q27 AB X-linked hypoparathyroidism (HPT) has been mapped to a 988-kb region on chromosome Xq27 that contains three genes, MCF2/DBL, SOX3, and U7snRNA homologue, and a partial cDNA, AS6. We isolated the full-length AS6 cDNA, determined its genomic organization, and sought for abnormalities in HPT patients. AS6 was identified as the 3' UTR of ATP11C, a novel member of the P-type ATPases, which consists of 31 exons with alternative transcripts. The colocalization of ATP11C with SOX3 and MCF2/DBL on Xq27 mirrors that of ATP11A with SOX1 and MCF2L on 13q34 and ATP11B with SOX2 on 3q26. These colocalizations are evolutionarily conserved in mouse, and analyses indicate that SOX2 divergence likely occurred before the separation of SOX1 and SOX3. Analyses of ATP11C, MCF2, SOX3, and U7snRNA in HPT patients did not reveal mutations, implicating regulatory changes or mutation of an as yet unidentified gene in the etiology of X-linked hypoparathyroidism. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Nuffield Dept Clin Med,Acad Endocrine Unit, Oxford OX3 7LJ, England. NIA, Genet Lab, Baltimore, MD 21224 USA. Washington Univ, Sch Med, Barnes Jewish Hosp, Div Bone & Mineral Dis, St Louis, MO 63110 USA. Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO 63131 USA. RP Thakker, RV (reprint author), Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Nuffield Dept Clin Med,Acad Endocrine Unit, Oxford OX3 7LJ, England. EM rajesh.thakker@ndm.ox.ac.uk OI Thakker, Rajesh/0000-0002-1438-3220 NR 41 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 2004 VL 84 IS 6 BP 1060 EP 1070 DI 10.1016/j.ygeno.2004.08.003 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 873UM UT WOS:000225306600017 ER PT J AU Muja, N Lovas, G Romm, E Machleder, D Ranjan, M Gallo, V Hudson, LD AF Muja, N Lovas, G Romm, E Machleder, D Ranjan, M Gallo, V Hudson, LD TI Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination SO GLIA LA English DT Article DE oligodendrocyte; differentiation; development; phosphorylation; retina ID NEURON-SPECIFIC ENOLASE; CRYSTAL-STRUCTURE; TRANSGENIC MICE; MOUSE; CLONING; CELLS; GENE; DIFFERENTIATION; SPECIFICITY; BRAIN AB Reversible tyrosine phosphorylation is integral to the process of oligodendrocyte differentiation. To interfere with the subset of the phosphorylation cycle overseen by protein tyrosine phosphatase epsilon (PTPepsilon) in oligodendrocytes, we applied a substrate-trapping approach in the development of transgenic mice overexpressing a catalytically inactive, transmembrane PTPepsilon-hemaglutinin (tm-PTPepsilon-HA) from the dual promoter element of the gene encoding the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Transgene expression peaked during the active myelinating period, at 2-3 weeks postnatal. Two tyrosine phosphoproteins, a-enolase and P-actin, were phosphorylated to a greater degree in transgenic mice. Despite a high degree of tm-PTPepsilon-HA expression, myelin was grossly normal in nearly all axonal tracts. Phenotypic abnormalities were limited to optic nerve, where a decrease in the degree of myelination was reflected by reduced levels of myelin proteins on postnatal day 21 (PND21), as well as a decrease in the density of differentiated oligodendrocytes. The optic chiasm was reduced in thickness in transgenic mice; optic nerves similarly exhibited a reduction in transverse width. Further analyses of the optic pathway demonstrated that transgenic protein was unexpectedly present in retinal ganglion cells, whose axons are the targets of myelination by optic nerve oligodendrocytes. On PND28, transgenic protein declined dramatically in both oligodendrocytes and retinal ganglion cells contributing to the recovery of optic nerve myelination. Thus, delayed myelination arises only when tm-PTPepsilon-HA is simultaneously expressed in myelin-forming glia and their neuronal targets. While tm-PTPepsilon related signaling pathways may figure in axonglial interactions, interfering with tm-PTPepsilon activity does not perceptibly affect the development or myelinating capacity of most oligodendrocytes. (C) 2004 Wiley-Liss, Inc. C1 NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. RP Hudson, LD (reprint author), NINDS, Sect Dev Genet, NIH, 49 Convent Dr,Bldg 49,Room 5A75, Bethesda, MD 20892 USA. EM hudson1@ninds.nih.gov NR 53 TC 6 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD DEC PY 2004 VL 48 IS 4 BP 278 EP 297 DI 10.1002/glia.20078 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 871PN UT WOS:000225145800002 PM 15390114 ER PT J AU Vautier, F Belachew, S Chittajallu, R Gallo, V AF Vautier, F Belachew, S Chittajallu, R Gallo, V TI Shaker-type potassium channel subunits differentially control oligodendrocyte progenitor proliferation SO GLIA LA English DT Article DE oligodendrocyte precursor cells; K+ channels; Kv1 subunits; mitogens ID CELL-CYCLE ARREST; K+ CHANNELS; MEMBRANE DEPOLARIZATION; SUBVENTRICULAR ZONE; RAT-BRAIN; EXPRESSION; PROGRESSION; ACCUMULATION; ASTROCYTES; GLUTAMATE AB Oligodendrocyte precursor (OP) cells are exposed to multiple extrinsic signals that control their proliferation and differentiation. Previous cell proliferation studies and electrophysiological analysis in cultured cells and in brain slices have suggested that outward potassium channels, particularly Kv1 subunits, may have a prominent role in OP cell proliferation. In the present study, we assessed to what extent overexpression of Kv1.3, Kv1.4, Kv1.5, and Kv1.6 can affect OP cell proliferation and differentiation in culture. We observed that overexpression of Kv1.3 or Kv1.4 increased OP cell proliferation in the absence of mitogens, whereas Kv1.6 overexpression inhibited mitogen-induced OP cell cycle progression. Interestingly, Kv1.3, Kv1.4, Kv1.5, and Kv1.6 overexpression did not interfere with the kinetics of oligodendrocyte differentiation. This study represents the first demonstration that the activity of potassium channels containing distinct Kv1 subunit proteins directly controls oligodendroglial proliferation in the presence of mitogens, as well as in growth factor-free conditions. (C) 2004 Wiley-Liss, Inc. C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Res Neurosci, Washington, DC 20010 USA. NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD USA. Univ Liege, Ctr Cellular & Mol Neurobiol, Liege, Belgium. RP Gallo, V (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Res Neurosci, Room 5345,111 Michigan Ave NW, Washington, DC 20010 USA. EM vgallo@cnmcresearch.org FU NICHD NIH HHS [P30HD40677] NR 34 TC 46 Z9 46 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD DEC PY 2004 VL 48 IS 4 BP 337 EP 345 DI 10.1002/glia.20088 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 871PN UT WOS:000225145800006 PM 15390108 ER PT J AU Bekisz, J Schmeisser, H Hernandez, J Goldman, ND Zoon, KC AF Bekisz, J Schmeisser, H Hernandez, J Goldman, ND Zoon, KC TI Human interferons alpha, beta and omega SO GROWTH FACTORS LA English DT Review DE type I interferons; human IFN alpha receptor; cytokines; polypeptide ID NF-KAPPA-B; SIGNALING PATHWAYS; RECEPTOR INTERACTIONS; ANTIVIRAL RESPONSES; LIGAND-BINDING; PROTEIN; TRANSCRIPTION; KINASE; COMPONENTS; RESOLUTION AB Type I interferons (IFNs), IFN-alpha, IFN-beta, IFN-omega, IFN-delta and IFN-tau are a family of structurally related, species-specific proteins found only in vertebrates. They exhibit a variety of biological functions, including antiviral, antiproliferative, immunomodulatory and developmental activities. Human Type I IFNs interact with the human IFN alpha receptor (IFNAR), which is composed of two identified subunits (IFNAR-1 and IFNAR-2). The interaction of IFN-alpha/beta with its receptor components results in the activation of a number of signaling pathways. The regulation of specific genes and proteins contributes to the numerous biological functions of Type I IFNs. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Zoon, KC (reprint author), Bldg 31,Room 3A11,31 Ctr Dr, Bethesda, MD 20892 USA. EM zoonk@mail.nih.gov NR 40 TC 108 Z9 122 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD DEC PY 2004 VL 22 IS 4 BP 243 EP 251 DI 10.1080/08977190400000833 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 893WV UT WOS:000226752400005 PM 15621727 ER PT J AU Cardoso, G Daly, RJ Haq, NA Hanton, L Rubinow, DR Bondy, CA Schmidt, PJ AF Cardoso, G Daly, RJ Haq, NA Hanton, L Rubinow, DR Bondy, CA Schmidt, PJ TI Current and lifetime psychiatric illness in women with Turner syndrome SO GYNECOLOGICAL ENDOCRINOLOGY LA English DT Article DE depression; hypogonadism; X chromosome; anxiety disorders; mood ID ANOREXIA-NERVOSA; DIAGNOSTIC-CRITERIA; GONADAL-DYSGENESIS; MENTAL-DISORDERS; UNITED-STATES; PRIMARY-CARE; X-MONOSOMY; BRAIN; DEPRESSION; AMYGDALA AB Abnormalities in quality of life and cognitive measures have been observed in women with Turner syndrome (TS), and a relationship between these phenomena and chromosomal constitution has been suggested. In contrast, few studies have systematically evaluated the present-e of mood and behavioral syndromes in these women. In this study, 100 TS women were administered the Structured Clinical Interview for DSM IV after a two-week period during which which their hormone replacement had been discontinued. The majority of women who met criteria fir a psychiatric condition had a mood or anxiety disorder. Overall, 52 (52%) of the TS women met criteria for a current or a past depressive or anxiety disorder. Eighteen of the women with TS met criteria for a current Axis I psychiatric disorder [Depression - major (n = 5), Minor (n = 5), dysthymia (n = 1); Anxiety (n = 9)]. Forty-six of the women with TS met critetia for a past Axis I psychiatric illness [Depression unipolar (n = 41), bipolar (n = 3); Anxiety (n = 7); eating disorder (n = 6); substance dependence (n = 3)]. Five women with TS met criteria for all Axis II persoriality disorder. Women with TS reported a hi;her rate of lifetime depression compared ivith rates observed in community-based studies but sintilar to those obtained from gynecologic samples. C1 NIMH, Behav Endocrinol Branch, Dept HHS, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Dept HHS, NIH, Bldg 10,Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. OI Cardoso, Graca/0000-0003-1756-0197 NR 55 TC 23 Z9 24 U1 2 U2 5 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 0951-3590 J9 GYNECOL ENDOCRINOL JI Gynecol. Endocrinol. PD DEC PY 2004 VL 19 IS 6 BP 313 EP 319 DI 10.1080/09513590400021227 PG 7 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA 888YX UT WOS:000226411600002 PM 15726728 ER PT J AU Smith, MJ Schmidt, PJ Su, TP Rubinow, DR AF Smith, MJ Schmidt, PJ Su, TP Rubinow, DR TI Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with premenstrual dysphoria SO GYNECOLOGICAL ENDOCRINOLOGY LA English DT Article DE follicle-stimulating hormone; luteinizing hormone; gonadotropin-releasing hormone; premenstrual syndrome ID LUTEINIZING-HORMONE; SYMPTOM SEVERITY; DEPRESSED WOMEN; HEALTHY-VOLUNTEERS; TENSION SYNDROME; MENSTRUAL-CYCLE; LUTEAL-PHASE; RADIOIMMUNOASSAY; LH; PROGESTERONE AB Despite consistent evidence that premenstrual dysphoria (PMD) is not characterized by abnormalities in basal ovarian hormone secretion, the possibility remains that PMD is associated with an abnormality in the regulation of the hypothalamic-pituitary-ovarian (HPO) axis. We studied HPO axis regulation in 11 women with prospectively confirmed PMD and 20 asymptomatic controls, during both the follicular and luteal phases of the menstrual cycle. Plasma levels of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), were obtained before and after stimulation with gonadotropin-releasing hormone (GnRH) (100 mug intravenously). Potential diagnostic- and menstrual cycle phase-related differences in basal and plasma hormone levels were anlyzed by repeated- measures analysis of variance. No significant differences were observed between women with PMD and controls in either basal or stimulated levels of FSH and LH. Stimulated FSH was significantly increased and stimulated LH was significantly decreased during the follicular compared with the luteal phase in both women with PMD and controls. These data are consistent with prior findings of normal basal reproductive hormone levels in women with PMD. Our data suggest the absence in women with PMD of an abnormality of dynamic ovarian function as measured by GnRH stimulation. C1 NIMH, Behav Endocrinol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), Bldg 10,Room 3N242,10 Ctr Dr,MSC 1277, Bethesda, MD 20892 USA. NR 42 TC 3 Z9 3 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 0951-3590 J9 GYNECOL ENDOCRINOL JI Gynecol. Endocrinol. PD DEC PY 2004 VL 19 IS 6 BP 335 EP 343 DI 10.1080/09513590400018199 PG 9 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA 888YX UT WOS:000226411600004 PM 15724808 ER PT J AU Marseille, E Dandona, L Saba, J McConnel, C Rollins, B Gaist, P Lundberg, M Over, M Bertozzi, S Kahn, JG AF Marseille, E Dandona, L Saba, J McConnel, C Rollins, B Gaist, P Lundberg, M Over, M Bertozzi, S Kahn, JG TI Assessing the efficiency of HIV prevention around the world: Methods of the PANCEA project SO HEALTH SERVICES RESEARCH LA English DT Article DE HIV prevention; cost; cost-effectiveness; voluntary counseling and testing; risk reduction ID SUB-SAHARAN AFRICA; DEVELOPING-COUNTRIES; HEALTH-CARE AB Objective. To develop data collection methods suitable to obtain data to assess the costs, cost-efficiency, and cost-effectiveness of eight types of HIV prevention programs in five countries. Data Source/Study Setting. Primary data collection from prevention programs for 2002-2003 and prior years, in Uganda, South Africa, India, Mexico, and Russia. Study Design. This study consisted of a retrospective review of HIV prevention programs covering one to several years of data. Key variables include services delivered (outputs), quality indicators, and costs. Data Collection/Extraction Methods. Data were collected by trained in-country teams during week-long site visits, by reviewing service and financial records and interviewing program managers and clients. Principal Findings. Preliminary data suggest that the unit cost of HIV prevention programs may be both higher and more variable than previous studies suggest. Conclusions. A mix of standard data collection methods can be successfully implemented across different HIV prevention program types and countries. These methods can provide comprehensive services and cost data, which may carry valuable information for the allocation of HIV prevention resources. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Axios Int, Dublin, Ireland. NIH, Off AIDS Res, Bethesda, MD 20892 USA. World Bank, Washington, DC 20433 USA. Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. RP Marseille, E (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, Box 0936, San Francisco, CA 94143 USA. NR 23 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2004 VL 39 IS 6 BP 1996 EP U52 PN 2 PG 25 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 893TZ UT WOS:000226743500005 ER PT J AU Peterson, CM Harvath, L AF Peterson, CM Harvath, L TI Current and future commitment to hematology research SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TRANSFUSION MEDICINE AB This article provides an overview of the National Heart, Lung, and Blood Institute's (NHLBI) current and future commitment to hematology research. The paper comprises nine sections: (1) a brief history of how NHLBI incorporated blood research in its mission; (2) a summary of the traditional areas of research interest for blood diseases and resources; (3) a description of how NHLBI has assured and continues to assure a safe blood supply; (4) the current and future plans for transfusion medicine and cellular therapy research; (5) research support for hemoglobinopathies and red cell disorders; (6) research support for thrombosis and hemostatic disorders; (7) current and future research of hematopoietic stem cell biology, and aplastic and preneoplastic conditions; (8) future training for hematologists, and (9) a concluding summary. C1 NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. RP Peterson, CM (reprint author), NHLBI, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,Rockledge 2,Room 10158, Bethesda, MD 20892 USA. EM petersoc@nhlbi.nih.gov NR 4 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2004 VL 18 IS 6 BP 1215 EP + DI 10.1016/j.hoc.2004.07.002 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA 873NE UT WOS:000225286300002 PM 15511613 ER PT J AU Kato, H Sugauchi, F Ozasa, A Kato, T Tanaka, Y Sakugawa, H Sata, M Hino, K Onji, M Okanoue, T Tanaka, E Kawata, S Suzuki, K Hige, S Ohno, T Orito, E Ueda, R Mizokami, M AF Kato, H Sugauchi, F Ozasa, A Kato, T Tanaka, Y Sakugawa, H Sata, M Hino, K Onji, M Okanoue, T Tanaka, E Kawata, S Suzuki, K Hige, S Ohno, T Orito, E Ueda, R Mizokami, M TI Hepatitis B virus genotype G is an extremely rare genotype in Japan SO HEPATOLOGY RESEARCH LA English DT Article DE distribution; genotypes; hepatitis B virus; Japan; polymerase chain reaction; restriction fragment length polymorphism ID CHRONIC HBV INFECTION; VIROLOGICAL CHARACTERISTICS; RECOMBINATION; SEQUENCE; STRAINS; ANTIGEN; GENOME; GENE AB Background: Hepatitis B virus (HBV) has been classified into seven genotypes (A-G). HBV genotypes have a geographically characteristic distribution. Since HBV genotype G (HBV/G) was identified recently, little is known about the distribution of HBV/G in Japan. The aim of this study was to clarify this issue. Patients and methods: Seven hundred and twenty-one serum samples obtained from patients with HBV in Japan were investigated. The patients included 149 asymptomatic carriers, 325 with chronic hepatitis, 129 with liver cirrhosis, and 118 with hepatocellular carcinoma. Six HBV genotypes (A-F) were determined by restriction fragment length polymorphim targeting to the S region of the HBV genome. Furthermore, HBV/G was investigated by polymerase chain reaction with hemi-nested primers derived from an HBV/G-specific nucleotide sequence. Results: Of the 721 serum samples investigated, 12 subjects were classified as having HBV/A, 88 HBV/B, 610 HBV/C, 3 HBV/D, and 1 HBV/F. Seven subjects had a mixed infection with distinct genotypes, two with HBV/A and HBV/D, and five with HBV/B and HBV/C. HBV/G was not identified among the 721 samples. Conclusion: HBV/G was not identified in a large cohort of patients with HBV, either single or dual infection. HBV/G seems to be an extremely rare genotype in Japan. (C) 2004 Elsevier B.V. All rights reserved. C1 Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Nagoya City Univ, Grad Sch Med Sci, Dept Internal Med & Mol Sci, Nagoya, Aichi, Japan. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD USA. Univ Ryukyus, Sch Med, Fac Med, Dept Internal Med 1, Okinawa, Japan. Kurume Univ, Sch Med, Dept Med, Div Gastroenterol, Kurume, Fukuoka, Japan. Yamaguchi Univ, Sch Med, Fac Hlth Sci, Dept Lab Sci, Ube, Yamaguchi, Japan. Ehime Univ, Sch Med, Dept Internal Med 3, Matsuyama, Ehime 790, Japan. Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Mol Gastroenterol & Hepatol, Kyoto, Japan. Shinshu Univ, Sch Med, Dept Internal Med 2, Matsumoto, Nagano, Japan. Yamagata Univ, Sch Med, Dept Internal Med 2, Yamagata, Japan. Iwate Med Univ, Dept Internal Med 1, Morioka, Iwate 020, Japan. Hokkaido Univ, Grad Sch Med, Dept Gastroenterol, Sapporo, Hokkaido, Japan. RP Mizokami, M (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Mizuho Ku, Kawasumi 1, Nagoya, Aichi 4678601, Japan. EM mizokami@med.nagoya-cu.ac.jp NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD DEC PY 2004 VL 30 IS 4 BP 199 EP 203 DI 10.1016/j.hepres.2004.09.004 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 884EB UT WOS:000226066300002 ER PT J AU Wersinger, SR Kelliher, KR Zufall, F Lolait, SJ O'Carroll, AM Young, WS AF Wersinger, SR Kelliher, KR Zufall, F Lolait, SJ O'Carroll, AM Young, WS TI Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task SO HORMONES AND BEHAVIOR LA English DT Article DE vasopressin V3 receptor; behavior; chemosensory; aggression ID HAMSTERS MESOCRICETUS-AURATUS; PAIR-BOND FORMATION; AGGRESSIVE-BEHAVIOR; MONOGAMOUS VOLE; GOLDEN-HAMSTERS; SEXUAL-BEHAVIOR; GENE-TRANSFER; BULB REMOVAL; AUTISM; HYPOTHALAMUS AB In this study, we characterized more thoroughly the social behavior of vasopressin 1b receptor null (V1bR-/-) mice. We confirmed that V1bR-/- males exhibit less social aggression than their wild-type (V1bR+/+) littermates. We tested social preference by giving male subjects a choice between pairs of soiled or clean bedding. In general, V1bR+/+ mice spent significantly more time engaged in chemoinvestigation of these social stimuli than V1bR-/- mice. Male V1bR+/+ mice preferred female-soiled bedding over male-soiled bedding, male-soiled bedding over clean bedding, and female-soiled bedding over clean bedding. In contrast, V1bR-/- males failed to exhibit a preference for any bedding. This difference in behavior is not explained by an anosmic condition as there were no differences between V1bR-/- and V1bR+/+ mice in their abilities to detect a cookie buried in clean bedding, or in their ability to perform in an operant conditioning task using a fully automated liquid dilution olfactometer. In the latter task, male V1bR-/- mice were fully capable of discriminating between male and female mouse urine. The latencies to learn this task did not differ between the two genotypes. Thus, a V1bR-/- male's ability to differentiate between male and female chemosensory cues appears no different than that of a V1bR+/+ male's. We propose that the V1bR plays an important role in social motivation, perhaps by coupling the processing, integration, and/or interpretation of chemosensory cues with the appropriate behavioral response. (C) 2004 Elsevier Inc. All rights reserved. C1 NIMH, Sect Neural Gene Express, DHHS, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, LINE, Bristol, Avon, England. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, DHHS, 9000 Rockville Pike 36,Room 2A11, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NIDCD NIH HHS [R01DC052490, R03DC00660301] NR 46 TC 68 Z9 72 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD DEC PY 2004 VL 46 IS 5 BP 638 EP 645 DI 10.1016/j.yhbeh.2004.07.004 PG 8 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 876TO UT WOS:000225520800016 PM 15555506 ER PT J AU Sun, M Kong, LX Wang, XD Holmes, C Gao, QS Zhang, GR Pfeilschifter, J Goldstein, DS Geller, AI AF Sun, M Kong, LX Wang, XD Holmes, C Gao, QS Zhang, GR Pfeilschifter, J Goldstein, DS Geller, AI TI Coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; DEFECTIVE HSV-1 VECTORS; SUBSTANTIA-NIGRA; NIGROSTRIATAL SYSTEM; DOPAMINERGIC-NEURONS; PLASMID VECTORS; L-DOPA; TRIPLE TRANSDUCTION; PRIMARY FIBROBLASTS; NEUROTROPHIC FACTOR AB Parkinson's disease is due to the selective loss of nigrostriatal dopaminergic neurons. Consequently, many therapeutic strategies have focused on restoring striatal dopamine levels, including direct gene transfer to striatal cells, using viral vectors that express specific dopamine biosynthetic enzymes. The central hypothesis of this study is that coexpression of four dopamine biosynthetic and transporter genes in striatal neurons can support the efficient production and regulated, vesicular release of dopamine: tyrosine hydroxylase (TH) converts tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), GTP cyclohydrolase I (GTP CH 1) is the rate-limiting enzyme in the biosynthesis of the cofactor for TH, aromatic amino acid decarboxylase (AADC) converts L-DOPA to dopamine, and a vesicular monoamine transporter (VMAT-2) transports dopamine into synaptic vesicles, thereby supporting regulated, vesicular release of dopamine and relieving feedback inhibition of TH by dopamine. Helper virus-free herpes simplex virus type 1 vectors that coexpress the three dopamine biosynthetic enzymes (TH, GTP CH 1, and AADC; 3-gene-vector) or these three dopamine biosynthetic enzymes and the vesicular monoamine transporter (TH, GTP CH 1, AADC, and VMAT-2; 4-gene-vector) were compared. Both vectors supported production of dopamine in cultured fibroblasts. These vectors were microinjected into the striatum of 6-hydroxydopamine-lesioned rats. These vectors carry a modified neurofilament gene promoter, and gamma-aminobutyric acid (GABA)-ergic neuron-specific gene expression was maintained for 14 months after gene transfer. The 4-gene-vector supported higher levels of correction of apomorphine-induced rotational behavior than did the 3-gene-vector, and this correction was maintained for 6 months. Proximal to the injection sites, the 4-gene-vector, but not the 3-gene-vector, supported extracellular levels of dopamine and dihydroxyphenylacetic acid (DOPAC) that were similar to those observed in normal rats, and only the 4-gene-vector supported significant K+-dependent release of dopamine. C1 Harvard Univ, Sch Med, W Roxbury VA Hosp, Dept Neurol, W Roxbury, MA 02132 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany. RP Geller, AI (reprint author), Harvard Univ, Sch Med, W Roxbury VA Hosp, Dept Neurol, Res Bldg 3,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM alfred_geller@hms.harvard.edu RI Geller, Alfred/C-6469-2012 FU NIA NIH HHS [AG20177, K01 AG020177, R01 AG016777, R01 AG021193, AG021193, AG16777]; NINDS NIH HHS [R01 NS043107, R01 NS045855, NS045855, NS42016] NR 67 TC 46 Z9 49 U1 0 U2 3 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 2004 VL 15 IS 12 BP 1177 EP 1196 DI 10.1089/hum.2004.15.1177 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 883HR UT WOS:000226002700003 PM 15684695 ER PT J AU Cortes, LM Baltazar, LM Lopez-Cardona, MG Olivares, N Ramos, C Salazar, M Sandoval, L Lorenz, MGO Chakraborty, R Paterson, AD Rivas, F AF Cortes, LM Baltazar, LM Lopez-Cardona, MG Olivares, N Ramos, C Salazar, M Sandoval, L Lorenz, MGO Chakraborty, R Paterson, AD Rivas, F TI HLA class II haplotypes in Mexican systemic lupus erythematosus patients SO HUMAN IMMUNOLOGY LA English DT Article DE haplotype; HLA class II; systemic lupus erythernatosus; association study ID PRIMERS PCR-SSP; LINKAGE DISEQUILIBRIUM; ETHNIC-GROUPS; ALLELES; SUSCEPTIBILITY; ASSOCIATION; DISEASE; REGION; DNA; AMPLIFICATION AB Systemic lupus erythematosus (SLE) is an autoimmune disease in which polymorphisms within the human leukocyte antigen (HLA) region have been associated to its etiology. For this study, HLA-DQB1, DQA1, and DRB1 genes were typed by polymerase chain reaction-sequence-specific primer in 237 individuals, taken from 74 families, who had a member with SLE, and who had their residence in the western region of Mexico; as well as in 159 ethnically matched healthy volunteers taken from 32 families. Genotype and allele frequency analysis was performed in 74 SLE patients and 54 unrelated controls. Precise three-loci identification of independent haplotypes was performed in 48 patients and 54 controls by familial segregation. Genotype distribution at each loci was concordant with Hardy-Weinberg's equilibrium in the control group. In general, no genotype effect was observed in SLE patients. Allele distribution comparison showed in the SLE group a significant increase of HLA-DQA1*0102, DQB1*0402, and DRB1*15; whereas alleles HLA-DQB1*0303 and *0501 were significantly decreased. SLE patients showed haplotype DQB1*0602-DQA1-*0102-DRB1*15 increased. As expected, patients with SLE have a reduced haplotype genetic diversity. The associations found in this study are related to an ancestral haplotype that has been observed in SLE populations of different origins. (C) American Society for Histocompatibility and Immunogenetics, 2004. Published by Elsevier Inc. C1 Inst Mexicano Seguro Social, Hosp Especialidades, Div Immunol, Guadalajara, Jalisco, Mexico. Inst Mexicano Seguro Social, Hosp Especialidades, Div Genet, Guadalajara, Jalisco, Mexico. Inst Mexicano Seguro Social, Hosp Especialidades, Div Mol Med, Guadalajara, Jalisco, Mexico. Inst Mexicano Seguro Social, Hosp Especialidades, Ctr Invest Biomed Occidente, Guadalajara, Jalisco, Mexico. Univ Guadalajara, Grad Studies Program Immunol, Ctr Univ Ciencias Salud, Guadalajara 44430, Jalisco, Mexico. Univ Colima, Sch Med, Colima, Mexico. Univ Cincinnati, Dept Environm Hlth, Ctr Genome Informat, Cincinnati, OH USA. Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON, Canada. USN, Med Res Ctr, Silver Spring, MD USA. RP Cortes, LM (reprint author), NEI, NIH, Immunoregulat Lab, Bldg 10-10N222,9000 Rockville Pike, Bethesda, MD 20892 USA. EM CortesL@nei.nih.gov RI Paterson, Andrew/A-4088-2011 OI Paterson, Andrew/0000-0002-9169-118X NR 42 TC 15 Z9 16 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 2004 VL 65 IS 12 BP 1469 EP 1476 DI 10.1016/j.humimm.2004.09.008 PG 8 WC Immunology SC Immunology GA 886RE UT WOS:000226245200010 PM 15603875 ER PT J AU Huentelman, MJ Zubcevic, J Prada, JAH Xiao, XD Dimitrov, DS Raizada, MK Ostrov, DA AF Huentelman, MJ Zubcevic, J Prada, JAH Xiao, XD Dimitrov, DS Raizada, MK Ostrov, DA TI Structure-based discovery of a novel angiotensin converting enzyme 2 inhibitor SO HYPERTENSION LA English DT Article DE angiotensin-converting enzyme; cardiovascular diseases; hypertension ID SARS CORONAVIRUS; FUNCTIONAL RECEPTOR; UP-REGULATION; ACE2; EXPRESSION; PROTEIN AB Angiotensin-converting enzyme 2 (ACE2) is considered an important therapeutic target for controlling cardiovascular diseases and severe acute respiratory syndrome (SARS) outbreaks. Recently solved high-resolution crystal structures of the apo-bound and inhibitor-bound forms of ACE2 have provided the basis for a novel molecular docking approach in an attempt to identify ACE2 inhibitors and compounds that block SARS coronavirus spike protein-mediated cell fusion. In this study, approximate to 140 000 small molecules were screened by in silico molecular docking. In this structure - activity relation study, the molecules with the highest predicted binding scores were identified and assayed for ACE2 enzymatic inhibitory activity and for their ability to inhibit SARS coronavirus spike protein-mediated cell fusion. This approach identified N-(2-aminoethyl)-1 aziridine-ethanamine as a novel ACE2 inhibitor that also is effective in blocking the SARS coronavirus spike protein-mediated cell fusion. Thus, the molecular docking approach resulting in the inhibitory capacity of N-(2-aminoethyl)-1 aziridine-ethanamine provides an attractive small molecule lead compound on which the development of more effective therapeutic agents could be developed to modulate hypertension and for controlling SARS infections. C1 Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Immunol & Lab Med, Gainesville, FL USA. McKnight Brain Inst, Gainesville, FL USA. NCI, Lab Expt & Computat Biol, CCR, NIH, Frederick, MD 21701 USA. RP Raizada, MK (reprint author), Univ Florida, Coll Med, Dept Physiol & Funct Genom, 1600 SW Archer Rd,Box 100274, Gainesville, FL 32610 USA. EM mraizada@phys.med.ufl.edu; ostroda@pathology.ufl.edu FU NHLBI NIH HHS [HL56912] NR 26 TC 35 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2004 VL 44 IS 6 BP 903 EP 906 DI 10.1161/01.HYP.0000146120.29648.36 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 874NG UT WOS:000225356500022 PM 15492138 ER PT J AU Wall, SM Kim, YH Stanley, L Glapion, DM Everett, LA Green, ED Verlander, JW AF Wall, SM Kim, YH Stanley, L Glapion, DM Everett, LA Green, ED Verlander, JW TI NaCl restriction upregulates renal Slc26a4 through subcellular redistribution - Role in Cl- conservation SO HYPERTENSION LA English DT Article DE hypertension; mineralocorticoid ID INTERCALATED CELL SUBTYPES; CORTICAL COLLECTING DUCTS; PENDRED-SYNDROME GENE; MOUSE KIDNEY; RAT-KIDNEY; INDUCED HYPERTENSION; SECRETION; TRANSPORT; CHLORIDE; COTRANSPORTER AB Slc26a4 (Pds, pendrin) is an anion transporter expressed in the apical region of type B and non-A, non-B intercalated cells of the distal nephron. It is upregulated by aldosterone analogues and is critical in the development of mineralocorticoid-induced hypertension. Thus, Slc26a4 expression and its role in blood pressure and fluid and electrolyte homeostasis was explored during NaCl restriction, a treatment model in which aldosterone is appropriately increased. Ultrastructural immunolocalization, balance studies, and cortical collecting ducts (CCDs) perfused in vitro were used. With moderate physiological NaCl restriction, Slc26a4 expression in the apical plasma membrane increased 2- to 3-fold in type B intercalated cells. Because Slc26a4 transports Cl-, we tested whether NaCl balance differs in Slc26a4((+/+)) and Slc26a4((-/-)) mice during NaCl restriction. Cl- absorption was observed in CCDs from Slc26a4((+/+)) but not from Slc26a4((-/-)) mice. After moderate NaCl restriction, urinary volume and Cl- excretion were increased in Slc26a4((-/-)) relative to Slc26a4((+/+)) mice. Moreover, Slc26a4((-/-)) mice had evidence of relative vascular volume depletion because they had a higher arterial pH, hematocrit, and blood urea nitrogen than wild-type mice. With moderate NaCl restriction, blood pressure was similar in Slc26a4((+/+)) and Slc26a4((-/-)) mice. However, on a severely restricted intake of NaCl, Slc26a4((-/-)) mice were hypotensive relative to wild-type mice. We conclude that Slc26a4 is upregulated with NaCl restriction and is critical in the maintenance of acid-base balance and in the renal conservation of Cl- and water during NaCl restriction. C1 Emory Univ, WMRB, Div Renal, Dept Med, Atlanta, GA 30322 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Wellcome Trust Sanger Inst, Cambridge, England. Univ Florida, Coll Med, Dept Med, Gainesville, FL USA. RP Wall, SM (reprint author), Emory Univ, WMRB, Div Renal, Dept Med, Room 338,1639 Pierce Dr NE, Atlanta, GA 30322 USA. EM smwall@emory.edu RI Verlander, Jill/I-5991-2015 FU NIDDK NIH HHS [DK 52935] NR 28 TC 91 Z9 92 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2004 VL 44 IS 6 BP 982 EP 987 DI 10.1161/01.HYP.0000145863.96091.89 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 874NG UT WOS:000225356500035 PM 15477386 ER PT J AU Mitchell, GF Parise, H Benjamin, EJ Larson, MG Keyes, MJ Vita, JA Vasan, RS Levy, D AF Mitchell, GF Parise, H Benjamin, EJ Larson, MG Keyes, MJ Vita, JA Vasan, RS Levy, D TI Changes in wave reflection with advancing age in normal subjects - Response SO HYPERTENSION LA English DT Letter C1 Cardiovasc Engn Inc, Holliston, MA 01746 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham Study, Framingham, MA USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, Holliston, MA 01746 USA. NR 2 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2004 VL 44 IS 6 BP E10 EP E11 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 874NG UT WOS:000225356500037 ER PT J AU Ryan, C Tewey, B Newman, S Turner, T Jaeger, RJ AF Ryan, C Tewey, B Newman, S Turner, T Jaeger, RJ TI Estimating research productivity and quality in assistive technology: A bibliometric analysis spanning four decades SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE databases; libraries; terminology ID JOURNALS; CITATION; INDICATORS; IMPACT; BIAS AB Objective: Conduct a quantitative assessment of the number of papers contained in MEDLINE related to selected types of assistive technology (AT), and to identify journals publishing significant numbers of papers related to AT, and evaluate them with quantitative productivity and quality measures. Design: Consecutive sample of all papers in MEDLINE identified by standard medical subject headings for selected types of AT from 1963-2003. Main Outcome Measures: Number of journals carrying AT papers, papers per journal (both total number and those specific to AT), journal impact factor, circulation, and number of AT citations per year over time for each area of AT. Results: We present search terms, estimates of the numbers of AT citations in MEDLINE, the journals most likely to contain articles related to AT, journal impact factors, and journal circulations (when available). We also present the number of citations in various areas of AT over time from 1963-2003. Suggestions are presented for possible future modifications of the MEDLINE controlled vocabulary, based on terminology used in existing AT classifications schemes, such as ISO 9999. Conclusion: Research papers in the areas of AT examined showed publication across a wide variety of journals. There are a number of journals publishing articles in AT that have impact factors above the median. Some areas of AT have shown an increase in publications per year over time, while others have shown a more constant level of productivity. C1 New Edit Consulting Inc, Mclean, VA 22101 USA. NIH, Dept Hlth & Human Serv, Warren G Magnuson Clin Ctr, Rehabil Med Dept,Phys Disabil Branch, Bethesda, MD 20892 USA. RP Ryan, C (reprint author), New Edit Consulting Inc, Mclean, VA 22101 USA. EM RJaeger@cc.nih.gov NR 15 TC 2 Z9 2 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD DEC PY 2004 VL 12 IS 4 BP 422 EP 429 DI 10.1109/TNSRE.2004.838568 PG 8 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 879UN UT WOS:000225744500007 PM 15614998 ER PT J AU Douek, D AF Douek, D TI Thymic output and HIV infection: On the right TREC SO IMMUNITY LA English DT Editorial Material ID T-CELL DEPLETION; HOMEOSTASIS; DISEASE AB The role of the thymus in HIV infection has been a matter of considerable debate. A new study by Dion et al. (2004) in this issue of Immunity provides the mechanism for reduced thymic output in HIV infection while illuminating the impact of recent thymic emigrants on peripheral T cell homeostasis. C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Douek, D (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr,Room 3509, Bethesda, MD 20892 USA. NR 10 TC 11 Z9 12 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2004 VL 21 IS 6 BP 744 EP 745 DI 10.1016/j.immuni.2004.11.005 PG 2 WC Immunology SC Immunology GA 881XB UT WOS:000225901600002 PM 15589163 ER PT J AU Dion, ML Poulin, JF Bordi, R Sylvestre, M Corsini, R Kettaf, N Dalloul, A Boulassel, MR Debre, P Routy, JP Grossman, Z Sekaly, RP Cheynier, R AF Dion, ML Poulin, JF Bordi, R Sylvestre, M Corsini, R Kettaf, N Dalloul, A Boulassel, MR Debre, P Routy, JP Grossman, Z Sekaly, RP Cheynier, R TI HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation SO IMMUNITY LA English DT Article ID T-CELL-RECEPTOR; RECENT THYMIC EMIGRANTS; EXCISION CIRCLE CONTENT; ANTIRETROVIRAL THERAPY; PERIPHERAL-BLOOD; TELOMERE LENGTH; OUTPUT; HOMEOSTASIS; TURNOVER; DISEASE AB The supply of naive T cells by the thymus normally requires precursor T cell proliferation within the thymus and would be particularly important in the setting of HIV infection when both naive and memory T cells are progressively depleted. As a robust, quantitative index of intrathymic proliferation, the ratio of different C1 Hop Hotel Dieu, CHUM, Immunol Lab, Ctr Rech, Montreal, PQ H2X 1P1, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H2X 1P1, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H2X 1P1, Canada. McGill Univ, Dept Med, Div Expt Med, Montreal, PQ H2X 1P1, Canada. Univ Montreal, Fac Med, Dept Microbiol & Immunol, Montreal, PQ H2X 1P1, Canada. Grp Hosp Pitie Salpetriere, INSERM, U543, F-75651 Paris 13, France. McGill Univ, Ctr Hlth, Royal Victoria Hosp, Immunodeficiency Serv, Montreal, PQ H3A 1A1, Canada. McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Hematol, Montreal, PQ H3A 1A1, Canada. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sekaly, RP (reprint author), Hop Hotel Dieu, CHUM, Immunol Lab, Ctr Rech, Montreal, PQ H2X 1P1, Canada. EM rafick-pierre.sekaly@umontreal.ca RI Grossman, Zvi/A-9643-2008; Cheynier, Remi/E-9921-2010 OI Cheynier, Remi/0000-0003-1146-660X NR 39 TC 145 Z9 152 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2004 VL 21 IS 6 BP 757 EP 768 DI 10.1016/j.immuni.2004.10.013 PG 12 WC Immunology SC Immunology GA 881XB UT WOS:000225901600004 PM 15589165 ER PT J AU Price, DA West, SM Betts, MR Ruff, LE Brenchley, JM Ambrozak, DR Edghill-Smith, Y Kuroda, MJ Bogdan, D Kunstman, K Letvin, NL Franchini, G Wolinsky, SM Koup, RA Douek, DC AF Price, DA West, SM Betts, MR Ruff, LE Brenchley, JM Ambrozak, DR Edghill-Smith, Y Kuroda, MJ Bogdan, D Kunstman, K Letvin, NL Franchini, G Wolinsky, SM Koup, RA Douek, DC TI T cell receptor recognition motifs govern immune escape patterns in acute SIV infection SO IMMUNITY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; ORIGINAL ANTIGENIC SIN; MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOCYTE ESCAPE; VIRAL ESCAPE; AIDS VACCINE; CLASS-I; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; HIV-1 INFECTION AB Escape from adaptive T cell immunity through transmutation of viral antigenic structure is a cardinal feature in the pathogenesis of SIV/HIV infection and a major obstacle to antiretroviral vaccine development. However, the molecular determinants of this phenomenon at the T cell receptor (TCR)-antigen interface are unknown. Here, we show that mutational escape is intimately linked to the structural configuration of constituent TCR clonotypes within virus-specific CD8(+) T cell populations. Analysis of 3416 SIV-specific TCR sequences revealed that polyclonal T cell populations characterized by highly conserved TCRB CDR3 motifs were rendered ineffectual by single residue mutations in the cognate viral epitope. Conversely, diverse clono-typic repertoires without discernible motifs were not associated with viral escape. Thus, fundamental differences in the mode of antigen engagement direct the pattern of adaptive viral evolution. These findings have profound implications for the development of vaccines that elicit T cell immunity to combat pathogens with unstable genomes. C1 NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. EM ddouek@nih.gov RI Wolinsky, Steven/B-2893-2012; Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Wolinsky, Steven/0000-0002-9625-6697 NR 56 TC 205 Z9 207 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2004 VL 21 IS 6 BP 793 EP 803 DI 10.1016/j.immuni.2004.10.010 PG 11 WC Immunology SC Immunology GA 881XB UT WOS:000225901600007 PM 15589168 ER PT J AU Zhang, P Iwasaki-Arai, J Iwasaki, H Fenyus, ML Dayaram, T Owens, BM Shigematsu, H Levantini, E Huettner, CS Lekstrom-Himes, JA Akashi, K Tenen, DG AF Zhang, P Iwasaki-Arai, J Iwasaki, H Fenyus, ML Dayaram, T Owens, BM Shigematsu, H Levantini, E Huettner, CS Lekstrom-Himes, JA Akashi, K Tenen, DG TI Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha. SO IMMUNITY LA English DT Article ID BINDING-PROTEIN-ALPHA; COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; IN-VIVO; GRANULOCYTIC DIFFERENTIATION; LINEAGE COMMITMENT; DEFICIENT MICE; KNOCKOUT MICE; GENE; GRANULOPOIESIS AB The transcription factor C/EBPalpha is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPalpha blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPalpha-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBPa-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBPalpha cooperates with other events in the development of leukemia. Therefore, C/EBPalpha is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP Tenen, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Inst Med, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu FU NCI NIH HHS [CA72009, CA78045]; NHLBI NIH HHS [HL56745] NR 42 TC 286 Z9 304 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2004 VL 21 IS 6 BP 853 EP 863 DI 10.1016/j.immuni.2004.11.006 PG 11 WC Immunology SC Immunology GA 881XB UT WOS:000225901600012 PM 15589173 ER PT J AU Kovanen, PE Leonard, WJ AF Kovanen, PE Leonard, WJ TI Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways SO IMMUNOLOGICAL REVIEWS LA English DT Review ID RECEPTOR-GAMMA-CHAIN; T-CELL DEVELOPMENT; BACILLE CALMETTE-GUERIN; DEFECTIVE LYMPHOID DEVELOPMENT; FORKHEAD TRANSCRIPTION FACTOR; BONE-MARROW-TRANSPLANTATION; COMBINED IMMUNE-DEFICIENCY; GROWTH-HORMONE RECEPTOR; JAK2 TYROSINE KINASE; HUMAN IL-2 RECEPTOR AB In this review, we discuss the role of cytokines and their signaling pathways in immunodeficiency. We focus primarily on severe combined immunodeficiency (SCID) diseases as the most severe forms of primary immunodeficiencies, reviewing the different genetic causes of these diseases. We focus in particular on the range of forms of SCID that result from defects in cytokine-signaling pathways. The most common form of SCID, X-linked SCID, results from mutations in the common cytokine receptor gamma-chain, which is shared by the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21, underscoring that X-linked SCID is indeed a disease of defective cytokine signaling. We also review the signaling pathways used by these cytokines and the phenotypes in humans and mice with defects in the cytokines or signaling pathways. We also briefly discuss other cytokines, such as interferon-gamma and IL-12, where mutations in the ligand or receptor or signaling components also cause clinical disease in humans. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 226 TC 232 Z9 239 U1 1 U2 26 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2004 VL 202 BP 67 EP 83 DI 10.1111/j.0105-2896.2004.00203.x PG 17 WC Immunology SC Immunology GA 870MO UT WOS:000225061500005 PM 15546386 ER PT J AU Watford, WT Hissong, BD Bream, JH Kanno, Y Muul, L O'Shea, JJ AF Watford, WT Hissong, BD Bream, JH Kanno, Y Muul, L O'Shea, JJ TI Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4 SO IMMUNOLOGICAL REVIEWS LA English DT Review ID IFN-GAMMA-PRODUCTION; NATURAL-KILLER-CELLS; CD4(+) T-CELLS; NF-KAPPA-B; SEQUENCE-BINDING-PROTEIN; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; LYMPHOCYTE MATURATION FACTOR; INTERLEUKIN-12 P40 PROMOTER; ADAPTIVE IMMUNE-RESPONSES AB Produced in response to a variety of pathogenic organisms, interleukin (IL)-12 and IL-23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses. These dimeric cytokines share a subunit, designated p40, and bind to a common receptor chain, IL-12Rbeta1. The receptor for IL-12 is composed of IL-12Rbeta1 and IL-12Rbeta2, whereas IL-23 binds to a receptor composed of IL-12Rbeta1 and IL-23R. Both cytokines activate the Janus kinases Tyk2 and Jak2, the transcription factor signal transducer and activator of transcription 4 (STAT4), as well as other STATs. A major action of IL-12 is to promote the differentiation of naive CD4(+) T cells into T-helper (Th) 1 cells, which produce interferon (IFN)-gamma, and deficiency of IL-12, IL-12R subunits or STAT4 is similar in many respects. In contrast, IL-23 promotes end-stage inflammation. Targeting IL-12, IL-23, and their downstream signaling elements would therefore be logical strategies for the treatment of immune-mediated diseases. C1 NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Dis Prevent & Control Program, Baltimore, MD 21205 USA. RP O'Shea, JJ (reprint author), NIAMS, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Rm 9N256,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 266 TC 287 Z9 301 U1 4 U2 19 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2004 VL 202 BP 139 EP 156 DI 10.1111/j.0105-2896.2004.00211.x PG 18 WC Immunology SC Immunology GA 870MO UT WOS:000225061500010 PM 15546391 ER PT J AU Mentink-Kane, MM Wynn, TA AF Mentink-Kane, MM Wynn, TA TI Opposing roles for IL-13 and IL-13 receptor alpha 2 in health and disease SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SCHISTOSOMA-MANSONI INFECTION; INTERLEUKIN (IL)-13 RESPONSES; PULMONARY GRANULOMA-FORMATION; MURINE SCHISTOSOMIASIS; INTERFERON-GAMMA; IN-VIVO; T-CELLS; HEPATIC-FIBROSIS; DECOY RECEPTOR; NITRIC-OXIDE AB Interleukin (IL)-13 is a key inducer of several type-2 cytokine-dependent pathologies. It regulates inflammation, mucus production, tissue remodeling, and fibrosis. Consequently, it has become an important therapeutic target for a number of debilitating illnesses, including asthma, idiopathic pulmonary fibrosis, ulcerative colitis, as well as several other diseases in which IL-13 is believed to be overproduced. In the murine model of schistosomiasis, IL-13 has emerged as a central mediator of chronic infection-induced liver pathology. Although IL-4, IL-5, IL-10, and IL-13 each regulate distinct aspects of the granulomatous inflammatory response, IL-13 was identified as the primary mediator of liver fibrosis. Thus, elucidating the mechanisms that regulate the production and function of IL-13 has become an intensive area of research. IL-13 signaling is mediated by the type-2 IL-4 receptor, which consists of the IL-4Ralpha and IL-13Ralpha1 chains. However, another IL-13-binding chain, IL-13Ralpha2, appears to strongly inhibit the activity of IL-13. Animals deficient in IL-13Ralpha2 fail to downmodulate granuloma formation in the chronic phase of infection. They also develop severe IL-13-dependent fibrosis and portal hypertension and quickly succumb to the infection. Here, we summarize findings from the schistosomiasis model, which illustrate opposing activities for IL-13 and IL-13Ralpha2 in health and disease. C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 50 South Dr,Rm 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 71 TC 66 Z9 74 U1 1 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2004 VL 202 BP 191 EP 202 DI 10.1111/j.0105-2896.2004.00210.x PG 12 WC Immunology SC Immunology GA 870MO UT WOS:000225061500013 PM 15546394 ER PT J AU Barouch, DH Letvin, NL Seder, RA AF Barouch, DH Letvin, NL Seder, RA TI The role of cytokine DNAs as vaccine adjuvants for optimizing cellular immune responses SO IMMUNOLOGICAL REVIEWS LA English DT Review ID COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; MEDIATED PROTECTIVE IMMUNITY; CELLS IN-VIVO; GM-CSF; PLASMID DNA; RHESUS MACAQUES; INNATE IMMUNITY; IFN-GAMMA; EXPRESSION CASSETTES AB Cytokines represent a diverse group of immunologic effector and regulatory proteins that are critical components of the host response to invading pathogens. They have also been utilized as adjuvants to enhance immune responses to vaccines. In particular, plasmid cytokines have been studied extensively as candidate adjuvants for DNA vaccines in preclinical models and are now entering early-phase clinical trials. Here, we review recent advances in our understanding of cytokine biology, T-lymphocyte differentiation, and potential applications of plasmid cytokines in the rational design of improved vaccines. C1 NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 40-3512,MSC 3025, Bethesda, MD 20892 USA. EM rseder@niaid.nih.gov NR 93 TC 76 Z9 85 U1 1 U2 7 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2004 VL 202 BP 266 EP 274 DI 10.1111/j.0105-2896.2004.00200.x PG 9 WC Immunology SC Immunology GA 870MO UT WOS:000225061500018 PM 15546399 ER PT J AU Carlson, JH Hughes, S Hogan, D Cieplak, G Sturdevant, DE McClarty, G Caldwell, HD Belland, RJ AF Carlson, JH Hughes, S Hogan, D Cieplak, G Sturdevant, DE McClarty, G Caldwell, HD Belland, RJ TI Polymorphisms in the Chlamydia trachomatis cytotoxin locus associated with ocular and genital isolates SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; GENOME SEQUENCE; TRYPTOPHAN SYNTHASE; MEMBRANE-PROTEIN; RHO GTPASES; GENES; PNEUMONIAE; O157-H7; CELLS; GLYCOSYLTRANSFERASES AB Chlamydia trachomatis is a strict human pathogen producing infections that cause medically important chronic inflammatory diseases, such as blinding trachoma and tubal factor infertility. Isolates exist as serotypes that fall into distinct biologic and pathological groups corresponding to differences in infection tissue tropism and invasion properties. Paradoxically, genome sequencing of several diverse strains has revealed a remarkable level of genomic synteny, suggesting that minor genetic differences determine the pathogen host- and tissue-specific infection characteristics. To better understand the genetic basis of chlamydial pathobiologic diversity, we performed comparative DNA-DNA microarray genomic hybridizations with all 15 C trachomatis serovariants. We found there are few major genetic differences among the 15 serovars. An exception was the cytotoxin locus located in the plasticity zone, a region that exhibited significant polymorphisms among serovars. We therefore sequenced this region from all 15 serovars. The cytotoxin gene was interrupted by extensive mutations and deletions among the different serovars; however, three basic open reading frame motifs were discovered that correlated with noninvasive oculotropic, urogenitotropic, and invasive serovars. Of interest, only noninvasive genitotropic serovars possessed an intact N-terminal portion of the putative toxin gene. This region contains the UDP-glucose binding domain and the glycosyltransferase domain required for enzymatic activity of the clostridial toxin homologs, suggesting a role in urogenital infection or pathogenesis. C1 Natl Inst Allergy & Infect Dis, Intracellular Parasites Lab, Rocky Mountain Labs, NIH, Hamilton, MT USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mountain Labs, NIH, Hamilton, MT USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. RP Belland, RJ (reprint author), Univ Tennessee, Memphis Hlth Sci Ctr, Coll Med, Dept Mol Sci, 858 Madison Ave, Memphis, TN 38163 USA. EM rbelland@UTMEM.edu NR 36 TC 71 Z9 72 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2004 VL 72 IS 12 BP 7063 EP 7072 DI 10.1128/IAI.72.12.7063-7072.2004 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 875WW UT WOS:000225453900036 PM 15557630 ER PT J AU Sebbane, F Jarrett, CO Linkenhoker, JR Hinnebusch, BJ AF Sebbane, F Jarrett, CO Linkenhoker, JR Hinnebusch, BJ TI Evaluation of the role of constitutive isocitrate lyase activity in Yersinia pestis infection of the flea vector and mammalian host SO INFECTION AND IMMUNITY LA English DT Article ID GLYOXYLATE BYPASS OPERON; ESCHERICHIA-COLI; GENOME SEQUENCE; PHOSPHORYLATION; DEHYDROGENASE; PROTEIN; IDENTIFICATION; MUTAGENESIS; EXPRESSION; EVOLUTION AB Yersinia pestis, unlike the closely related Yersinia pseudotuberculosis, constitutively produces isocitrate lyase (ICL). Here we show that the Y. pestis aceA homologue encodes ICL and is required for growth on acetate but not for flea infection or virulence in mice. Thus, deregulation of the glyoxylate pathway does not underlie the recent adaptation of Y. pestis to arthropod-borne transmission. C1 NIAID, Rocky Mt Lab, NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Rocky Mt Lab, NIH, Lab Human Bacterial Pathogenesis, 903 S 4th St, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov RI Sebbane, Florent/D-4213-2009 NR 37 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2004 VL 72 IS 12 BP 7334 EP 7337 DI 10.1128/IAI.72.12.7334-7337.2004 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 875WW UT WOS:000225453900069 PM 15557663 ER PT J AU Weisblat, DA Rivera, AS Gonsalves, FC Song, MH Zhang, SO AF Weisblat, DA Rivera, AS Gonsalves, FC Song, MH Zhang, SO TI Segmentation in Helobdella robusta, a glossiphoniid leech SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 04-08, 2005 CL San Diego, CA SP Soc Integrat & Comparat Biol C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. NIDDK, NIH, Bethesda, MD 20892 USA. EM weisblat@berkeley.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2004 VL 44 IS 6 BP 662 EP 662 PG 1 WC Zoology SC Zoology GA 893LU UT WOS:000226721401150 ER PT J AU Frazier, M Huey, RB Berrigan, D AF Frazier, M Huey, RB Berrigan, D TI Insect population growth: Hotter is better SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 04-08, 2005 CL San Diego, CA SP Soc Integrat & Comparat Biol C1 Univ Washington, Seattle, WA 98195 USA. NCI, Bethesda, MD 20892 USA. EM mfrazier@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2004 VL 44 IS 6 BP 697 EP 697 PG 1 WC Zoology SC Zoology GA 893LU UT WOS:000226721401289 ER PT J AU Menon, J Militello, F Buchholz, D AF Menon, J Militello, F Buchholz, D TI Oxidative stress during intestine remodeling in anuran tadpoles, Xenopus laevis SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology (SICB) CY JAN 04-08, 2005 CL San Diego, CA SP Soc Integrat & Comparat Biol C1 William Paterson Univ New Jersey, Wayne, NJ USA. NIH, Bethesda, MD 20892 USA. EM menonj@wpunj.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2004 VL 44 IS 6 BP 728 EP 728 PG 1 WC Zoology SC Zoology GA 893LU UT WOS:000226721401412 ER PT J AU Hess, K Yang, YH Golech, S Sharov, A Becker, KG Weng, NP AF Hess, K Yang, YH Golech, S Sharov, A Becker, KG Weng, NP TI Kinetic assessment of general gene expression changes during human naive CD4(+) T cell activation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE activation; cytokine; cDNA microarray; resting ID GDP-DISSOCIATION INHIBITOR; DOWN-REGULATION; CYCLIN D3; LYMPHOCYTES; KINASE; CD28; PROLIFERATION; INTERLEUKIN-2; MODULATION; QUIESCENCE AB The consequence of naive CD4(+) T cell activation is the differentiation and generation of effector cells. How the engagement of T cell receptors and co-stimulatory receptors leads to profound differential changes is not fully understood. To assess the transcription changes during T cell activation, we developed human T cell specific cDNA microarray gene filters and examined the gene expression profiles in human naive CD4(+) T cells for 10 continuous time points during the first 24 h after anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation. We report here a global and kinetic analysis of gene expression changes during naive CD4(+) T cell activation and identify 196 genes having expression levels that significantly changed after activation. Based on the temporal change, there are 15 genes that changed between 0-1 h (early), 25 genes between 2-8 h (middle) and 156 genes between 16-24 h (late) after stimulation. Further analyses of the functions of those genes indicate their roles in maintenance of resting status, activation, adhesion/migration, cell cycle progression and cytokine production. However, a significant majority of these genes are novel to T cells and their functions in T cell activation require further study. Together, these results present a kinetic view of the gene expression changes of naive CD4(+) T cells in response to T cell receptor-mediated activation for the first time, and provide a basis in understanding how the complex network of gene expression regulation is programmed during CD4(+) T cell activation. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. EM wengn@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 43 TC 20 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 2004 VL 16 IS 12 BP 1711 EP 1721 DI 10.1093/intimm/dxh172 PG 11 WC Immunology SC Immunology GA 873BX UT WOS:000225254900004 PM 15492022 ER PT J AU Liberski, PP Sikorska, B Bratosiewicz-Wasik, J Gajdusek, DC Brown, P AF Liberski, PP Sikorska, B Bratosiewicz-Wasik, J Gajdusek, DC Brown, P TI Neuronal cell death in transmissible spongiform encephalopathies (prion diseases) revisited: from apoptosis to autophagy SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE autophagy; apoptosis; prion diseases; neurons; ultrastructure ID CREUTZFELDT-JAKOB-DISEASE; KUDU TRAGELAPHUS-STREPSICEROS; FATAL FAMILIAL INSOMNIA; CHRONIC WASTING DISEASE; SCRAPIE-INFECTED MICE; CAPTIVE MULE DEER; ELECTRON-MICROSCOPY; MURINE SCRAPIE; NEURODEGENERATIVE DISEASES; ULTRASTRUCTURAL PATHOLOGY AB Neuronal autophagy, like apoptosis, is one of the mechanisms of the programmed cell death (PCD). In this review, we summarize the presence of autophagic vacuoles in experimentally induced scrapie, Creutzfeldt-Jakob disease and GerstmannStraussier-Scheinker (GSS) syndrome. Initially, a part of the neuronal cytoplasm was sequestrated by concentric arrays of double membranes; the enclosed cytoplasm appeared relatively normal except that its density was often increased. Next, electron density of the central area dramatically increased. The membranes then proliferated within the cytoplasm in a labyrinth-like manner and the area sequestrated by these membranes enlarged into a more complex structure consisting of vacuoles, electron-dense areas and areas of normally-looking cytoplasm connected by convoluted membranes. Of note, autophagic vacuoles form not only in neuronal perikarya but also in neurites and synapses. Finally, a large area of the cytoplasm was transformed into a collection of autophagic vacuoles of different sizes. On a basis of ultrastructural studies, we suggest that autophagy plays a major role in transmissible spongiform encephalopathies (TSEs) and may even participate in a formation of spongiform change. (C) 2004 Elsevier Ltd. All rights reserved. C1 Med Univ Lodz, Dept Mol Pathol & Neuropathol, PL-92216 Lodz, Poland. Med Univ Silesia, Dept Virol, Katowice, Poland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Liberski, PP (reprint author), Med Univ Lodz, Dept Mol Pathol & Neuropathol, Czechoslowacka St 8-10, PL-92216 Lodz, Poland. EM ppliber@csk.am.lodz.pl NR 145 TC 81 Z9 83 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD DEC PY 2004 VL 36 IS 12 BP 2473 EP 2490 DI 10.1016/j.biocel.2004.04.016 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 856GO UT WOS:000224033900011 PM 15325586 ER PT J AU Sikorska, B Liberski, PP Giraud, P Kopp, N Brown, P AF Sikorska, B Liberski, PP Giraud, P Kopp, N Brown, P TI Autophagy is a part of ultrastructural synaptic pathology in Creutzfeldt-Jakob disease : a brain biopsy study SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE autophagy; synapse; prion; Creutzfeldt-Jakob disease; ultrastructure ID PROGRAMMED CELL-DEATH; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; SPONGIFORM ENCEPHALOPATHY; PARKINSONS-DISEASE; PRION DISEASES; GUINEA-PIGS; SCRAPIE; ELECTRON; NEURONS AB Ultrastructural correlates of synaptic and dendritic spines loss have never been studied in detail in human transmissible spongiform encephalopathies (TSEs)-Creutzfeldt-Jakob disease (CJD), Gerstmann-Striiussler-Scheinker (GSS) disease and fatal familial insomnia (FFI). In this paper, we describe synaptic alterations as found in brain biopsies from Creutzfeldt-Jakob disease and fatal familial insomnia patients. Our material consisted of brain biopsies obtained by open surgery from one FFI case, one case of variant Creutzfeldt-Jakob disease (vCJD), seven cases of sporadic Creutzfeldt-Jakob disease (sCJD) and one case of iatrogenic (human growth hormone) Creutzfeldt-Jakob disease (iCJD). For electron microscopy, approximately 2 mm 3 samples were immersion fixed in 2.5% glutaraldehyde for less than 24 h, embedded in Epon and routinely processed. Grids were examined and photographed in a transmission electron microscope. The synaptic alterations were found constantly; in practically every brain biopsy they were frequent. The accumulation of different subcellular organelles (neuroaxonal dystrophy), dark synapses and branching cisterns were the most frequent findings while concentric arrays of membranes were only rarely found. Autophagic vacuoles are formed in many synapses in all categories of human transmissible encephalopathies. We conclude that synaptic autophagy contributes to overall synaptic loss in brains affected in prion diseases. (C) 2004 Elsevier Ltd. All rights reserved. C1 Med Univ Lodz, Dept Mol Pathol & Neuropathol, PL-90131 Lodz, Poland. Hop Neurol & Neurochirurg P Wertheimer, Lab Anat Pathol & Neuropathol, Lyon, France. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Liberski, PP (reprint author), Med Univ Lodz, Dept Mol Pathol & Neuropathol, Lindleya 3, PL-90131 Lodz, Poland. EM ppliber@csk.am.lodz.pl NR 50 TC 66 Z9 68 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD DEC PY 2004 VL 36 IS 12 BP 2563 EP 2573 DI 10.1016/j.biocel.2004.04.014 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 856GO UT WOS:000224033900018 PM 15325593 ER PT J AU Gould, TD Einat, H Bhat, R Manji, HK AF Gould, TD Einat, H Bhat, R Manji, HK TI AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE behaviour; depression; forced swim test; glycogen synthase kinase-3; mania; manic-depressive illness ID GLYCOGEN-SYNTHASE KINASE-3; LITHIUM AB The mechanism by which lithium exerts either its anti-manic or antidepressant effects remains to be fully elucidated. Although lithium inhibits the enzyme glycogen synthase kinase-3 (GSK-3) at concentrations that are relevant for treatment of bipolar disorder, it is unclear whether GSK-3-related mechanisms are responsible for its therapeutic effects in the treatment of this disease. We report that AR-A014418 (a selective GSK-3 inhibitor) induces behavioural changes that are consistent with the effects of antidepressant medications. Subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, a well-established model for antidepressant efficacy. In addition, the specificity of this effect is supported by our finding that AR-A014418 decreased spontaneous as well as amphetamine-induced activity. Taken together, these data support the hypothesis that lithium may exert its antidepressant effects through inhibition of GSK-3, and that novel small-molecule GSK-3 inhibitors may be useful for the treatment of bipolar disorder and depression. C1 NIMH, Mol Pathophysiol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. AstraZeneca R&D, Sodertalje, Sweden. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 35,Room 16-912, Bethesda, MD 20892 USA. EM manji@nih.gov RI Einat, Haim/A-7203-2009 NR 10 TC 196 Z9 208 U1 0 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD DEC PY 2004 VL 7 IS 4 BP 387 EP 390 DI 10.1017/S1461145704004535 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 878OK UT WOS:000225655900002 PM 15315719 ER PT J AU Jiao, XD Ritter, R Hejtmancik, JF Edwards, AO AF Jiao, XD Ritter, R Hejtmancik, JF Edwards, AO TI Genetic linkage of snowflake vitreoretinal degeneration to chromosome 2q36 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RECESSIVE ALPORT-SYNDROME; STOP CODON MUTATION; STICKLER-SYNDROME; AUTOSOMAL-DOMINANT; MOLECULAR-GENETICS; RETINAL-DETACHMENT; COL2A1 GENE; FOLLOW-UP; FAMILY; COLLAGEN AB PURPOSE. To identify the chromosomal location of the gene causing snowflake vitreoretinal degeneration (SVD), an autosomal dominant retinal degeneration characterized by small yellow-white dots in the retina, fibrillar anomaly of the vitreous humor, and retinal detachment. METHODS. Clinical data were collected on 31 family members by history and examination. Thirteen family members underwent prospective examination. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point and multipoint linkage analysis was performed (FASTLINK version of the MLINK program and the VITESSE algorithm, both available at http://linkage. rockefeller.edu/soft/list.html). Direct DNA sequencing of amplified genomic DNA and mRNA was performed for candidate gene analysis. RESULTS. The SVD locus was linked to markers in a region of chromosome 2q36 defined by D2S2158 and D2S2202, based on meiotic breakpoint mapping of affected individuals. A maximum two-point lod score of 5.5 was obtained with marker D2S172 at theta = 0 within this region. Direct DNA sequencing of all 52 exons of the COL4A3 gene revealed no potentially pathogenic coding sequence variation or evidence for deletion. CONCLUSIONS. The genetic locus for SVD lies in a 9 Mb region flanked by D2S2158 and D2S2202. Localization of SVD to a genomic region distinct from both Wagner disease and the Stickler syndromes indicates that SVD is a distinct genetic entity. The absence of coding sequence variation in the only collagen gene within the disease-region, suggests a novel pathogenesis for vitreoretinal degeneration. Snowflake vitreoretinal degeneration should be considered in the differential diagnosis of families with fibrillar anomaly of the vitreous. C1 Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA. NEI, Ophthalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. RP Edwards, AO (reprint author), Univ Texas, SW Med Ctr, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM albert.edwards@utsouthwestern.edu FU NEI NIH HHS [EY12699, EY14467] NR 37 TC 9 Z9 10 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2004 VL 45 IS 12 BP 4498 EP 4503 DI 10.1167/iovs.04-0722 PG 6 WC Ophthalmology SC Ophthalmology GA 873GZ UT WOS:000225269200036 PM 15557460 ER PT J AU Tzchori, I Zak, T Sachs, O AF Tzchori, I Zak, T Sachs, O TI Masculinization of genetic females of the common carp (Cyprinus carpio L.) by dietary administration of an aromatase inhibitor SO ISRAELI JOURNAL OF AQUACULTURE-BAMIDGEH LA English DT Article DE aromatase inhibitor; common carp; methyltestosterone; sex determination; sex inversion ID GONADAL SEX-DIFFERENTIATION; OREOCHROMIS-NILOTICUS; NILE TILAPIA; TEMPERATURE; FISH; INVIVO; 17-ALPHA-METHYLTESTOSTERONE; METHYLTESTOSTERONE; FEMINIZATION; CGS-16949A AB In the present study, we demonstrated the ability of Fadrozole, an aromatase inhibitor, to induce sex inversion of genetically female common carp fry during the critical sex differentiation period. Thirty-day-old female fingerlings with a mean initial weight of 4.0 g (experiment I) and 3.5 g (experiment II) were fed a diet containing Fadrozole for 36 or 50 days, respectively. Not a single male was found in the control groups of both experiments. In experiment I, Fadrozole at 200 mg/kg feed resulted in 58.6% males, while fish receiving 17alpha-methyltestosterone at 50 or 100 mg/kg feed resulted in only 5-10% males. In experiment II, the efficiency of Fadrozole was close-dependent; the lower dose of 100 mg/kg caused masculinization in 86% of the treated fry while the higher doses of 200 and 400 mg/kg feed increased the percentage of males to 97%. These results confirm the importance of aromatization during the labile period in common carp since low aromatase activity during this period, regardless of genotype, resulted in masculinization. C1 Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel. Aquaculture Res Stn, IL-30820 DN Hof Hacarmel, Israel. RP Tzchori, I (reprint author), NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. EM tzchorii@mail.nih.gov NR 30 TC 9 Z9 9 U1 0 U2 6 PU LAB RESEARCH FISH DISEASES PI NIR-DAVID PA BAMIDGEH EDITORIAL OFFICE, NIR-DAVID 19150, ISRAEL SN 0792-156X J9 ISR J AQUACULT-BAMID JI Isr. J. Aquac.-Bamidgeh PD DEC PY 2004 VL 56 IS 4 BP 239 EP 246 PG 8 WC Fisheries SC Fisheries GA 885PD UT WOS:000226168500001 ER PT J AU Winkler, CA Hendel, H Carrington, M Smith, MW Nelson, GW O'Brien, SJ Phair, J Vlahov, D Jacobson, LP Rappaport, J Vasilescu, A Bertin-Maghit, S An, P Lu, W Andrieu, JM Schachter, F Therwath, A Zagury, JF AF Winkler, CA Hendel, H Carrington, M Smith, MW Nelson, GW O'Brien, SJ Phair, J Vlahov, D Jacobson, LP Rappaport, J Vasilescu, A Bertin-Maghit, S An, P Lu, W Andrieu, JM Schachter, F Therwath, A Zagury, JF TI Dominant effects of CCR2-CCR5 haplotypes in HIV-1 disease progression SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; CCR2; CCR5; haplotype; HIV; disease progression ID IMMUNODEFICIENCY-VIRUS TYPE-1; MULTICENTER AIDS COHORT; CHEMOKINE RECEPTOR CCR2; INTERNATIONAL METAANALYSIS; PROMOTER POLYMORPHISM; GENETIC RESTRICTION; INFECTION; ALLELES; RANTES; PLASMA AB Three haplotypes for the CCR2-CCR5 region previously have been shown to affect AIDS progression; however, it is not known if the protective and accelerating effects of the haplotypes are relatively constant throughout infection or exert their effects early or late in HIV type I infection. The authors report the relative contributions to AIDS progression of CCR2 64I, CCR5 Delta32, and the CCR5 promoter haplotype +.P1.+ in the GRIV cohort, which included patients representing the extremes of the distribution for AIDS progression: rapid progressors (RP) who developed CD4(+) T-cell counts of <300/ mm(3) within 3 years after the last HIV-1-seronegative test and slow progressors (SP) who were HIV-1 infected for greater than or equal to8 years with CD4(+) T-cell counts of >500/mm(3). Comparing the R-P with a seroconverter control group including intermediate progressors to AIDS, we observed the early protective effect of CCR5 Delta32 (odds ratio = 0.25; P = 0.007) was similar in strength to the early susceptible effect of CCR5 +.P1.+ (odds ratio = 2.1, P = 0.01). Comparison of the intermediate control group to the SP showed weaker and less significant odd ratios, suggesting that the effect of these factors tended to be stronger on early progession; the tendency towards a disproportionately early effect was significant for CCR5 Delta32 (P = 0.04) but not for CCR5 +.P1.+ (P = 0.12). Follow-up of S P demonstrated that these polymorphisms have little effect after 8 years, because the subset of SP who had progression after study entry bad the same genotype distribution as the global population of SP, suggesting that factors other than CCR5 or CCR2 genetic variants must be responsible for the long-term maintenance of nonprogression. C1 Univ Paris 06, Ctr Rech Cordeliers, F-75006 Paris, France. NCI, SAIC Frederick, Div Basic Res, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Lab Genom Divers, NIH, Frederick, MD 21701 USA. Northwestern Univ, Comprehens AIDS Ctr, Fineberg Sch Med, Chicago, IL 60611 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Temple Univ, Ctr Neurovirol & Canc, Philadelphia, PA 19122 USA. Ctr Natl Genotypage, Evry, France. Hop Georges Pompidou, Unite Oncol Med, Paris, France. Univ Paris 07, Oncol Mol Lab, Paris, France. RP Zagury, JF (reprint author), Univ Paris 06, Ctr Rech Cordeliers, 15 Rue Ecole Med, F-75006 Paris, France. EM jfz@ccr.jussieu.fr RI Smith, Michael/B-5341-2012 FU NCI NIH HHS [N01-CO-12400] NR 38 TC 28 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2004 VL 37 IS 4 BP 1534 EP 1538 DI 10.1097/01.qai.0000127353.01578.63 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 876FL UT WOS:000225481800014 PM 15602133 ER PT J AU Hertle, RW Dell'Osso, LF FitzGibbon, EJ Yang, DS Mellow, SD AF Hertle, RW Dell'Osso, LF FitzGibbon, EJ Yang, DS Mellow, SD TI Horizontal rectus muscle tenotomy in children with infantile nystagmus syndrome: A pilot study SO JOURNAL OF AAPOS LA English DT Article ID CONGENITAL NYSTAGMUS; EYE-MOVEMENTS; SURGERY; PROPRIOCEPTION; STIMULATION; RECORDINGS; DISORDERS; FIXATION; HEAD AB Purpose: We wished to determine the effectiveness of horizontal rectus tenotomy in changing the nystagmus of children with infantile nystagmus syndrome. Design: This was a prospective, noncomparative, interventional case series in five children with varied sensory and oculographic subtypes of congenital nystagmus (including asymmetric (a)periodic alternating nystagmus) and no nystagmus treatment options. Simple tenotomy of all four horizontal recti with reattachment at the original insertion was accomplished. Search-coil and infrared eye movement recordings and clinical examinations were performed before and 1, 6, 26, and 52 weeks after surgery. Outcome measures included masked pre- and postoperative expanded nystagmus acuity function (NAFX), foveation time obtained directly from ocular motility recordings, and masked measures of visual acuity. Results: At 1 year after tenotomy and under binocular conditions, two of the three patients for whom the NAFX could be measured had persistent, significant postoperative increases in the NAFX of their fixating eye. Average foveation times increased in these patients' fixating eyes. Measured binocular visual acuity increased in four patients; the remaining patient had retinal dystrophy. There were no adverse events due to surgery. Conclusions: In the two children who could fixate the targets for several seconds and for whom we could obtain accurate measurements of their infantile nystagmus, tenotomy resulted in significant improvements in nystagmus foveation measures. In those patients plus two others (four of five), measured visual function improved. C1 Childrens Hosp Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15213 USA. Case Western Reserve Univ, Louis Stokes Cleveland VA Med Ctr, Ocular Motor Neurophysiol Lab, Dept Neurol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Louis Stokes Cleveland VA Med Ctr, Ocular Motor Neurophysiol Lab, Dept Biomed Engn, Cleveland, OH 44106 USA. NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. NIH, NEI, Bethesda, MD 20892 USA. RP Hertle, RW (reprint author), Childrens Hosp Pittsburgh, Dept Ophthalmol, 3705 5th Ave, Pittsburgh, PA 15213 USA. NR 43 TC 51 Z9 54 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD DEC PY 2004 VL 8 IS 6 BP 539 EP 548 DI 10.1016/j.jaapos.2004.08.005 PG 10 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 884JM UT WOS:000226080900006 PM 15616501 ER PT J AU Wynne, SM Kwon-Chung, KJ Shea, YR Filie, AC Varma, A Lupo, P Holland, SM AF Wynne, SM Kwon-Chung, KJ Shea, YR Filie, AC Varma, A Lupo, P Holland, SM TI Invasive infection with Trichosporon inkin in 2 siblings with chronic granulomatous disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE neutrophil dysfunction; posaconazole; voriconazole; caspofungin; amphotericin ID AMBULATORY PERITONEAL-DIALYSIS; ENDOCARDITIS; PATIENT AB A 9-year-old girl with autosomal recessive chronic granulomatous disease (CGD) presented with asymptomatic bilateral pulmonary infiltrates on routine computed tomography. Fine-needle aspirate of the infiltrates was obtained and showed fungal cells resembling Trichosporon inkin. The specimen grew in culture, and testing by means of both API 20C and PCR amplification confirmed the diagnosis of T inkin. The infiltrates increased in size, despite sequential therapy with voriconazole, liposomal amphotericin B, caspofungin, and posaconazole. The patient required resection of the infected lung tissue, after which she recovered completely. While she was undergoing therapy, her 13-year-old brother, also with CGD, was given a diagnosis of bilateral T inkin-induced pulmonary infection. He also required bilateral pulmonary resection for cure. These cases demonstrate the predisposition of patients with CGD to have invasive infections with unusual fungal organisms, such as T inkin. They also illustrate the difficulty of treating invasive T inkin infections with antifungal agents alone. There are 9 previously reported cases of invasive infections caused by T inkin, 3 of which are in patients with CGD. All patients required removal of infected prosthetic devices or surgical resection of infected tissue for cure. C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NIAID, Lab clin Infect Dis, Bethesda, MD 20892 USA. NCI, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov NR 17 TC 21 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2004 VL 114 IS 6 BP 1418 EP 1424 DI 10.1016/j.jaci.2004.07.066 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 877NN UT WOS:000225577400026 PM 15577847 ER PT J AU Kim, YJ Prussin, C Martin, B Law, MA Haverty, TP Nutman, TB Klion, AD AF Kim, YJ Prussin, C Martin, B Law, MA Haverty, TP Nutman, TB Klion, AD TI Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE anti-IL-5; hypereosinophilic syndrome; eosinophilic gastroenteritis; monoclonal antibody; eosinophil ID ANTI-INTERLEUKIN-5 ANTIBODY; HUMAN INTERLEUKIN-5; BLOOD EOSINOPHILS; IMATINIB MESYLATE; RECEPTOR-ALPHA; IL-5; EFFICACY; THERAPY; MUCOSA; ASTHMA AB Background: Hypereosinophilic syndrome and eosinophilic gastroenteritis with peripheral eosinophilia are characterized by sustained eosinophilia and eosinophil-mediated tissue damage. Although treatment with the humanized monoclonal anti-IL-5 antibody SCH55700 resulted in improvement of eosinophilia and clinical symptoms in 6 of 8 of patients with hypereosinophilic syndrome or eosinophilic gastroenteritis with peripheral eosinophilia for as long as 12 weeks, eosinophil counts subsequently rose above baseline levels, accompanied by an exacerbation of symptoms. Objective: To identify the mechanism underlying this rebound eosinophilia. Methods: Purified eosinophils from patients or normal donors were cultured with IL-5, patient serum, and/or anticytokine antibodies, and eosinophil survival was assessed by flow cytometry. Serum and intracellular cytokine levels were measured by multiplex sandwich ELISA and flow cytometry, respectively. Results: Before treatment with SCH55700, in vitro eosinophil survival in media and in response to recombinant IL-5 was similar in patients and normal donors. At 1 month posttreatment, the eosinophil survival curves were unchanged in 4 of 5 patients in media and in all 5 patients in response to recombinant IL-5. Normal eosinophil survival was prolonged in cultures containing posttreatment but not pretreatment sera (pretreatment vs posttreatment, 10.74% vs 73.02% live cells; P = .01). This posttreatment serum effect on eosinophil survival was reversed by the addition of the monoclonal anti-IL-5 antibody TRFK5. Although increased levels of serum IL-5 were observed at 1 month compared with 2 to 3 days posttreatment in 5 of 6 patients (P =.04), intracellular cytokine analysis did not reveal increased production of IL-5 by peripheral blood mononuclear cells. Conclusions: The rebound eosinophilia after SCH55700 treatment is a result of a serum factor that enhances eosinophil survival. Reversal of this effect by the addition of antibody to IL-5 suggests that this factor may be IL-5 itself. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Schering Plough Corp, Inst Res, Kenilworth, NJ 07033 USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room B1-05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM aklion@niaid.nih.gov OI Prussin, Calman/0000-0002-3917-3326; Klion, Amy/0000-0002-4986-5326 NR 24 TC 59 Z9 61 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2004 VL 114 IS 6 BP 1449 EP 1455 DI 10.1016/j.jaci.2004.08.027 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 877NN UT WOS:000225577400030 PM 15577851 ER PT J AU Schrager, MA Roth, SM Ferrell, RE Metter, EJ Russek-Cohen, E Lynch, NA Lindle, RS Hurley, BF AF Schrager, MA Roth, SM Ferrell, RE Metter, EJ Russek-Cohen, E Lynch, NA Lindle, RS Hurley, BF TI Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE muscle mass; muscle strength; muscle power; genetics; gender ID II IGF-II; SKELETAL-MUSCLE; BIRTH-WEIGHT; GENE REGION; STRENGTH; AGE; MEN; EXPRESSION; WOMEN; MALES AB The influence of insulin-like growth factor-2 (IGF2) genotype on total body fat-free mass (FFM), muscle strength, and sustained power (SP) was evaluated repeatedly at similar to2-yr intervals in two cohorts from the Baltimore Longitudinal Study of Aging. Cohort 1 was comprised of 94 men tested for isometric grip strength and SP. Cohort 2 was comprised of 246 men and 239 women tested for total body FFM and isokinetic peak torque. Subjects were retrospectively genotyped for the IGF2 gene's ApaI polymorphism. Differences between genotype groups for total FFM, strength, and SP at first visit, at peak age ( 35 yr), at age 65, and across the adult age span were analyzed using either two-sample t-tests or mixed-effects models, depending on the specific comparisons made. Isokinetic arm strength at the time of first visit was lower in A/A men than in G/G men ( P < 0.05). Compared with G/G women, A/A women had lower total body FFM, lower isokinetic arm and leg strength at the time of first visit, and lower values at age 35 ( all P < 0.05) for these muscle phenotypes. Furthermore, this difference between the genotype groups was maintained at age 65 and across the adult age span ( P < 0.05). No genotype-associated differences in rates of loss of grip strength or SP were found in cohort 1. These results from cohort 2 support the hypothesis that variation within a gene known to influence developing muscle affects muscle mass and muscle function in later life. C1 Univ Maryland, Dept Kinesiol, Coll Hlth & Human Performance, College Pk, MD 20742 USA. Univ Maryland, Dept Anim & Avian Sci, Biometr Program, College Pk, MD 20742 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Maryland, Sch Med, Baltimore Vet Affairs Med Ctr, Div Gerontol, Baltimore, MD 21201 USA. RP Hurley, BF (reprint author), Univ Maryland, Dept Kinesiol, Coll Hlth & Human Performance, College Pk, MD 20742 USA. EM benhur@umd.edu OI Roth, Stephen/0000-0002-7841-3695 NR 58 TC 33 Z9 36 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2004 VL 97 IS 6 BP 2176 EP 2183 DI 10.1152/japplphysiol.00985.2003 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 868FM UT WOS:000224899500021 PM 15298990 ER PT J AU Spouge, JL AF Spouge, JL TI Path reversal, islands, and the gapped alignment of random sequences SO JOURNAL OF APPLIED PROBABILITY LA English DT Article DE bioinformatics; island in gapped alignment; Lindley process ID APPROXIMATE P-VALUES; STATISTICAL SIGNIFICANCE; PARTIAL-SUMS; SEARCH; DISTRIBUTIONS; SCORE; GAPS AB In bioinformatics, the notion of an 'island' enhances the efficient simulation of gapped local alignment statistics. This paper generalizes several results relevant to gapless local alignment statistics from one to higher dimensions, with a particular eye to applications in gapped alignment statistics. For example, reversal of paths (rather than of discrete time),generalizes a distributional equality, from queueing theory, between the Lindley (local sum) and maximum processes. Systematic investigation of an 'ownership' relationship among vertices in Z(2) formalizes the notion of an island as a set of vertices having a common owner. Predictably, islands possess some stochastic ordering and spatial averaging properties. Moreover, however, the average number of vertices in a subcritical stationary island is 1, generalizing a theorem of Kac about stationary point processes. The generalization leads to alternative ways of simulating some island statistics. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov NR 31 TC 3 Z9 3 U1 0 U2 1 PU APPLIED PROBABILITY TRUST PI SHEFFIELD PA THE UNIVERSITY, SCHOOL MATHEMATICS STATISTICS, SHEFFIELD S3 7RH, ENGLAND SN 0021-9002 J9 J APPL PROBAB JI J. Appl. Probab. PD DEC PY 2004 VL 41 IS 4 BP 975 EP 983 DI 10.1239/jap/1101840544 PG 9 WC Statistics & Probability SC Mathematics GA 883BF UT WOS:000225984300004 ER PT J AU Wang, ML Sharkey, PF Tuan, RS AF Wang, ML Sharkey, PF Tuan, RS TI Particle bioreactivity and wear-mediated osteolysis SO JOURNAL OF ARTHROPLASTY LA English DT Review DE wear debris; osteolysis; reactive oxygen species; mesenchymal stein cells ID TOTAL HIP-ARTHROPLASTY; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; MACROPHAGE CYTOKINE RESPONSE; MESENCHYMAL STEM-CELLS; IN-VITRO; TITANIUM PARTICLES; BONE-RESORPTION; PERIPROSTHETIC OSTEOLYSIS; OSTEOCLAST FORMATION AB This review focuses on wear debris-mediated osteolysis, a major factor compromising the long-term success of total joint arthroplasty. Studies on retrieved implants and animal models, as well as in vitro studies on particle bioreactivity, Suggest that wear-mediated periprosthetic osteolysis is unlikely to be caused solely by 1 particular cell type or particulate species, but is rather the cumulative consequence of a number of biological reactions. Our recent findings Suggest 3 novel mechanisms of particle bioreactivity that may contribute to osteolysis: 1) exacerbated inflammation caused by elevated reactive oxygen species production by activated macrophages and osteoclasts, (2) impaired periprosthetic bone formation secondary to disrupted osteogenesis, and (3) compromised bone regeneration resulting from increased cytotoxic response of mesenchymal osteoprogenitor cells. Understanding the pathogenesis of wear-mediated osteolysis is needed to improve orthopedic implant biocompatibility and wear reduction, and to develop effective pharmacotherapies. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bldg 50,Room 1503,50 S Dr,MSC 8022, Bethesda, MD 20892 USA. NR 101 TC 51 Z9 53 U1 1 U2 10 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2004 VL 19 IS 8 BP 1028 EP 1038 DI 10.1016/j.arth.2004.03.024 PG 11 WC Orthopedics SC Orthopedics GA 881FS UT WOS:000225849400012 PM 15586339 ER PT J AU Thomason, LC Court, DL Datta, AR Khanna, R Rosner, JL AF Thomason, LC Court, DL Datta, AR Khanna, R Rosner, JL TI Identification of the Escherichia coli K-12 ybhE gene as pgl, encoding 6-phosphogluconolactonase SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BIFUNCTIONAL ENZYME; GENOME SEQUENCE; MUTANTS; SYSTEM; CLONING AB We report identification of the Escherichia coli ybhE gene as the pgl gene that encodes 6-phosphoglucono-lactonase. A tentative identification was first made based on the known approximate location of the pgl gene and the similarity of the presumptive ybhE-encoded protein sequence to a known Pgl enzyme. To test this notion, the ybhE gene was deleted and replaced with a drug marker. Like previously characterized pgl mutants, the ybhE deletion mutant had a Blu(-) phenotype (dark-blue staining with iodine due to accumulation of starch after growth on minimal maltose) and demonstrated impaired growth on minimal glucose medium when combined with a pgi mutation. Biochemical assay of crude extracts for 6-phosphogluconolactonase enzymatic activity showed that ybhE encodes this activity. The ybhE gene was transferred from the E. coli chromosome to an expression vector. This ybhE clone complemented both the precise deletion of the ybhE gene and a larger deletion, pglDelta8, for the Blu(-) phenotype and for phosphogluconolactonase activity, confirming that ybhE is the pgl gene. A newly observed phenotype of pgl strains is a lowered frequency of appearance of Bgl(+) mutants that can utilize the P-glucoside salicin. This is likely due to poor growth of Bgl(+) pgl strains on salicin due to the accumulation of 6-phosphogluconolactone. C1 NCI, Gene Regulat & Chromosome Biol Lab, Canc Res Ctr, Frederick, MD 21702 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Thomason, LC (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Canc Res Ctr, Bldg 539,Room 243, Frederick, MD 21702 USA. EM lthomason@ncifcrf.gov NR 22 TC 14 Z9 15 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2004 VL 186 IS 24 BP 8248 EP 8253 DI 10.1128/JB.186.24.8248-8253.2004 PG 6 WC Microbiology SC Microbiology GA 878TQ UT WOS:000225670300011 PM 15576773 ER PT J AU Davydov, IV Woods, D Safiran, YJ Oberoi, P Fearnhead, HO Fang, S Jensen, JP Weissman, AM Kenten, JH Vousden, KH AF Davydov, IV Woods, D Safiran, YJ Oberoi, P Fearnhead, HO Fang, S Jensen, JP Weissman, AM Kenten, JH Vousden, KH TI Assay for ubiquitin ligase activity: High-throughput screen for inhibitors of HDM2 SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE HDM2; Mdm2; ubiquitin; E3; p53 ID RIBOSOMAL-PROTEIN L11; TUMOR-SUPPRESSOR P53; ONCOPROTEIN MDM2; CANCER; PROTEASOME; EXPRESSION; DEGRADATION; ACTIVATION; APOPTOSIS; P14(ARF) AB An assay for the autoubiquitination activity of the E3 ligase HDM2 (Mdm2) was developed and adapted to a high-throughput formal to identify inhibitors of this activity. The assay can also be used to measure the activity of other E3s and may be useful in finding both inhibitors and activators of a wide range of different ubiquitin ligases. C1 Meso Scale Diagnost LLC, Meso Scale Discovery, Gaithersburg, MD USA. NCI, Regulat Cell Growth Lab, Canc Res Ctr, Frederick, MD 21701 USA. NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21701 USA. RP Vousden, KH (reprint author), Beatson Inst Canc Res, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland. EM k.vousden@beatson.gla.ac.uk RI Fang, Shengyun/H-3802-2011; Fearnhead, Howard/D-4826-2012; OI Fearnhead, Howard/0000-0002-8054-9794 NR 34 TC 33 Z9 34 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD DEC PY 2004 VL 9 IS 8 BP 695 EP 703 DI 10.1177/1087057104267956 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 882BS UT WOS:000225914100005 PM 15634796 ER PT J AU Nguyen, TL AF Nguyen, TL TI Three-dimensional model of the pore form of anthrax protective antigen. Structure and biological implications SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID LETHAL FACTOR; EDEMA FACTOR; CELLULAR RECEPTOR; ADENYLATE-CYCLASE; CRYSTAL-STRUCTURE; TOXIN RECEPTOR; BINDING; CHANNEL; MUTATIONS; IDENTIFICATION AB Although pore formation by protective antigen (PA) is critical to cell intoxication by anthrax toxin (AT), the structure of the pore form of PA (the PA63 pore) has not been determined. Hence, in this study, the PA63 pore was modeled using the X-ray structures of monomeric PA and heptameric alpha-hemolysin (alpha-HL) as templates. The PA63 pore model consists of two weakly associated domains, namely the cap and stem domains. The ring-like cap domain has a length of 80 Angstrom and an outside diameter of 120 Angstrom, while the cylinder-like stem domain has a length of 100 Angstrom and outside diameter of similar to28 Angstrom. This provides the PA63 pore model with a length of 180 Angstrom. Based on experimental results, the channel in the PA63 pore model was built to have a minimum diameter of similar to12 Angstrom, depending on side chain conformations. Because of its large size and structural complexity, the all-atom model of the PA63 pore is the end-stage construction of four separate modeling projects described herein. The final model is consistent with published experimental results, including mutational analysis and channel conductance experiments. In addition, the model was energetically and hydropathically refined to optimize molecular packing within the protomers and at the protomer-protomer interfaces. By providing atomic detail to biochemical and biophysical data, the PA63 pore model may afford new insights into the binding mode of PA on the membrane surface, the prepore-pore transition, and the mechanism of cell entry by anthrax toxin. C1 NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Nguyen, TL (reprint author), NCI, Dev Therapeut Program, 378 Ware Dr, Frederick, MD 21702 USA. EM nguyent@ncifcrf.gov FU NCI NIH HHS [Y3-CM-1005-05] NR 38 TC 44 Z9 45 U1 1 U2 4 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 2004 VL 22 IS 3 BP 253 EP 265 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 870TT UT WOS:000225081900001 PM 15473701 ER PT J AU Wu, G Marin-Garcia, J Rogers, TB Lakatta, EG Long, X AF Wu, G Marin-Garcia, J Rogers, TB Lakatta, EG Long, X TI Phosphorylation and hypoxia-induced heme oxygenase-1 gene expression in cardiomyocytes SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE hypoxia; heme oxygenase; protein kinases; protein phosphatases ID NF-KAPPA-B; CARDIAC MYOCYTES; CARBON-MONOXIDE; OKADAIC ACID; PROTEIN PHOSPHATASES; TRANSCRIPTIONAL ACTIVATION; HEAT-SHOCK; CELLS; RAT; KINASE AB Background: Heme oxygenase-1 (HO-1) is a stress protein and the rate-limiting enzyme in heme degradation. We sought to examine the notion that protein kinases and phosphatases through phosphorylation and dephosphorylation modulate the HO-1 expression in cardiomyocytes under hypoxic conditions. Methods and Results: Exposure of neonatal rat cardiomyocytes to hypoxia markedly induced the HO-1 expression, as assessed by Northern blot, Western blot, and transfection assay. The hypoxia-induced HO-1 expression was blocked by the kinase inhibitors staurosporine and SB202190 in a dose-dependent manner. Hypoxia decreased the activity of phosphatase-1 (PP-1). To examine the effect of PP-1 inhibition on HO-1 expression we used the phosphatase inhibitor okadaic acid (OA) and an antisense vector. OA treatment or overexpression of the antisense PP-1 transcript markedly induced HO-1 expression. Furthermore, transfection assay using HO-1 promoter constructs revealed the involvement of the nuclear factor kB (NF-kB) and Activator protein-1 (AP-1) in the hypoxia-induced activation of the HO-1 gene. The HO-1 promoter activity was modulated by OA under normoxic conditions or staurosporine under hypoxia. Conclusions: Our results suggest that activation of protein kinases and downregulation of PP-1 activity contribute to the hypoxia-induced HO-1 gene expression and that the proximal HO-1 promoter region containing NF-kB and AP-1 binding sites is likely to play a role in the transcriptional activation of the HO-1 gene in cardiomyocytes in response to hypoxic stress. C1 Mol Cardiol & Neuromuscular Inst, Highland Pk, NJ 08904 USA. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Long, X (reprint author), Mol Cardiol & Neuromuscular Inst, 75 Raritan Ave, Highland Pk, NJ 08904 USA. NR 51 TC 12 Z9 15 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2004 VL 10 IS 6 BP 519 EP 526 DI 10.1016/j.cardfail.2004.02.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 884QE UT WOS:000226100000011 PM 15599843 ER PT J AU Stacey, TTI Nie, ZZ Stewart, A Najdovska, M Hall, NE He, H Randazzo, PA Lock, P AF Stacey, TTI Nie, ZZ Stewart, A Najdovska, M Hall, NE He, H Randazzo, PA Lock, P TI ARAP3 is transiently tyrosine phosphorylated in cells attaching to fibronectin and inhibits cell spreading in a RhoGAP-dependent manner SO JOURNAL OF CELL SCIENCE LA English DT Article DE ARAP3; GTPase activating protein; Rho; Src-family kinase; fibronectin; adhesion ID GTPASE-ACTIVATING PROTEIN; FOCAL ADHESION KINASE; ACTIN CYTOSKELETON; C-SRC; BINDING-PROTEIN; ARF; FAMILY; INTEGRIN; ASAP1; SH3 AB ARAP3 is a GTPase activating protein (GAP) for Rho and Arf GTPases that is implicated in phosphoinositide 3-kinase (PI 3-kinase) signalling pathways controlling lamellipodia formation and actin stress fibre assembly. We have identified ARAP3 as a phosphorylated target of protein tyrosine kinases. In cells, ARAP3 was tyrosine phosphorylated when co-expressed with Src-family kinases (SFKs), upon stimulation with growth factors and during adhesion to the extracellular matrix (ECM) substrate fibronectin. Adhesion-induced phosphorylation of ARAP3 was suppressed by selective inhibitors of Src-family kinases and PI 3-kinase and by a Src dominant interfering mutant. Inducible expression of ARAP3 in HEK293 epithelial cells resulted in increased cell rounding, membrane process formation and cell clustering on ECM substrates. In contrast, ARAP3 dramatically slowed the kinetics of cell spreading on fibronectin but had no effect on cell adhesion. These effects of ARAP3 required a functional Rho GAP domain and were associated with reduced cellular levels of active RhoA and Rac1 but did not require the sterile alpha motif (SAM) or Arf GAP domains. Mutation of two phosphorylation sites, Y1399 and Y1404, enhanced some ARAP3 activities, suggesting that ARAP3 may be negatively regulated by phosphorylation on these tyrosine residues. These results implicate ARAP3 in integrin-mediated tyrosine kinase signalling pathways controlling Rho GTPases and cell spreading. C1 Univ Melbourne, Dept Surg, Royal Melbourne Hosp, Melbourne, Vic 3050, Australia. NCI, Cellular Oncol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Royal Melbourne Hosp, Cooperat Res Ctr Cellular Growth Factors, Melbourne, Vic 3050, Australia. Royal Melbourne Hosp, Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. Austin & Repatriat Med Ctr, Dept Surg, Melbourne, Vic 3084, Australia. RP Lock, P (reprint author), Univ Melbourne, Dept Surg, Royal Melbourne Hosp, Level 5 Clin Sci Bldg, Melbourne, Vic 3050, Australia. EM petelock@unimelb.edu.au NR 49 TC 27 Z9 28 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD DEC 1 PY 2004 VL 117 IS 25 BP 6071 EP 6084 DI 10.1242/jcs.01526 PG 14 WC Cell Biology SC Cell Biology GA 891OC UT WOS:000226589400014 ER PT J AU Jain, A Ma, CA Lopez-Granados, E Means, G Brady, W Orange, JS Liu, SY Holland, S Derry, JMJ AF Jain, A Ma, CA Lopez-Granados, E Means, G Brady, W Orange, JS Liu, SY Holland, S Derry, JMJ TI Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; HYPER-IGM SYNDROME; ECTODERMAL DYSPLASIA; IKK-GAMMA; AID; GENE; UBIQUITINATION; HYPERMUTATION AB Hypomorphic mutations in the zinc finger domain of NF-kappaB essential modulator (NEMO) cause X-linked hyper-IgM syndrome with ectodermal dysplasia (XHM-ED). Here we report that patient B cells are characterized by an absence of Ig somatic hypermutation (SHM) and defective class switch recombination (CSR) despite normal induction of activation-induced cytidine deaminase (AID) and Iepsilon-Cepsilon transcripts. This indicates that AID expression alone is insufficient to support neutralizing antibody responses. Furthermore, we show that patient B cells stimulated with CD40 ligand are impaired in both p65 and c-Rel activation, and whereas addition of IL-4 can enhance p65 activity, c-Rel activity remains deficient. This suggests that these NF-kappaB components have different activation requirements and that IL-4 can augment some but not all NEMO-dependent NF-kappaB signaling. Finally, using microarray analysis of patient B cells we identified downstream effects of impaired NF-kappaB activation and candidate factors that may be necessary for CSR and SHM in B cells. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Amgen Inc, Seattle, WA USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. RP Derry, JMJ (reprint author), NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM derryjmj@amgen.com RI Orange, Jordan/D-5239-2009; OI orange, jordan/0000-0001-7117-7725 NR 41 TC 59 Z9 60 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2004 VL 114 IS 11 BP 1593 EP 1602 DI 10.1172/JCI21345 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 876DK UT WOS:000225475900011 PM 15578091 ER PT J AU Horai, R Nakajima, A Habiro, K Kotani, M Nakae, S Matsuki, T Nambu, A Saijo, S Kotaki, H Sudo, K Okahara, A Tanioka, H Ikuse, T Ishii, N Schwartzberg, PL Abe, R Iwakura, Y AF Horai, R Nakajima, A Habiro, K Kotani, M Nakae, S Matsuki, T Nambu, A Saijo, S Kotaki, H Sudo, K Okahara, A Tanioka, H Ikuse, T Ishii, N Schwartzberg, PL Abe, R Iwakura, Y TI TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; DEPENDENT ANTIBODY-PRODUCTION; RHEUMATOID-ARTHRITIS; T-CELLS; SYNOVIAL INFLAMMATION; IL-17-DEFICIENT MICE; INTERLEUKIN-1; INDUCTION; JOINT AB IL-1 receptor antagonist-deficient (IL-1Ra(-/-)) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra(-/-) mice did not develop arthritis, and transfer of IL-1Ra(-/-) T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-alpha deficiency. We found that TNF-alpha induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-alpha plays an important role in activating T cells through induction of OX40. C1 Univ Tokyo, Inst Med Sci, Ctr Med Expt, Minato Ku, Tokyo 1088639, Japan. NHGRI, NIH, Bethesda, MD 20892 USA. Sci Univ Tokyo, Res Inst Biol Sci, Chiba, Japan. Santen Pharmaceut Co Ltd, Osaka 533, Japan. Tohoku Univ, Grad Sch Med, Dept Microbiol & Immunol, Sendai, Miyagi 980, Japan. RP Iwakura, Y (reprint author), Univ Tokyo, Inst Med Sci, Ctr Med Expt, Minato Ku, Tokyo 1088639, Japan. EM iwakura@ims.u-tokyo.ac.jp RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 29 TC 82 Z9 87 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2004 VL 114 IS 11 BP 1603 EP 1611 DI 10.1172/JCI200420742 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 876DK UT WOS:000225475900012 PM 15578092 ER PT J AU Miura, M Chen, XD Allen, MR Bi, YM Gronthos, S Seo, BM Lakhani, S Flavell, RA Feng, XH Robey, PG Young, M Shi, ST AF Miura, M Chen, XD Allen, MR Bi, YM Gronthos, S Seo, BM Lakhani, S Flavell, RA Feng, XH Robey, PG Young, M Shi, ST TI A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; OSTEOBLAST APOPTOSIS; IN-VITRO; EPITHELIAL-CELLS; CYCLE ARREST; MURINE MODEL; TNF-ALPHA; INHIBITION; MICE; ACTIVATION AB Caspase-3 is a critical enzyme for apoptosis and cell survival. Here we report delayed ossification and decreased bone mineral density in caspase-3-deficient (Casp3(-/-) and Casp3(+/-)) mice due to an attenuated osteogenic differentiation of bone marrow stromal stem cells (BMSSCs). The mechanism involved in the impaired differentiation of BMSSCs is due, at least partially, to the overactivated TGF-beta/Smad2 signaling pathway and the upregulated expressions of p53 and p21 along with the downregulated expressions of Cdk2 and Cdc2, and ultimately increased replicative senescence. In addition, the overactivated TGF-beta/Smad2 signaling may result in the compromised Runx2/Cbfa1 expression in preosteoblasts. Furthermore, we demonstrate that caspase-3 inhibitor, a potential agent for clinical treatment of human diseases, caused accelerated bone loss in ovariectomized mice, which is also associated with the overactivated TGF-beta/Smad2 signaling in BMSSCs. This study demonstrates that caspase-3 is crucial for the differentiation of BMSSCs by influencing TGF-beta/Smad2 pathway and cell cycle progression. C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN USA. Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Grp, Adelaide, SA 5000, Australia. Yale Univ, Sch Med, Immunol Sect, New Haven, CT USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Shi, ST (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 222,30 Convent Dr MSC-4320, Bethesda, MD 20892 USA. EM sshi@dir.nidcr.nih.gov RI Robey, Pamela/H-1429-2011; Allen, Matthew/A-8799-2015 OI Robey, Pamela/0000-0002-5316-5576; Allen, Matthew/0000-0002-1174-9004 NR 52 TC 132 Z9 148 U1 1 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2004 VL 114 IS 12 BP 1704 EP 1713 DI 10.1172/JCI200420427 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 879DE UT WOS:000225695800005 PM 15599395 ER PT J AU Shaheen, HI Khalil, SB Rao, MR Abu Elyazeed, R Wierzba, TF Peruski, LF Putnam, S Navarro, A Morsy, BZ Cravioto, A Clemens, JD Svennerholm, AM Savarino, SJ AF Shaheen, HI Khalil, SB Rao, MR Abu Elyazeed, R Wierzba, TF Peruski, LF Putnam, S Navarro, A Morsy, BZ Cravioto, A Clemens, JD Svennerholm, AM Savarino, SJ TI Phenotypic profiles of enterotoxigenic Escherichia coli associated with early childhood diarrhea in rural Egypt SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COLONIZATION FACTOR ANTIGENS; YOUNG-CHILDREN; MONOCLONAL-ANTIBODIES; IMMUNOSORBENT-ASSAY; PROSPECTIVE COHORT; ETEC; PREVALENCE; TRAVELERS; INFANTS; DISEASE AB Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed heat-labile enterotoxin (LT) alone, and 12% expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (We), CS14 (6%), and CS1 plus CS3 (4%). Fifty-nine percent of the strains did not express any of the 12 CFs included in our test panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim-sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to quinolone antibiotics was rarely detected. As for the distribution of observed serotypes, there was an unusually wide diversity of 0 antigens and H types represented among the 915 ETEC strains. The most commonly recognized composite ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal episodes associated with ETEC strains bearing common composite phenotypes were consistent with discrete community outbreaks either within a single or over successive warm seasons. These data suggest that a proportion of the disease that is endemic to young children in rural Egypt represents the confluence of small epidemics by clonally related ETEC strains that are transiently introduced or that persist in a community reservoir. C1 USN, Med Res Ctr, Silver Spring, MD 20910 USA. USN, Med Res Unit 3, Cairo, Egypt. Egyptian Minist Hlth & Populat, Abu Homos, Beheira Governo, Egypt. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Natl Autonomous Univ Mexico, Mexico City 04510, DF, Mexico. Int Vaccine Inst, Seoul, South Korea. Univ Gothenburg, Dept Med Microbiol & Immunol, Gothenburg, Sweden. RP Savarino, SJ (reprint author), USN, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM savarinos@nmrc.navy.mil FU NICHD NIH HHS [Y1-HD-0026-01] NR 44 TC 70 Z9 74 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2004 VL 42 IS 12 BP 5588 EP 5595 DI 10.1128/JCM.42.12.5588-5595.2004 PG 8 WC Microbiology SC Microbiology GA 883SK UT WOS:000226035800025 PM 15583286 ER PT J AU Anderson, BD Adamson, PC Weiner, SL McCabe, MS Smith, MA AF Anderson, BD Adamson, PC Weiner, SL McCabe, MS Smith, MA TI Tissue collection for correlative studies in childhood cancer clinical trials: Ethical considerations and special imperatives SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RISK; PERCEPTIONS; PHYSICIANS; CHILDREN AB Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families. C1 NCI, Canc Therapy Evaluat Program, Rockville, MD 20892 USA. Childrens Cause Inc, Silver Spring, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Childrens Oncol Grp, Phase Consortium 1, Arcadia, CA USA. RP Anderson, BD (reprint author), NCI, Canc Therapy Evaluat Program, 6130 Execut Blvd,EPN 7025, Rockville, MD 20892 USA. EM andersonb@ctep.nci.nih.gov NR 19 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2004 VL 22 IS 23 BP 4846 EP 4850 DI 10.1200/JCO.2004.02.138 PG 5 WC Oncology SC Oncology GA 886NW UT WOS:000226236600027 PM 15570088 ER PT J AU Jatoi, I Soballe, PW Anderson, WF AF Jatoi, I Soballe, PW Anderson, WF TI Delayed benefit of mammography screening in premenopausal women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID BREAST-CANCER C1 USN, Med Ctr, Dept Surg, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, NCI, Bethesda, MD 20814 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Jatoi, I (reprint author), USN, Med Ctr, Dept Surg, Bethesda, MD 20814 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2004 VL 22 IS 23 BP 4860 EP 4860 DI 10.1200/JCO.2004.99.017 PG 1 WC Oncology SC Oncology GA 886NW UT WOS:000226236600033 PM 15570095 ER PT J AU Chiu, CC Lane, HY Huang, MC Liu, HC Jann, MW Hon, YY Chang, WH Lu, ML AF Chiu, CC Lane, HY Huang, MC Liu, HC Jann, MW Hon, YY Chang, WH Lu, ML TI Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE olonzapine; fluvoxamine; drug interactions; schizophrenia ID ANTIPSYCHOTIC AGENT OLANZAPINE; SEROTONIN REUPTAKE INHIBITORS; IN-VITRO; DEPRESSIVE SYMPTOMS; HEALTHY-VOLUNTEERS; DRUG-INTERACTION; CLOZAPINE; PLASMA; DISPOSITION; SMOKING AB Olonzapine, an atypical antipsychotic agent, is a substrate Of the cytochrome P4501A2 (CYP1A2) enzyme. Administration of a potent CYP1A2 inhibitor (eg, fluvoxamine) may alter the pharmacokinetics of olanzapine. This study investigated the pharmacokinetic interactions between olanzapine and fluvoxamine in patients with schizophrenia. Ten male smokers were administrated a single dose of olanzapine 10 mg at baseline, followed by 2 weeks of fluvoxomine 50 mg/day and another 2 weeks of fluvoxamine 100 mg/day. Olanzapine 10 mg was given at day 10 during each fluvoxamine treatment. After pretreatment with fluvoxamine, the area under the curve, maximal plasma concentration, and half-time of olanzapine were significantly increased by 30% to 55%, 12% to 64%, and 25% to 32%, respectively. Volume of distribution and apparent clearance were significantly reduced by 4% to 26% and 26% t O 38%, respectively, after administration of fluvoxamine. Increases in area under the plasma concentration-time curve from time 0 to infinity appear to be dose dependent. Presumably, altered olanzapine pharmacokinetics are attributed to the inhibition of CYP1A2. Patients treated with the combination of olanzapine and fluvoxamine should be monitored carefully. C1 Taipei Med Univ, Wan Fang Hosp, Dept Psychiat, Taipei, Taiwan. Taipei City Psychiat Ctr, Lab Biol Psychiat, Taipei, Taiwan. China Med Univ & Hosp, Dept Psychiat, Taichung, Taiwan. Hung Chi Psychiat Hosp, Taipei, Taiwan. Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, Atlanta, GA USA. Natl Inst Hlth, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD USA. Tzu Chi Univ, Hualien, Taiwan. Dalin Tzu Chi Gen Hosp, Dept Psychiat, Hualien, Taiwan. RP Lu, ML (reprint author), Taipei Med Univ, Wan Fang Hosp, Dept Psychiat, 111,Hsin Long Rd Sec 3, Taipei, Taiwan. NR 33 TC 18 Z9 18 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2004 VL 44 IS 12 BP 1385 EP 1390 DI 10.1177/0091270004270291 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 871YV UT WOS:000225173500006 PM 15545309 ER PT J AU Dionne, RA Haynes, D Brahim, JS Rowan, JS Guivarch, PH AF Dionne, RA Haynes, D Brahim, JS Rowan, JS Guivarch, PH TI Analgesic effect of sustained-release flurbiprofen administered at the site of tissue injury in the oral surgery model SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE nonsteroidal anti-inflammatory drugs; flurbiprofen; analgesia; postoperative pain ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POSTSURGICAL DENTAL PAIN; DOUBLE-BLIND; EFFICACY; PLACEBO; ASPIRIN; KIDNEY; RISK; ACETAMINOPHEN; KETOPROFEN AB Nonsteroidal anti-inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues. The authors evaluated the therapeutic potential of administering a sustained-release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity. Subjects (N = 98) received 1 of 8 treatments: flurbiprofen in a microparticle formulation in doses of 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, or 50 mg; PO flurbiprofen 25 mg or 50 mg, or placebo, The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery (removal of 2 lower impacted third molars). The sum of the pain visual analog scale over the 6-hour observation period demonstrated significantly less pain (P < .05) for flurbiprofen microparticle in comparison with placebo. Fewer subjects remedicated in the flurbiprofen microparticle drug groups, primarily for the 12.5-mg and higher doses. The incidence of adverse effects and local complications did not differ across groups. These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Pharma Log, Miami, FL USA. SkyePharma Canada, Quebec City, PQ, Canada. RP Dionne, RA (reprint author), NIDCR, NIH, 10 Ctr Dr 1N-103, Bethesda, MD 20892 USA. NR 23 TC 6 Z9 9 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2004 VL 44 IS 12 BP 1418 EP 1424 DI 10.1177/009127000426703 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 871YV UT WOS:000225173500011 PM 15545314 ER PT J AU Agwale, SM Tanimoto, L Womack, C Odama, L Leung, K Duey, D Negedu-Momoh, R Audu, I Mohammed, SB Inyang, U Graham, B Ziermann, R AF Agwale, SM Tanimoto, L Womack, C Odama, L Leung, K Duey, D Negedu-Momoh, R Audu, I Mohammed, SB Inyang, U Graham, B Ziermann, R TI Prevalence of HCV coinfection in HIV-infected individuals in Nigeria and characterization of HCV genotypes SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV; HCV; HIV /HCV coinfection; HCV genotypes; VERSANT((R)) HCV qualitative assay (TMA); VERSANT((R)) HCV genotyping assay (LiPA) ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION-MEDIATED AMPLIFICATION; CLINICAL-TRIALS GROUP; LINE PROBE ASSAY; QUALITATIVE DETECTION; RNA; PROGRESSION; SPECIMENS; AIDS AB Background: Coinfection with hepatitis C virus (HCV) in individuals infected with HIV is associated with a higher incidence of liver injury, hepatic decompensation, and decreased survival time than that seen in an HIV-monoinfected population. While prevalence studies on HIV/HCV coinfection have been performed in the U.S. and in some European countries, little is known about coinfection rates in Africa. Design: Retrospectively collected specimens from 146 confirmed HIV-positive individuals in Nigeria who had access to antiretroviral therapy (ART) were tested for HCV RNA, using the VERSANT(R) HCV RNA qualitative assay (TMA), and, if HCV RNA-positive, for HCV genotype using the VERSANT(R) HCV genotype assay (LiPA). Results: Twelve out of the 146 individuals tested (8.2%) were HCV positive. Nine of the 12 HCV-positive individuals were infected with HCV genotype 1 (five 1a, three 1b, one non-subtypable) and three were infected with HCV genotype 2 (all non-subtypable). Coinfected individuals were more likely to be male, older, and have lower CD4+ cell counts than HIV-monoinfected individuals, although none of the differences reached statistical significance. Conclusion: The results highlight the potential public health impact of HCV infection in Nigeria, where anti-HCV testing is generally not performed in HIV-infected populations or in most blood transfusion centers. (C) 2004 Elsevier B.V. All rights reserved. C1 Bayer Healthcare LLC, Div Diagnost, Berkeley, CA 94720 USA. Bayer Reference Testing Lab, Berkeley, CA 94702 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Gede AIDS & Infect Dis Res Inst, Wuse, Abuja, Nigeria. RP Ziermann, R (reprint author), Bayer Healthcare LLC, Div Diagnost, POB 2466, Berkeley, CA 94720 USA. EM rainer.ziermann.b@bayer.com NR 17 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2004 VL 31 SU 1 BP S3 EP S6 DI 10.1016/j.jcv.2004.09.001 PG 4 WC Virology SC Virology GA 880YO UT WOS:000225826700002 PM 15567088 ER PT J AU Kuznetsov, VA Stepanov, VS Berzofsky, JA Belyakov, IM AF Kuznetsov, VA Stepanov, VS Berzofsky, JA Belyakov, IM TI Assessment of the relative therapeutic effects of vaccines on virus load and immune responses in small groups at several time points: efficacy of mucosal and subcutaneous polypeptide vaccines in rhesus macaques exposed to SHIV SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE SHIV; virus load; CD4; CD8; mucosal and subcutaneous vaccines; relative treatment effect; rank test; non-parametric repeated measures ANOVA; longitudinal data analysis; small groups ID HUMAN-IMMUNODEFICIENCY-VIRUS; FACTORIAL-DESIGNS; NEW-GENERATION; INFECTION; AIDS; TESTS AB Background: Due to the high cost, subject availability and ethical constraints, it is often critically important in pre-clinical and clinical studies to carry out an adequate statistical analysis of longitudinal multivariate data over several time points in trials in several small groups. Objectives: We aim to accurately assess and develop an appropriate distribution-free longitudinal model for an estimate of the comparative treatment effects of several biological factors in several small groups even if data sets should contain outlier measurements and censored values. This approach is used to evaluate the relative efficacy of mucosal and subcutaneous polypeptide vaccines in rhesus macaques exposed to SHIV. Study design: The algorithms of the non-parametric repeated measures ANOVA models [Mack GA. A quick and easy distribution-free test for main effects in a two-factor ANOVA. Communic Stat Part B: Simp Comp 1981;10:571-91; Akritas MG, Brunner, E. A unified approach to rank tests for mixed models. J Star Plan Inference 1997;61:249-77; Brunner E, Puri ML. Nonparametric methods in factorial designs. Stat Pap 2001;42:1-52.] are described, programmed and assessed. The viral loads, CD4(+) and CD8(+) cell counts were analyzed at several time points in peripheral blood of the 11 MamuA*01 positive macaques intrarectally challenged with pathogenic SHIV-Ku2 and immunized intrarectally with synthetic HIV/SIV peptide vaccine. Results: Using nonparametric ANOVA tests, we demonstrated with statistical significance that after intrarectal challenge with pathogenic SHIV-Ku2, intrarectally immunized monkeys expressed viral titers that fell below the level of detection in blood and intestine (which is a major reservoir of viral replication), whereas the subcutaneously immunized or control macaques had residual viraemia. Moreover, the proliferative response of T cells and both CD4(+) and CD8(+) cells were better preserved in intrarectally immunized animals. Robustness of the comparisons was confirmed by gradual removal of up to 50% of data points. Conclusion: Despite limited data, our analysis shows better preservation of both CD4(+) and CD8(+) cells in intrarectally immunized animals. The result is consistent with our hypothesis that mucosal immunization is more effective than systemic immunization and that an induction of specific CTLs in the intestinal mucosa, a key site of virus replication, with a mucosal AIDS vaccine ameliorates SHIV infection in non-human primates. Our analytical methodology can be applicable in comparative estimates of the different treatment-associated effects and their synergy for a variety of longitudinal data sets in small treatment groups. (C) 2004 Elsevier B.V. All rights reserved. C1 SRA Inc, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Russian Acad Sci, Cent Econ & Math Inst, Moscow 117418, Russia. NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Bethesda, MD 20892 USA. RP Kuznetsov, VA (reprint author), SRA Inc, 12A S Dr,Rm 1018, Bethesda, MD 20892 USA. EM kuznetsv@mail.nih.gov NR 14 TC 5 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2004 VL 31 SU 1 BP S69 EP S82 DI 10.1016/j.jcv.2004.09.006 PG 14 WC Virology SC Virology GA 880YO UT WOS:000225826700011 PM 15567097 ER PT J AU Nason, M Emerson, S LeBlanc, M AF Nason, M Emerson, S LeBlanc, M TI CARTscans: A tool for visualizing complex models SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE bagging; boosting; classification and regression trees; color coding; graphics; linear regression; random forests; visualization AB We present CARTscans, a graphical tool that displays predicted values across. a four-dimensional subspace. We show how these plots are useful for understanding the structure and relationships between variables in a wide variety of models. including (but not limited to) regression trees, ensembles of trees, and linear regressions with varving degrees of interactions. In addition, the common visualization framework allows diverse complex models to be visually compared in a way that illuminates the similarities and differences in the underlying methods, facilitates the choice of a particular model structure, and provided a useful check for implausible predictions of future observations in regions With little or no data. C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Nason, M (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM mnason@niaid.nih.gov NR 13 TC 5 Z9 5 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD DEC PY 2004 VL 13 IS 4 BP 807 EP 825 DI 10.1198/106186004X11417 PG 19 WC Statistics & Probability SC Mathematics GA 879SO UT WOS:000225739400005 ER PT J AU Karki, RG Tang, Y Burke, TR Nicklaus, MC AF Karki, RG Tang, Y Burke, TR Nicklaus, MC TI Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE docking; drug-design; human immunodeficiency virus; integrase; molecular modeling ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHOTO-CROSS-LINKING; METAL-DEPENDENT INHIBITION; ACTIVE-SITE; CATALYTIC DOMAIN; BINDING DOMAIN; CRYSTAL-STRUCTURE; IN-VITRO; HYDRODYNAMIC PROPERTIES; TERMINAL DOMAINS AB We report structural models of the full-length integrase enzyme (IN) of the human immunodeficiency virus type 1 (HIV-1) and its complex with viral and human DNA. These were developed by means of molecular modeling techniques using all available experimental evidence, including X-ray crystallographic and NMR structures of portions of the full-length protein. Special emphasis was placed on obtaining a model of the enzyme's active site with the viral DNA apposed to it, based on the hypothesis that such a model would allow structure-based design of inhibitors that retain activity in vivo. This was because bound DNA might be present in vivo after 3'-processing but before strand transfer. These structural models were used to study the potential binding modes of various diketo-acid HIV-1 IN inhibitors (many of them preferentially inhibiting strand transfer) for which no experimentally derived complexed structures are available. The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3'-processed end of the viral DNA to human DNA. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. RP Nicklaus, MC (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, 376 Boyles St, Frederick, MD 21702 USA. EM mn1@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014; OI Nicklaus, Marc/0000-0002-4775-7030 NR 79 TC 49 Z9 55 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD DEC PY 2004 VL 18 IS 12 BP 739 EP 760 DI 10.1007/s10822-005-0365-5 PG 22 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 940JZ UT WOS:000230142100001 PM 16075307 ER PT J AU Guillon, J Reynolds, RC Leger, JM Guie, MA Massip, S Dallemagne, P Jarry, C AF Guillon, J Reynolds, RC Leger, JM Guie, MA Massip, S Dallemagne, P Jarry, C TI Synthesis and preliminary in vitro evaluation of antimycobacterial activity of new pyrrolo[1,2-a]quinoxaline-carboxylic acid hydrazide derivatives SO JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY LA English DT Article; Proceedings Paper CT 12th European Conferene of Pharmacochemistry Grouping of the Atlantic Arc (GP2A) CY 2003 CL La Rochelle, FRANCE DE pyrrolo[1,2-a]quinoxaline-carboxylic acid hydrazide derivatives; Mycobacterium tuberculosis; antimycobacterial agents; tuberculosis ID MYCOBACTERIUM-AVIUM; CYANOBORANE ADDUCTS; TUBERCULOSIS AB New pyrrolo[1,2-a]quinoxaline-2- or -4-carboxylic acid hydrazide derivatives were synthesized from nitroaniline or 1,2-phenylenediamine, and evaluated in vitro for their antimycobacterial activity as part of a TAACF TB screening program. Two compounds 7c and 13 showed an interesting activity at 6.25 mug/mL against Mycobacterium tuberculosis H(37)Rv, with a 94 and 100 percentage inhibition, respectively. C1 Univ Bordeaux 2, UFR Sci Pharmaceut, EA Pharmacochim 2962, F-33076 Bordeaux, France. NIAID, TAACF, So Res Inst, Birmingham, AL 35255 USA. Univ Caen, UFR Sci Pharmaceut, Ctr Etud & Rech Med Normandie, F-14032 Caen, France. RP Jarry, C (reprint author), Univ Bordeaux 2, UFR Sci Pharmaceut, EA Pharmacochim 2962, 146 Rue Leo Saignat, F-33076 Bordeaux, France. EM christian.jarry@chimphys.u-bordeaux2.fr RI Dallemagne, Patrick/D-3237-2013 OI Dallemagne, Patrick/0000-0002-4845-615X NR 25 TC 23 Z9 25 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1475-6366 J9 J ENZYM INHIB MED CH JI J. Enzym. Inhib. Med. Chem. PD DEC PY 2004 VL 19 IS 6 BP 489 EP 495 DI 10.1080/14756360412331280464 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 883SO UT WOS:000226036200007 PM 15662953 ER PT J AU Allhusen, V Belsky, J Booth-LaForce, C Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Houts, R Huston, A Kelly, JF Lanza, S Marshall, N McCartney, K O'Brien, M Parke, R Payne, C Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M AF Allhusen, V Belsky, J Booth-LaForce, C Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Houts, R Huston, A Kelly, JF Lanza, S Marshall, N McCartney, K O'Brien, M Parke, R Payne, C Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M CA Natl Inst Child Hlth Human Dev TI Fathers' and mothers' parenting behavior and beliefs as predictors of children's social adjustment in the transition to school SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE mother-child relationships; father-child relationships; parental beliefs; transition to school; child adjustment ID PATERNAL INVOLVEMENT; HYPERACTIVITY; INFANCY AB The current study focuses on the association between children's social adjustment in the transition to school and the early elementary school years and their fathers' and mothers' parenting behaviors and beliefs and quality of marital relationship. The authors found that the most competent and least problematic children from the teachers' perspectives are those whose fathers are sensitive and supportive of their children's autonomy, whose mothers' parenting beliefs support self-directed child behavior, and whose parents maintain an emotionally intimate relationship. These findings have implications for efforts to prevent early school problems in children and support the children's transitions into formal schooling. C1 Univ N Carolina, NICHD, Early Child Res Network, Chapel Hill, NC 27599 USA. RP Cox, M (reprint author), Univ N Carolina, NICHD, Early Child Res Network, 100 E Franklin St,CB 8115, Chapel Hill, NC 27599 USA. EM martha_cox@unc.edu RI Marshall, Nancy/C-3428-2012 NR 39 TC 3 Z9 3 U1 2 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD DEC PY 2004 VL 18 IS 4 BP 628 EP 638 DI 10.1037/0893-3200.18.4.628 PG 11 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 879DX UT WOS:000225697700008 ER PT J AU Pan, D Stroncek, DF Whitley, CB AF Pan, D Stroncek, DF Whitley, CB TI Improved gene transfer and normalized enzyme levels in primitive hematopoietic progenitors from patients with mucopolysaccharidosis type I using a bioreactor SO JOURNAL OF GENE MEDICINE LA English DT Article DE hollow-fiber bioreactor; stem cell; gene therapy; retroviral; mucopolysaccharidosis; long-term in vitro hematopoiesis ID LONG-TERM CULTURES; RETROVIRAL VECTOR TRANSDUCTION; PERIPHERAL-BLOOD LYMPHOCYTES; STEM-CELL TRANSPLANTATION; HOLLOW-FIBER BIOREACTOR; APE LEUKEMIA-VIRUS; EX-VIVO EXPANSION; HUMAN BONE-MARROW; CORD-BLOOD; CD34(+) CELLS AB Background One of the major barriers to the clinical application of hematopoietic stem cell (HSC) gene therapy has been relatively low gene transfer efficiency. Other inadequacies of current transduction protocols are related to their multi-step procedures. e.g., using tissue-culture flasks, roller bottles or gas-permeable bags for clinical application. Methods In comparison with a conventional bag transduction protocol. a 'closed' hollow-fiber bioreactor system (HBS) was exploited to culture and transduce human peripheral blood CD34(+) progenitor cells (PBPCMPS) from patients with mucopolysaccharidosis type I (MPS 1) using an amphocropic 0 retroviral vector based on a murine Moloney leukemia virus UN protocype. Both short-term colony-forming cell (CFC) and long-term culture initiating cell (LTCIC) assays were employed to determine transduction frequency and transgene expression in committed progenitor cells and primitive progenitors with multi-lineage potentials. Results A novel ultrafiltration-transduction method was established to culture and transduce enzyme-deficient PBPCMPS over a 5-day period without loss in viability and CD34 identity (n = 5). Significantly higher transduction efficiencies were achieved in primary CFC that derived from the HBS (5.8-14.2%) in comparison wich those from gas-permeable bags (undetectable to 1.7%; p < 0.01). Up to 15-fold higher-than-normal enzyme activity was found in selected PBPCMPS-LP1CD transductants. higher gene transfer (4.4-fold) and expression in very primitive progenitors were observed in products from the HBS compared with bag experiments as indicated by CFC derived from primitive LTCIC. Remarkably, with relatively modest gene transfer levels in LTCIC from HBS experiments. the expression of the IDUA transgene corrected the enzyme-deficiency in 5-week long-term cultures (LTC). Conclusions MPS I progenitor cells achieved normalized enzyme levels in LTC after transduction in a HBS system. These studies demonstrate the advantages of a bioreactor-transducton system for viral-mediated stem cell gene transfer. Copyright (C) 2004 John Wiley Sons. Ltd. C1 Univ Minnesota, Dept Pediat, Gene Therapy Program, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Pan, D (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Expt Hematol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM Dao.Pan@cchmc.org FU NICHD NIH HHS [P01-HD32652] NR 55 TC 5 Z9 5 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD DEC PY 2004 VL 6 IS 12 BP 1293 EP 1303 DI 10.1002/jgm.621 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 887SX UT WOS:000226326900001 PM 15538732 ER PT J AU Holman, WL Park, SJ Long, JW Weinberg, A Gupta, L Tierney, AR Adamson, RM Watson, JD Raines, EP Couper, GS Pagani, FD Burton, NA Miller, LW Naka, Y AF Holman, WL Park, SJ Long, JW Weinberg, A Gupta, L Tierney, AR Adamson, RM Watson, JD Raines, EP Couper, GS Pagani, FD Burton, NA Miller, LW Naka, Y CA REMATCH invest TI Infection in permanent circulatory support: Experience from the REMATCH trial SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID VENTRICULAR ASSIST DEVICE; MULTICENTER CLINICAL-EVALUATION; HEART-TRANSPLANTATION; SYSTEM; IMPLANTATION AB Background: This analysis of the REMATCH Trial focuses on infection, which was an important source of morbidity and mortality. We use the information to suggest ways to decrease the incidence and effects of device-related infection. Methods: Patients were randomized prospectively to receive left ventricular assist devices (LVADs) or optimal medical management (OMM) for end-stage heart failure. Infection variables included sepsis adjudicated as the cause of death; sepsis reported as a serious adverse event; percutaneous site or pocket infection; and pump housing, inflow- or outflow-tract infection. We compared the incidence and prevalence of events between groups and generated time-related descriptions. Results: Survival with LVAD (n = 68 patients) was superior to OMM survival (n = 61 patients) with a 47% decrease in risk of death (p < 0.001), but the aggregate adverse event rate was greater for patients with LVADs (risk ratio, 2.29; 95% confidence interval, 1.85-2.84). Freedom from sepsis in patients with LVADs was 58% at 1 year and 48% at 2 years after implantation with superior survival in non-septic patients (60% vs 39% at 1 year and 38% vs 8% at 2 years in non-septic vs septic patients with LVADs, p < 0.06). Percutaneous site or pocket infection did not affect survival (p = 0.86). The hazard for onset of sepsis peaked within the first 3 weeks after implantation. Conclusions: Survival is improved with permanent LVAD implantation compared with OMM therapy. However, infection causes substantial morbidity and mortality. Decreasing infections will increase survival and decrease morbidity in permanent LVAD recipients and will improve the risk-benefit ratio for permanent LVAD therapy. Copyright (C) 2004 by the International Society for Heart and Lung Transplantation. C1 Univ Alabama, Birmingham, AL USA. Univ Minnesota, Minneapolis, MN USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. Columbia Univ, Int Ctr Hlth Outcomes & Innovat Res, New York, NY USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. Bryan LGH Heart Inst, Lincoln, NE USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Fairfax Hosp, Annandale, VA USA. NIH, Bethesda, MD 20892 USA. RP Holman, WL (reprint author), Dept Surg, ZRB 719,703 S 19th St, Birmingham, AL 35294 USA. EM wholman@its.uab.edu NR 16 TC 112 Z9 113 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2004 VL 23 IS 12 BP 1359 EP 1365 DI 10.1016/j.healun.2003.09.025 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 884LS UT WOS:000226087100006 PM 15607664 ER PT J AU Dong, ZJ Wei, HM Sun, R Hu, ZQ Gao, B Tian, ZG AF Dong, ZJ Wei, HM Sun, R Hu, ZQ Gao, B Tian, ZG TI Involvement of natural killer cells in PolyI : C-induced liver injury SO JOURNAL OF HEPATOLOGY LA English DT Article DE liver injury; inflammation; VCAM-1; interleukin 12; natural killer cells ID A-INDUCED HEPATITIS; POLYINOSINIC-POLYCYTIDYLIC ACID; PRONE BB RAT; CONCANAVALIN-A; T-CELLS; NK CELLS; INTERFERON-GAMMA; IFN-GAMMA; MEDIATED HEPATITIS; KUPFFER CELLS AB Background/Aims: The roles of T cells, natural killer T cells (NKT) and macrophages in autoimmune hepatitis have been well documented. However, the roles of natural killer (NK) cells in liver injury remain obscure. Here we examined the effect of Polyinosinic: polycytidylic acid (PolyI:C)-activated NK cells on liver injury. Methods: Mice were intraperitoneally injected with PolyI:C at a dose of 20 mug/g body wt. The percentage and absolute number of NK cells in the liver were analyzed with flow cytometry. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) assay and H-E staining were used to evaluate the liver injury. Results: Following PolyI:C injection, NK cells accumulation and activation occurred in the liver. Meanwhile, slight elevation of ALT/AST in the serum, mild inflammation and focal necrosis in the liver were also observed. Depletion of NK cells markedly attenuated PolyI:C-induced liver injury. Neutralization of endogenous Interleukin-12 produced by Kupffer cells abrogated the accumulation of NK cells in the liver and subsequent liver injury. The liver injury was also alleviated by neutralization of vascular cell adhesive molecule-1. Conclusions: These findings suggest that PolyI:C preferentially recruits and activates hepatic NK cells, which may be responsible for the mild hepatitis. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. Shandong Univ, Sch Pharm, Shandong 250012, Peoples R China. Showa Univ, Sch Med, Dept Microbiol & Immunol, Shinagawa Ku, Tokyo 1428555, Japan. NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), Univ Sci & Technol China, Sch Life Sci, 443 Huangshan Rd, Hefei 230027, Anhui, Peoples R China. EM bgao@mail.nih.gov; ustctzg@yahoo.com.cn RI Tian, Zhigang/J-3512-2013 NR 49 TC 70 Z9 82 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD DEC PY 2004 VL 41 IS 6 BP 966 EP 973 DI 10.1016/j.jhep.2004.08.021 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882CG UT WOS:000225915600012 PM 15582130 ER PT J AU Devadas, K Hardegen, NJ Wahl, LM Hewlett, IK Clouse, KA Yamada, KM Dhawan, S AF Devadas, K Hardegen, NJ Wahl, LM Hewlett, IK Clouse, KA Yamada, KM Dhawan, S TI Mechanisms for macrophage-mediated HIV-1 induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED U1 CELLS; LONG TERMINAL REPEAT; FACTOR-ALPHA; T-CELLS; ENDOTHELIAL-CELLS; TNF-ALPHA AB Viral latency is a long-term pathogenic condition in patients infected with HIV-1. Low but sustained virus replication in chronically infected cells can be activated by stimulation with proinflammatory cytokines such as TNF-alpha, IL-1 beta, or other host factors. However, the precise mechanism by which cellular activation induces. latently infected cells to produce virions has remained unclear. In the present report, we present evidence that activation of HIV-1 replication in latently infected U1 or ACH2 cells by human macrophages is mediated by a rapid nuclear localization of NF-kappaB p50/p65 dimer with concomitant increased expression of proinflammatory cytokines. Multiplexed RT-PCR amplification of mRNA isolated from cocultures of macrophages and U1 and ACH2 cells showed significant induction of IL-1beta, IL-6, IL-8, TNF-alpha, and TGF-beta expression within 3 h of coincubation. Fixation of macrophages, U-1, or ACH2 cells with paraformaldehyde before coculture completely abrogated the induction of NF-kappaB subunits and HIV-1 replication, suggesting that cooperative interaction between the two cell types is an essential process for cellular activation. Pretreatment of macrophage-U1 or macrophage-ACH2 cocultures with neutralizing anti-TNF-alpha Ab down-regulated the replication of HIV-1. In addition, pretreatment of macrophage-U1 or macrophage-ACH2 cocultures with the NF-kappaB inhibitor (E)3-[(4-methylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7082) prevented the induction of cytokine expression, indicating a pivotal role of NF-kappaB-mediated signaling in the reactivation of HIV-1 in latently infected cells by macrophages. These results provide a mechanism by which macrophages induce HIV-1 replication in latently infected cells. C1 US FDA, Immunopatholgenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Dev Mech Sect, Cranofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Devadas, K (reprint author), US FDA, Immunopatholgenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. EM devadas@cber.fda.gov; dhawan@cber.fda.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 66 TC 27 Z9 28 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2004 VL 173 IS 11 BP 6735 EP 6744 PG 10 WC Immunology SC Immunology GA 873UV UT WOS:000225307500030 PM 15557166 ER PT J AU Davis, BJ Flanagan, BF Gilfillan, AM Metcalfe, DD Coleman, JW AF Davis, BJ Flanagan, BF Gilfillan, AM Metcalfe, DD Coleman, JW TI Nitric oxide inhibits IgE-dependent cytokine production and fos and jun activation in mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA; ALVEOLAR MACROPHAGES; INTERFERON-GAMMA; LIPOPOLYSACCHARIDE; DEGRANULATION; INFLAMMATION; EXPRESSION; SYNTHASE; RELEASE; PATHWAY AB NO is a cell-derived radical reported to inhibit mast cell degranulation and subsequent allergic inflammation, although whether its action is nonspecific or occurs via specific molecular mechanisms remains unknown. To examine this question, we set out to determine whether NO inhibits mast cell cytokine production, and, if so, whether it also alters Fcis an element ofRI-dependent signal transduction. As hypothesized, the radical inhibited IgE/Ag-induced IL-4, IL-6, and TNF production. Although NO did not influence phosphorylated JNK, p38 MAPK, or p44/42 MAPK, it did inhibit phosphorylation of phospholipase Cgamma1 and the AP-1 transcription factor protein c-Jun, but not NF-kappaB or CREB. NO further completely abrogated IgE/Ag-induced DNA-binding activity of the nuclear AP-1 proteins Fos and Jun. These results show that NO is capable of inhibiting Fcis an element ofRI-dependent mast cell cytokine production at the level of gene regulation, and suggest too that NO may contribute to resolution of allergic inflammation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Liverpool, Dept Pharmacol, Liverpool L69 3BX, Merseyside, England. Univ Liverpool, Dept Immunol, Liverpool L69 3BX, Merseyside, England. RP Coleman, JW (reprint author), NIAID, Lab Allerg Dis, NIH, Room 11C213,Bldg 10, Bethesda, MD 20892 USA. EM jwcoleman@niaid.nih.gov NR 40 TC 34 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2004 VL 173 IS 11 BP 6914 EP 6920 PG 7 WC Immunology SC Immunology GA 873UV UT WOS:000225307500051 PM 15557187 ER PT J AU Brown, KE Liu, ZW Gallinella, G Wong, S Mills, IP O'Sullivan, MG AF Brown, KE Liu, ZW Gallinella, G Wong, S Mills, IP O'Sullivan, MG TI Simian parvovirus infection: A potential zoonosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Society-for-Virology CY JUL 20-24, 2002 CL LEXINGTON, KY SP Amer Soc Virol ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TRANSIENT APLASTIC-ANEMIA; B19 PARVOVIRUS; TRANSPLANT RECIPIENTS; CYNOMOLGUS MONKEYS; CELL-LINE; IDENTIFICATION; RHESUS; PERSISTENT; MACAQUES AB Introduction. Simian parvovirus (SPV) causes severe anemia in immunocompromised macaques. The closely related erythrovirus, parvovirus B19, causes anemia in susceptible humans and can be grown in human bone marrow mononuclear cells in vitro. We hypothesized that SPV may infect humans and replicate in human bone marrow mononuclear cells. Methods. Serum samples from handlers of an SPV-seropositive macaque colony were tested by Western blot for evidence of antibodies to SPV. SPV capsid protein was expressed in insect cells, and SPV was cultured in human and macaque bone marrow mononuclear cells. Results. Fifty-one percent of exposed handlers (n = 65) were found to be SPV seropositive, compared with 35% of nonexposed individuals (n = 124). In 17% of exposed handlers, compared with 6% of nonexposed individuals, antibodies were directed to SPV but not to B19. SPV capsid proteins, like those of B19, self- assembled to form parvovirus-like particles, and these capsids, like B19 capsids, bound to globoside, suggesting that globoside is also the receptor for SPV. We demonstrated that SPV could replicate in vitro in both human and macaque bone marrow mononuclear cells and that it was cytotoxic to erythroid progenitor cells. Conclusions. Our data suggest that SPV may infect human bone marrow mononuclear cells in vitro and in vivo and should be considered a potential zoonosis. C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Comparat Med Res Ctr, Winston Salem, NC USA. RP Brown, KE (reprint author), NHLBI, NIH, Hematol Branch, Bldg 10 Room CRC-3-5130,9000 Rockville Pike, Bethesda, MD 20892 USA. EM brownk@nhlbi.nih.gov NR 38 TC 17 Z9 17 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2004 VL 190 IS 11 BP 1900 EP 1907 DI 10.1086/425420 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 870GO UT WOS:000225045800003 PM 15529252 ER PT J AU Nag, P Kim, J Sapiega, V Landay, AL Bremer, JW Mestecky, J Reichelderfer, P Kovacs, A Cohn, J Weiser, B Baum, LL AF Nag, P Kim, J Sapiega, V Landay, AL Bremer, JW Mestecky, J Reichelderfer, P Kovacs, A Cohn, J Weiser, B Baum, LL TI Women with cervicovaginal antibody-dependent cell-mediated cytotoxicity have lower genital HIV-1 RNA loads SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th Conference on Retroviruses and Opportunistic Infection CY FEB 24-28, 2002 CL SEATTLE, WA ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX-VIRUS; TYPE-1 RNA; TRACT; INFECTION; QUANTITATION; PLASMA; FEMALE; AIDS; IGA AB Antibodies that mediate human immunodeficiency virus (HIV)-specific antibody-dependent cell-mediated cytotoxicity ( ADCC) are present in the cervical fluid of many HIV-positive women; however, the role that these antibodies play in host defense against HIV is not known. To understand the contribution of ADCC in cervical secretions as a protective mechanism against HIV, we evaluated ADCC titers in paired serum and cervical-lavage (CVL) samples from >300 HIV-1-positive women who participated in the multicenter Division of AIDS Treatment Research Initiative Study 009. The present study demonstrates that women with CVL ADCC activity had lower genital viral loads than did women with serum ADCC activity only. Women with CVL ADCC activity were likely to have HIV-1 gp120-specific immunoglobulin (Ig) G, but not IgA, in their cervical fluid. This finding suggests that specific IgG in cervical fluid can mediate ADCC activity that inversely correlates with genital viral load. C1 Rosalind Franklin Univ Med & Sci, Dept Microbiol & Immunol, N Chicago, IL 60064 USA. Lutheran Gen Hosp, Park Ridge, IL 60068 USA. Rush Med Coll, Dept Immunol Microbiol, Chicago, IL 60612 USA. Univ Alabama, Birmingham, AL USA. NICHD, Rockville, MD USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Wayne State Univ, Sch Med, Detroit, MI USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. RP Baum, LL (reprint author), Rosalind Franklin Univ Med & Sci, Dept Microbiol & Immunol, 3333 Green Bay Rd, N Chicago, IL 60064 USA. EM linda.baum@rosalindfranklin.edu FU NIAID NIH HHS [N01 AI 15123, R01 AI052065, R01 AI052065-01]; NICHD NIH HHS [P01 HD 40539, P01 HD040539] NR 31 TC 47 Z9 49 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2004 VL 190 IS 11 BP 1970 EP 1978 DI 10.1086/425582 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 870GO UT WOS:000225045800013 PM 15529262 ER PT J AU Ribeiro, JMC AF Ribeiro, JMC TI Bugs, blood, and blisters SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material C1 NIAID, Rockville, MD USA. RP Ribeiro, JMC (reprint author), NIAID, Rockville, MD USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 6 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2004 VL 123 IS 6 BP XVI EP XVI DI 10.1111/j.0022-202X.2004.23483.x PG 1 WC Dermatology SC Dermatology GA 875QL UT WOS:000225436700004 PM 15610501 ER PT J AU Diaz, LA Arteaga, LA Hilario-Vargas, J Valenzuela, JG Li, N Warren, S Aoki, V Hans-Filho, G Eaton, D dos Santos, V Nutman, TB de Mayolo, AA Qaqish, BF Sampaio, SAP Rivitti, EA AF Diaz, LA Arteaga, LA Hilario-Vargas, J Valenzuela, JG Li, N Warren, S Aoki, V Hans-Filho, G Eaton, D dos Santos, V Nutman, TB de Mayolo, AA Qaqish, BF Sampaio, SAP Rivitti, EA CA Cooperative Grp Fogo Selvegem Res TI Anti-desmoglein-1 antibodies in onchocerciasis, leishmaniasis and chagas disease suggest a possible etiological link to fogo selvagern SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoantibody; chagas; desmogleins; etiology; fogo selvagem; leishmaniasis; onchocerciasis; pemphigus ID ENDEMIC PEMPHIGUS FOLIACEUS; ENVIRONMENTAL RISK-FACTORS; AMERINDIAN RESERVATION; HIGH PREVALENCE; DESMOGLEIN 1; AUTOANTIBODIES; BRAZIL; SPECIFICITY; DISTINCT; EPITOPE AB Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem (FS) are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS. C1 NIAID, Parasit Dis Labs, Bethesda, MD 20892 USA. Univ Sao Paulo, Dept Dermatol, Sao Paulo, Brazil. Univ Fed Mato Grosso Sul, Dept Dermatol, Campo Grande, Brazil. Univ Peruana Cayetano Heredia, Dept Pathol, Lima, Peru. Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. RP Diaz, LA (reprint author), Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. EM ldiaz@med.unc.edu RI Aoki, Valeria/H-1415-2012; OI Hilario-Vargas, Julio/0000-0002-8656-6843 FU NIAMS NIH HHS [R01-AR30281, R01-AR32599, T32 AR07369] NR 29 TC 40 Z9 42 U1 3 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2004 VL 123 IS 6 BP 1045 EP 1051 DI 10.1111/j.0022-202X.2004.23438.x PG 7 WC Dermatology SC Dermatology GA 875QL UT WOS:000225436700015 PM 15610512 ER PT J AU McBride, C AF McBride, C TI The JIM interview - Colleen McBride, PhD SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 NHGRI, SBRB, NIH, Bethesda, MD USA. RP McBride, C (reprint author), NHGRI, SBRB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD DEC PY 2004 VL 52 IS 8 BP 489 EP 491 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 887TD UT WOS:000226327500001 PM 15682680 ER PT J AU Mosher, J Hingson, R Bunker, JF Bonnie, RJ AF Mosher, J Hingson, R Bunker, JF Bonnie, RJ TI Reducing underage drinking: The role of law SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article; Proceedings Paper CT Conference on the Publics Health and the Law in the 21st Century CY JUN 14-16, 2004 CL Atlanta, GA SP Amer Soc Law Med Ethics, Ctr Disease Control Prevention, US Dept Hlth Human Serv C1 Pacific Inst Rech & Educ, Div Legal Policy & Anal, Calverton, MD USA. NIAAA, NIH, Bethesda, MD USA. New Futures, Portsmouth, Hants, England. Univ Virginia, Inst Law Psychiat & Publ Policy, Charlottesville, VA USA. RP Mosher, J (reprint author), Pacific Inst Rech & Educ, Div Legal Policy & Anal, Calverton, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, SUITE 1634, BOSTON, MA 02215 USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 2004 VL 32 IS 4 SU S BP 38 EP 41 DI 10.1111/j.1748-720X.2004.tb00182.x PG 4 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 890RL UT WOS:000226528400010 PM 15807321 ER PT J AU Sconocchia, G Fujiwara, H Rezvani, K Keyvanfar, K El Ouriaghli, F Grube, M Melenhorst, J Hensel, N Barrett, AJ AF Sconocchia, G Fujiwara, H Rezvani, K Keyvanfar, K El Ouriaghli, F Grube, M Melenhorst, J Hensel, N Barrett, AJ TI G-CSF-mobilized CD34+ cells cultured in interleukin-2 and stem cell factor generate a phenotypically novel monocyte SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE NK cells; monocyles/macrophages; cellular proliferation; cellular differentiation ID NATURAL-KILLER-CELLS; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW PROGENITORS; CORD BLOOD; NK CELLS; DENDRITIC CELLS; IMMATURE PROGENITORS; ACUTE-LEUKEMIA; IN-VITRO; DIFFERENTIATION AB To study the early stages of development from stem cells of the CD56+ cell population [which includes natural killer (NK) cells], granulocyte-colony stimulating factor-mobilized peripheral blood CD34+ cells from healthy donors were sorted to >99% purity and cultured in the presence of stem cell factor and interleukin (IL)-2. After 3 weeks in culture, the majority of cells acquired CD33, with or without human leukocyte antigen-DR and CD14. In 20 stem cell donors tested, 8.7 +/- 8.8% of cells were CD56+. Two major CD56+ subsets were identified: CD56(bright), mainly CD33- cells (7 +/- 10%, n=11) with large, granular lymphocyte morphology, and CD56(dim), mainly CD33+ (2.5 +/- 2, n=11) cells with macrophage morphology. The CD56(bright) population had cytoplasmic granzyme A but lacked killer inhibitory receptor, suggesting they were immature NK cells. The CD56(dim), CD33+, population lacked NK markers. They may represent a minor subset of normal monocytes at a developmental stage comparable with the rare CD56+ CD33+ hybrid myeloid/NK cell leukemia. Consistent with a monocyte nature, CD56(dim)CD33+ proliferated and produced a variety of cytokines upon lipopolysaccharide stimulation, including IL-8, IL-6, monocyte chemoattractant protein-1, and macrophage-derived chemokine but not interferon-gamma. In a short-term cytotoxicity assay, they failed to kill but powerfully inhibited the proliferation of the NK-resistant cell line P815. The generation of CD56+ cells was negatively regulated by hyaluronic acid and IL-4, indicating that extracellular matrix may play an important role in the commitment of CD34+ cells into CD56 myeloid and lymphoid lineages. C1 NHLBI, Hematol Branch, Hematopoiet Stem Cell Transplant Sect, NIH, Bethesda, MD 20892 USA. RP Sconocchia, G (reprint author), NHLBI, Hematol Branch, Hematopoiet Stem Cell Transplant Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM giuseppe.sconocchia@roswellpark.org NR 32 TC 15 Z9 15 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2004 VL 76 IS 6 BP 1214 EP 1219 DI 10.1189/jlb.0504278 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 877IM UT WOS:000225561600017 PM 15345723 ER PT J AU Skwor, TA Cho, HS Cassidy, C Yoshimura, T McMurray, DN AF Skwor, TA Cho, HS Cassidy, C Yoshimura, T McMurray, DN TI Recombinant guinea pig CCL5 (RANTES) differentially modulates cytokine production in alveolar and peritoneal macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE IL-1 beta; lipopolysaccharide; TNF-alpha; CXCL8; CCL2 ID TUMOR-NECROSIS-FACTOR; BOVIS BCG VACCINATION; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MESSENGER-RNA EXPRESSION; FACTOR-ALPHA; TNF-ALPHA; GENE-EXPRESSION; IN-VIVO; MURINE ALVEOLAR; IL-10 SYNTHESIS AB The CC chemokine ligand 5 (CCL5; regulated on activation, normal T expressed and secreted) is known to recruit and activate leukocytes; however, its role in altering the responses of host cells to a subsequent encounter with a microbial pathogen has rarely been studied. Recombinant guinea pig (rgp)CCL5 was prepared, and its influence on peritoneal and alveolar macrophage activation was examined by measuring cytokine and chemokine mRNA expression in cells stimulated with rgpCCL5 alone or exposed to rgpCCL5 prior to lipopolysaccharide (LPS) stimulation. Levels of mRNA for guinea pig tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, CCL2 (monocyte chemoattractant protein-1), and CXC chemokine ligand 8 (IL-8) were analyzed by reverse transcription followed by real-time polymerase chain reaction analysis using SYBR Green. Bioactive TNF-alpha protein concentration was measured using the L929 bioassay. Both macrophage populations displayed significant enhancement of all the genes and TNF-a protein levels when stimulated with rgpCCL5, except for CCL2 in alveolar macrophages. When peritoneal or alveolar macrophages were pretreated with rgpCCL5 for 2 h and then exposed to low concentrations of LPS, diminished cytokine and chemokine mRNA levels were apparent at 6 h compared with LPS alone. At the protein level, there was a reduction in TNF-a protein at 6 h in the CCL5-pretreated cells compared with LPS alone. These results further support a role for CCL5 in macrophage activation in addition to chemotactic properties and suggest a role in regulating the inflammatory response to LPS in the guinea pig by modulating the production of proinflammatory cytokines by macrophages. C1 Texas A&M Univ, Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. Inst Biosci & Technol, Houston, TX USA. NCI, Frederick, MD 21701 USA. RP Skwor, TA (reprint author), Texas A&M Univ, Hlth Sci Ctr, Dept Med Microbiol & Immunol, 407 Reynolds Med Bldg, College Stn, TX 77843 USA. EM skwor@medicine.tamu.edu FU NIAID NIH HHS [R01 AI 15495] NR 66 TC 24 Z9 24 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2004 VL 76 IS 6 BP 1229 EP 1239 DI 10.1189/jlb.0704414 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 877IM UT WOS:000225561600019 PM 15377675 ER PT J AU Martinez, M Brice, A Vaughan, JR Zimprich, A Breteler, MMB Meco, G Filla, A Farrer, MJ Betard, C Hardy, J De Michele, G Bonifati, V Oostra, B Gasser, T Wood, NW Durr, A AF Martinez, M Brice, A Vaughan, JR Zimprich, A Breteler, MMB Meco, G Filla, A Farrer, MJ Betard, C Hardy, J De Michele, G Bonifati, V Oostra, B Gasser, T Wood, NW Durr, A CA French Parkinsons Dis Genetics Stu European Consortium Genetic Susc TI Genome-wide scan linkage analysis for Parkinson's disease: the European genetic study of Parkinson's disease SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID EARLY-ONSET PARKINSONISM; ALPHA-SYNUCLEIN; CHROMOSOME 2P13; COMPLEX TRAITS; PARK3 LOCUS; MUTATIONS; FAMILIES; GENEPD; TESTS; MAPS AB Objective: To undertake a full genome-wide screen for Parkinson's disease susceptibility loci. Methods: A genome-wide linkage study was undertaken in 227 affected sibling pairs from 199 pedigrees with Parkinson's disease. The pedigree sample consisted of 188 pedigrees from five European countries, and 11 from the USA. Individuals were genotyped for 391 microsatellite markers at similar to10 cM intervals throughout the genome. Multipoint model-free affected sibling pair linkage analyses were carried out using the MLS (maximum LOD score) test. Results: There were six chromosomal regions with maximum MLS peaks of 1 or greater (pointwise p<0.018). Four of these chromosomal regions appear to be newly identified regions, and the highest MLS values were obtained on chromosomes 11q (MLS = 1.60, at 91 cM, D11S4175) and 7p (MLS = 1.51, at 5 cM, D7S531). The remaining two MLS peaks, on 2p11-q12 and 5q23, are consistent with excess sharing in regions reported by other studies. The highest MLS peak was observed on chromosome 2p11-q12 (MLS = 2.04, between markers D2S2216 and D2S160), within a relatively short distance (, 17 cM) from the PARK3 region. Although a stronger support of linkage to this region was observed in the late age of onset subgroup of families, these differences were not significant. The peak on 5q23 (MLS = 1.05, at 130 cM, D5S471) coincides with the region identified by three other genome scans. All peak locations fell within a 10 cM distance. Conclusions: These stratified linkage analyses suggest linkage heterogeneity within the sample across the 2p11-q12 and 5q23 regions, with these two regions contributing independently to Parkinson's disease susceptibility. C1 INSERM EM100 06, Unite Rech, F-91068 Evry, France. INSERM, U289, Paris, France. Hop La Pitie Salpetriere, Dept Genet Cytogenet & Embryol, Paris, France. Charing Cross Hosp, Dept Neurol, London, England. Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, D-72074 Tubingen, Germany. Erasmus Univ, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Univ Roma La Sapienza, Dept Neurol Sci, Rome, Italy. Univ Naples Federico 2, Dept Neurol Sci, Naples, Italy. Mayo Clin Jacksonville, Neurogenet Lab, Jacksonville, FL USA. Ctr Natl Genotypage, Evry, France. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. UCL, Inst Neurol, Dept Mol Neurosci, London, England. RP Martinez, M (reprint author), INSERM EM100 06, Unite Rech, Tour Evry 2,523 Pl Terrasses Agora, F-91068 Evry, France. EM maria@evry.inserm.fr RI Hardy, John/C-2451-2009; Wood, Nicholas/C-2505-2009; Breteler, Monique /J-5058-2014; Martinez, Maria/B-3111-2013 OI Wood, Nicholas/0000-0002-9500-3348; Martinez, Maria/0000-0003-2180-4537 FU NINDS NIH HHS [NS41723-01A1, P01 NS40256] NR 43 TC 32 Z9 32 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 2004 VL 41 IS 12 BP 900 EP 907 DI 10.1136/jmg.2004.022632 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 878UW UT WOS:000225673600003 PM 15591275 ER PT J AU Griffin, KJ Kirschner, LS Matyakhina, L Stergiopoulos, SG Robinson-White, A Lenherr, SM Weinberg, FD Claflin, ES Batista, D Bourdeau, I Voutetakis, A Sandrini, F Meoli, EM Bauer, AJ Cho-Chung, YS Bornstein, SR Carney, JA Stratakis, CA AF Griffin, KJ Kirschner, LS Matyakhina, L Stergiopoulos, SG Robinson-White, A Lenherr, SM Weinberg, FD Claflin, ES Batista, D Bourdeau, I Voutetakis, A Sandrini, F Meoli, EM Bauer, AJ Cho-Chung, YS Bornstein, SR Carney, JA Stratakis, CA TI A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: Comparison with Carney complex and other PRKAR1A induced lesions SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; CUSHINGS-SYNDROME; CYCLIC-AMP; RI-ALPHA; I-ALPHA; MUTATIONS; GENE; GROWTH; CELLS; MICE AB Background: Inactivation of the human type Ialpha regulatory subunit (RIalpha) of cyclic AMP dependent protein kinase (PKA) (PRKAR1A) leads to altered kinase activity, primary pigmented nodular adrenocortical disease (PPNAD), and sporadic adrenal and other tumours. Methods and results: A transgenic mouse carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline responsive promoter (the Tg(Prkar1a*x2as)1Stra, Tg(tTAhCMV)3Uh or tTA/X2AS line) developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia and other features reminiscent of PPNAD, including late onset weight gain, visceral adiposity, and non-dexamethasone suppressible hypercorticosteronaemia, with histiocytic, epithelial hyperplasias, lymphomas, and other mesenchymal tumours. These lesions were associated with allelic losses of the mouse chromosome 11 Prkar1a locus, an increase in total type II PKA activity, and higher RIIbeta protein levels; the latter biochemical and protein changes were also documented in Carney complex tumours associated with PRKAR1A inactivating mutations and chromosome 17 PRKAR1A locus changes. Conclusion: We conclude that the tTA/X2AS mouse line with a downregulated Prkar1a gene replicates several of the findings in Carney complex patients and their affected tissues, supporting the role of RIa as a candidate tumour suppressor gene. C1 NICHD, SEGEN, DEB, NIH,CRC, Bethesda, MD 20892 USA. NCI, Cellular Biochem Sect, BRL, CCR, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Internal Med, Div Endocrinol, D-40225 Dusseldorf, Germany. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Griffin, KJ (reprint author), NICHD, SEGEN, DEB, NIH,CRC, 1-3330,MSC1103,10 Ctr Dr, Bethesda, MD 20892 USA. EM griffiku@mail.nih.gov; stratakc@mail.nih.gov RI Levesque, Isabelle/A-1899-2012; Kirschner, Lawrence/E-3392-2011; OI Claflin, Edward/0000-0003-4142-0047; Lenherr, Sara/0000-0002-4162-1546 NR 32 TC 80 Z9 83 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 2004 VL 41 IS 12 BP 923 EP 931 DI 10.1136/jmg.2004.028043 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 878UW UT WOS:000225673600006 PM 15591278 ER PT J AU Goker-Alpan, O Schiffmann, R LaMarca, ME Nussbaum, RL McInerney-Leo, A Sidransky, E AF Goker-Alpan, O Schiffmann, R LaMarca, ME Nussbaum, RL McInerney-Leo, A Sidransky, E TI Parkinsonism among Gaucher disease carriers SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MUTATIONS; RISK AB An association between Gaucher disease and Parkinson disease has been demonstrated by the concurrence of Gaucher disease and parkinsonism in rare patients and the identification of glucocerebrosidase mutations in probands with sporadic Parkinson disease. Using a different and complementary approach, we describe 10 unrelated families of subjects with Gaucher disease where obligate or confirmed carriers of glucocerebrosidase mutations developed parkinsonism. These observations indicate that mutant glucocerebrosidase, even in heterozygotes, may be a risk factor for the development of parkinsonism. Understanding the relationship between altered glucocerebrosidase and the development of parkinsonian manifestations will provide insights into the genetics, pathogenesis, and treatment of Parkinson disease. C1 NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Sect Mol Neurogenet, NIH, 35 Convent Dr MSC 3708,35-1A213, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 15 TC 140 Z9 144 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 2004 VL 41 IS 12 BP 937 EP 940 DI 10.1136/jmg.2004.024455 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 878UW UT WOS:000225673600008 PM 15591280 ER PT J AU Sidtis, DV Hanson, W Jackson, C Lanto, A Kempler, D Metter, EJR AF Sidtis, DV Hanson, W Jackson, C Lanto, A Kempler, D Metter, EJR TI Fundamental frequency (F0) measures comparing speech tasks in aphasia and Parkinson disease SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article; Proceedings Paper CT Conference on Motor Speech CY MAR, 2004 CL Albuquerque, NM ID BROCAS APHASIA; DYSARTHRIA; INTONATION; PROSODY AB Mean fundamental frequency (F0) and F0 variability were studied in Broca, Wernicke, anomic aphasic, Parkinson, and normal control subjects, performing four speech tasks: reading, conversation, counting, and sustained vowel phonation (mean F0 only). The groups differed significantly on both measures, and a significant task by group interaction was observed for F0 mean. The higher F0 mean in clinical groups and the effect of task on performance suggest that further information is needed to understand brain processes underlying prosodic function. C1 NYU, Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. Sepulveda VA Med Ctr, Los Angeles, CA USA. Los Angeles Kaiser Permanente Hosp, Los Angeles, CA USA. Emerson Coll, Boston, MA 02116 USA. NIA, Intramural Res Program, Bethesda, MD 20892 USA. RP Sidtis, DV (reprint author), Nathan S Kline Inst Psychiat Res, Div Geriatr, Bldg 35,140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. EM drv1@nyu.edu NR 20 TC 5 Z9 5 U1 0 U2 2 PU DELMAR LEARNING PI CLIFTON PARK PA EXECUTIVE WOODS, 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD DEC PY 2004 VL 12 IS 4 BP 207 EP 212 PG 6 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 877IT UT WOS:000225562500015 ER PT J AU Park, JH Ju, SK Park, JS Park, YK Kang, MH You, KH AF Park, JH Ju, SK Park, JS Park, YK Kang, MH You, KH TI The effect of overexpression of rat clusterin in L929 fibroblasts SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE apoptosis; clusterin; green fluorescent protein; oxidants ID OXIDATIVE STRESS; CELL-DEATH; IN-VITRO; APOLIPOPROTEIN J/CLUSTERIN; MESSENGER-RNA; EXPRESSION; THYMOCYTES; PROTECTS; GENE AB Oxidants such as hydrogen peroxide are powerful inducers of cell damage, ageing, and apoptosis. Since clusterin, a 75-80 kDa mammalian glycoprotein, is frequently found to be inducible in apoptotic cells and tissues, this study inquired into whether this would be a protective mechanism against further cell death. The aim was to find out whether overexpression of clusterin could protect cells from oxidant-induced stress and apoptosis. To clarify this issue, we generated and analyzed stable cell lines expressing fusion proteins of a rat clusterin with an enhanced green fluorescent protein (EGFP). When treated with varying concentrations of hydrogen peroxides, clusterin transfectants indeed showed increased resistance to apoptosis and exhibited a much higher survival rate than mock-transfected cells. On the other hand, neither intracellular re-distribution nor local concentration of clusterin-EGFP was observed, which leaves the question open about its anti-apoptotic mechanism. In conclusion, the overexpression of clusterin provides a means for protecting cells against oxidative stress and subsequent cell death. C1 Chungnam Natl Univ, Sch Biosci & Biotechnol, Taejon 305764, South Korea. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Hannam Univ, Dept Food & Nutr, Taejon 306791, South Korea. RP You, KH (reprint author), Chungnam Natl Univ, Sch Biosci & Biotechnol, Taejon 305764, South Korea. EM khyou@cnu.ac.kr NR 22 TC 0 Z9 1 U1 1 U2 2 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD DEC PY 2004 VL 14 IS 6 BP 1333 EP 1337 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 883IQ UT WOS:000226005200033 ER PT J AU Mills, EM Rusyniak, DE Sprague, JE AF Mills, EM Rusyniak, DE Sprague, JE TI The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE 3,4-methylenedioxymethamphetamine; rhabdomyolysis; hyperthermia; uncoupling proteins UCP-3 ID NEUROLEPTIC MALIGNANT SYNDROME; BROWN ADIPOSE-TISSUE; MITOCHONDRIAL PROTON LEAK; METHAMPHETAMINE-INDUCED HYPERTHERMIA; SEROTONIN SYNDROME; SKELETAL-MUSCLE; THYROID-HORMONE; MDMA ECSTASY; BETA-3-ADRENERGIC AGONIST; CLINICAL-PHARMACOLOGY AB Body temperature regulation involves a homeostatic balance between heat production and dissipation. Sympathetic agents such as 3,4-methylenedioxymethamphetarnine (MDMA, ecstasy) can disrupt this balance and as a result produce an often life-threatening hyperthermia. The hyperthermia induced by MDMA appears to result from the activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-thyroid/adrenal axis. Norepinephrine release mediated by MDMA creates a double-edged sword of heat generation through activation of uncoupling protein (UCP3) along with alpha(1)- and beta(3)-adrenoreceptors and loss of heat dissipation through SNS-mediated vasoconstriction. This review examines cellular mechanisms involved in MDMA-induced thermogenesis from UCP activation to vasoconstriction and how these mechanisms are related to other thermogenic conditions and potential treatment modalities. C1 Virginia Polytech Inst & State Univ, Edward Via Virginia Coll Osteopath Med, Blacksburg, VA 24060 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24060 USA. RP Sprague, JE (reprint author), Virginia Polytech Inst & State Univ, Edward Via Virginia Coll Osteopath Med, 2265 Kraft Dr, Blacksburg, VA 24060 USA. EM jsprague@vcom.vt.edu OI Rusyniak, Daniel/0000-0002-6199-0840 NR 157 TC 49 Z9 49 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD DEC PY 2004 VL 82 IS 12 BP 787 EP 799 DI 10.1007/s00109-004-0591-7 PG 13 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 902EB UT WOS:000227333800003 PM 15602689 ER PT J AU Chadwick, LR Nikolic, D Burdette, JE Overk, CR Bolton, JL van Breemen, RB Frohlich, R Fong, HHS Farnsworth, NR Pauli, GF AF Chadwick, LR Nikolic, D Burdette, JE Overk, CR Bolton, JL van Breemen, RB Frohlich, R Fong, HHS Farnsworth, NR Pauli, GF TI Estrogens and congeners from spent hops (Humulus lupulus) SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID LIQUID-CHROMATOGRAPHY; PRENYLATED FLAVONOIDS; NMR-SPECTROSCOPY; XANTHOHUMOL; PRENYLFLAVONOIDS; CHALCONES; BEER; OLIGOSACCHARIDES; ELUCIDATION; FLAVANONES AB Estrogenicity-directed fractionation of a methanol extract of the strobiles of Humulus lupulus that had been extracted previously with supercritical CO2, known as "spent hops", led to the isolation and identification of 22 compounds including 12 prenylated chalcones (1-8, 10-13), five prenylflavanones (14-17), 4-hydroxybenzaldehyde (18), sitosterol-3-O-beta-glueopyranoside (19), humulmone (20), and coliumulmone (21). In addition, the prenylated chalcone xanthohumol C (9a) was obtained as a 6:1 mixture along with its 1",2"-dihydro derivative (9b). Three new chalcones (4, 11, 12) and four previously unreported constituents of hops (5, 6, 9b, 13) are reported. The structures of the new compounds were determined through a combination of spectrometric techniques including 1D and 2D NMR, HRESIMS, and ESIMS-MS. Full H-1 NMR spin system analyses were performed to characterize the higher-order glueopyranosyl, prenyl, and chalcone B-ring spectra of the isolates. The principle estrogen 8-prenyl-naringenin (15) from hops is an artifact formed along with its positional isomer 6-prenylnaringenin (16) through the spontaneous isomerization of the pro-estrogenic chalcone DMX (7). C1 Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Dept Med Chem & Pharmacognosy,Coll Pharm, Chicago, IL 60612 USA. Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. RP Pauli, GF (reprint author), Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Dept Med Chem & Pharmacognosy,Coll Pharm, Chicago, IL 60612 USA. EM gfp@uic.edu OI Pauli, Guido/0000-0003-1022-4326 FU NCCIH NIH HHS [P50 AT00155] NR 44 TC 61 Z9 66 U1 3 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2004 VL 67 IS 12 BP 2024 EP 2032 DI 10.1021/np049783i PG 9 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 884FQ UT WOS:000226070600012 PM 15620245 ER PT J AU Kozlovsky, N Shanon-Weickert, C Tomaskovic-Crook, E Kleinman, JE Belmaker, RH Agam, G AF Kozlovsky, N Shanon-Weickert, C Tomaskovic-Crook, E Kleinman, JE Belmaker, RH Agam, G TI Reduced GSK-3 beta mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Glycogen Synthase Kinase (GSK)-3; mRNA; schizophrenia ID GLYCOGEN-SYNTHASE KINASE-3; NEURODEVELOPMENTAL HYPOTHESIS; MOLECULAR-CLONING; GENE-EXPRESSION; FRONTAL-CORTEX; PATHWAY; CATENIN; BRAINS; WNTS AB Glycogen Synthase Kinase (GSK)-3 is a ubiquitous serine/threonine protein kinase highly abundant in brain which plays a key role in neural development and neuron survival. We have previously reported that GSK-3beta protein levels and GSK-3 activity are reduced by over 40% in postmortem prefrontal cortex of schizophrenic patients compared to patients with bipolar illness, unipolar depression and to normal controls, and Emamian et al. have recently presented convergent evidence for impaired AKT1-GSK-3beta signaling in schizophrenia. Using specimens of dorsolateral prefrontal cortex tissue obtained from The Stanley Medical Research Institute's Brain Collection, from the same subjects used previously, we now show that GSK-3beta, but not GSK-3beta, mRNA levels are 36% lower in the patients with schizophrenia compared to all other comparison groups. The present study lends further support to the finding of low GSK-3beta levels in schizophrenia and extends this observation by suggesting that the decrease in GSK-3beta may be due to reduced protein synthesis possibly due to altered transcriptional drive of the GSK-3beta gene. C1 Mental Hlth Ctr, Psychiat Res Unit, IL-84170 Beer Sheva, Israel. Ben Gurion Univ Negev, Stanley Res Ctr, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, Beer Sheva, Israel. NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Agam, G (reprint author), Mental Hlth Ctr, Psychiat Res Unit, POB 4600, IL-84170 Beer Sheva, Israel. EM galila@bgumail.bgu.ac.il RI Shannon Weickert, Cynthia/G-3171-2011; Tomaskovic-Crook, Eva/C-9339-2016 OI Tomaskovic-Crook, Eva/0000-0002-7818-9013 NR 42 TC 62 Z9 65 U1 0 U2 2 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD DEC PY 2004 VL 111 IS 12 BP 1583 EP 1592 DI 10.1007/s00702-004-0166-3 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 873VY UT WOS:000225310700007 PM 15565492 ER PT J AU DeMar, JC Ma, KZ Bell, JM Rapoport, SI AF DeMar, JC Ma, KZ Bell, JM Rapoport, SI TI Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE brain; deprivation; docosahexaenoic; n-3 polyunsaturated fatty acids; phospholipids; rat ID ALPHA-LINOLENIC ACID; RANDOMIZED CONTROLLED-TRIAL; AGE-RELATED-CHANGES; ARACHIDONIC-ACID; SIGNAL-TRANSDUCTION; TERM INFANTS; IN-VIVO; UNANESTHETIZED RATS; ALZHEIMERS-DISEASE; MAMMALIAN BRAIN AB Male rat pups (21 days old) were placed on a diet deficient in n-3 polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing alpha-linolenic acid (alpha-LNA; 18 : 3n-3). After 15 weeks on a diet, [4,5-H-3]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral cerebral ventricle, and the rats were killed at fixed times over a period of 60 days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by plotting log(10) (DHA radioactivity) against time after tracer injection, equaled 33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in phosphatidylserine; all had a decay slope significantly greater than 0 (p < 0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or greater, and calculated rates of DHA loss from brain, J(out), were reduced. Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and to do so even more effectively in the face of reduced n-3 PUFA availability for only 15 weeks. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP DeMar, JC (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6 N202, Bethesda, MD 20892 USA. EM demarj@mail.nih.gov NR 105 TC 121 Z9 127 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2004 VL 91 IS 5 BP 1125 EP 1137 DI 10.1111/j.1471-4159.2004.02789.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 873FG UT WOS:000225264700010 PM 15569256 ER PT J AU Bosetti, F Langenbach, R Weerasinghe, GR AF Bosetti, F Langenbach, R Weerasinghe, GR TI Prostaglandin E-2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A(2) SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE arachidonic acid; cyclooxygenase; cytosolic phospholipase A(2); knockout; prostaglandin E synthase; secretory phospholipase A(2) ID ARACHIDONIC-ACID RELEASE; RAT-BRAIN; P388D(1) MACROPHAGES; MPTP-NEUROTOXICITY; ALZHEIMERS-DISEASE; E-2 BIOSYNTHESIS; NEURONAL DAMAGE; GENE-EXPRESSION; MICE DEFICIENT; UP-REGULATION AB We previously demonstrated that brain cyclooxygenase (COX)-2 mRNA and protein levels, and prostaglandin E-2 (PGE(2)) level, are down-regulated in cytosolic phospholipase A(2) (cPLA(2))-deficient mice. To further investigate the interaction between upstream and downstream enzymes involved in brain prostaglandin synthesis, we examined expression and activity of COX-1, of different PLA(2) enzymes and of prostaglandin E synthase (PGES) enzymes in COX-2(-/-) mice. We found that the PGE2 level was decreased by 51.5% in the COX-2(-/-) mice brains, indicating a significant role of COX-2 in brain formation of PGE2. However, when we supplied exogenous arachidonic acid (AA) to brain homogenates, COX activity was increased in the COX-2(-/-) mice, suggesting a compensatory activation of COX-1 and an intracellular compartmentalization of the COX isozymes. Consistent with COX-1 increased activity, brain expression of COX-1 protein and mRNA also was increased. Activity and expression of cPLA(2) and secretory PLA(2) (sPLA(2)) enzymes, supplying AA to COX, were significantly increased. Also, the PGE(2) biosynthetic pathway downstream from COX-2 was affected in the COX-2(-/-) mice, as decreased expression of microsomal prostaglandin E synthase-2 (mPGES-2), but not mPGES-1 or cytosolic PGES, was observed. Overall, the data suggest that compensatory mechanisms exist in COX-2(-/-) mice and that mPGES-2 is functionally coupled with COX-2. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM frances@mail.nih.gov NR 63 TC 52 Z9 55 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2004 VL 91 IS 6 BP 1389 EP 1397 DI 10.1111/j.1471-4159.2004.02829.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 884VX UT WOS:000226115900014 PM 15584915 ER PT J AU Joseph, J Sharp, B Fox, HS Gendelman, HE AF Joseph, J Sharp, B Fox, HS Gendelman, HE TI Special issue - Molecular markers and mechanisms of HIV-induced nervous system disease SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Editorial Material C1 NIMH, HIV Neurovirol Genet & Mol Therapeut Program, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. Univ Nebraska, Med Ctr, Dept Pharmacol,Nebraska Med Ctr 985215, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA. RP Gendelman, HE (reprint author), NIMH, HIV Neurovirol Genet & Mol Therapeut Program, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. EM hegendel@unmc.edu 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 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 2004 VL 157 IS 1-2 BP 1 EP 2 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 881LQ UT WOS:000225869400001 ER PT J AU Royal, W Leander, M Chen, YQE Major, EO Bissonnette, RP AF Royal, W Leander, M Chen, YQE Major, EO Bissonnette, RP TI Nuclear receptor activation and interaction with morphine SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Markers and Mechanisms of HIV-Induced Nervous System Disease CY JUN 03-04, 2004 CL Washington, DC SP Natl Inst Ment Hlth, Natl Inst Drug Abuse, Natl Inst Neurol Disorders & Stroke DE nuclear receptor; morphine; HIV infection ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; 9-CIS RETINOIC ACID; AIDS DEMENTIA; X-RECEPTOR; GAMMA; EXPRESSION; INDUCTION AB Nervous system disease in HIV infection is associated with toxic damage induced by effects from proinflammatory responses and oxidative stress, and such effects may be more prominent among opioid abusers. In these studies, the effects of activating retinoid receptor (retinoic acid receptor(RAR) and retinoid X receptor(RXR)) and peroxisome proliferator activated receptor(PPAR) gamma, which belong to the steroid-lipid nuclear receptor family, on tumor necrosis factor (TNF)-alpha production and inducible nitric oxide synthase (iNOS) gene expression by Stimulated U937 and SVG cells, respectively, were examined. Also studied were the effects of morphine on these responses. These studies showed that, in stimulated cells, the observed responses were suppressed by activation of the nuclear receptors as compared to non-stimulated control cells. Moreover, in phytohemagglutinin (PHA)-stimulated U937 cells, morphine reversed the TNF-alpha suppression that was induced by LG101305 and ciglitazone. Preliminary data in SVG cells suggest a tendency for morphine to have a similar effect on LG101305-exposed SVG cells stimulated with a combination of lipopolysaccharide (LPS) and interferon-gamma, whereas this effect was not induced when these cells were incubated with ciglitazone. Therefore, specific nuclear receptor activation may be potentially beneficial in the treatment of neurological disease associated with HIV infection and may show specific interactions with opioids. The mechanisms that underlie these effects require further study. (C) 2004 Elsevier B.V. All rights reserved. C1 Morehouse Sch Med, Inst Neurosci, MRC 214, Atlanta, GA 30310 USA. Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Ligand Pharmaceut Inc, San Diego, CA USA. RP Royal, W (reprint author), Morehouse Sch Med, Inst Neurosci, MRC 214, 720 Westview Dr,SW, Atlanta, GA 30310 USA. EM wroyal@msm.edu NR 37 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 2004 VL 157 IS 1-2 BP 61 EP 65 DI 10.1016/j.jneuroim.2004.08.023 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 881LQ UT WOS:000225869400009 PM 15579281 ER PT J AU Sacktor, N Haughey, N Cutler, R Tamara, A Turchan, J Pardo, C Vargas, D Nath, A AF Sacktor, N Haughey, N Cutler, R Tamara, A Turchan, J Pardo, C Vargas, D Nath, A TI Novel markers of oxidative stress in actively progressive HIV dementia SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Markers and Mechanisms of HIV-Induced Nervous System Disease CY JUN 03-04, 2004 CL Washington, DC SP Natl Inst Ment Hlth, Natl Inst Drug Abuse, Natl Inst Neurol Disorders & Stroke DE oxidative stress; HIV; dementia; ceramide; sphingomyelin ID VIRUS-ASSOCIATED DEMENTIA; NECROSIS-FACTOR-ALPHA; ANTIRETROVIRAL THERAPY; HIPPOCAMPAL-NEURONS; CELL-DEATH; NEUTRAL SPHINGOMYELINASE; ACIDIC SPHINGOMYELINASE; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; TNF-ALPHA AB Oxidative stress leads to the production of reactive oxygen species that can attack lipid membranes resulting in cellular dysfunction and death. Cellular redox state is closely linked to ceramide, sphingomyelin, and 4-hydroxynonenal (HNE) levels. We describe data showing increased levels of these oxidative stress markers in HIV encephalitis. In addition, actively progressing HIV dementia is associated with increases in HNE and ceramide, while inactive HIV dementia is associated with increases in sphingomyelin. These markers may be useful for distinguishing between different clinical phenotypes of HIV dementia. (C) 2004 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, John Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Sacktor, N (reprint author), Johns Hopkins Univ, Sch Med, John Hopkins Bayview Med Ctr, Dept Neurol, 4940 Easter Ave,B-122, Baltimore, MD 21224 USA. EM sacktor@jhmi.edu FU NIDA NIH HHS [K08 DA016160-02, K08 DA016160]; NIMH NIH HHS [MH070056]; NINDS NIH HHS [NS36519, NS0392531, NS26643] NR 57 TC 62 Z9 63 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 2004 VL 157 IS 1-2 BP 176 EP 184 DI 10.1016/j.jneuroim.2004.08.037 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 881LQ UT WOS:000225869400023 PM 15579295 ER PT J AU Li, Q Holmes, A Ma, L Van de Kar, LD Garcia, F AF Li, Q Holmes, A Ma, L Van de Kar, LD Garcia, F TI Medial hypothalamic 5-hydroxytryptamine (5-HT)(1A) receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: Application of recombinant adenovirus containing 5-HT1A sequences SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 5-HT1A promoter; ACTH; I-125-MPPI binding; elevated plus maze; open-field test; SERT knock-out ID TRANSPORTER KNOCKOUT MICE; ANXIETY-LIKE BEHAVIOR; DEFENSE TEST BATTERY; ELEVATED PLUS-MAZE; NULL MUTANT MICE; SEROTONIN TRANSPORTER; BRAIN; MOUSE; DISORDERS; SYSTEM AB Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors. C1 Univ Texas, Dept Psychiat & Behav Sci, Med Branch, Galveston, TX 77555 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Behav Sci & Genet, NIH, Bethesda, MD 20892 USA. Loyola Univ, Dept Pharmacol, Maywood, IL 60153 USA. RP Li, Q (reprint author), Univ Texas, Dept Psychiat & Behav Sci, Med Branch, 5-232 Mary Moody No Pavil,300 Univ Blvd, Galveston, TX 77555 USA. EM qili@utmb.edu FU NINDS NIH HHS [NS34153] NR 38 TC 44 Z9 44 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2004 VL 24 IS 48 BP 10868 EP 10877 DI 10.1523/JNEUROSCI.3223-04.2004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 875YW UT WOS:000225460300011 PM 15574737 ER PT J AU Hongpaisan, J Winters, CA Andrews, SB AF Hongpaisan, J Winters, CA Andrews, SB TI Strong calcium entry activates mitochondrial superoxide generation, upregulating kinase signaling in hippocampal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE superoxide; reactive oxygen species; mitochondria; calcium; calcium signaling; calcium/calmodulin-dependent protein kinase II; CaMKII; protein kinase A; PKA; protein kinase C; PKC; protein phosphatases; hippocampus ID GENE-EXPRESSION; CREB PHOSPHORYLATION; SYNAPTIC PLASTICITY; ENDOPLASMIC-RETICULUM; PROTEIN PHOSPHATASES; SYMPATHETIC NEURONS; CA ACCUMULATION; NERVOUS-SYSTEM; TRANSCRIPTION; STIMULATION AB Large increases in cytosolic free Ca2+ ([Ca2+](i)) activate several kinases that are important for neuronal plasticity, including Ca2+/calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC). Because it is also known, mainly in non-neuronal systems, that superoxide radicals (O-2(-)) activate these (and other) kinases and because O-2(-) generation by mitochondria is in part [Ca2+](i) dependent, we examined in hippocampal neurons the relationship between Ca2+ entry, O-2(-) production, and kinase activity. We found that, after large stimulus-induced [Ca2+](i) increases, O-2(-) selectively produced by mitochondria near plasmalemmal sites of Ca2+ entry acts as a modulator to upregulate the two kinases, namely, CaMKII and PKA, whose activities are directly or indirectly phosphorylation dependent. The common mechanism involves O-2(-) inhibition of inactivating protein phosphatases. Conversely, because small [Ca2+](i) increases do not promote mitochondrial respiration and O-2(-) generation, weak stimuli favor enhanced phosphatase activity, which therefore leads to suppressed kinase activity. Enhanced O-2(-) production also promoted PKC activity but by a phosphatase-independent pathway. These results suggest that Ca2+-dependent upregulation of mitochondrial O-2(-) production may be a general mechanism for linking Ca2+ entry to enhanced kinase activity and therefore to synaptic plasticity. This mechanism also represents yet another way that mitochondria, acting as calcium sensors, can play a role in neuronal signal transduction. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Andrews, SB (reprint author), NINDS, Neurobiol Lab, NIH, 36-2A-21,36 Convent Dr, Bethesda, MD 20892 USA. EM sba@helix.nih.gov NR 49 TC 69 Z9 70 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2004 VL 24 IS 48 BP 10878 EP 10887 DI 10.1523/JNEUROSCI.3278-04.2004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 875YW UT WOS:000225460300012 PM 15574738 ER PT J AU Gorbach, AM Heiss, JD Kopylev, L Oldfield, EH AF Gorbach, AM Heiss, JD Kopylev, L Oldfield, EH TI Intraoperative infrared imaging of brain tumors SO JOURNAL OF NEUROSURGERY LA English DT Article DE infrared imaging; tumor vasculature; blood flow; brain temperature ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; GLUCOSE-UTILIZATION; TEMPERATURE; EDEMA AB Object. Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear. Methods. An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis-astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow. Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery. Conclusions. Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion. C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NINDS, Biostat Branch, Bethesda, MD 20892 USA. RP Gorbach, AM (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bldg 13,Room 3N-15, Bethesda, MD 20892 USA. EM gorbach@helix.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 24 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2004 VL 101 IS 6 BP 960 EP 969 DI 10.3171/jns.2004.101.6.0960 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 879CY UT WOS:000225695200011 PM 15599965 ER PT J AU Kawakami, K Kawakami, M Kioi, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Kioi, M Husain, SR Puri, RK TI Distribution kinetics of targeted cytotoxin in glioma by bolus or convection-enhanced delivery in a murine model SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain tumor; cytotoxin; convection-enhanced delivery; continuous infusion; toxicity; maximum tolerated dose; mouse ID RECEPTOR ALPHA-2 CHAIN; INTERLEUKIN-13 RECEPTOR; BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; INFUSION; THERAPY; PROTEIN; CARCINOMA; BINDING AB Object. Interleukin-13 receptor (IL-13R)-targeted cytotoxin (IL-13-PE38) displays a potent antitumor activity against a variety of human tumors including glioblastoma multiforme (GBM) and, thus, this agent is being tested in the clinical trial for the treatment of recurrent GBM. In this study, the authors determined the safety and distribution kinetics of IL-13 cytotoxin when infused intracranially by a bolus injection and by convection-enhanced delivery (CED) in an athymic nude mouse model of GBM. Methods. For the safety studies, athymic nude mice were given intracranial infusions of IL-13 cytotoxin into normal parenchyma by either a bolus injection or a 7-day-long CED. Toxicity was assessed by performing a histological examination of the mouse brains. For the drug distribution studies, nude mice with intracranially implanted U251 GBM tumors were given an intratumor bolus or a CED infusion of IL-13 cytotoxin. Brain tumor samples obtained between 0.25 and 72 hours after the infusion were assessed for drug distribution kinetics by performing immunohistochemical and Western blot analyses. Based on the histological changes in the tumor and brain, the maximum tolerated dose of intracranial IL-13 cytotoxin infusion in nude mice was determined to be 4 mug when delivered by a bolus injection and 10 mug when CED was used. Drug distribution reached the maximum level I hour after the bolus injection and the volume of distribution was determined to be 19.3 +/- 5.8 mm(3). Interleukin-13 cytotoxin was barely detectable 6 hours after the injection. Interestingly, when delivered by bolus injections IL-13 cytotoxin exhibited superior distribution in larger rather than smaller tumors. Convection-enhanced delivery was superior for drug distribution in the U251 tumors because when CED was used the drug remained in the tumors 6 hours after the infusion. Conclusions. These studies provide confirmation of a previous hypothesis that CED of IL-13 cytotoxin is superior to bolus injections not only for the safety of the normal brain but also for maintaining drug levels for a prolonged period in infused brain tumors. These findings are highly relevant and important for the optimal clinical development of IL-13 cytotoxin or any other targeted antitumor agent for GBM therapy, in which multiple routes of delivery of an agent are being contemplated. C1 NIH, Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy,Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy,Lab Mol Tumor Biol, Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM pufi@cber.fda.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 32 TC 47 Z9 48 U1 1 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2004 VL 101 IS 6 BP 1004 EP 1011 DI 10.3171/jns.2004.101.6.1004 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 879CY UT WOS:000225695200016 PM 15597761 ER PT J AU Marcario, JK Manaye, KF SantaCruz, KS Mouton, PR Berman, NEJ Cheney, PD AF Marcario, JK Manaye, KF SantaCruz, KS Mouton, PR Berman, NEJ Cheney, PD TI Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE AIDS; basal ganglia; globus pallidus; motor; stereology; substantia nigra ID SLOWLY PROGRESSING DISEASE; AIDS DEMENTIA COMPLEX; HIV-INFECTION; EVOKED-POTENTIALS; NEURONAL DENSITY; CEREBRAL ATROPHY; RHESUS MACAQUES; FRONTAL-CORTEX; BASAL GANGLIA; MONKEYS AB Infection with human immunodeficiency virus-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS) in humans, causes a spectrum of neuropathology that includes alterations in behavior, changes in evoked potentials, and neuronal degeneration. In the simian immunodeficiency virus (SIV) model of HIV infection, affected monkeys show clinical symptoms and neurological complications that mimic those observed in human neuro-AIDS. To investigate the relationship between morphological correlates and neurophysiological deficits, unbiased stereology was used to assess total neuron number, volume, and neuronal density for all neurons in the globus pallidus (GP) and for dopamine (DA)-containing neurons in the substantia nigra (SN) in eight macaques inoculated with macrophage-tropic, neurovirulent SIV (SIVmac R71/17E), and five control animals. There was a significant difference between rapid progressors and controls for both neuron number (P < .01) and neuronal density (P < .05) in the GP, and for neuron number (P < 05) in the SN. Neuron loss ranged from 6% to 70% in the GP and from 10% to 50% in the SN. Neuropathological analyses confirmed neuroAIDS-like changes in brain, including microglial nodules, extensive perivascular cuffing and/or the presence of multinucleated giant cells, and alterations in neuronal morphology in the majority of the rapid progressors. By comparison, slow progressors showed little, if any, neuropathology. These neuropathological changes in SIV-infected monkeys indicate that neuron death and morphological alterations in the basal ganglia may contribute to the motor impairments reported in the SIV model and, by analogy, in the subset of patients afflicted with motor impairment in human neuro-AIDS. C1 Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Mental Retardat Res Ctr, Kansas City, KS 66160 USA. Howard Univ, Dept Physiol & Biophys, Washington, DC 20059 USA. Johns Hopkins Univ, NIH, NIA, Lab Expt Gerontol,Dept Pathol, Baltimore, MD USA. RP Marcario, JK (reprint author), Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, 3901 Rainbow Blvd,Mail Stop 1031, Kansas City, KS 66160 USA. EM jmarcari@kumc.edu FU NICHD NIH HHS [HD02528]; NIDA NIH HHS [NDA12827] NR 41 TC 16 Z9 17 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2004 VL 10 IS 6 BP 387 EP 399 DI 10.1080/13550280490521131 PG 13 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 884WL UT WOS:000226117300007 PM 15765810 ER PT J AU Patel, AC Nunez, NP Perkins, SN Barrett, JC Hursting, SD AF Patel, AC Nunez, NP Perkins, SN Barrett, JC Hursting, SD TI Effects of energy balance on cancer in genetically altered mice SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board DE energy balance; diet; nutrition; chemoprevention; transgenic; calorie restriction; insulin-like growth factor-1; leptin ID GROWTH-FACTOR-I; CALORIE RESTRICTION; LIFE-SPAN; DIETARY RESTRICTION; P53-DEFICIENT MICE; SPONTANEOUS TUMORIGENESIS; BREAST-CANCER; CYCLOOXYGENASE-2 INHIBITOR; BINDING PROTEIN-3; TRANSGENIC MICE AB Evidence has accumulated from laboratory-based animal experiments and population-based human epidemiological studies that lifestyle factors that affect energy balance, such as caloric intake, nutritional status, and exercise, act in concert with genetic susceptibility to influence cancer development and progression. The use of animal models with specific genetic alterations, in combination with lifestyle modifications that alter overall energy balance, has contributed to a greater understanding of the mechanistic changes occurring during carcinogenesis and to the identification of points of intervention. Studies in our laboratory focusing on the role of energy balance and genetic susceptibility in mice deficient in one (+/-) or both (-/-) alleles of the p53 tumor suppressor gene and mice with a mutant APC allele (APC(min)) Showed that calorie restriction decreases tumor burden, increases tumor latency, and decreases serum insulin-like growth factor (IGF)-1 and leptin levels. Data from our studies, combined with results from other animal and human studies, have established a role for IGF-1 in carcinogenesis. Studies using genetic models of cancer that have been interbred with mice with abnormal levels of IGF-1 will enable the examination of combined effects of energy balance and genetic alterations on the cancer process. Models that integrate lifestyle and genetic effects in a single system provide a physiologically intact system in which combination interventions and therapies for cancer prevention can be tested and validated, thus building a strong preclinical foundation that will inform the development of clinical trials and add perspective to epidemiological studies. C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. RP Hursting, SD (reprint author), NCI, Canc Res Ctr, Bethesda, MD 20892 USA. EM sh63v@nih.gov NR 61 TC 28 Z9 31 U1 1 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3394S EP 3398S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900002 PM 15570044 ER PT J AU Terry, PD Terry, JB Rohan, TE AF Terry, PD Terry, JB Rohan, TE TI Long-chain (n-3) fatty acid intake and risk of cancers of the breast and the prostate: Recent epidemiological studies, biological mechanisms, and directions for future research SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board DE (n-3); (n-6); breast neoplasms; prostate neoplasms; hormone-dependent ID NESTED CASE-CONTROL; ADIPOSE-TISSUE; DIETARY FACTORS; FISH-OIL; SERUM PHOSPHOLIPIDS; MEAT INTAKE; CHEMOPREVENTIVE AGENTS; MAMMARY CARCINOGENESIS; DOCOSAHEXAENOIC ACID; POSTMENOPAUSAL WOMEN AB The association between dietary (n-3) fatty acids and hormone-responsive cancers continues to attract considerable attention in epidemiological, clinical, and experimental studies. We previously reviewed the epidemiological literature on the association between hormone-responsive cancers and the long-chain fatty acids eicosapentaenoic acid and docosahexaenoic acid. We concluded that the compelling evidence from ecological studies, animal models, and mechanistic experiments in vitro was not supported clearly by the available epidemiological data. To various degrees, epidemiological studies published more recently attempted to address some of the methodological limitations plaguing earlier studies by using validated questionnaires, examining specific fatty acids and their interrelationships, and adjusting estimates for a wider range of potentially confounding factors than in previous studies. In this review, our aim was to update the previous review with the results of recent epidemiological studies and to discuss possible biological mechanisms and directions for future research. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Emory Univ, Sch Med, Gen Clin Res Ctr, Nutr Unit, Atlanta, GA 30332 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. RP Terry, PD (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM terry2@niehs.nih.gov NR 118 TC 64 Z9 66 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3412S EP 3420S PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900005 PM 15570047 ER PT J AU Greenwald, P AF Greenwald, P TI Clinical trials in cancer prevention: Current results and perspectives for the future SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board DE cancer; prevention; clinical trials; breast cancer; prostate cancer ID BREAST-CANCER; PROSTATE-CANCER; VITAMIN-E; ESTROGEN-RECEPTOR; UNITED-STATES; CHEMOPREVENTION; RISK; SUPPLEMENTATION; TAMOXIFEN; PHYTOESTROGENS AB Cancer prevention remains the ideal strategy for reducing the burden of cancer on society. Progress in cancer prevention has been accelerated as prevention clinical trials are completed and reported. A promising strategy is the identification of cancer risk factors through epidemiologic and experimental research with lifestyle and medical approaches that allow translation of clinical trial results to clinical practice. A major focus of cancer prevention clinical trials has been on modulation of hormones and nutritional modifications using natural or synthetic bioactive food components for breast and prostate cancer. Breast cancer prevention clinical trials have investigated the role of estrogen antagonists with agents such as tamoxifen, raloxifene, and newer agents such as aromatase inhibitors and bioactive food components. Among the promising bioactive food components being investigated at the National Cancer Institute in prevention clinical trials to reduce breast cancer risk are indole-3-carbinol, sulforaphanes, phytoestrogen isoflavones, perillyl alcohol, and green tea polyphenols. Prostate cancer prevention trials have focused on hormone modulation with the 5-alpha-reductase inhibitor finasteride and bioactive food components such as selenium and vitamin E. Soy isoflavones, green tea polyphenols, and doxercalciferol also are being investigated for prostate cancer prevention. Future prevention clinical trials will rely on multidisciplinary medical approaches that bring together expertise in many fields to address disease across the cancer spectrum. Nutritional science can play an important role in this effort through the use of new and emerging technologies to better understand the influence of bioactive food components on the genes, proteins, and cellular processes that are associated with cancer risk. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Greenwald, P (reprint author), NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. EM pg37g@nih.gov NR 46 TC 55 Z9 58 U1 0 U2 8 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3507S EP 3512S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900019 PM 15570061 ER PT J AU McCarthy, DO AF McCarthy, DO TI Dietary recommendations: Where are we now? SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 NINR, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. EM dm433w@nih.gov RI McCarthy, Donna/A-3291-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3518S EP 3518S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900026 ER PT J AU Kushi, LH Bandera, EV Moore, DF Burley, V Cade, J Forman, D Freudenheim, JL Greenwood, DC Jacobs, DR McCullough, ML Rastogi, T AF Kushi, LH Bandera, EV Moore, DF Burley, V Cade, J Forman, D Freudenheim, JL Greenwood, DC Jacobs, DR McCullough, ML Rastogi, T TI Dietary lipids and endometrial cancer risk: Systematic literature reviews and meta-analyses. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 Kaiser Permanente, Div Res, Oakland, CA USA. Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Biostat, Piscataway, NJ 08854 USA. Univ Leeds, Ctr Biostat & Epidemiol, Leeds LS2 9JT, W Yorkshire, England. SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Univ Leeds, Sch Med, Biostat Unit, Leeds LS2 9JT, W Yorkshire, England. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Oslo, Dept Nutr, N-0316 Oslo, Norway. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RI Greenwood, Darren/C-3220-2008; Bandera, Elisa/M-4169-2014 OI Greenwood, Darren/0000-0001-7035-3096; Bandera, Elisa/0000-0002-8789-2755 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3521S EP 3522S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900034 ER PT J AU Miles, LM Bandera, EV Burley, V Butrum, RR Cade, J Cannon, GJ Forman, D Freudenheim, JL Gordon, I Greenwood, D Heggie, SJ Jacobs, DR James, CA Kalliecharian, R Kushi, LH McCullough, ML Moreton, J Rastogi, T Stone, EM Thompson, RL Wiseman, MJ AF Miles, LM Bandera, EV Burley, V Butrum, RR Cade, J Cannon, GJ Forman, D Freudenheim, JL Gordon, I Greenwood, D Heggie, SJ Jacobs, DR James, CA Kalliecharian, R Kushi, LH McCullough, ML Moreton, J Rastogi, T Stone, EM Thompson, RL Wiseman, MJ TI Food, nutrition, physical activity, and endometrial cancer: a comparison of two systematic literature reviews as a test of WCRF international's new methodology. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 World Canc Res Fund Int, London, England. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. Univ Leeds, Nuffield Inst Hlth, Leeds LS2 9JT, W Yorkshire, England. Amer Inst Canc Res, Washington, DC USA. Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England. SUNY Buffalo, Dept Social & Prevent Med, Sch Med, Buffalo, NY 14260 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Amer Canc Soc, Atlanta, GA 30329 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Southampton, Inst Human Nutr, Southampton SO9 5NH, Hants, England. EM m.wiseman@wcrf.org RI Greenwood, Darren/C-3220-2008; Heggie, Steven/I-1014-2013; Bandera, Elisa/M-4169-2014 OI Greenwood, Darren/0000-0001-7035-3096; Bandera, Elisa/0000-0002-8789-2755 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3521S EP 3521S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900033 ER PT J AU Silvera, SAN Mayne, ST Risch, H Gammon, MD Vaughan, T Chow, WH Dubin, JA Dubrow, R Schoenberg, J Stanford, JL West, AB Rotterdam, H Blot, W Fraumeni, JF AF Silvera, SAN Mayne, ST Risch, H Gammon, MD Vaughan, T Chow, WH Dubin, JA Dubrow, R Schoenberg, J Stanford, JL West, AB Rotterdam, H Blot, W Fraumeni, JF TI Dietary and lifestyle patterns and risk of subtypes of esophageal and gastric cancer: Factor analysis. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. New Jersey Dept Hlth & Senior Serv, Canc Epidemiol Serv, Trenton, NJ USA. NYU, Med Ctr, Dept Anat Pathol, New York, NY 10016 USA. Columbia Univ, Dept Pathol, New York, NY 10027 USA. Int Epidemiol Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3531S EP 3531S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900062 ER PT J AU Csizmadi, I Subar, A Kahle, L Ullman, R Dawe, U Zimmerman, T Friedenreich, C Bryant, H AF Csizmadi, I Subar, A Kahle, L Ullman, R Dawe, U Zimmerman, T Friedenreich, C Bryant, H TI Adaptation of the National Cancer Institute's Diet History Questionnaire and Nutrient Database for Canadian Populations. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 Alberta Canc Board, Calgary, AB, Canada. NCI, Bethesda, MD 20892 USA. Informat Management Serv Inc, Bethesda, MD USA. Westat Corp, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3532S EP 3532S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900065 ER PT J AU Bottone, FG Kim, JS Ishibashi, M Alston-Mills, B Eling, TE AF Bottone, FG Kim, JS Ishibashi, M Alston-Mills, B Eling, TE TI Activating transcription factor 3 has antitumorigenic properties and is induced by diallyl disulfide in human colorectal cancer cells. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3534S EP 3534S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900073 ER PT J AU Roesler, J Horwitz, ME Picard, C Bordigoni, P Davies, G Koscielniak, F Levin, M Veys, P Reuter, UF Schulz, A Thede, C Klingebiel, T Fischer, A Holland, SM Casanova, JL Friedrich, W AF Roesler, J Horwitz, ME Picard, C Bordigoni, P Davies, G Koscielniak, F Levin, M Veys, P Reuter, UF Schulz, A Thede, C Klingebiel, T Fischer, A Holland, SM Casanova, JL Friedrich, W TI Hematopoietic stem cell transplantation for complete IFN-gamma receptor 1 deficiency: A multi-institutional survey SO JOURNAL OF PEDIATRICS LA English DT Article ID BACILLE CALMETTE-GUERIN; INTERFERON-GAMMA; IFN-GAMMA-R1 DEFICIENCY; MYCOBACTERIAL INFECTION; INTERLEUKIN-12; CHILD; MUTATION; DISEASE; CHAIN; SUSCEPTIBILITY AB Objectives To evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in a series of patients with inherited complete IFN-gamma receptor 1 (IFNgammaR1) deficiency. Study design We report S patients who received altogether 11 HSCT from family donors, including 10 HLA-identical (5 siblings and 5 relatives) and I HLA-haplo-identical donors. Five grafts were T-cell depleted, and conditioning regimens varied in intensity. Results Four patients died within S months after HSCT. Two of these deaths were due to specific complications related to mycobacterial infection. There was no or very low (2%) donor cell engraftment in 2 survivors. Only 2 patients are in full remission of mycobacterial disease 5 years after HSCT. These are the only patients who received non-T-cell-depleted grafts from an HLA-identical sibling after a fully myeloablative conditioning regimen. Conclusions HSCT can lead to prolonged remission of mycobacterial disease in children with complete IFNgammaRI deficiency. However, optimal control of mycobacterial infection before HSCT and the use of a non-T-cell-depleted transplant from an HLA-identical sibling after a fully myeloablative conditioning regimen are recommended. C1 Univ Clin Carl Gustav Carus, Dept Pediat, D-01307 Dresden, Germany. Univ Clin Carl Gustav Carus, Dept Internal Med, D-01307 Dresden, Germany. NIAID, NIH, Bethesda, MD 20892 USA. Hop Necker Enfants Malad, Pediat Immunol Hematol Unit, Paris, France. Univ Paris Rene Descartes, INSERM, Lab Human Genet Infect Dis, U 550, Paris, France. Brabais Childrens Hosp, Vandoeuvre Les Nancy, France. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Olga Hosp, Dept Pediat, Stuttgart, Germany. Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, London, England. Univ Ulm, Dept Pediat, D-7900 Ulm, Germany. Univ Clin Johann Wolfgang Goethe, Dept Pediat, D-6000 Frankfurt, Germany. RP Roesler, J (reprint author), Univ Clin Carl Gustav Carus, Dept Pediat, Fetscherstr 74, D-01307 Dresden, Germany. EM roeslerj@rcs.urz.tu-dresden.de OI Thiede, Christian/0000-0003-1241-2048; Picard, Capucine/0000-0001-8788-5056 NR 34 TC 43 Z9 43 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2004 VL 145 IS 6 BP 806 EP 812 DI 10.1016/j.jpeds.2004.08.021 PG 7 WC Pediatrics SC Pediatrics GA 879FR UT WOS:000225702300020 PM 15580206 ER PT J AU Goker-Alpan, O Schiffmann, R Sidransky, E AF Goker-Alpan, O Schiffmann, R Sidransky, E TI Gaucher disease phenotype - Reply SO JOURNAL OF PEDIATRICS LA English DT Letter ID TYPE-3 C1 NIH, Bethesda, MD 20892 USA. RP Goker-Alpan, O (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2004 VL 145 IS 6 BP 860 EP 861 DI 10.1016/j.jpeds.2004.06.002 PG 2 WC Pediatrics SC Pediatrics GA 879FR UT WOS:000225702300037 ER PT J AU Chu, JW Yin, J Brooks, BR Wang, DIC Ricci, MS Brems, DN Trout, BL AF Chu, JW Yin, J Brooks, BR Wang, DIC Ricci, MS Brems, DN Trout, BL TI A comprehensive picture of non-site specific oxidation of methionine residues by peroxides in protein pharmaceuticals SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE protein oxidation; peroxides; methionine; molecular dynamics; ab initio calculations; GCSF; hPTH(1-34) ID COLONY-STIMULATING FACTOR; MEMBRANE CA-ATPASE; HYDROGEN-PEROXIDE; WATER OXIDE; CALMODULIN; SOLVENT; H2O2; HYDROPEROXIDE; FORMULATIONS; DEAMIDATION AB In this article, a comprehensive picture of the oxidation of protein pharmaceuticals by peroxides is developed based on our earlier computational and experimental studies. We propose a new mechanism, the water-mediated mechanism, for the oxidation of methionine residues, and it has been shown to satisfy all available experimental data including new data reported here. Based on the water-mediated mechanism, we found a structural property, average 2-shell water coordination number, that correlates well to the relative rates of oxidation of methionine groups. We used this to study the oxidation of granulocyte colony-stimulating factor (G-CSF) and 1-34 human parathyroid hormone hPTH(1-34). We believe that this comprehensive picture should aid researchers in the pharmaceutical sciences to develop solvent formulations for therapeutic proteins in a more rational way. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. Amgen Inc, Dept Pharmaceut, Thousand Oaks, CA 91320 USA. RP Trout, BL (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM trout@mit.edu RI Chu, Jhih-Wei/D-2257-2012; Chu, Jhih-Wei/M-2870-2013 OI Chu, Jhih-Wei/0000-0003-3842-2893 NR 37 TC 25 Z9 26 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD DEC PY 2004 VL 93 IS 12 BP 3096 EP 3102 DI 10.1002/jps.20207 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 876TJ UT WOS:000225520200023 PM 15514984 ER PT J AU Jain, AK Moore, SM Yamaguchi, K Eling, TE Baek, SJ AF Jain, AK Moore, SM Yamaguchi, K Eling, TE Baek, SJ TI Selective nonsteroidal anti-inflammatory drugs induce thymosin beta-4 and alter actin cytoskeletal organization in human colorectal cancer cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACTIVATED GENE NAG-1; SUPERFAMILY MEMBER; COLON-CANCER; EXPRESSION; METASTASIS; APOPTOSIS; NSAIDS; MOUSE; CYCLOOXYGENASE-2; CHEMOPREVENTION AB Nonsteroidal anti-inflammatory drugs ( NSAIDs) are widely used for their anti-inflammatory effects and have been shown to have chemopreventive effects as well. NSAIDs inhibit cyclooxygenase (COX) activity to exert their anti-inflammatory effects, but it is not clear whether their antitumorigenic ability is through COX inhibition. Using subtractive hybridization, we previously identified a novel member of the transforming growth factor-beta superfamily that has antitumorigenic activity from indomethacin-treated HCT-116 human colorectal cancer cells. On further investigation of this library, we now report the identification of a new cDNA corresponding to the thymosin beta-4 gene. Thymosin beta-4 is a small peptide that is known for its actin-sequestering function, and it is associated with the induction of angiogenesis, accelerated wound healing, and metastatic potential of tumor cells. However, only selective NSAIDs induce thymosin beta-4 expression in a time- and concentration-dependent manner. For example, indomethacin and SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazole] induce thymosin beta-4 expression whereas sulindac sulfide does not. We show that selective NSAIDs induce actin cytoskeletal reorganization, a precursory step to many dynamic processes regulating growth and motility including tumorigenesis. This is the first report to link thymosin beta-4 induction with NSAIDs. These data suggest that NSAIDs alter the expression of a diverse number of genes and provide new insights into the chemopreventive and biological activity of these drugs. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37901 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov NR 40 TC 12 Z9 13 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2004 VL 311 IS 3 BP 885 EP 891 DI 10.1124/jpet.104.070664 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 872HL UT WOS:000225198200004 PM 15292456 ER PT J AU Chhatriwala, M Ravi, RG Patel, RI Boyer, JL Jacobson, KA Harden, TK AF Chhatriwala, M Ravi, RG Patel, RI Boyer, JL Jacobson, KA Harden, TK TI Induction of novel agonist selectivity for the ADP-activated P2Y1 receptor versus the ADP-activated P2Y12 and P2Y13 receptors by conformational constraint of an ADP analog SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INDUCED PLATELET-AGGREGATION; P2Y(1) RECEPTOR; PHOSPHOLIPASE-C; ADENYLYL-CYCLASE; ANTAGONISTS; IDENTIFICATION; NUCLEOTIDES; ADENINE; METABOLISM; POTENCY AB ADP is the cognate agonist of the P2Y(1), P2Y(12), and P2Y(13) receptors. With the goal of identifying a high potency agonist that selectively activates the P2Y(1) receptor, we examined the pharmacological selectivity of the conformationally constrained nonnucleotide analog (N)-methanocarba-2MeSADP [(1'S, 2'R, 3'S, 4'R, 5'S)-4-[(6-amino-2-methylthio-9H-purin-9-yl)-1-diphosphoryloxymethyl] bicyclo[3.1.0] hexane-2,3-diol] among the three ADP-activated receptors. Each P2Y receptor was expressed transiently in COS-7 cells, and inositol lipid hydrolysis was quantified as a measure of receptor activity. In the case of the G(i)-linked P2Y(12) and P2Y(13) receptors, a chimeric G protein, Galpha(q/i), was coexpressed to confer a capacity of these G(i)-linked receptors to activate phospholipase C. 2MeSADP (2-methylthio-ADP) was a potent agonist at all three receptors exhibiting EC50 values in the sub to low nanomolar range. In contrast, whereas (N)-methanocarba-2MeSADP was an extremely potent (EC50 = 1.2 +/- 0.2 nM) agonist at the P2Y(1) receptor, this non-nucleotide analog exhibited no agonist activity at the P2Y(12) receptor and very low activity at the P2Y(13) receptor. (N)-Methanocarba-2MeSADP also failed to block the action of 2MeSADP at the P2Y(12) and P2Y(13) receptors, indicating that the (N)-methanocarba analog is not an antagonist at these receptors. The P2Y(1) receptor selectivity of (N)methanocarba- 2MeSADP was confirmed in human platelets where it induced the shape change promoted by P2Y(1) receptor activation without inducing the sustained platelet aggregation that requires simultaneous activation of the P2Y(12) receptor. These results provide the first demonstration of a high-affinity agonist that discriminates among the three ADP-activated P2Y receptors, and therefore, introduce a potentially important new pharmacological tool for delineation of the relative biological action of these three signaling proteins. C1 Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Inspire Pharmaceut Inc, Durham, NC USA. RP Harden, TK (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA. EM tkh@med.unc.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20]; NHLBI NIH HHS [R01 HL054889, HL54889, R29 HL054889]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 33 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2004 VL 311 IS 3 BP 1038 EP 1043 DI 10.1124/jpet.104.068650 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 872HL UT WOS:000225198200021 PM 15345752 ER PT J AU Park, DY Ma, DS Horowitz, AM AF Park, DY Ma, DS Horowitz, AM TI Oral health education courses for university students: Why not? SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material ID DENTAL-HEALTH C1 NIDCR, NIH, Bethesda, MD 20892 USA. Kangnung Natl Univ, Coll Dent, Kangnung, South Korea. RP Park, DY (reprint author), NIDCR, NIH, 45 Ctr Dr,Rm 4As-43C, Bethesda, MD 20892 USA. EM ParkDe@mail.nih.gov NR 8 TC 3 Z9 3 U1 0 U2 1 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2004 VL 64 IS 1 BP 3 EP 4 DI 10.1111/j.1752-7325.2004.tb02718.x PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 804HT UT WOS:000220290500001 PM 15078054 ER PT J AU Macek, MD Heller, KE Selwitz, RH Manz, MC AF Macek, MD Heller, KE Selwitz, RH Manz, MC TI Is 75 percent of dental caries really found in 25 percent of the population? SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT National Oral Health Conference CY MAY, 2001 CL PORTLAND, OREGON DE dental caries; dental health survey; children; adults; United States ID ORAL-HEALTH AB Objectives: Dental caries prevalence is used to quantify inequalities and to target high-risk populations for interventions. Prevalence can be described via measures of centrality, however, some have used cumulative frequency distribution curves (Lorenz curves). This investigation provides dental caries Lorenz curves for the primary and permanent dentitions at selected ages. Results provide accurate age-specific and dentition-specific X values for the general statement, 75 percent of dental caries is found in X percent of the population." Methods: Data were derived from the Third National Health and Nutrition Examination Survey, a cross-sectional study conducted between 1988 and 1994. Cumulative frequency distributions for total dfs or DMFS were plotted against cumulative frequency distributions for the total population. Results: X values varied substantially between dentitions and across ages. Total dental caries experience in the permanent dentition was more dispersed than it was in the primary dentition, and the total dental caries experience in older persons was more dispersed than it was in younger persons. For those aged 2-5 years, 75 percent of dental caries (primary dention) was found in 8.1 percent of the population. For those aged 6 years or older, 75 percent of dental caries (permanent dentition) was found in 33. 0 percent of the population. Conclusions: For accuracy and relevancy, the statement, 75 percent of dental caries is found in X percent of the population" must be applied to a particular dentition or age group, and must account for appropriate severity and prevalence reference points. C1 Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Oral Hlth Care Delivery, Baltimore, MD 21201 USA. Univ Iowa, Coll Dent, Iowa City, IA 52242 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Macek, MD (reprint author), Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Oral Hlth Care Delivery, 666 W Baltimore St,Room 3-E-02, Baltimore, MD 21201 USA. EM mdm002@dental.umaryland.edu NR 17 TC 30 Z9 37 U1 0 U2 4 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2004 VL 64 IS 1 BP 20 EP 25 DI 10.1111/j.1752-7325.2004.tb02721.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 804HT UT WOS:000220290500004 PM 15078057 ER PT J AU Kino, T Ichijo, T Chrousos, GP AF Kino, T Ichijo, T Chrousos, GP TI FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE FLASH; p160 coactivators; nuclear receptor-binding domain; LXXLL motif; steroid hormone receptors ID NUCLEAR RECEPTOR; GLUCOCORTICOID-RECEPTOR; BINDING; SPECIFICITY; ACTIVATION; ESTROGEN; MOTIF AB We previously reported that tumor necrosis factor a receptor- and Fas-associated FLASH interacts with one of the p 160 nuclear receptor coactivators, glucocorticoid receptor-interacting protein (GRIP) 1, at its nuclear receptor-binding (NRB) domain, and that inhibits the transcriptional activity of the glucocorticoid receptor (GR) by interfering with association of GR and GRIP1. Here, we further examined the specificity of FLASH suppressive effect and the physical/functional interactions between this protein and two other p160 family subtypes. The suppressive effect of FLASH on GR transactivation was observed in several cell lines and on the chromatin-integrated mouse mammary tumor virus (MMTV) promoter. FLASH strongly interacted with the NRB domain of the thyroid hormone receptor activator molecule (TRAM) 1, a member of the steroid hormone receptor coactivator (SRC) 3/nuclear receptor coactivator (N-CoA) 3 subtypes, as well as with SRC2/N-CoA2 p160 coactivator GRIP1, while its interaction with SRC1a, one of the SRC1/N-CoA1 proteins, was faint in yeast two-hybrid assays. Accordingly, FLASH strongly suppressed TRAM1- and GRIP1-induced enhancement of GR-stimulated transactivation of the MMTV promoter in HCT116 cells, while it did not affect SRC1a-induced potentiation of transcription. Furthermore, FLASH suppressed androgenand progesterone receptor- induced transcriptional activity, but did not influence estrogen receptor-induced transactivation, possibly due to their preferential use of p160 coactivators in HCT116 and HeLa cells. Thus, FLASH differentially suppresses steroid hormone receptor-induced transcriptional activity by interfering with their association with SRC2/N-CoA2 and SRC3/N-CoA3 but not with SRC I /N-CoA1. Published by Elsevier Ltd. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Clin Res Ctr, Bethesda, MD 20892 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, Clin Res Ctr, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov NR 22 TC 23 Z9 26 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD DEC PY 2004 VL 92 IS 5 BP 357 EP 363 DI 10.1016/j.jsbmb.2004.09.003 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 898VR UT WOS:000227104800003 PM 15698540 ER PT J AU Kang, SG Maurizi, MR Thompson, M Mueser, T Ahvazi, B AF Kang, SG Maurizi, MR Thompson, M Mueser, T Ahvazi, B TI Crystallography and mutagenesis point to an essential role for the N-terminus of human mitochondrial ClpP SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE mitochondrial ClpP; CIp/Hsp100; X-ray crystallography; ATP-dependent protease ID ATP-DEPENDENT PROTEASE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; DEGRADATION MACHINE; CHAPERONE; SEQUENCE; TRANSLOCATION; PROTEOLYSIS; RESOLUTION; HYDROLYSIS AB We have determined a 2.1 Angstrom crystal structure for human mitochondrial ClpP (hClpP), the proteolytic component of the ATP-dependent ClpXP protease. HClpP has a structure similar to that of the bacterial enzyme, with the proteolytic active sites sequestered within an aqueous chamber formed by face-to-face assembly of the two heptameric rings. The hydrophobic N-terminal peptides of the subunits are bound within the narrow (12 Angstrom) axial channel, positioned to interact with unfolded substrates translocated there by the associated ClpX chaperone. Mutation or deletion of these residues causes a drastic decrease in ClpX-mediated protein and peptide degradation. Residues 8-16 form a mobile loop that extends above the ring surface and is also required for activity. The 28 amino acid C-terminal domain, a unique feature of mammalian ClpP proteins, lies on the periphery of the ring, with its proximal portion forming a loop that extends out from the ring surface. Residues at the start of the C-terminal domain impinge on subunit interfaces within the ring and affect heptamer assembly and stability. We propose that the N-terminal peptide of ClpP is a structural component of the substrate translocation channel and may play an important functional role as well. Published by Elsevier Inc. C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Struct Biol Res Lab, Bethesda, MD 20892 USA. NIAMSD, NIH, Xray Crystallog Facil, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM mmaurizi@helix.nih.gov; ahvazib@mail.nih.gov NR 42 TC 52 Z9 55 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD DEC PY 2004 VL 148 IS 3 BP 338 EP 352 DI 10.1016/j.jsb.2004.07.004 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 872JZ UT WOS:000225204800009 PM 15522782 ER PT J AU Greenhill, LL Vitiello, B Fisher, P Levine, J Davies, M Abikoff, H Chrisman, AK Chuang, S Findling, RL March, J Sc-Ahill, L Walkup, J Riddle, MA AF Greenhill, LL Vitiello, B Fisher, P Levine, J Davies, M Abikoff, H Chrisman, AK Chuang, S Findling, RL March, J Sc-Ahill, L Walkup, J Riddle, MA TI Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE psychopharmacology; safety; adverse events; methodology ID SYSTEMATIC INQUIRY; SAFTEE; CHILDREN; SAFETY AB Objective: To improve the gathering of adverse events (AEs) in pediatric psychopharmacology by examining the value and acceptability of increasingly detailed elicitation methods. Method: Trained clinicians administered the Safety Monitoring Uniform Report Form (SMURF) to 59 parents and outpatients (mean age +/- SD = 11.9 +/- 3.2 years) in treatment, with 36% on stimulants, 29% on selective serotonin reuptake inhibitor drugs, 10% on both, and 25% on other drug combinations. The SMURF included a brief general inquiry, a drug-specific inquiry, and a comprehensive body system review (BSR). Results: SMURF administration took 24.6 +/- 13.9 minutes (median, 21). The BSR took 15.5 +/- 8.1 minutes (median, 14) longer (p < .0001) than the general inquiry (4.3 +/- 5.4 minutes) and the drug-specific inquiry (4.2 +/- 2.9 minutes). The general inquiry elicited 48 AEs, the drug-specific inquiry elicited 16 additional AlEs, and the BSR 129 additional AEs. Of all the clinically relevant AEs elicited by the SMURF (n = 36),19 (53%) were elicited by the BSR. The BSR length and detail were acceptable to parents but not to clinicians. Conclusions: The BSR elicited additional clinically significant AEs that had been missed with less detailed methods. Parents, but not clinicians, rated satisfaction and acceptability of the BSR as good. C1 Columbia Univ, Div Child & Adolescent Psychiat, New York State Psychiat Inst, New York, NY 10032 USA. NIMH, Bethesda, MD 20892 USA. NYU, Ctr Child Study, New York, NY USA. Duke Univ, Durham, NC USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Yale Univ, New Haven, CT USA. Johns Hopkins Univ, Baltimore, MD USA. RP Greenhill, LL (reprint author), Columbia Univ, Div Child & Adolescent Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA. EM greenhil@child.cpmc.columbia.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [N01MH60016, N01MH60005] NR 10 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2004 VL 43 IS 12 BP 1488 EP 1496 DI 10.1097/01.chi.0000142668.29191.13 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 874EK UT WOS:000225333500006 PM 15564818 ER PT J AU Palacio, JD Castellanos, FX Pineda, DA Lopera, F Arcos-Burgos, M Quiroz, YT Henao, GC Puerta, IC Ramirez, DL Rapoport, JL Bailey-Wilson, J Berg, K Muenke, M AF Palacio, JD Castellanos, FX Pineda, DA Lopera, F Arcos-Burgos, M Quiroz, YT Henao, GC Puerta, IC Ramirez, DL Rapoport, JL Bailey-Wilson, J Berg, K Muenke, M TI Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-cleficit/hyperactivity disorder; comorbidity; conduct disorder; genetics; phenotype; population isolate ID DEFICIT HYPERACTIVITY DISORDER; SEGREGATION ANALYSIS; GENOMEWIDE SCAN; ADHD; LINKAGE; CHILDREN; COMMUNITY; SYMPTOMS; DISEASES; GENES AB Objective: Eighteen extended multigenerational families were recruited from the genetically isolated Paisa community in Colombia to conduct genetic studies of aftention-deficit/hyperactivity disorder (ADHD). This report describes the inclusion strategy and clinical features of participants to facilitate comparisons with other data sets. Method: Families were selected through a fixed-sampling scheme beginning with child probands referred for clinical evaluation for ADHD. Direct structured psychiatric interviews were conducted with 433 informative individuals, including 92 children aged 4 to 11, 57 adolescents aged 12 to 17, and 284 adults. Best estimate ADHD diagnoses were established for each informative pedigree member. Results: These families contained a high proportion of individuals affected with ADHD (32.8%), which was highly comorbid with conduct disorder (50%; odds ratio 11.5, 95% confidence interval = 6.4-20.9), oppositional defiant disorder (25.4%; odds ratio 2.7, confidence interval = 1.5-4.8), and associated conditions including nicotine dependence and alcohol abuse and/or dependence. Conclusions: ADHD in these extended Paisa families is highly comorbid with conduct and oppositional defiant disorders. This pattern of comorbidity, as well as the large dense pedigrees of the sample, suggests that it will be particularly useful for molecular genetic studies that are currently under way. C1 NYU, Ctr Child Study, Inst Pediat Neurosci, New York, NY 10016 USA. Univ Antioquia, Neurosci Grp, Medellin, Colombia. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ San Buenaventura, Masters Program Neuropsychol, Medellin, Colombia. Univ San Buenaventura, Neuropsychol & Conuct Disorder Grp, Medellin, Colombia. NHGRI, NIH, Bethesda, MD 20892 USA. RP Castellanos, FX (reprint author), NYU, Ctr Child Study, Inst Pediat Neurosci, 125 Lexington Ave,14th Floor, New York, NY 10016 USA. EM caste01@med.nyu.edu OI Puerta Lopera, Isabel Cristina/0000-0002-3533-8015; Bailey-Wilson, Joan/0000-0002-9153-2920; Palacio, Juan David/0000-0002-1584-4391 NR 30 TC 32 Z9 32 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2004 VL 43 IS 12 BP 1506 EP 1515 DI 10.1097/01.chi.0000142279.79805.de PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 874EK UT WOS:000225333500008 PM 15564820 ER PT J AU Chang, M Cohen-Mansfield, J Ferrucci, L Leveille, S Volpato, S de Rekeneire, N Guralnik, JM AF Chang, M Cohen-Mansfield, J Ferrucci, L Leveille, S Volpato, S de Rekeneire, N Guralnik, JM TI Incidence of loss of ability to walk 400 meters in a functionally limited older population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mobility; incident of disability; 400-meter walk; functional limitation; aging ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; 6-MINUTE WALK; SUBSEQUENT DISABILITY; MAINTAINING MOBILITY; WOMENS-HEALTH; LATE-LIFE; ADULTS; MORTALITY; RISK AB OBJECTIVES: To assess the incidence of and factors related to nondisabled but functionally limited older adults aged 75 to 85 years losing the ability to walk 400 m. DESIGN: Observational study with average follow-up of 21 months. SETTING: Community. PARTICIPANTS: At baseline, 101 persons with objective signs of functional limitations and intact cognitive function agreed to participate in the study. Of these, 81 were able to walk 400 m at baseline, and 62 participated in the follow-up examination. MEASUREMENTS: Mobility disability was defined as an inability to complete a 400-m walk test. At baseline, eligible participants (n=81) had the ability to walk 400 m, scored between 4 and 9 on the Short Physical Performance Battery (SPPB; range 0-12), and scored 18 or more on the Mini-Mental State Examination. Demographics, difficulty in daily activities, disease status, behavioral risk factors, and muscle strength were assessed at baseline and follow-up. RESULTS: Of 62 persons at follow-up, 21 (33.9%) developed incident mobility disability. The strongest predictors of loss of mobility were the time to complete the 400-m walk at baseline (odds ratio (OR)=1.6 per 1-minute difference, 95% confidence interval (CI)=1.04-2.45), and decline in SPPB score over the follow-up (OR=1.4 per 1-point difference, 95% CI=1.01-1.92). CONCLUSION: Older persons with functional limitations have a high rate of loss of ability to walk 400 m. The 400-m walk test is a highly relevant, discrete outcome that is an ideal target for testing preventive interventions in vulnerable older populations. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Hebrew Home Greater Washington Res Inst, Res Inst Aging, Rockville, MD USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. RP Chang, M (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, 7201 Wiscinson Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. EM changmi@hjarta.is RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 26 TC 39 Z9 39 U1 1 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2004 VL 52 IS 12 BP 2094 EP 2098 DI 10.1111/j.1532-5415.2004.52570.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 872DT UT WOS:000225188300020 PM 15571549 ER PT J AU Sayers, SP Brach, JS Newman, AB Heeren, TC Guralnik, JM Fielding, RA AF Sayers, SP Brach, JS Newman, AB Heeren, TC Guralnik, JM Fielding, RA TI Use of self-report to predict ability to walk 400 meters in mobility-limited older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE function; disability; mobility; self-report ID PHYSICAL FUNCTION; ELDERLY PEOPLE; PERFORMANCE; HEALTH; DISABILITY; LIFE; ASSOCIATIONS; VALIDATION AB OBJECTIVES: To determine whether the ability to walk 400 m could be predicted from self-reported walking habits and abilities in older adults and to develop an accurate self-report measure appropriate for observational trials of mobility when functional measures are impractical to collect. DESIGN: Cross-sectional. SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred fifty community-dwelling older men and women (mean age+/-standard error= 79.8+/-0.3). MEASUREMENTS: An 18-item questionnaire assessing walking habits and ability was administered to each participant, followed by a 400-m walk test. Ninety-eight (65%) volunteers were able to complete the 400-m walk; 52 (35%) were unable. Logistic regression was performed using response items from a questionnaire as predictors and 400-m walk as the outcome. RESULTS: Three questions (Do you think you could walk one-quarter of a mile now without sitting down to rest. Because of a health or physical problem, do you have difficulty walking 1 mile? Could you walk up and down every aisle of a grocery store without sitting down to rest or leaning on a cart?) were predictive of 400-m walking ability and were included in the model. If participants answered all three questions compatible with the inability to walk 400 m, there was a 91% probability that they were unable to walk 400 m, with a sensitivity of 46% and a specificity of 97%. CONCLUSION: A three-item self-report developed in the study was able to accurately predict mobility disability. The utility of this instrument may be in evaluating self-reported mobility in large observational trials on mobility when functional mobility tasks are impractical to collect. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Phys Therapy, Pittsburgh, PA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol Biostat, Boston, MA USA. Boston Univ, Dept Hlth Sci, Human Physiol Lab, Sargent Coll Rehabil Sci, Boston, MA 02215 USA. RP Sayers, SP (reprint author), Univ Missouri, Sch Hlth Profess, Dept Phys Therapy, 114 Lewis Hall, Columbia, MO 65211 USA. EM sayerss@missouri.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [R01-AG18844]; PHS HHS [263-MA-202876] NR 12 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2004 VL 52 IS 12 BP 2099 EP 2103 DI 10.1111/j.1532-5415.2004.52571.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 872DT UT WOS:000225188300021 PM 15571550 ER PT J AU Mehta, KM Simonsick, EM Rooks, R Newman, AB Pope, SK Rubin, SM Yaffe, K AF Mehta, KM Simonsick, EM Rooks, R Newman, AB Pope, SK Rubin, SM Yaffe, K TI Black and white differences in cognitive function test scores: What explains the difference? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognition; dementia; race; ethnicity; literacy ID CARDIOVASCULAR HEALTH COGNITION; MENTAL-STATE-EXAMINATION; TEST-PERFORMANCE; AFRICAN-AMERICANS; ALZHEIMERS-DISEASE; BODY-COMPOSITION; OLDER-ADULTS; DEMENTIA; EDUCATION; ELDERS AB Several studies have reported that older black and Latino adults have lower cognitive function test scores than older white adults, but few have comprehensively examined reasons for score differences. This study evaluates whether differences in health and socioeconomic indicators, including literacy level, can explain differences in cognitive function test scores between older black and white adults. C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Kent State Univ, Dept Sociol, Kent, OH 44242 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. RP Mehta, KM (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM kala@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01 AG062106, N01 AG062101, N01 AG062103, P30 AG015272, P30 AG015272-07S1, P30AG15272, R01 AG021918] NR 38 TC 41 Z9 41 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2004 VL 52 IS 12 BP 2120 EP 2127 DI 10.1111/j.1532-5415.2004.52575.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 872DT UT WOS:000225188300025 PM 15571554 ER PT J AU Piontek, KB Huso, DL Grinberg, A Liu, LJ Bedja, DH Zhao, HD Gabrielson, K Qian, F Mei, CL Westphal, H Germino, GG AF Piontek, KB Huso, DL Grinberg, A Liu, LJ Bedja, DH Zhao, HD Gabrielson, K Qian, F Mei, CL Westphal, H Germino, GG TI A functional floxed allele of pkd1 that can be conditionally inactivated in vivo SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; MICE; CRE; DEFECTS; GENE; EXPRESSION; MUTANT AB Gene targeting has been used to create a variety of lines of trice with Pkd1 mutations that share many common features. Homozygous Pkd1 mutants invariably develop pancreatic and renal cysts if they survive to day 15.5 post coitum and die in either the fetal or the perinatal. period. In contrast, mice with heterozygous mutations of Pkd1 are generally normal and have few if any renal cysts. These features have limited the utility of these models as tools to study the pathogenesis of cyst formation and the effect of various therapeutic interventions on disease progression. This report describes a new line of mice with a floxed allele of Pkd1 (Pkd1(cond)) that has an FRT-flanked neomycin cassette inserted into intron 1 and lox P sites inserted into intron 1 and intron 4. The Pkd1(cond) allele is fully functional, and homozygotes are viable and healthy. It is shown that the lox P and FRT sites can be selectively induced to recombine to produce two new alleles, Pkd1(del2-4) and Pkd1(cond-Deltaneo), by crossing to animals that express either the cre or FLPe recombinase, respectively. It is found that Pkd1(del2-4) allele functions as a true null, whereas presence or absence of the neomycin gene has no functional effects. It also is shown that somatic loss of Pkd1 results in renal and hepatic cysts. This new line of mice will be invaluable in the study of Pkd1 biology and serve as a powerful new tool that can be used to study the pathogenesis of autosomal dominant polycystic kidney disease. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Div Nephrol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Shanghai Changzheng Hosp, Dept Med, Shanghai, Peoples R China. RP Germino, GG (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Ross 958,720 Rutland Ave, Baltimore, MD 21205 USA. EM ggermino@jhmi.edu OI Germino, Gregory/0000-0002-3609-5588 FU NCRR NIH HHS [RR 00171]; NIDDK NIH HHS [DK 48006] NR 16 TC 73 Z9 73 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2004 VL 15 IS 12 BP 3035 EP 3043 DI 10.1097/01.ASN.0000.44204.01352.86 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 876NW UT WOS:000225504800011 PM 15579506 ER PT J AU Abbott, KC Lentine, KL Bucci, JR Agodoa, LY Koff, JM Holtzmuller, KC Schnitzler, MA AF Abbott, KC Lentine, KL Bucci, JR Agodoa, LY Koff, JM Holtzmuller, KC Schnitzler, MA TI Impact of diabetes and hepatitis after kidney transplantation on patients who are affected by hepatitis C virus SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CADAVERIC RENAL-TRANSPLANTATION; UNITED-STATES; MODERN IMMUNOSUPPRESSION; EVALUATING INVESTMENT; ALLOGRAFT RECIPIENTS; COST-EFFECTIVENESS; WAITING-LIST; DONOR ACTION; INFECTION; MELLITUS AB Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-, 6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. St Louis Univ, Sch Med, Ctr Outcomes Res, St Louis, MO 63103 USA. NIDDK, Natl Inst Hlth, Bethesda, MD USA. Walter Reed Army Med Ctr, Gastroenterol Serv, Washington, DC 20307 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 FU NIDDK NIH HHS [K25 DK 02916-01] NR 37 TC 48 Z9 49 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2004 VL 15 IS 12 BP 3166 EP 3174 DI 10.1097/01.ASN.0000145439.48387.BF PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 876NW UT WOS:000225504800025 PM 15579520 ER PT J AU Jordan, SC Tyan, D Stablein, D Mcintosh, M Rose, S Vo, A Toyoda, M Davis, C Shapiro, R Adey, D Milliner, D Graff, R Steiner, R Ciancio, G Sahney, S Light, J AF Jordan, SC Tyan, D Stablein, D Mcintosh, M Rose, S Vo, A Toyoda, M Davis, C Shapiro, R Adey, D Milliner, D Graff, R Steiner, R Ciancio, G Sahney, S Light, J TI Evaluation of intravenous immunoglobulin as are agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: Report of the NIHIG02 trial SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID KIDNEY-TRANSPLANTATION; HUMORAL REJECTION; IMMUNE GLOBULIN; GAMMA-GLOBULIN; RESISTANT REJECTION; FC-RECEPTOR; IVIG; DESENSITIZATION; RECIPIENTS; IMMUNOMODULATION AB Reported are the reduction of anti-HLA antibody levels and improvement of transplant rates by intravenous immunoglobulin (IVIG) in a randomized, double-blind, placebo-controlled clinical trial. Between 1997 and 2000, a total of 101 adult patients with ESRD who were highly sensitized to HLA antigens (panel reactive antibody [PRA] greater than or equal to50% monthly for 3 mo) enrolled onto an NIH-sponsored trial (IG02). Patients received IVIG or placebo. Subjects received IVIG 2 g/kg monthly for 4 mo or an equivalent volume of placebo with additional infusions at 12 and 24 mo after entry if not transplanted. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. However, IVIG significantly reduced PRA levels in study subjects compared with placebo. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Seven graft failures occurred (four IVIG, three placebo) among adherent patients with similar 2-yr graft survival rates (80% IVIG, 75% placebo). With a median follow-up of 2 yr after transplant, the viable transplants functioned normally with a mean SEM serum creatinine of 1.68 0.28 for IVIG versus 1.28 0.13 mg/dl for placebo. Adverse events rates were similar in both groups. We conclude that IVIG is better than placebo in reducing anti-HLA antibody levels and improving transplantation rates in highly sensitized patients with ESRD. Transplant rates for highly sensitized patients with ESRD awaiting kidney transplants are improved with IVIG therapy. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Renal Transplant Program, Sch Med, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Transplant Immunol Lab, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Immunogenet Lab, Los Angeles, CA 90048 USA. EMMMES Corp, Stat Coordinating Ctr, Rockville, MD USA. NIAID, NIH, Controlled Clin Trials Kidney Transplantat Progra, Bethesda, MD 20892 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Mayo Clin, Rochester, MN USA. St Louis Univ, Med Ctr, St Louis, MO 63103 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Miami, Med Ctr, Miami, FL 33152 USA. Loma Linda Univ, Med Ctr, Loma Linda, CA 92350 USA. Washington Hosp Ctr, Washington, DC 20010 USA. RP Jordan, SC (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Renal Transplant Program, Sch Med, 8635 W 3rd St,Suite 590W, Los Angeles, CA 90048 USA. EM sjordan@cshs.org FU NIAID NIH HHS [1U01 AI 37313, 1U01 AI 40129] NR 35 TC 240 Z9 253 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2004 VL 15 IS 12 BP 3256 EP 3262 DI 10.1097/01.ASN.0000145878.92906.9F PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 876NW UT WOS:000225504800035 PM 15579530 ER PT J AU McCaskill-Stevens, W Wilson, J Bryant, J Mamounas, E Garvey, L James, J Cronin, W Wickerham, DL AF McCaskill-Stevens, W Wilson, J Bryant, J Mamounas, E Garvey, L James, J Cronin, W Wickerham, DL TI Contralateral breast cancer and thromboembolic events in African American women treated with tamoxifen SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL ADJUVANT BREAST; ITALIAN RANDOMIZED-TRIAL; RISK-FACTORS; WHITE WOMEN; 1ST PRIMARY; PREVENTION; CARCINOMA; THERAPY; EPIDEMIOLOGY; OUTCOMES AB Background: Information about breast cancer treatment and prevention in African American women is scant, and recommendations for therapy from clinical trials for breast cancer are based primarily on data obtained from white women. Methods: We compared the effects of tamoxifen on risk of contralateral breast cancer and thromboembolic events in African American women and white women with a history of primary breast cancer. Data from 13 National Surgical Adjuvant Breast and Bowel Project clinical trials were pooled for analyses of time to contralateral breast cancer as a first event (eight trials and 10 619 patients) and of time to any thromboembolic phenomenon as a first event (all 13 trials and 20 878 patients). Risk factors for contralateral breast cancer and thromboembolic events among all women were determined using univariate proportional hazards models. (For each racial group, the rate of events associated with tamoxifen use was calculated as the ratio of the incidence rate with tamoxifen to that without tamoxifen.) Proportional hazards regression models were used to calculate 95% confidence intervals (CIs) and risk ratios. All statistical tests were two-sided. Results: Risk factors for contralateral breast cancer were body mass index (BMI) and lymph node positivity; those for thromboembolic events were BMI and age. In women of both ethnicities with estrogen receptor-positive breast cancer, those who took tamoxifen experienced a similar reduction in contralateral breast cancer (risk ratio for African American women = 0.74, 95% CI = 0.46 to 1.17, n = 690; risk ratio for white women = 0.76, 95% CI = 0.59 to 0.98, n = 9929; P = .92). Tamoxifen was also associated with an increase in thromboembolic events. The relative risk for thromboembolic events was higher in both African American and white women treated with tamoxifen and chemotherapy than in those who were treated with tamoxifen alone (risk ratio for African American women = 10.70, 95% CI = 5.94 to 19.28 versus 2.16, 95% CI = 1.26 to 3.71; n = 1842; risk ratio for white women = 15.49, 95% CI = 9.53 to 25.17 versus 3.13, 95% CI = 2.04 to 4.79, n = 19 036), and this effect was similar between the races (P = .10). Conclusions: African American and white women appear to have the same risks of contralateral breast cancer and thromboembolic events in response to tamoxifen treatment. C1 NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. Aultman Hosp, Ctr Canc, Canton, OH USA. Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP McCaskill-Stevens, W (reprint author), NCI, NIH, Div Canc Prevent, 6130 Execut Blvd,EPN 2014, Bethesda, MD 20892 USA. EM wm57h@nih.gov FU NCI NIH HHS [U10 CA 12027, U10 CA 69974, U10 CA37377, U10 CA 69651] NR 44 TC 19 Z9 22 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 1 PY 2004 VL 96 IS 23 BP 1762 EP 1769 DI 10.1093/jnci/djh321 PG 8 WC Oncology SC Oncology GA 876FB UT WOS:000225480800009 PM 15572758 ER PT J AU Lee, WJ Blair, A Hoppin, JA Lubin, JH Rusiecki, JA Sandler, DP Dosemeci, M Alavanja, MCR AF Lee, WJ Blair, A Hoppin, JA Lubin, JH Rusiecki, JA Sandler, DP Dosemeci, M Alavanja, MCR TI Cancer incidence among pesticide applicators exposed to chlorpyrifos in the agricultural health study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IMMUNOLOGICAL ABNORMALITIES; HYALELLA-AZTECA; METHYL MERCURY; UNITED-STATES; LUNG-CANCER; FARMERS; COHORT; RISK; ORGANOPHOSPHATES; DROSOPHILA AB Background: Chlorpyrifos is one of the most widely used insecticides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Methods: A total of 54 383 pesticide applicators were included in this analysis. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed at the time of enrollment (December 1993-December 1997). Poisson regression analysis was used to evaluate the association between chlorpyrifos exposure and cancer incidence after adjustment for potential confounders. All statistical tests were two-sided. Results: A total of 2070 incident malignant neoplasms were diagnosed through 2001. The rate ratio for all cancers combined among chlorpyrifos-exposed applicators compared with nonexposed applicators was 0.97 (95% confidence interval = 0.87 to 1.08). For most cancers analyzed, there was no evidence of an exposure-response relationship. However, the incidence of lung cancer was statistically significantly associated with both chlorpyrifos lifetime exposure-days (P-trend = .002) and chlorpyrifos intensity-weighted exposure days (P-trend = .036). After adjustment for other pesticide exposures and demographic factors, individuals in the highest quartile of chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer 2.18 (95% confidence interval = 1.31 to 3.64) times that of those with no chlorpyrifos exposure. Conclusion: Our findings suggest an association between chlorpyrifos use and incidence of lung cancer that deserves further evaluation. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Korea Univ, Dept Prevent Med, Coll Med, Seoul 136701, South Korea. RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, 6120 Execut Blvd,EPS 8000, Rockville, MD 20852 USA. EM alavanjm@mail.nih.gov OI Sandler, Dale/0000-0002-6776-0018 NR 43 TC 75 Z9 87 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 1 PY 2004 VL 96 IS 23 BP 1781 EP 1789 DI 10.1093/jnci/djh324 PG 9 WC Oncology SC Oncology GA 876FB UT WOS:000225480800011 PM 15572760 ER PT J AU Tsurutani, J Dennis, PA AF Tsurutani, J Dennis, PA TI Re: Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID EXPRESSION; NSCLC C1 NCI, Canc Therapeut Branch, NIH, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, NIH, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM dennisp@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 1 PY 2004 VL 96 IS 23 BP 1795 EP 1795 DI 10.1093/jnci/djh342 PG 1 WC Oncology SC Oncology GA 876FB UT WOS:000225480800015 PM 15572763 ER PT J AU Miller, FG Kaptchuk, TJ AF Miller, FG Kaptchuk, TJ TI Sham procedures and the ethics of clinical trials SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Article ID PARKINSONS-DISEASE; PLACEBO SURGERY C1 NIH, Dept Clin Bioethics, Ctr Clin, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioethics, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU NCCIH NIH HHS [R01 AT001414, 1R01 AT00402-01, 1R01 AT01414-01] NR 20 TC 25 Z9 25 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD DEC PY 2004 VL 97 IS 12 BP 576 EP 578 DI 10.1258/jrsm.97.12.576 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 878EE UT WOS:000225628600005 PM 15574854 ER PT J AU Reddy, RM Tsai, WS Ziauddin, MF Zuo, JT Cole, GW Maxhimer, JB Fang, BL Schrump, DS Nguyen, DM AF Reddy, RM Tsai, WS Ziauddin, MF Zuo, JT Cole, GW Maxhimer, JB Fang, BL Schrump, DS Nguyen, DM TI Cisplatin enhances apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 25-MAY 28, 2004 CL Toronto, CANADA SP Amer Assoc Throac Surg ID TRANSGENE EXPRESSION; GENE-THERAPY; CELL-LINES; APO2L/TRAIL; CANCER; DEATH; ACTIVATION AB Background: Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression. Objective: This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/ gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein. Methods: Cultured cancer cells and normal human cells were infected with Ad/ gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit. Results: Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL- mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL. Conclusion: Cisplatin pretreatment enhances Ad/gTRAIL cytotoxicity in malignant cells while not affecting normal cells. The mechanisms underlying this effect might include both enhancement of the susceptibility of cisplatin-treated cells to TRAIL and cisplatin-mediated enhancement of TRAIL expression in Ad/gTRAIL infected cells. These findings provide a rationale for development of Ad/gTRAIL-based therapy for thoracic malignancies. C1 NCI, NIH, Sect Thorac Oncol, Surg Branch,Ctr Canc Res, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. RP Nguyen, DM (reprint author), NCI, NIH, Sect Thorac Oncol, Surg Branch,Ctr Canc Res, Room 2B07,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM Dao_Nguyen@nih.gov NR 17 TC 9 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2004 VL 128 IS 6 BP 883 EP 891 DI 10.1016/j.jtcvs.2004.06.036 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 876DI UT WOS:000225475700016 PM 15573073 ER PT J AU Goncalves, LF Espinoza, J Lee, W Schoen, ML Devers, P Mazor, M Chaiworapongsa, T DeVore, GR Romero, R AF Goncalves, LF Espinoza, J Lee, W Schoen, ML Devers, P Mazor, M Chaiworapongsa, T DeVore, GR Romero, R TI Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with Down syndrome - Description by 3-dimensional ultrasonography and clinical significance SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE abnormalities; Down syndrome; nasal bone; 3-dimensional; ultrasonography ID ULTRASOUND EVALUATION; NUCHAL TRANSLUCENCY; RISK POPULATION; TRISOMY-21; GESTATION; LENGTH; POSTMORTEM; PREGNANCY; ABNORMALITIES; DIAGNOSIS AB Objective. To determine the frequency and clinical significance of bilateral and unilateral hypoplastic nasal bones for the detection of Down syndrome by 3-dimensional ultrasonography. Methods. Thirty-seven volumes of the fetal skull from fetuses with Down syndrome and 37 from fetuses without abnormalities were analyzed by 1 investigator blinded to fetal karyotype. The maximum intensity projection algorithm was used to reconstruct nasal bones. Ossification patterns were identified in anteroposterior and profile views. Sensitivity, false-positive rates (FPRs), and likelihood ratios (LRs) for detection of Down syndrome were calculated. Results. After exclusions (coronal acquisition [n = 11], hand in front of the face [n = 4], poor imaging [n = 2], incomplete follow-up fn = 2], and anomalies detected after delivery [n = 2]), 53 volumes were analyzed (26 fetuses with Down syndrome and 27 without abnormalities; median gestational age, 21(6)/(7) weeks [interquartile range, 19(6)/(7)-25(2)/(7) weeks]). Rendered profile views revealed absent nasal bones in 18.9% (10 of 53) of the fetuses, and, among these, 90% (9 of 10) had Down syndrome (sensitivity, 34.6% [9 of 26]; FPR, 3.7% [1 of 27]; LR, 9.3 [95% confidence interval (0), 1.3-68.71). Three ossification patterns were identified in anteroposterior views: (1) normally developed, (2) delayed ossification, and (3) absent nasal bones. Sensitivity, FPR, and LR of absent nasal bones for detecting Down syndrome were 34.6% (9 of 26), 3.7% (1 of 27), and 9.0 (95% CI, 1.3-68.7), respectively. Sensitivity, FPR, and LR of delayed ossification for detecting Down syndrome were 42.3% (11 of 26), 22% (6 of 27), and 1.83 (95% CI, 0.8-4.4). Conclusions. Absence of nasal bones is associated with the highest risk of Down syndrome. Delayed ossification is associated with a lower risk of Down syndrome than absent nasal bones. These ossification patterns may be indistinguishable on 2-dimensional ultrasonography. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. Fetal Diagnost Ctr, Pasadena, CA USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHHD, Dept Obstet & Gynecol,Hutzel Hosp, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 36 TC 16 Z9 17 U1 1 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2004 VL 23 IS 12 BP 1619 EP 1627 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 876RP UT WOS:000225515300009 PM 15557305 ER PT J AU Compton, WM Horton, JC Cottler, LB Booth, R Leukefeld, CG Singer, M Cunningham-Williams, R Reich, W Corsi, KF Staton, M Fink, JL Stopka, TJ Spitznagel, EL AF Compton, WM Horton, JC Cottler, LB Booth, R Leukefeld, CG Singer, M Cunningham-Williams, R Reich, W Corsi, KF Staton, M Fink, JL Stopka, TJ Spitznagel, EL TI A multistate trial of pharmacy syringe purchase SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE HIV/AIDS prevention; injection drug use; pharmacies; syringe purchase ID INJECTION-DRUG USERS; ACQUISITION; PROGRAM; ACCESS; SALES; HIV AB Pharmacies are a potential site for access to sterile syringes as a means for preventing human immunodeficiency virus (HIV), but the type and extent of their utility is uncertain. To examine pharmacy syringe purchase, we conducted a standardized, multistate study in urban and rural areas of four states in which attempts to purchase syringes were documented. Of 1,600 overall purchase attempts, 35% were refused. Colorado (25%) and Connecticut (28%) bad significantly lower rates of refusal than Kentucky (41%) and Missouri (47%). Furthermore, urban settings bad higher rates of refusal (40%) than rural settings (31%, P <.01). Race and gender did not have a consistent impact on rates of refusal. Despite potential advantages of pharmacies as sites for access to sterile syringes, pharmacy purchase of syringes faces significant obstacles in terms of the practices in different jurisdictions. C1 Natl Inst Drug Abuse, Bethesda, MD USA. Entrenar Inc, St Louis, MO USA. Washington Univ, St Louis, MO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Kentucky, Lexington, KY USA. Hispan Res Council, Hartford, CT USA. Calif Dept Hlth Serv, Off AIDS, Sacramento, CA USA. RP Compton, WM (reprint author), 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA. EM wcompton@nida.nih.gov RI Cunningham-Williams, Renee/C-2350-2013; OI Cunningham-Williams, Renee/0000-0002-3940-3216 FU NIDA NIH HHS [DA00488, DA05786, DA12340] NR 32 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 2004 VL 81 IS 4 BP 661 EP 670 DI 10.1093/jurban/jth149 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 862PU UT WOS:000224504000012 PM 15466847 ER PT J AU Sylvestre, DL Loftis, JM Hauser, P Genser, S Cesari, H Borek, N Kresina, TF Seeff, L Francis, H AF Sylvestre, DL Loftis, JM Hauser, P Genser, S Cesari, H Borek, N Kresina, TF Seeff, L Francis, H TI Co-occurring hepatitis C, substance use, and psychiatric illness: Treatment issues and developing integrated models of care SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE comorbidities; HIV; HCV; psychiatric illness; treatment ID ALCOHOL-USE DISORDERS; IDENTIFICATION TEST AUDIT; SEVERE MENTAL-ILLNESS; METHADONE-MAINTENANCE PATIENTS; SEROTONIN REUPTAKE INHIBITORS; INJECTING DRUG-USERS; INTERFERON-ALPHA; SCREENING-TEST; RATING-SCALE; DEPRESSIVE DISORDER AB Hepatitis C virus (HCV) infection is transmitted by injection drug use and associated with psychiatric conditions. Patients with drug use or significant psychiatric illness have typically been excluded from HCV treatment trials noting the 1997 National Institutes of Health Consensus Statement on HCV that indicated active drug use and major depressive illness were contraindications to treatment of HCV infection. However, the 2002 NIH Consensus Statement recognized that these patients could be effectively treated for HCV infection and recommended that treatment be considered on a case-by-case basis. Treating HCV infection in these patients is challenging, with drug use relapse possibly leading to psychosocial instability, poor adherence, and HCV reinfection. Interferon therapy may exacerbate preexisting psychiatric symptoms. Co-occurring human immunodeficiency virus or hepatitis B virus provide additional challenges, and access to ancillary medical and psychiatric services may be limited. Patients with co-occurring HCV infection, substance use, and psychiatric illness can complete interferon treatment with careful monitoring and aggressive intervention. Clinicians must integrate early interventions for psychiatric conditions and drug use into their treatment algorithm. Few programs or treatment models are designed to manage co-occurring substance use, psychiatric illness, and HCV infection and therapy. The National Institute on Drug Abuse convened a panel of experts to address the current status and the long-range needs through a 2-day workshop, Co-occurring Hepatitis C, Substance Abuse, and Psychiatric Illness: Addressing the Issues and Developing Integrated Models of Care. This conference report summarizes current data, medical management issues, and strategies discussed. C1 Natl Inst Drug Abuse, Ctr AIDS & Other Med Consequences Drug Abuse, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hauser, P (reprint author), Natl Inst Drug Abuse, Ctr AIDS & Other Med Consequences Drug Abuse, NIH, 6001 Execut Blvd,MSC 9593, Bethesda, MD 20892 USA. EM peter.hauser2@med.va.gov NR 89 TC 61 Z9 61 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 2004 VL 81 IS 4 BP 719 EP 734 DI 10.1093/jurban/jth153 PG 16 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 862PU UT WOS:000224504000016 PM 15466851 ER PT J AU Becker, GJ Vogelzang, RL AF Becker, GJ Vogelzang, RL TI SIR 2004 film panel case: Left renal vein compression with regional venous hypertension and resultant systemic arterial hypertension secondary to adrenal congestion SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID NUTCRACKER PHENOMENON; DIAGNOSIS; HEMATURIA C1 NCI, Canc Imaging Program, Bethesda, MD 20892 USA. NW Mem Hosp, Dept Radiol, Chicago, IL 60611 USA. RP Becker, GJ (reprint author), NCI, Canc Imaging Program, Execut Blvd,Suite 3007,MSC7319, Bethesda, MD 20892 USA. EM beckerga@mail.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2004 VL 15 IS 12 BP 1367 EP 1370 DI 10.1097/01.RVI.0000143771.12850.D7 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XT UT WOS:000227678900004 PM 15590788 ER PT J AU Biacchesi, S Skiadopoulos, MH Yang, LJ Lamirande, EW Tran, KC Murphy, BR Collins, PL Buchholz, UJ AF Biacchesi, S Skiadopoulos, MH Yang, LJ Lamirande, EW Tran, KC Murphy, BR Collins, PL Buchholz, UJ TI Recombinant human metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: Deletion of G yields a promising vaccine candidate SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; REPLICATION IN-VITRO; SUBGROUP-B; GENETIC DIVERSITY; FUSION PROTEIN; F-PROTEIN; SEQUENCE; IDENTIFICATION; ACTIVATION; INFECTION AB Human metapneumovirus (HMPV) has recently been identified as a significant cause of serious respiratory tract disease in humans. In particular, the emerging information on the contribution of HMPV to pediatric respiratory tract disease suggests that it will be important to develop a vaccine against this virus for use in conjunction with those being developed for human respiratory syncytial virus and the human parainfluenza viruses. A recently described reverse genetic system (S. Biacchesi, M. H. Skiadopoulos, K. C. Tran, B. R. Murphy, P. L. Collins, and U. J. Buchholz, Virology 321:247-259, 2004) was used to generate recombinant HMPVs (rHMPVs) that lack the G gene, the SH gene, or both. The DeltaSH, DeltaG, and DeltaSH/G deletion mutants were readily recovered and were found to replicate efficiently during multicycle growth in cell culture. Thus, the SH and G proteins are not essential for growth in cell culture. Apart from the absence of the deleted protein(s), the virions produced by the gene deletion mutants were similar by protein yield and gel electrophoresis protein profile to wild-type HMPV. When administered intranasally to hamsters, the DeltaG and DeltaSH/G mutants replicated in both the upper and lower respiratory tracts, showing that HMPV containing F as the sole viral surface protein is competent for replication in vivo. However, both viruses were at least 40-fold and 600-fold restricted in replication in the lower and upper respiratory tract, respectively, compared to wild-type rHMPV. They also induced high titers of HMPV-neutralizing serum antibodies and conferred complete protection against replication of wild-type HMPV challenge virus in the lungs. Surprisingly, G is dispensable for protection, and the DeltaG and DeltaSH/G viruses represent promising vaccine candidates. In contrast, DeltaSH replicated somewhat more efficiently in hamster lungs compared to wild-type rHMPV (20-fold increase on day 5 postinfection). This indicates that SH is completely dispensable in vivo and that its deletion does not confer an attenuating effect, at least in this rodent model. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Buchholz, UJ (reprint author), Bldg 50,Room 6505,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov RI Biacchesi, Stephane/A-6924-2010 NR 34 TC 123 Z9 134 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 12877 EP 12887 DI 10.1128/JVI.78.23.12877-12887.2004 PG 11 WC Virology SC Virology GA 870VT UT WOS:000225087500016 PM 15542640 ER PT J AU Goncalvez, AP Men, R Wernly, C Purcell, RH Lai, CJ AF Goncalvez, AP Men, R Wernly, C Purcell, RH Lai, CJ TI Chimpanzee Fab fragments and a derived humanized immunoglobulin G1 antibody that efficiently cross-neutralize dengue type 1 and type 2 viruses SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; JAPANESE ENCEPHALITIS-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; HEMORRHAGIC-FEVER; NUCLEOTIDE-SEQUENCE; REPERTOIRE CLONING; HUMAN INFECTION; RHESUS-MONKEYS; V(H) SEGMENTS; UNITED-STATES AB Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative to vaccines for prevention of illness caused by dengue viruses (DENV) and other flaviviruses, including the West Nile virus. In a previous study, repertoire cloning to recover Fab fragments from bone marrow mRNA of chimpanzees infected with all four DENV serotypes (dengue virus serotype 1 [DENV-1] to DENV-4) was described. In that study, a humanized immunoglobulin G1 (IgG1) antibody that efficiently neutralized DENV-4 was recovered and characterized. In this study, the phage library constructed from the chimpanzees was used to recover Fab antibodies against the other three DENV serotypes. Serotypespecific neutralizing Fabs were not identified. Instead, we recovered DENV-neutralizing Fabs that specifically precipitated the envelope protein and were cross-reactive with all four DENV serotypes. Three of the Fabs competed with each other for binding to DENV-1 and DENV-2, although each of these Fabs contained a distinct complementarity determining region 3 (CDR3)-H sequence. Fabs that shared an identical or nearly identical CDR3-H sequences cross-neutralized DENV-1 and DENV-2 at a similar high 50% plaque reduction neutralization test (PRNT50) titer, ranging from 0.26 to 1.33 mu/ml, and neutralized DENV-3 and DENV-4 but at a titer 10- to 20-fold lower. One of these Fabs, 1A5, also neutralized the West Nile virus most efficiently among other flaviviruses tested. Fab 1A5 was converted to a full-length antibody in combination with human sequences for production in mammalian CHO cells. Humanized IgG1 1A5 proved to be as efficient as Fab 1A5 for cross-neutralization of DENV-1 and DENV-2 at a titer of 0.48 and 0.95 mug/ml, respectively. IgG1 1A5 also neutralized DENV-3, DENV-4, and the West Nile virus at a PRNT50 titer of approximately 3.2 to 4.2 mug/ml. This humanized antibody represents an attractive candidate for further development of immunoprophylaxis against DENV and perhaps other flavivirus-associated diseases. C1 NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. RP Lai, CJ (reprint author), NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6349,50 S Dr, Bethesda, MD 20892 USA. EM clai@niaid.nih.gov NR 46 TC 34 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 12910 EP 12918 DI 10.1128/JVI.78.23.12910-12918.2004 PG 9 WC Virology SC Virology GA 870VT UT WOS:000225087500019 PM 15542643 ER PT J AU Goncalvez, AP Purcell, RH Lai, CJ AF Goncalvez, AP Purcell, RH Lai, CJ TI Epitope determinants of a chimpanzee Fab antibody that efficiently cross-neutralizes dengue type 1 and type 2 viruses map to inside and in close proximity to fusion loop of the dengue type 2 virus envelope glycoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; YELLOW-FEVER VIRUS; WEST NILE VIRUS; STRUCTURAL PROTEINS; LOW-PH; MONOCLONAL-ANTIBODIES; MOUSE NEUROVIRULENCE; ANTIGENIC STRUCTURE; RESISTANT MUTANTS AB The epitope determinants of chimpanzee Fab antibody 1A5, which have been shown to be broadly reactive to flaviviruses and efficient for cross-neutralization of dengue virus type 1 and type 2 (DENV-1 and DENV-2), were studied by analysis of DENV-2 antigenic variants. Sequence analysis showed that one antigenic variant contained a Gly-to-Val substitution at position 106 within the flavivirus-conserved fusion peptide loop of the envelope protein (E), and another variant contained a His-to-Gln substitution at position 317 in E. Substitution of Gly(106)Val in DENV-2 E reduced the binding affinity of Fab 1A5 by approximately 80-fold, whereas substitution of HiS(317)Gln had little or no effect on antibody binding compared to the parental virus. Treatment of DENV-2 with beta-mercaptoethanol abolished binding of Fab 1A5, indicating that disulfide bridges were required for the structural integrity of the Fab 1A5 epitope. Binding of Fab 1A5 to DENV-2 was competed by an oligopeptide containing the fusion peptide sequence as shown by competition enzyme-linked immunosorbent assay. Both DENV-2 antigenic variants were shown to be attenuated, or at least similar to the parental virus, when evaluated for growth in cultured cells or for neurovirulence in mice. Fab 1A5 inhibited low pH-induced membrane fusion of mosquito C6/36 cells infected with DENV-1 or DENV-2, as detected by reduced syncytium formation. Both substitutions in DENV-2 E lowered the pH threshold for membrane fusion, as measured in a fusion-from-within assay. In the three-dimensional structure of E, Gly(106) in domain II and His(317) in domain III of the opposite E monomer were spatially close. From the locations of these amino acids, Fab 1A5 appears to recognize a novel epitope that has not been mapped before with a flavivirus monoclonal antibody. C1 NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lai, CJ (reprint author), NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6349,50 S Dr,MSC 8009, Bethesda, MD 20892 USA. EM clai@niaid.nih.gov NR 52 TC 65 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 12919 EP 12928 DI 10.1128/JVI.78.23.12919-12928.2004 PG 10 WC Virology SC Virology GA 870VT UT WOS:000225087500020 PM 15542644 ER PT J AU Liu, ZW Qiu, JM Cheng, F Chu, YL Yoto, Y O'Sullivan, MG Brown, KE Pinte, DJ AF Liu, ZW Qiu, JM Cheng, F Chu, YL Yoto, Y O'Sullivan, MG Brown, KE Pinte, DJ TI Comparison of the transcription profile of simian parvovirus with that of the human erythrovirus B19 reveals a number of unique features SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS TYPE-5 RNA; ALTERNATIVE POLYADENYLATION; CYNOMOLGUS MONKEYS; INTERNAL INTRON; SEVERE ANEMIA; IDENTIFICATION; INFECTION; GENOME; ACCUMULATION; INITIATION AB Simian parvovirus (SPV) is a member of the genus Erythrovirus and is closely related to the human parvovirus B19. Natural and experimental infection of monkeys with SPV resembles B19 infection of human. We report a detailed characterization of the viral RNAs and proteins generated following transfection of cloned SPV into COS cells and SPV infection of the human erythroid progenitor line UT-7/Epo-S1. SPV and B19 are 50% identical at the nucleotide level, and although their basic transcription and protein expression profiles were generally similar, there were also significant differences. SPV pre-mRNAs contain three introns, compared to two found for B19: an additional intron was found within the capsid-coding region. RNAs in which this intron was spliced were abundant and encoded the SPV 14-kDa protein (analogous to the B19 11-kDa protein), which initiated at an AUG in the exon preceding the third intron. Unlike B19, SPV RNAs were also spliced between the donor of the first intron and the acceptor of the second intron. The third intron was additionally spliced from a portion of these molecules; these mRNAs encoded the 14-kDa protein. A portion was not spliced further and encoded VP2. Like B19, SPV has a polyadenylation signal [AAUAAA (pA)p] in the middle of the genome, which directed efficient polyadenylation of both spliced and unspliced mRNAs (encoding a putative 10-kDa protein, analogous to the B19 7.5-kDa protein, and SPV NS1, respectively). The 14-kDa protein was localized to both in the nucleus and cytoplasm. C1 Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. Xian Jiaotong Univ, First Hosp, Dept Infect Dis, Xian 710049, Peoples R China. Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Qiu, JM (reprint author), Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, M621 Med Sci Bldg, Columbia, MO 65212 USA. EM qiuj@missouri.edu FU NIAID NIH HHS [R01 AI56310, R01 AI046458, R01 AI056310, R01 AI46458] NR 34 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 12929 EP 12939 DI 10.1128/JVI.78.23.12929-12939.2004 PG 11 WC Virology SC Virology GA 870VT UT WOS:000225087500021 PM 15542645 ER PT J AU Peterson, KE Hughes, S Dimcheff, DE Wehrly, K Chesebro, B AF Peterson, KE Hughes, S Dimcheff, DE Wehrly, K Chesebro, B TI Separate sequences in a murine retroviral envelope protein mediate neuropathogenesis by complementary mechanisms with differing requirements for tumor necrosis factor alpha SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIMIAN IMMUNODEFICIENCY VIRUS; HIV-ASSOCIATED DEMENTIA; ENDOPLASMIC-RETICULUM STRESS; TNF-ALPHA; LEUKEMIA-VIRUS; SPONGIFORM NEURODEGENERATION; PROINFLAMMATORY CYTOKINES; CEREBROSPINAL-FLUID; MICE DEFICIENT AB The innate immune response, through the induction of proinflammatory cytokines and antiviral factors, plays an important role in protecting the host from pathogens. Several components of the innate response, including tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein 1, interferon-inducible protein 10, and RANTES, are upregulated in the brain following neurovirulent retrovirus infection in humans and in animal models. However, it remains unclear whether this immune response is protective, pathogenic, or both. In the present study, by using TNF-alpha(-/-) mice we analyzed the contribution of TNF-alpha to neurological disease induced by four neurovirulent murine retroviruses, with three of these viruses encoding portions of the same neurovirulent envelope protein. Surprisingly, only one retrovirus (EC) required TNF-alpha for disease induction, and this virus induced less TNF-alpha expression in the brain than did the other retroviruses. Analysis of glial fibrillary acidic protein and F4/80 in EC-infected TNF-alpha(-/-) mice showed normal activation of astrocytes but not of microglia. Thus, TNF-alpha-mediated microglial activation may be important in the pathogenic process initiated by EC infection. In contrast, TNF-alpha was not required for pathogenesis of the closely related BE virus and the BE virus induced disease in TNF-alpha(-/-) mice by a different mechanism that did not require microglial activation. These results provide new insights into the multifactorial mechanisms involved in retrovirus-induced neurodegeneration and may also have analogies to other types of neurodegeneration. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Peterson, KE (reprint author), Louisiana State Univ, Dept Pathobiol Sci, Sch Vet Med, Skip BertmanDr, Baton Rouge, LA 70803 USA. EM kpeterson@vetmed.lsu.edu RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 47 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 13104 EP 13112 DI 10.1128/JVI.78.23.13104-13112.2004 PG 9 WC Virology SC Virology GA 870VT UT WOS:000225087500038 PM 15542662 ER PT J AU Julias, JG McWilliams, MJ Sarafianos, SG Alvord, WG Arnold, E Hughes, SH AF Julias, JG McWilliams, MJ Sarafianos, SG Alvord, WG Arnold, E Hughes, SH TI Effects of mutations in the G tract of the human immunodeficiency virus type 1 polypurine tract on virus replication and RNase H cleavage SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; MURINE LEUKEMIA-VIRUS; SEQUENCE FEATURES IMPORTANT; STRAND DNA-SYNTHESIS; CRYSTAL-STRUCTURE; RIBONUCLEASE-H; ANGSTROM RESOLUTION; SPECIFICITY; INTEGRATION; POLYMERASE AB The RNase H cleavages that generate and remove the polypurine tract (PPT) primer during retroviral reverse transcription must be specific in order to create a linear viral DNA that is suitable for integration. Lentiviruses contain a highly conserved sequence consisting of six guanine residues at the 3' end of the PPT (hereafter referred to as the G tract). We introduced mutations into the G tract of a human immunodeficiency virus type 1-based vector and determined the effects on the virus titer and RNase H cleavage specificity. Most mutations in the G tract had little or no effect on the virus titer. Mutations at the second and fifth positions of the G tract increased the proportion of two-long-terminal-repeat (2-LTR) circle junctions with one or two nucleotide insertions. The second and fifth positions of the G tract make specific contacts with amino acids in the RNase H domain that are important for RNase H cleavage specificity. These complementary data define protein-nucleic acid interactions that help control the specificity of RNase H cleavage. When the G-tract mutants were analyzed in a viral background that was deficient in integrase, in most cases the proportion of consensus 2-LTR circle junctions increased. However, in the case of a mutant with Ts at the second and fifth positions of the G tract, the proportion of 2-LTR circle junctions containing the one-nucleotide insertion increased, suggesting that linear viral DNAs containing an extra base are substrates for integration. This result is consistent with the idea that the 3' end-processing reactions of retroviral integrases may help to generate defined ends from a heterogenous population of linear viral DNAs. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv, Frederick, MD 21702 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08855 USA. Rutgers State Univ, CABM, Piscataway, NJ 08855 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov OI Sarafianos, Stefan G/0000-0002-5840-154X FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 39 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 13315 EP 13324 DI 10.1128/JVI.78.23.13315-13324.2004 PG 10 WC Virology SC Virology GA 870VT UT WOS:000225087500058 PM 15542682 ER PT J AU Krempl, CD Collins, PL AF Krempl, CD Collins, PL TI Reevaluation of the virulence of prototypic strain 15 of pneumonia virus of mice SO JOURNAL OF VIROLOGY LA English DT Article ID PNEUMOVIRUS INFECTIONS; NUCLEOTIDE-SEQUENCES; GENES; PROTEINS; GLYCOPROTEIN; EXPRESSION AB Prototypic strain 15 of pneumonia virus of mice (PVM) has been described as being nonpathogenic in mice, in contrast to the mouse-passaged, highly virulent strain J3666. Previous sequence analysis also indicated that strain 15 encodes an attachment G protein that is truncated at the amino terminus, which for the amino terminally anchored protein deletes the cytoplasmic tail. However, we found that PVM strain 15 obtained from the American Type Culture Collection was highly virulent in mice and was essentially indistinguishable on that basis from strain J3666. Sequence analysis showed that this preparation of virus encodes a G protein with an intact cytoplasmic tail: the truncated predicted protein in the previous sequence appeared to be due to a single nucleotide insertion that disrupted the upstream end of the open reading frame and shifted the translational start site to the next downstream AUG. Taken together, the two studies indicate that strain 15 is an inherently virulent strain but that a nonpathogenic variant that was generated during passage in vitro and encodes a truncated G protein exists. Interestingly, the majority sequence of strain J3666 was found to encode a G protein with an extended cytoplasmic tail, suggesting that there is the potential for considerable plasticity in the cytoplasmic tail of the G protein of PVM. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), Bldg 50,Room 6503,50 S Dr MSC 8007, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov RI Krempl, Christine/O-2081-2015 NR 19 TC 13 Z9 13 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 23 BP 13362 EP 13365 DI 10.1128/JVI.78.23.13362-13365.2004 PG 4 WC Virology SC Virology GA 870VT UT WOS:000225087500064 PM 15542688 ER PT J AU Zhou, MS Deng, LW Lacoste, V Park, HU Pumfery, A Kashanchi, F Brady, JN Kumar, A AF Zhou, MS Deng, LW Lacoste, V Park, HU Pumfery, A Kashanchi, F Brady, JN Kumar, A TI Coordination of transcription factor phosphorylation and histone methylation by the P-TEFb kinase during human immunodeficiency virus type 1 transcription SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; PROTEINS SPECIFICALLY ASSOCIATE; CYCLIN-DEPENDENT KINASES; TAT-ASSOCIATED KINASE; HIV-1 TAT; IN-VIVO; ELONGATION-FACTOR; MESSENGER-RNA; ACTIVATING KINASE AB The human immunodeficiency virus type 1 (HIV-1) Tat protein recruits positive transcription elongation factor b (P-TEFb) to the transactivation response (TAR) RNA structure to facilitate formation of processive transcription elongation complexes (TECs). Here we examine the role of the Tat/TAR-specified cyclin-dependent kinase 9 (CDK9) kinase activity in regulation of HIV-1 transcription elongation and histone methylation. In HIV-1 TECs, P-TEFb phosphorylates the RNA polymerase II (RNAP II) carboxyl-terminal domain (CTD) and the transcription elongation factors SPT5 and Tat-SF1 in a Tat/TAR-dependent manner. Using in vivo chromatin immunoprecipitation analysis, we demonstrate the following distinct properties of the HIV-1 transcription complexes. First, the RNAP II CTD is phosphorylated at Ser 2 and Ser 5 near the promoter and at downstream coding regions. Second, the stable association of SPT5 with the TECs is dependent upon P-TEFb kinase activity. Third, P-TEFb kinase activity is critical for the induction of methylation of histone H3 at lysine 4 and lysine 36 on HIV-1 genes. Flavopiridol, a potent P-TEFb kinase inhibitor, inhibits CTD phosphorylation, stable SPT5 binding, and histone methylation, suggesting that its potent antiviral activity is due to its ability to inhibit several critical and unique steps in HIV-1 transcription elongation. C1 NCI, Cellular Oncol Lab, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC USA. Inst Genom Res, Rockville, MD USA. RP Brady, JN (reprint author), NCI, Cellular Oncol Lab, Virus Tumor Biol Sect, NIH, Bldg 41,Room B201, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov; akumar@gwu.edu FU NIAID NIH HHS [R01 AI043894, AI44357, AI054222, AI43894, R21 AI054222, R29 AI044357]; PHS HHS [A13969] NR 78 TC 50 Z9 55 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 24 BP 13522 EP 13533 DI 10.1128/JVI.78.24.13522-13533.2004 PG 12 WC Virology SC Virology GA 875HC UT WOS:000225409900014 PM 15564463 ER PT J AU Ambrose, Z Boltz, V Palmer, S Coffin, JM Hughes, SH KewalRamani, VN AF Ambrose, Z Boltz, V Palmer, S Coffin, JM Hughes, SH KewalRamani, VN TI In vitro characterization of a simian immunodeficiency virus-human immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral resistance in pigtail macaques SO JOURNAL OF VIROLOGY LA English DT Article ID THIOCARBOXANILIDE NONNUCLEOSIDE INHIBITOR; CORECEPTOR SPECIFICITY; MACROPHAGE TROPISM; DRUG-RESISTANCE; CELL-LINE; REPLICATION; INFECTION; SENSITIVITY; GENE; MECHANISM AB Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-I)-infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies of NNRTI resistance, we examined whether a SIV that causes immunopathogenesis in pigtail macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIVmne: SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIVmne contains the entire HIV-1 RT coding region. Both mutant viruses grew to high titers in vitro but had reduced fitness relative to wild-type SIVmne. Although the HIV-1 RT was properly processed into p66 and p51 subunits in RT-SHIVmne particles, the RT-SHIVmne virions had lower levels of RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT activity in RT-SHIVmne and SIV-RT-YY particles. HIV-1 and RT-SHIVmne were similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However, SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIVmne. Classical NNRTI resistance mutations were selected in RT-SHIVmne after in vitro drug treatment and were monitored in a sensitive allele-specific real-time RT-PCR assay. Collectively, these results indicate that RT-SHIVmne may be a useful model in macaques for the preclinical evaluation of NNRTIs and for studies of the development of drug resistance in vivo. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. RP KewalRamani, VN (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 108, Ft Detrick, MD 21702 USA. EM vineet@ncifcrf.gov NR 49 TC 42 Z9 43 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 24 BP 13553 EP 13561 DI 10.1128/JVI.78.24.13553-13561.2004 PG 9 WC Virology SC Virology GA 875HC UT WOS:000225409900017 PM 15564466 ER PT J AU Lu, M Suen, J Frias, C Pfeiffer, R Tsai, MH Chuang, E Zeichner, SL AF Lu, M Suen, J Frias, C Pfeiffer, R Tsai, MH Chuang, E Zeichner, SL TI Dissection of the Kaposi's sarcoma-associated herpesvirus gene expression program by using the viral DNA replication inhibitor cidofovir SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; EPSTEIN-BARR-VIRUS; MACROMOLECULAR-SYNTHESIS; LYTIC CYCLE; TRANSCRIPTION PROGRAM; CELL-PROLIFERATION; MESSENGER-RNA; SIMPLEX VIRUS; K-BZIP; HUMAN-HERPESVIRUS-8 AB Treatment of primary effusion lymphoma cells latently infected by Kaposi's sarcoma-associated herpesvirus (KSRV; human herpesvirus-8 [HHV-8]) with agents such as 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a lytic viral replication cycle, with an ordered gene expression program. Initial studies of the KSHV expression program following TPA induction using viral microarrays yielded useful information concerning the viral expression program, but precise kinetic assignments for some genes remained unclear. Classically, late herpesvirus genes require viral DNA replication for maximal expression. We used cidofovir (CDV), a nucleotide-analogue KSHV DNA polymerase inhibitor, to dissect KSHV expression into two components: genes expressed without viral DNA replication and those requiring it. The expression of known immediate-early or early genes (e.g., open reading frames [OPFs] 50, K8 bZIP, and 57) serving lytic regulatory roles was relatively unaffected by the presence of CDV, while known late capsid and tegument structural genes (e.g., ORFs 25, 26, 64, and 67) were CDV sensitive. Latency-associated transcript ORF 73 was unaffected by the presence of TPA or CDV, suggesting that it was constitutively expressed. Expression of several viral cellular gene homologs, including K2 (vIL-6), ORF 72 (vCyclin), ORF 74 (vGPCR), and K9 (vIRF-1), was unaffected by the presence of CDV, while that of others, such as K4.1 (vMIP-III), K11.1 (vIRF-2), and K10.5 (LANA2, vIRF-3), was inhibited. The results distinguish KSRV genes whose full expression required viral DNA replication from those that did not require it, providing additional insights into KSHV replication and pathogenesis strategies and helping to show which viral cell homologs are expressed at particular times during the lytic process. C1 NCI, HIV & AIDS Maligancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Sci Program, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. RP Zeichner, SL (reprint author), NCI, HIV & AIDS Maligancy Branch, NIH, Bldg 10,Room 10S255 MSC1868, Bethesda, MD 20892 USA. EM zeichner@nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 85 TC 41 Z9 43 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 24 BP 13637 EP 13652 DI 10.1128/JVI.78.24.13637-13652.2004 PG 16 WC Virology SC Virology GA 875HC UT WOS:000225409900025 PM 15564474 ER PT J AU Martin, MP Lederman, MM Hutcheson, HB Goedert, JJ Nelson, GW van Kooyk, Y Detels, R Buchbinder, S Hoots, K Vlahov, D O'Brien, SJ Carrington, M AF Martin, MP Lederman, MM Hutcheson, HB Goedert, JJ Nelson, GW van Kooyk, Y Detels, R Buchbinder, S Hoots, K Vlahov, D O'Brien, SJ Carrington, M TI Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID DENDRITIC CELLS; HIV-1; AIDS; CCR5; PROGRESSION; HEMOPHILIA AB There is considerable debate about the fundamental mechanisms that underlie and restrict acquisition of human immunodeficiency virus type 1 (HIV-1) infection. In light of recent studies demonstrating the ability of C type lectins to facilitate infection with HIV-1, we explored the potential relationship between polymorphisms in the DC-SIGN promoter and risk for acquisition of HIV-1 according to route of infection. Using samples obtained from 1,611 European-American participants at risk for parenteral (n = 713) or mucosal (n = 898) infection, we identified single-nucleotide polymorphisms in the DC-SIGN promoter using single-strand conformation polymorphism. Individuals at risk for parenterally acquired infection who had -336C were more susceptible to infection than were persons with -336T (odds ratio = 1.87, P = 0.001). This association was not observed in those at risk for mucosally acquired infection. A potential role for DC-SIGN specific to systemic acquisition and dissemination of infection is suggested. C1 NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Case Western Reserve Univ, Univ Hosp, Ctr AIDS Res, Cleveland, OH 44106 USA. Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. RP Carrington, M (reprint author), NCI, SAIC Frederick, Basic Res Program, POB B, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 18 TC 88 Z9 94 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2004 VL 78 IS 24 BP 14053 EP 14056 DI 10.1128/JVI.78.24.14053-14056.2004 PG 4 WC Virology SC Virology GA 875HC UT WOS:000225409900065 PM 15564514 ER PT J AU Russanova, VR Hirai, TH Howard, BH AF Russanova, VR Hirai, TH Howard, BH TI Semirandom sampling to detect differentiation-related and age-related epigenome remodeling SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BETA-GLOBIN LOCUS; DIPHTHERIA-TOXIN RESISTANCE; POSITION EFFECT VARIEGATION; HISTONE LYSINE METHYLATION; INACTIVE X-CHROMOSOME; GENE-EXPRESSION; DNA METHYLATION; CHROMATIN-STRUCTURE; HUMAN GENOME; CPG ISLANDS AB With completion of the human genome project, patterns of higher order chromatin structure can be easily related to other features of genome organization. A well-studied aspect of chromatin, histone H4 acetylation, is examined here on the basis of its role in setting competence for gene activation. Three applications of a new hybrid genome sampling-chromatin immunoprecipitation strategy are described. The first explores aspects of epigenome architecture in human fibroblasts. A second focuses on chromatin from HL-60 promyelocytic leukemia cells before and after differentiation into macrophage-like cells. A third application explores age-related epigenome change. In the latter, acetylation patterns are compared in human skin fibroblast chromatin from donors of various ages. Two sites are reported at which observed histone H4 acetylation differences suggest decreasing acetylation over time. The sites, located in chromosome 4p16.1 and 4q35.2 regions, appear to remodel during late fetal-early child development and from preadolescence through adult life, respectively. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP NICHHD, NIH, Bethesda, MD 20892 USA. EM howard@helix.nih.gov NR 72 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2004 VL 59 IS 12 BP 1221 EP 1233 PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 896WF UT WOS:000226964200001 PM 15699521 ER PT J AU Russanova, VR Hirai, TH Tchernov, AV Howard, BH AF Russanova, VR Hirai, TH Tchernov, AV Howard, BH TI Mapping development-related and age-related chromatin remodeling by a high throughput ChIP-HPLC approach SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SACCHAROMYCES-CEREVISIAE; HISTONE ACETYLATION; CELLULAR SENESCENCE; RIBOSOMAL GENES; MOUSE; METHYLATION; DNA; HETEROCHROMATIN; CELLS; H4 AB Common to numerous differentiation pathways in vertebrate organisms is the regulation of key genes through epigenetic mechanisms. Less well studied is to what extent cells of a given differentiation state, but examined at different points within the life history of an organism, are distinct at the level of the epigenome. A few instances of such variation have been reported, and it would be of considerable value to have at hand a means to characterize additional examples more efficiently. We describe an integrated approach to this task, and further present evidence for regions of age-related historic H4 acetylation change extending over tens to hundreds of kilobases. Broad similarity between two distinct regions of such change suggests a previously unsuspected link between developmental programs and aging. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Howard, BH (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM howard@helix.nih.gov NR 56 TC 7 Z9 8 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2004 VL 59 IS 12 BP 1234 EP 1243 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 896WF UT WOS:000226964200002 PM 15699522 ER PT J AU Glenn, CF Chow, DK David, L Cooke, CA Gami, MS Iser, WB Hanselman, KB Goldberg, IG Wolkow, CA AF Glenn, CF Chow, DK David, L Cooke, CA Gami, MS Iser, WB Hanselman, KB Goldberg, IG Wolkow, CA TI Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID C-ELEGANS; SYNAPTIC-TRANSMISSION; WILD-TYPE; CHEMOTAXIS; LONGEVITY; MUTANTS; NEURONS; GENETICS; DIAPAUSE; GENES AB Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits on behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration was not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Wolkow, CA (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA. EM wolkowca@grc.nia.nih.gov RI David, Lawrence/B-1044-2010; Goldberg, Ilya/H-5307-2011 OI David, Lawrence/0000-0002-3570-4767; Goldberg, Ilya/0000-0001-8514-6110 NR 31 TC 67 Z9 72 U1 0 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2004 VL 59 IS 12 BP 1251 EP 1260 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 896WF UT WOS:000226964200004 PM 15699524 ER PT J AU Melzer, D Lan, TY Tom, BDM Deeg, DJH Guralnik, JM AF Melzer, D Lan, TY Tom, BDM Deeg, DJH Guralnik, JM TI Variation in thresholds for reporting mobility disability between national population subgroups and studies SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OLDER ADULTS; HEALTH; RISK; LIMITATION; INDEX; EPESE; PERFORMANCE; PREVALENCE; MORTALITY; DYNAMICS AB Background. Disability questions require older people to report difficulties with everyday activities, using broad categorical responses. Relatively little is known about population group differences in the thresholds for reporting difficulty or inability with medium-distance mobility against tested mobility-related performance. We aimed to estimate the thresholds on tested performance at which self-reports change from one category to another, across a range of sociodemographic subgroups. We also aimed to compare reported and tested performance across two national population studies. Methods. The samples were from the third U.S. National Health and Nutrition Examination Study (NHANES III) and the Longitudinal Aging Study Amsterdam (LASA). Measures of gait speed, chair stands, and peak expiratory flow rate in both studies yielded the validated index of mobility-related physical limitations (MOBLI). Latent probit models were used to estimate cutpoints (thresholds) on the index for reporting difficulty or inability to walk a medium distance. Results. Thresholds for reporting difficulty or inability were Studied by age, sex, race, educational level, and income in NHANES III. In models ad adjusting for the other factors, performance thresholds for reporting disability categories varied by age and income. The younger elderly persons in NHANES III on average reported difficulties or inabilities only when they reached a more severe level of tested limitation compared with older old persons. A similar pattern exists for those on higher incomes. For race, differences in threshold were present only for reporting inability, but not difficulty. Significant differences in thresholds were not present between groups defined by sex or for years of education. Comparisons between the NHANES and LASA studies show that lower reported mobility difficulty or inability prevalence in the Dutch sample is attributable both to reporting at higher levels of limitation and to better functioning. Conclusions. There is evidence of differences in thresholds for reporting mobility disability, especially across age and income groups in older Americans. Further work is needed to understand the perceptual, attitudinal, or environmental factors that cause these reporting differences. C1 Univ Cambridge, Dept Publ Hlth Primary Care, Cambridge, England. Inst Publ Hlth, MRC Biostat Unit, Cambridge, England. Vrije Univ Amsterdam, Dept Psychiat, Amsterdam, Netherlands. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. RP Melzer, D (reprint author), Univ Cambridge, Dept Publ Hlth Primary Care, Cambridge, England. EM dm214@medschl.cam.ac.uk RI Lan, Tzuo-Yun /E-3844-2010; OI Melzer, David/0000-0002-0170-3838 NR 31 TC 44 Z9 44 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2004 VL 59 IS 12 BP 1295 EP 1303 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 896WF UT WOS:000226964200009 PM 15699529 ER PT J AU Blake, P Grafman, J AF Blake, P Grafman, J TI The neurobiology of aggression SO LANCET LA English DT Article C1 Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. RP Blake, P (reprint author), Georgetown Univ Hosp, Dept Neurol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM pamelablakemd@msn.com OI Grafman, Jordan H./0000-0001-8645-4457 NR 0 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD DEC PY 2004 VL 364 SI SI BP 12 EP 13 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 880OU UT WOS:000225799900007 ER PT J AU Brady, RO Schiffmann, R AF Brady, RO Schiffmann, R TI Enzyme-replacement therapy for metabolic storage disorders SO LANCET NEUROLOGY LA English DT Review ID ANDERSON-FABRY-DISEASE; GAUCHERS-DISEASE; ALPHA-GALACTOSIDASE; MUCOPOLYSACCHARIDOSIS-I; CLINICAL-TRIAL; POMPES-DISEASE; DEFICIENCY; GLUCOCEREBROSIDASE; GLUCOSIDASE; IDURONIDASE C1 NIH, Dev & Metab Neurol Branch, NINDS, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), NIH, Dev & Metab Neurol Branch, NINDS, Bldg 10,Room 3D04, Bethesda, MD 20892 USA. EM rb57v@nih.gov NR 36 TC 60 Z9 63 U1 1 U2 6 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD DEC PY 2004 VL 3 IS 12 BP 752 EP 756 DI 10.1016/S1474-4422(04)00938-X PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 873MD UT WOS:000225283500022 PM 15556808 ER PT J AU Malhotra, PS Malekfzali, A Bonner, RF Juhn, S Van Waes, C Chen, Z AF Malhotra, PS Malekfzali, A Bonner, RF Juhn, S Van Waes, C Chen, Z TI Assessment of gene expression in head and neck carcinoma using laser capture microdissection and real-time reverse transcription polymerase chain reaction SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the Triological-Society CY MAY 12-14, 2002 CL BOCA RATON, FL SP Triol Soc DE laser capture microdissection; real time RT-PCR; head and neck cancer; gene expression; VEGF ID ENDOTHELIAL GROWTH-FACTOR; NUCLEIC-ACID; TISSUE; RNA; QUANTITATION AB Objectives. To quantify gene expression in tumor cells from human head and neck squamous cell carcinomas (HNSCC) using laser capture microdissection (LCM). Study Design: Histopathologically identified HNSCC cells were microdissected from frozen sections, RNA was isolated, and vascular endothelial growth factor (VEGF) gene expression was measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Materials and Methods: Two human HNSCC tumor samples and matched normal mucosal biopsies and five human xenograft tumor specimens were harvested, embedded, and frozen in OCT. The frozen tumors were sectioned to 8 to 10 mum in thickness, and hematoxylin-eosin (H&E) staining was performed before LCM. An estimated 2,000 to 3,000 tumor cells were microdissected from frozen sections and processed for RNA isolation. mRNA for VEGF was analyzed by real time RT-PCR (TaqMan) with commercially available primers and probes. Results: Two thousand to 3000 cells were necessary to obtain a suitable quantity of RNA for subsequent gene expression study by real-time RT-PCR. The gene expression of VEGF, a major tumor angiogenic factor, was tested in microdissected HNSCC and compared with uninvolved normal mucosal controls. A greater than seven-fold increase of VEGF expression in tumor specimens versus mucosal controls was observed. Conclusions: LCM is a novel sample conserving technique that allows the precise selection of tumor cells from a heterogeneous architecture. The combination of LCM and real-time RT-PCR appears particularly efficacious for studying HNSCC molecular pathogenesis and identifying tissue-specific biomarkers. C1 NIDCD, Head & Neck Surg Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. Univ Minnesota Hosp, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. NICHHD, Sect Med Biophys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Arcturus Corp Headquarters, Arcturus Syst Microgenom Mountain View, Bethesda, MD USA. RP Chen, Z (reprint author), NIDCD, Head & Neck Surg Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. EM chenz@nided.nih.gov RI Bonner, Robert/C-6783-2015 FU NIDCD NIH HHS [DC 00016] NR 15 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2004 VL 114 IS 12 BP 2123 EP 2128 DI 10.1097/01.mlg.0000149446.14770.52 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 878IE UT WOS:000225639300009 PM 15564832 ER PT J AU Robyn, J Noel, P Wlodarska, I Choksi, M O'Neal, P Arthur, DC Dunbar, C Nutman, TB Klion, AD AF Robyn, J Noel, P Wlodarska, I Choksi, M O'Neal, P Arthur, DC Dunbar, C Nutman, TB Klion, AD TI Imatinib-responsive hypereosinophilia in a patient with B cell ALL SO LEUKEMIA & LYMPHOMA LA English DT Article DE hypereosinophilic syndrome; imatinib mesylate; ALL/Eo ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; MYELOPROLIFERATIVE VARIANT; INTERLEUKIN-3 GENE; T-CELLS; EOSINOPHILIA; TRANSLOCATION; MESYLATE; DISEASE AB Hypereosinophilia is a rare presenting sign of acute lymphocytic leukemia. A 29-year-old male was diagnosed with idiopathic hypereosinophilic syndrome with respiratory symptoms. Although his peripheral blood eosinophilia decreased in response to treatment with imatinib mesylate, a follow-up bone marrow showed a diffuse infiltrate of myeloperoxidase-negative blasts. He was subsequently diagnosed with CD10 positive precursor B lymphoblastic leukemia. This case underscores the importance of follow-up bone marrow examination in patients who demonstrate imatinib mesylate-responsive eosinophilia. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. Univ Louvain, Interuniv Inst Biotechnol, Ctr Human Genet, Louvain, Belgium. Winthrop Univ Hosp, Div Hematol & Oncol, Long Isl City, NY USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Robyn, J (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7B08, Bethesda, MD 20892 USA. EM robynj@nih.gov OI Klion, Amy/0000-0002-4986-5326 NR 33 TC 10 Z9 11 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2004 VL 45 IS 12 BP 2497 EP 2501 DI 10.1080/10428190400005288 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 879JB UT WOS:000225711900019 PM 15621767 ER PT J AU Leonard, GD Posadas, E Herrmann, PC Anderson, VL Jaffe, ES Holland, SM Wilson, WH AF Leonard, GD Posadas, E Herrmann, PC Anderson, VL Jaffe, ES Holland, SM Wilson, WH TI Non-Hodgkin's lymphoma in Job's syndrome: A case report and literature review SO LEUKEMIA & LYMPHOMA LA English DT Article DE Job's syndrome; lymphoma; chemotherapy; rituximab; prognostic index ID HYPER-IGE SYNDROME; HYPERIMMUNOGLOBULINEMIA-E; RECURRENT INFECTIONS; CELL LYMPHOMAS; DEFICIENCY AB Job's or hyper immunoglobulin E recurrent infection syndrome (Hyper-IgE syndrome) is a rare, often inherited multisystem disorder, characterized by cutaneous abscesses, pneumonia, elevated IgE levels and skeletal defects. We report a case of a 22-year-old man with Job's syndrome who presented with back pain. He was found to have diffuse large B-cell lymphoma involving his second lumbar vertebrae and spleen. Treatment with dose-adjusted EPOCH-rituximab (DA-EPOCH-R) chemotherapy achieved a complete remission after 4 cycles. A review of reported cases of lymphoma in Job's syndrome indicates an increase in relative risk of 259 (95% confidence interval 102, 416). The cause of the increased risk has yet to be defined but has similarities to a pathogenetic model of AIDS related lymphoma. In previous reports of lymphoma in Job's syndrome, patients presented with extranodal disease and had poor outcomes. With appropriate chemotherapy and hematological support, lymphoma associated with Job's syndrome can achieve complete remission. C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Med Oncol Clin Res Unit, Bldg 10,Room 12N 226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 25 TC 38 Z9 40 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2004 VL 45 IS 12 BP 2521 EP 2525 DI 10.1080/10428190400004463 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 879JB UT WOS:000225711900024 PM 15621772 ER PT J AU Rauscher, GH Shore, D Sandler, DP AF Rauscher, GH Shore, D Sandler, DP TI Alcohol intake and incidence of de novo adult acute leukemia SO LEUKEMIA RESEARCH LA English DT Article DE leukemia; alcohol; case-control study; bias ID NON-HODGKINS-LYMPHOMA; RISK; CONSUMPTION; CANCER AB In a case-control study of adult acute leukemia we defined alcohol intake as either non-regular (<1 drink per week), light (1-5 drinks per week), moderate (6-8 drinks per week) or heavy (>8 drinks per week). An inverse association was found for light and moderate beer intake (RR = 0.58; 95% CI: 0.44, 0.76). In contrast, a positive association was found for moderate and heavy wine intake (RR = 2.1; 95% CI: 1.2, 3.8). Divergent results might reflect the effect of different nutrients in beer and wine, unmeasured confounding, or differing impacts of selection bias on these associations. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, Chicago, IL 60612 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Rauscher, GH (reprint author), Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, 816 SPHPI,1603 W Taylor, Chicago, IL 60612 USA. EM garthr@uic.edu OI Rauscher, Garth/0000-0003-0374-944X; Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA57699-06] NR 11 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2004 VL 28 IS 12 BP 1263 EP 1265 DI 10.1016/j.leukres.2004.04.004 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 866NM UT WOS:000224780200004 PM 15475066 ER PT J AU Hibbeln, JR Nieminen, LRG Lands, WEM AF Hibbeln, JR Nieminen, LRG Lands, WEM TI Increasing homicide rates and linoleic acid consumption among five western countries, 1961-2000 SO LIPIDS LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; MALE WISTAR RATS; DOUBLE-BLIND; DOCOSAHEXAENOIC ACID; AGGRESSIVE-BEHAVIOR; INCOME COUNTRIES; YOUNG-ADULTS; N-3; DISORDER; FISH AB Clinical intervention trials and animal studies indicate that increasing dietary intakes of long chain n-3 FA or reducing linoleic acid intake may reduce aggressive and violent behaviors. Here we examine if economic measures of greater n-6 consumption across time and countries correlate with greater risk of homicide. Linoleic acid available for human consumption was calculated from World Health Organization disappearance data for 12 major seed oils in the food supply for the years 1961 to 2000 in Argentina, Australia, Canada, the United Kingdom, and the United States (US). Homicide mortality rates, adjusted for age, were obtained from the central judicial authority of each country. Apparent linoleic acid intake from seed oil sources ranged from 0.29 en% (percentage of daily food energy) (Australia 1962) to 8.3 en% (US 1990s). Greater apparent consumption of linoleic acid correlated with higher rates of homicide mortality over a 20-fold range (0.51-10.2/100,000) across countries and time in an exponential growth regression model (r=0.94, F=567, P<0.00001). Within each country, correlations between greater linoleic acid disappearance and homicide mortality over time were significant in linear regression models. Randomized controlled trials are needed to determine if reducing high intakes of linoleic acid by seed oils with alternative compositions can reduce the risk of violent behaviors. These dietary interventions merit exploration as relatively cost-effective measures for reducing the pandemic of violence in Western societies, just as dietary interventions are reducing cardiovascular mortality. Low linoleate diets may prevent behavioral maladies that correctional institutions, social service programs, and mental health providers intend to treat. C1 NIAAA, Sect Nutrit Neurochem, LMBB, NIH, Bethesda, MD 20892 USA. RP Hibbeln, JR (reprint author), NIAAA, Sect Nutrit Neurochem, LMBB, NIH, 31 Ctr Dr,Bldg 31-1B 58, Bethesda, MD 20892 USA. EM jhibbeln@mail.nih.gov NR 41 TC 39 Z9 50 U1 0 U2 2 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 221 W BRADLEY AVE, CHAMPAIGN, IL 61821-1827 USA SN 0024-4201 J9 LIPIDS JI Lipids PD DEC PY 2004 VL 39 IS 12 BP 1207 EP 1213 DI 10.1007/s11745-004-1349-5 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 889NB UT WOS:000226448600008 PM 15736917 ER PT J AU Jeong, WI Do, SH Yun, HS Song, BJ Kim, SJ Kwak, WJ Yoo, SE Park, HY Jeong, KS AF Jeong, WI Do, SH Yun, HS Song, BJ Kim, SJ Kwak, WJ Yoo, SE Park, HY Jeong, KS TI Hypoxia potentiates transforming growth factor-beta expression of hepatocyte during the cirrhotic condition in rat liver SO LIVER INTERNATIONAL LA English DT Article DE cirrhosis; hypoxia; liver; myofibroblast; smad protein; transforming growth factor beta ID HEPATIC STELLATE CELLS; OXYGEN SUPPLEMENTATION; SMAD PROTEINS; MESSENGER-RNA; SIGNAL-TRANSDUCTION; CELLULAR-RESPONSE; GENE-EXPRESSION; FIBROSIS; FIBROGENESIS; MYOFIBROBLASTS AB Background/Aims: Many studies have reported that hypoxia might be associated with angiogenesis and fibrogenesis, and the level of transforming growth factor-beta1 (TGF-beta1) was increased in fibrotic liver and maximal at cirrhosis. Therefore, we examined the expression of TGF-beta1, phosphorylated-Smad2/3 (p-Smad2/3) of the TGF-beta immediate down stream signaling system and hypoxic status during hepatic fibrogenesis. Methods: Fibrosis of rats was induced by carbon tetrachloride. Collagens were detected with Azan stain. Immunohistochemistry and immunoblotting was used. Results: TGF-beta1 was mainly produced by hypoxic hepatocytes at cirrhosis although myofibroblasts (MFBs) and macrophages producing TGF-beta1 were decreased. Moreover, distribution of p-Smad2/3 in hepatocytes was consistent with those of hypoxic hepatocytes regardless of MFBs. Furthermore, in recovery, most MFBs disappeared, whereas positive reactions of p-Smad2/3 still existed in the hepatocytes of hypoxic areas. Therefore, TGF-beta1 expression in hepatocytes might have been associated with hypoxia. Conclusions: We put forward the hypothesis that TGF-beta1 is mainly produced by MFBs and macrophages at early and middle stages of fibrotic processes, but it is predominantly released by hypoxic hepatocytes in the last fibrotic stage or cirrhosis. C1 Kyungpook Natl Univ, Coll Vet Med, Taegu 702701, South Korea. Natl Inst Alcohol Abuse & Alcoholism, Lab Membrane Biochem & Biophys, Rockville, MD USA. Natl Canc Inst, Lab Cell Regulat & Carcinogenesis, Bethesda, MD USA. SK Chem, Suwon, South Korea. Korea Res Inst Chem Technol, Taejon 305606, South Korea. Korea Res Inst Biosci & Biotechnol, Taejon, South Korea. RP Jeong, KS (reprint author), Kyungpook Natl Univ, Coll Vet Med, Taegu 702701, South Korea. EM jeongks@knu.ac.kr RI JEONG, WON IL/B-6615-2011 NR 41 TC 29 Z9 32 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1478-3223 J9 LIVER INT JI Liver Int. PD DEC PY 2004 VL 24 IS 6 BP 658 EP 668 DI 10.1111/j.1478-3231.2004.0961.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 874NU UT WOS:000225357900021 PM 15566519 ER PT J AU Nossal, R AF Nossal, R TI Assembly of clathrin baskets SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc DE clathrin; elasticity; endocytosis; self-assembly; triskelia ID COATED VESICLES; PROTEINS; TRISKELIONS; CURVATURE; FAMILY; PITS AB The creation and internalization of small, protein-coated vesicles is a central factor in the uptake of materials from the surfaces of eucaryotic cells through a process known as receptor mediated endocytosis. Under appropriate in vitro conditions, the principal coat component, viz., clathrin, which is found in the cell as a trimer joined at a common hub, assembles into polyhedral 'baskets' ('cages') containing pentagonal and hexagonal facets. These reconstituted cages have the appearance of miniscule soccer-ball like structures. Their sizes vary over a finite range whose limits depend on the presence or absence of ancillary proteins ('assembly proteins') that are known to increase the tendency for the baskets to form. By fitting data on basket size distributions to simple energetic (thermodynamic) models, one is able to estimate mechanical properties of the clathrin constituents of the baskets and infer the role of assembly proteins in strengthening interactions between the clathrin components of the struts that constitute the edges of the baskets. C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM nossalr@mail.nih.gov NR 34 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD DEC PY 2004 VL 219 BP 1 EP 8 DI 10.1002/masy.200550101 PG 8 WC Polymer Science SC Polymer Science GA 906RC UT WOS:000227658900002 ER PT J AU Zimmerberg, J Kumar, M Verma, A Farrington, J Roth, M Kenworthy, A Hess, ST AF Zimmerberg, J Kumar, M Verma, A Farrington, J Roth, M Kenworthy, A Hess, ST TI Studying spatial distributions of influenza hemagglutinin on the plasma membrane of fibroblasts: A work in progress SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc DE cholesterol; fibroblasts; FRET; microdomains; raft; sphingomyelin ID LIPID RAFT MICRODOMAINS; DETERGENT-RESISTANT MEMBRANES; VIRUS HEMAGGLUTININ; CELL-MEMBRANES; TARGETING PROTEINS; ANCHORED PROTEINS; CHOLESTEROL; DOMAINS; ORGANIZATION; FUSION AB The major envelope protein of influenza virus, hemagglutinin (HA), mediates the fusion of virus to cell for infection, and can mediate cell-cell fusion. It has been studied as a "raft" protein, as it is found in detergent-resistant membranes (DRM) and trafficks apically in polarized epithelia. Moreover, the viral envelope of influenza itself is rich in sphingomyelin and cholesterol. Using both immunogold electron microscopy and fluorescence resonance energy transfer (FRET) microscopy, we are examining the distribution of HA on the surface of fibroblasts expressing wild-type HA. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Univ Maine, Dept Phys & Astron, Orono, ME 04469 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov NR 39 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD DEC PY 2004 VL 219 BP 17 EP 23 DI 10.1002/masy.200550103 PG 7 WC Polymer Science SC Polymer Science GA 906RC UT WOS:000227658900004 ER PT J AU Petrache, HI Harries, D Parsegian, VA AF Petrache, HI Harries, D Parsegian, VA TI Alteration of lipid membrane rigidity by cholesterol and its metabolic precursors SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc DE bending rigidity; cholesterol biosynthesis; intrinsic curvature; stress profile; X-ray ID X-RAY-DIFFRACTION; THERMAL-MECHANICAL FLUCTUATIONS; DIMYRISTOYLPHOSPHATIDYLCHOLINE-CHOLESTEROL; PHOSPHATIDYLCHOLINE BILAYERS; PHYSICAL-PROPERTIES; NEUTRON-SCATTERING; LATERAL DIFFUSION; PHASE-TRANSITIONS; LECITHIN BILAYERS; FLUID MEMBRANES AB Caused by biosynthesis defects, cholesterol deficiency can lead to developmental disorders and malformations, with possible implication of lipid membrane properties. We show that modification of sterol chemical structure alters membrane physical properties significantly. By X-ray diffraction and osmotic stress, we measure changes in the bending rigidity of bilayers containing either cholesterol or one of its metabolic precursors. Membrane elasticity differs dramatically between slightly different sterols and varies in the sequence lanosterol < 7-dehydrocholesterol < lathosterol < cholesterol. We interpret the results in terms of sterol location within lipid structures and modification of lateral stress, a structural feature relevant to interactions within biological membranes. We find that cholesterol is most efficient in enhancing membrane rigidity, a possible clue to why depletion or replacement with other sterols can affect cellular structures. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Petrache, HI (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM petrachh@mail.nih.gov RI Harries, Daniel/F-7016-2012 OI Harries, Daniel/0000-0002-3057-9485 NR 57 TC 8 Z9 9 U1 1 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD DEC PY 2004 VL 219 BP 39 EP 50 DI 10.1002/masy.200550105 PG 12 WC Polymer Science SC Polymer Science GA 906RC UT WOS:000227658900006 ER PT J AU Pfeuffer, J Merkle, H Beyerlein, M Steudel, T Logothetis, NK AF Pfeuffer, J Merkle, H Beyerlein, M Steudel, T Logothetis, NK TI Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 23-27, 2004 CL Erice, ITALY SP Ettore Majorana Fdn & Ctr Sci Culture, Univ della Ricerca, Minist Istruz, Reg Siciliana, Banca Italia, Museo Storico Fis Ctr Studi Ricerche Enrico Fermi, Ist Nazl Fis Nucl, Bruker Biospin S R L, Gen Elect Healthcare, Groupement AMPERE DE functional imaging; monkey brain; high-field MR system; cerebral blood flow ID SPIN-ECHO FMRI; MAGNETIC-RESONANCE; HUMAN BRAIN; HIGH-FIELD; IN-VIVO; BLOOD OXYGENATION; SURFACE COIL; 7 TESLA; VISUAL-CORTEX; RESOLUTION AB Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75x150x300 mum(3) and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, Tl was 2.01/1.84/1.54 s in GM/GM-VI/ WM. T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, TI was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and -2.4%, respectively. Finally, the first high-resolution (500 mum in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, Vl Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity. (C) 2004 Elsevier Inc. All rights reserved. C1 Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72012 Tubingen, Germany. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Pfeuffer, J (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72012 Tubingen, Germany. EM josef.pfeuffer@tuebingen.mpg.de NR 59 TC 54 Z9 55 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD DEC PY 2004 VL 22 IS 10 SI SI BP 1343 EP 1359 DI 10.1016/j.mri.2004.10.004 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 899RU UT WOS:000227163300002 PM 15707785 ER PT J AU Pfeuffer, J Juchem, C Merkle, H Nauerth, A Logothetis, NK AF Pfeuffer, J Juchem, C Merkle, H Nauerth, A Logothetis, NK TI High-field localized H-1 NMR spectroscopy in the anesthetized and in the awake monkey SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 23-27, 2004 CL Erice, ITALY SP Ettore Majorana Fdn & Ctr Sci Culture, Univ della Ricerca, Minist Istruz, Reg Siciliana, Banca Italia, Museo Storico Fis Ctr Studi Ricerche Enrico Fermi, Ist Nazl Fis Nucl, Bruker Biospin S R L, Gen Elect Healthcare, Groupement AMPERE DE in vivo H-1 NMR spectroscopy; short echo time; monkey brain; quantification; macromolecules; respiration artifacts; motion artifacts; neurochemistry ID MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY; IN-VIVO; HUMAN BRAIN; ECHO-TIME; RAT-BRAIN; MACROMOLECULE RESONANCES; NEUROCHEMICAL PROFILE; SPECTRA; MODEL AB Localized cerebral in vivo H-1 NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cut MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than I rum, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr-Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6-10 cerebral metabolites of l-ml volumes. (C) 2004 Elsevier Inc. All rights reserved. C1 Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Bruker BioSpin MRI GMBH, D-76275 Ettlingen, Germany. RP Pfeuffer, J (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, Spemannstr 38, D-72076 Tubingen, Germany. EM josef.pfeuffer@tuebingen.mpg.de NR 47 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD DEC PY 2004 VL 22 IS 10 SI SI BP 1361 EP 1372 DI 10.1016/j.mri.2004.10.002 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 899RU UT WOS:000227163300003 PM 15707786 ER PT J AU Juchem, C Merkle, H Schick, F Logothetis, NK Pfeuffer, J AF Juchem, C Merkle, H Schick, F Logothetis, NK Pfeuffer, J TI Region and volume dependencies in spectral line width assessed by H-1 2D MR chemical shift imaging in the monkey brain at 7 T SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 23-27, 2004 CL Erice, ITALY SP Ettore Majorana Fdn & Ctr Sci Culture, Univ della Ricerca, Minist Istruz, Reg Siciliana, Banca Italia, Museo Storico Fis Ctr Studi Ricerche Enrico Fermi, Ist Nazl Fis Nucl, Bruker Biospin S R L, Gen Elect Healthcare, Groupement AMPERE DE in vivo H-1 NMR spectroscopy; spectroscopic imaging; chemical shift imaging; monkey brain; glutamate; spectral line width ID MAGNETIC-RESONANCE-SPECTROSCOPY; IN-VIVO MICRODIALYSIS; H-1-NMR SPECTROSCOPY; RAT-BRAIN; MACROMOLECULE RESONANCES; PROTON SPECTROSCOPY; N-ACETYLASPARTATE; RELAXATION-TIMES; WILSONS-DISEASE; HIGH-FIELD AB High magnetic fields increase the sensitivity and spectral dispersion in magnetic resonance spectroscopy (MRS). In contrast, spectral peaks are broadened in vivo at higher field strength due to stronger susceptibility-induced effects. Strategies to minimize the spectral line width are therefore of critical importance. In the present study, H-1 2D chemical shift imaging at short echo times was performed in the macaque monkey brain at 7 T. Large brain coverage was obtained at high spatial resolution with voxel sizes down to 50 mul being able to quantify up to nine metabolites in vivo with good reliability. Measured line widths of metabolites decreased from 14.2 to 7.6 Hz with voxel volumes of 3.14 ml to 50 mul (at increased spatial resolution). The line width distribution of the metabolites (7.6 +/- 1.6 Hz, ranging from 5.5 to 10 Hz) was considerably smaller compared to that of water (10.6 +/- 2.4 Hz) and was also smaller than reported in 1H MRS at 7 T in the human brain. Our study showed that even in well-shimmed areas assumed to have minimal macroscopic susceptibility variations, spectral line widths are tissue-specific exhibiting considerable regional variation. Therefore, an overall improvement of a gross spectral line width - directly correlated with improved spectral quality - can only be achieved when voxel volumes are significantly reduced. Our line width optimization was sufficient to permit clear glutamate (Glu)-glutamine separation, yielding distinct Glu maps for brain areas including regions of greatly different Glu concentration (e.g., ventricles vs. surrounding tissue). (C) 2004 Elsevier Inc. All rights reserved. C1 Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Dept Diagnost Radiol, Sect Expt Radiol, D-72076 Tubingen, Germany. RP Pfeuffer, J (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, Spemannstr 38, D-72076 Tubingen, Germany. EM josef.pfeuffer@tuebingen.mpg.de NR 54 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD DEC PY 2004 VL 22 IS 10 SI SI BP 1373 EP 1383 DI 10.1016/j.mri.2004.10.005 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 899RU UT WOS:000227163300004 PM 15707787 ER PT J AU Yang, YH Gu, H Stein, EA AF Yang, YH Gu, H Stein, EA TI Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE functional MRI; cerebral blood volume; cerebral blood flow; cerebral blood oxygenation; brain activation ID VASCULAR-SPACE-OCCUPANCY; FUNCTIONAL MRI; CORTICAL ACTIVATION; TRANSIT-TIME; PERFUSION; BOLD; MULTISLICE; FMRI; STIMULATION; QUANTIFICATION AB Simultaneous acquisition of complementary functional hemodynamic indices reflecting different aspects of brain activity would be a valuable tool for functional brain-imaging studies offering enhanced detection power and improved data interpretation. As such, a new MRI technique is presented that is able to achieve concurrent acquisition of three hemodynamic images based primarily on the changes of cerebral blood volume, blood flow, and blood oxygenation, respectively, associated with brain activation. Specifically, an inversion recovery pulse sequence has been designed to measure VASO (vascular space occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation-level-dependent) signals in a single scan. The MR signal characteristics in this sequence were analyzed, and image parameters were optimized for the simultaneous acquisition of these functional images. The feasibility and efficacy of the new technique were assessed by brain activation experiments with visual stimulation paradigms. Experiments on healthy volunteers showed that this technique provided efficient image acquisition, and thus higher contrast-to-noise ratio per unit time, compared with conventional techniques collecting these functional images separately. In addition, it was demonstrated that the proposed technique was able to be utilized in event-related functional MRI experiments, with potential advantages of obtaining accurate transient information of the activation-induced hemodynamic responses. Published 2004 Wiley-Liss, Inc.(dagger) C1 NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21042 USA. RP Yang, YH (reprint author), NIDA, Neuroimaging Res Branch, NIH, 5500 Nathan Shock Dr,Bldg C,Room 383, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov RI Stein, Elliot/C-7349-2008 NR 36 TC 45 Z9 45 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2004 VL 52 IS 6 BP 1407 EP 1417 DI 10.1002/mrm.20302 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 876HA UT WOS:000225486200024 PM 15562477 ER PT J AU Mantelli, M Pastorino, L Ghiorzo, P Barile, M Bruno, W Gargiulo, S Sormani, MP Gliori, S Vecchio, S Ciotti, P Sertoli, MR Queirolo, P Goldstein, AM Bianchi-Scarra, G AF Mantelli, M Pastorino, L Ghiorzo, P Barile, M Bruno, W Gargiulo, S Sormani, MP Gliori, S Vecchio, S Ciotti, P Sertoli, MR Queirolo, P Goldstein, AM Bianchi-Scarra, G CA Italian Melanoma Intergrp TI Early onset may predict G101W CDKN2A founder mutation carrier status in Ligurian melanoma patients SO MELANOMA RESEARCH LA English DT Article DE CDKN2A; early age at onset; G101W founder mutation; Liguria; melanoma patients ID MULTIPLE PRIMARY MELANOMAS; FAMILY-HISTORY; PREVALENCE; P16(INK4A); CANCER; CDK4; RISK; GENE AB Although the presence of multiple cases of melanoma on the same side of a family is the best predictor of germline CDKN2A mutation, other features (i.e. early age at onset) may be useful to identify carriers. We analysed the records of 682 hospital-based Ligurian melanoma patients. Of these, 238 cases (34 familial, 14 non-familial multiple primary and 190 non-familial single primary melanomas) were consecutively enrolled for screening of the CDKN2A and CDK4 genes. Screening of the 34 familial patients revealed that nine were carriers of the CDKN2A G101W founder mutation. Of the 14 non-familial multiple primary melanoma patients, three carried the G101W founder mutation and one the P48T mutation. For the non-familial patients with a single melanoma, 17 of 190 carried germline CDKN2A mutations, with most (16/17) carrying the G101W Ligurian founder mutation and one a novel single base pair substitution, D74Y. The effect of mutation on age at diagnosis was significant (P= 0.012) after correcting for melanoma type (familial or non-familial), number of primaries (single or multiple), gender and disease occurrence (incident or prevalent). Early age at onset may be a good predictor of CDKN2A mutation in Liguria, where the G101W founder mutation is prevalent among melanoma patients, independent of family history. (C) 2004 Lippincott Williams Wilkins. C1 Univ Genoa, Dipartimento Oncol Biol & Genet, I-16132 Genoa, Italy. Ist Nazl Ric Canc, IST, I-16132 Genoa, Italy. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Bianchi-Scarra, G (reprint author), Univ Genoa, Dipartimento Oncol Biol & Genet, Vle Benedetto XV 6, I-16132 Genoa, Italy. EM vanceci@unige.it RI Bianchi Scarra, Giovanna/G-8933-2014; Bruno, William/N-7477-2013; Queirolo, Paola/K-6778-2016 OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; Bruno, William/0000-0002-0337-0168; Queirolo, Paola/0000-0002-9917-6633 FU NCI NIH HHS [1-R01-CA-83115OIAI] NR 17 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 2004 VL 14 IS 6 BP 443 EP 448 DI 10.1097/00008390-200412000-00002 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 897MU UT WOS:000227009100002 PM 15577313 ER PT J AU De Groot, AS Berzofsky, JA AF De Groot, AS Berzofsky, JA TI From genome to vaccine - new immunoinformatics tools for vaccine design SO METHODS LA English DT Editorial Material C1 Epivax Inc, Providence, RI 02903 USA. Brown Univ, Providence, RI 02912 USA. NCI, NIH, Bethesda, MD 20892 USA. RP De Groot, AS (reprint author), Epivax Inc, Providence, RI 02903 USA. EM AnnieD@Brown.edu RI De Groot, Anne/B-6221-2013 OI De Groot, Anne/0000-0001-5911-1459 NR 9 TC 51 Z9 54 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD DEC PY 2004 VL 34 IS 4 BP 425 EP 428 DI 10.1016/j.ymeth.2004.06.004 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874XT UT WOS:000225384600001 PM 15542367 ER PT J AU Sung, MH Simon, R AF Sung, MH Simon, R TI Candidate epitope identification using peptide property models: application to cancer immunotherapy SO METHODS LA English DT Article DE MHC binding peptides; statistical modeling; biophysical parameters; immunotherapy; melanoma; breast cancer; T cell epitopes ID MHC-BINDING PEPTIDES; T-CELL EPITOPES; MELANOMA ANTIGEN; TUMOR-ANTIGEN; PERIPHERAL-BLOOD; HUMAN BREAST; HLA-DR; EXPRESSION; CTL; RECOGNITION AB Peptides derived from pathogens or tumors are selectively presented by the major histocompatibility complex proteins (MHC) to the T lymphocytes. Antigenic peptide-MHC complexes on the cell surface are specifically recognized by T cells and, in conjunction with co-factor interactions, can activate the T cells to initiate the necessary immune response against the target cells. Peptides that are capable of binding to multiple MHC molecules are potential T cell epitopes for diverse human populations that may be useful in vaccine design. Bioinformatical approaches to predict MHC binding peptides can facilitate the resource-consuming effort of T cell epitope identification. We describe a new method for predicting MHC binding based on peptide property models constructed using biophysical parameters of the constituent amino acids and a training set of known binders. The models can be applied to development of anti-tumor vaccines by scanning proteins over-expressed in cancer cells for peptides that bind to a variety of MHC molecules. The complete algorithm is described and illustrated in the context of identifying candidate T cell epitopes for melanomas and breast cancers. We analyzed MART-1, S-100, MBP, and CD63 for melanoma and p53, MUC1, cyclin B1, HER-2/neu, and CEA for breast cancer. In general, proteins over-expressed in cancer cells may be identified using DNA microarray expression profiling. Comparisons of model predictions with available experimental data were assessed. The candidate epitopes identified by such a computational approach must be evaluated experimentally but the approach can provide an efficient and focused strategy for anti-cancer immunotherapy development. Published by Elsevier Inc. C1 NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Sung, MH (reprint author), NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, 6130 Exec Blvd,EPN 8146,MSC 7434, Bethesda, MD 20892 USA. EM sungm@mail.nih.gov NR 47 TC 11 Z9 12 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 1046-2023 J9 METHODS JI Methods PD DEC PY 2004 VL 34 IS 4 BP 460 EP 467 DI 10.1016/j.ymeth.2004.06.001 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874XT UT WOS:000225384600006 PM 15542372 ER PT J AU Gottesman, ME Weisberg, RA AF Gottesman, ME Weisberg, RA TI Little Lambda, who made thee? SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID SITE-SPECIFIC RECOMBINATION; COHESIVE END SITE; INT GENE-EXPRESSION; BACTERIES LYSOGENES DEFECTIVES; HOST-CONTROLLED MODIFICATION; COLI PHAGE-LAMBDA; BACTERIOPHAGE-LAMBDA; ESCHERICHIA-COLI; COLIPHAGE-LAMBDA; N-GENE AB The study of the bacteriophage X has been critical to the discipline of molecular biology. It was the source of key discoveries in the mechanisms of, among other processes, gene regulation, recombination, and transcription initiation and termination. We trace here the events surrounding these findings and draw on the recollections of the participants. We show how a particular atmosphere of interactions among creative scientists yielded spectacular insights into how living things work. C1 Columbia Univ, Inst Canc Res, New York, NY 10032 USA. NIH, Mol Genet Lab, Bethesda, MD 20892 USA. RP Gottesman, ME (reprint author), Columbia Univ, Inst Canc Res, 701 W 168th St, New York, NY 10032 USA. EM gottesman@cuccfa.ccc.columbia.edu NR 209 TC 22 Z9 23 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD DEC PY 2004 VL 68 IS 4 BP 796 EP + DI 10.1128/MMBR.68.4.796-813.2004 PG 19 WC Microbiology SC Microbiology GA 881HN UT WOS:000225854100010 PM 15590784 ER PT J AU Park, S Lee, YJ Lee, HJ Seki, T Hong, KH Park, J Beppu, H Lim, IK Yoon, JW Li, E Kim, SJ Oh, SP AF Park, S Lee, YJ Lee, HJ Seki, T Hong, KH Park, J Beppu, H Lim, IK Yoon, JW Li, E Kim, SJ Oh, SP TI B-cell translocation gene 2 (Btg2) regulates vertebral patterning by modulating bone morphogenetic protein/Smad signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSLOCATION GENE-2 PROTEIN; CELLULAR-RESPONSE; AXIAL SKELETON; DNA-DAMAGE; EXPRESSION; DIFFERENTIATION; IDENTIFICATION; TRANSCRIPTION; COMPONENT; RECEPTOR AB Btg2 is a primary p53 transcriptional target gene which may function as a coactivator-corepressor and/or an adaptor molecule that modulates the activities of its interacting proteins. We have generated Btg2-null mice to elucidate the in vivo function of Btg2. Btg2-null mice are viable and fertile but exhibit posterior homeotic transformations of the axial vertebrae in a dose-dependent manner. Consistent with its role in vertebral patterning, Btg2 is expressed in the presomitic mesoderm, tail bud, and somites during somitogenesis. We further provide biochemical evidence that Btg2 interacts with bone morphogenetic protein (BMP)-activated Smads and enhances the transcriptional activity of BMP signaling. In view of the genetic evidence that reduced BMP signaling causes posteriorization of the vertebral pattern, we propose that the observed vertebral phenotype in Btg2-null mice is due to attenuated BMP signaling. C1 Univ Florida, Dept Physiol & Funct Genom, Coll Med, Gainesville, FL 32610 USA. Rosalind Franklin Univ Med & Sci, Dept Microbiol & Immunol, Immunol Res Ctr, Bligh Canc Res Labs, N Chicago, IL USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Ajou Univ, Dept Biochem & Mol Biol, Sch Med, Suwon 441749, South Korea. RP Oh, SP (reprint author), Univ Florida, Dept Physiol & Funct Genom, Coll Med, 1600 SW Archer Rd,Room D533D, Gainesville, FL 32610 USA. EM ohp@phys.med.ufl.edu OI Park, Sean/0000-0003-3814-853X FU NHLBI NIH HHS [HL64024, R01 HL064024] NR 43 TC 44 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2004 VL 24 IS 23 BP 10256 EP 10262 DI 10.1128/MCB.24.23.10256-10262.2004 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 871WR UT WOS:000225167800015 PM 15542835 ER PT J AU Intine, RV Dundr, M Vassilev, A Schwartz, E Zhao, YM Zhao, YX Depamphilis, ML Maraia, RJ AF Intine, RV Dundr, M Vassilev, A Schwartz, E Zhao, YM Zhao, YX Depamphilis, ML Maraia, RJ TI Nonphosphorylated human La antigen interacts with nucleolin at nucleolar sites involved in rRNA biogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SS-B AUTOANTIGEN; SMALL CYTOPLASMIC RIBONUCLEOPROTEINS; PROTEIN PROTEIN INTERACTIONS; PRECURSOR TRANSFER-RNAS; MESSENGER-RNAS; IN-VIVO; NUCLEAR TRAFFICKING; LOCALIZATION SIGNAL; NASCENT RNA; SERINE 366 AB La is a RNA-binding protein implicated in multiple pathways related to the production of tRNAs, ribosomal proteins, and other components of the translational machinery (D. J. Kenan and J. D. Keene, Nat. Struct. Mol. Biol. 11:303-305, 2004). While most La is phosphorylated and resides in the nucleoplasm, a fraction is in the nucleolus, the site of ribosome production, although the determinants of this localization are incompletely known. In addition to its conserved N-terminal domain, human La harbors a C-terminal domain that contains an atypical RNA recognition motif and a short basic motif (SBM) adjacent to phosphoserine-366. We report that nonphosphorylated La (npLa) is concentrated in nucleolar sites that correspond to the dense fibrillar component that harbors nascent pol I transcripts as well as fibrillarin and nucleolin, which function in early phases of rRNA maturation. Affinity purification and native immunoprecipitation of La and fluorescence resonance energy transfer in the nucleolus reveal close association with nucleolin. Moreover, La lacking the SBM does not localize to nucleoli. Lastly, La exhibits SBM-dependent, phosphorylation-sensitive interaction with nucleolin in a yeast two-hybrid assay. The data suggest that interaction with nucleolin is, at least in part, responsible for nucleolar accumulation of La and that npLa may be involved in ribosome biogenesis. C1 NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. RP Maraia, RJ (reprint author), NICHHD, Lab Mol Growth Regulat, 6 Ctr Dr,Rm 416, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov NR 77 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2004 VL 24 IS 24 BP 10894 EP 10904 DI 10.1128/MCB.24.24.10894-10904.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 876LI UT WOS:000225497900033 PM 15572691 ER PT J AU Pecon-Slattery, J Wilkerson, AJP Murphy, WJ O'Brien, SJ AF Pecon-Slattery, J Wilkerson, AJP Murphy, WJ O'Brien, SJ TI Phylogenetic assessment of introns and SINEs within the Y chromosome using the cat family Felidae as a species tree SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE ZFY; SMCY UBEIY; SINE; evolution; Felidae; Y chromosome ID MAMMALIAN RETROPOSONS; MOLECULAR EVOLUTION; CYTOCHROME-B; HUMAN GENOME; GENE; INTEGRATION; SEQUENCES; INSERTION; SELECTION; REGION AB The cat family Felidae was used as a species tree to assess the phylogenetic performance of genes, and their embedded SINE elements, within the nonrecombining region of the Y chromosome (NRY). Genomic segments from single-copy X-Y homologs SMCY, UBE1Y, and ZFY (3,604 bp) were amplified in 36 species of cat. These genes are located within the X-degenerate region of the NRY and are thought to be molecular "fossils" that ceased conventional recombination with the X chromosome early within the placental mammal evolution. The pattern and tempo of evolution at these three genes is significant in light of the recent, rapid evolution of the family over approximately 12 Myr and provides exceptional support for each of the eight recognized felid lineages, as well as clear diagnostic substitutions identifying nearly all species. Bootstrap support and Bayesian posterior probabilities are uniformly high for defining each of the eight monophyletic lineages. Further, the preferential use of specific target-site motifs facilitating SINE insertion is empirically supported by sequence analyses of SINEs embedded within the three genes. Target-site insertion is thought to explain the contradiction between intron phylogeny and results of the SMCY SINE phylogeny that unites distantly related species. Overall, our data suggest X-degenerate genes within the NRY are singularly powerful markers and offer a valuable patrilineal perspective in species evolution. C1 SAIC Frederick Inc, NCI, Frederick, MD 21701 USA. SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD 21701 USA. RP Pecon-Slattery, J (reprint author), SAIC Frederick Inc, NCI, Frederick, MD 21701 USA. EM Slattery@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 59 TC 37 Z9 44 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD DEC PY 2004 VL 21 IS 12 BP 2299 EP 2309 DI 10.1093/molbev/msh241 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 870RG UT WOS:000225074900011 PM 15329385 ER PT J AU Ayaydin, F Dasso, M AF Ayaydin, F Dasso, M TI Distinct in vivo dynamics of vertebrate SUMO paralogues SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID UBIQUITIN-LIKE PROTEINS; TOPOISOMERASE-II; SENTRIN FAMILY; NUCLEAR; PML; CONJUGATION; YEAST; SUMOYLATION; APOPTOSIS; COHESION AB There are three mammalian SUMO paralogues: SUMO-1 is similar to 45% identical to SUMO-2 and SUMO-3, which are 96% identical to each other. It is currently unclear whether SUMO-1, -2, and -3 function in ways that are unique, redundant, or antagonistic. To address this question, we examined the dynamics of individual SUMO paralogues by using cell lines that stably express each of the mammalian SUMO proteins fused to the yellow fluorescent protein (YFP). Whereas SUMO-2 and -3 showed very similar distributions throughout the nucleoplasm, SUMO-1 was uniquely distributed to the nuclear envelope and to the nucleolus. Photobleaching experiments revealed that SUMO-1 dynamics was much slower than SUMO-2 and -3 dynamics. Additionally, the mobility of SUMO paralogues differed between subnuclear structures. Finally, the timing and distributions were dissimilar between paralogues as cells exited from mitosis. SUMO-1 was recruited to nuclear membrane as nuclear envelopes reformed in late anaphase, and accumulated rapidly into the nucleus. SUMO-2 and SUMO-3 localized to chromosome earlier and accumulated gradually during telophase. Together, these findings demonstrate that mammalian SUMO-1 shows patterns of utilization that are clearly discrete from the patterns of SUMO-2 and -3 throughout the cell cycle, arguing that it is functionally distinct and specifically regulated in vivo. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov RI Ayaydin, Ferhan/C-4849-2011; OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD001902-13] NR 23 TC 119 Z9 124 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2004 VL 15 IS 12 BP 5208 EP 5218 DI 10.1091/mbc.E04-07.0589 PG 11 WC Cell Biology SC Cell Biology GA 874TN UT WOS:000225372800002 PM 15456902 ER PT J AU Jhaveri, MS Rait, AS Chung, KN Trepel, JB Chang, EH AF Jhaveri, MS Rait, AS Chung, KN Trepel, JB Chang, EH TI Antisense oligonucleotides targeted to the human alpha folate receptor inhibit breast cancer cell growth and sensitize the cells to doxorubicin treatment SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID P53 GENE-THERAPY; OVARIAN-CANCER; BINDING PROTEINS; MEDIATED ENDOCYTOSIS; TRANSFERRIN RECEPTOR; KB-CELLS; IN-VIVO; EXPRESSION; LINES; COMBINATION AB Folates are essential for cell survival and are required for numerous biochemical processes. The human a isoform folate receptor (alphahFR) has a very high affinity for folic acid and is considered an essential component in the cellular accumulation of folates and folate analogues used in chemotherapy. The expression of alphahFR is not detected in most normal tissues. In contrast, high levels of the expression of ahFR have been reported in a variety of cancer cells. The significance of alphahFR overexpression in malignant tissues has not been elucidated, but it is possible that it promotes cell proliferation not only by mediating folate uptake but also by generating other regulatory signals. The purpose of the present study was to evaluate alphahFR as a potential target for the treatment of breast cancer. Initial studies were done in nasopharyngeal carcinoma (KB) cells, which express high levels of alphahFR. In KB cells, antisense oligodeoxyribonucleotides (ODN) complementary to the alphahFR gene sequences were found to reduce newly synthesized ahFR protein up to 60%. To examine the effect of alphahFR antisense ODNs in a panel of cultured human breast cancer cell lines, we used a tumor cell-targeted, transferrin-liposome-mediated delivery system. The data show that alphahFR antisense ODNs induced a dose-dependent decrease in cell survival. Finally, we determined that alphahFR antisense ODNs sensitized MDA-MB-435 breast cancer cells by 5-fold to treatment with doxorubicin. The data support the application of alphahFR antisense ODNs as a potential anticancer agent in combination with doxorubicin. C1 Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20007 USA. Washington Univ, Sch Med, St Louis, MO USA. NCI, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. RP Chang, EH (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Canc Ctr, Res Bldg,E420,3970 Reservoir Rd NW, Washington, DC 20007 USA. EM change@georgetown.edu NR 43 TC 61 Z9 66 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2004 VL 3 IS 12 BP 1505 EP 1512 PG 8 WC Oncology SC Oncology GA 882QX UT WOS:000225954500001 PM 15634643 ER PT J AU Westcott, MM Abi-Habib, RJ Cohen, KA Willingham, MC Liu, SH Bugge, TH Leppla, SH Frankel, AE AF Westcott, MM Abi-Habib, RJ Cohen, KA Willingham, MC Liu, SH Bugge, TH Leppla, SH Frankel, AE TI Diphtheria toxin-murine granulocyte-macrophage colony-stimulating factor-induced hepatotoxicity is mediated by Kupffer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; FACTOR FUSION PROTEIN; FACTOR-RECEPTOR; RAT-LIVER; T-CELLS; GM-CSF; THERAPY; ACTIVATION; MICE AB DT(388)GMCSF, a fusion toxin composed of the NH2-terminal region of diphtheria toxin (DT) fused to human granulocyte-macrophage colony-stimulating factor (GMCSF) has shown efficacy in the treatment of acute myeloid leukemia. However, the primary dose-limiting side effect is liver toxicity. We have reproduced liver toxicity in rats using the rodent cell-tropic DT-murine GMCSF (DT(390)mGMCSF). Serum aspartate aminotransferase and alanine aminotransferase were elevated 15- and 4-fold, respectively, in DT(390)mGMCSF-treated rats relative to controls. Histologic analysis revealed hepatocyte swelling; however, this did not lead to hepatic necrosis or overt histopathologic changes in the liver. Immumohistochemical staining showed apoptotic cells in the sinusoids, and depletion of cells expressing the monocyte/macrophage markers, ED1 and ED2, indicating that Kupffer cells (KC) are targets of DT(390)mGMCSF. In contrast, sinusoidal endothelial cells seemed intact. In vitro, DT(390)mGMCSF was directly cytotoxic to primary KC but not hepatocytes. Two related fusion toxins, DT(388)GMCSF, which targets the human GMCSF receptor, and DT(390)mIL-3, which targets the rodent IL-3 receptor, induced a less than 2-fold elevation in serum transaminases and did not deplete KC in vivo. In addition, DTU2mGMCSF, a modified form of DT(390)mGMCSF with enhanced tumor cell specificity, was not hepatotoxic and was significantly less toxic to KC in vivo and in vitro. These results show that DT390 mGMCSF causes liver toxicity by targeting KC, and establish a model for studying how this leads to hepatocyte injury. Furthermore, alternative fusion toxins with potentially reduced hepatotoxicity are presented. C1 Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27157 USA. Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA. NIAID, Microbial Pathogenesis Sect, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Frankel, AE (reprint author), Wake Forest Univ, Sch Med, Dept Internal Med, Hanes 5045,Med Ctr Blvd, Winston Salem, NC 27157 USA. EM afrankel@wfubmc.edu FU NCI NIH HHS [R01CA90263, R01CA76178] NR 30 TC 12 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2004 VL 3 IS 12 BP 1681 EP 1689 PG 9 WC Oncology SC Oncology GA 882QX UT WOS:000225954500020 PM 15634662 ER PT J AU Kreitman, RJ AF Kreitman, RJ TI Confirmation and prevention of targeted toxicity by a recombinant fusion toxin SO MOLECULAR CANCER THERAPEUTICS LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; MARROW PROGENITOR CELLS; ACUTE MYELOID-LEUKEMIA; PHASE-I TRIAL; PSEUDOMONAS EXOTOXIN; DENILEUKIN DIFTITOX; CONTINUOUS-INFUSION; KUPFFER CELLS; IMMUNOTOXIN; RECEPTOR 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 NR 30 TC 4 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2004 VL 3 IS 12 BP 1691 EP 1692 PG 2 WC Oncology SC Oncology GA 882QX UT WOS:000225954500021 PM 15634663 ER PT J AU Jones, JW Culver, M David, V Struthers, J Johnson, NA Neves, RJ O'Brien, SJ Hallerman, EM AF Jones, JW Culver, M David, V Struthers, J Johnson, NA Neves, RJ O'Brien, SJ Hallerman, EM TI Development and characterization of microsatellite loci in the endangered oyster mussel Epioblasma capsaeformis (Bivalvia : Unionidae) SO MOLECULAR ECOLOGY NOTES LA English DT Article DE DNA; Epioblasma; freshwater mussel; microsatellites AB Primers for 10 polymorphic microsatellite loci were developed and characterized for the endangered oyster mussel Epioblasma capsaeformis from the Clinch River, Tennessee. Microsatellite loci also were tested in four other populations or species. Amplification was successful for most loci in these closely related endangered species or populations; therefore, a high level of flanking sequence similarity was inferred for this group of species and populations. Allelic diversity ranged from nine to 20 alleles/locus, and averaged 13.6/locus. This study demonstrated the feasibility of using polymerase chain reaction (PCR) primers to amplify microsatellite loci across freshwater mussel species to conduct population genetics studies. C1 Virginia Polytech Inst & State Univ, Dept Fisheries & Wildlife Sci, Coll Nat Resources, Blacksburg, VA 24061 USA. Univ Arizona, Sch Renewable Nat Resources, Tucson, AZ 85721 USA. FCRDC, Lab Genom Divers, Ft Detrick, MD 21702 USA. FCRDC, NCI, Ft Detrick, MD 21702 USA. Virginia Polytech Inst & State Univ, Virginia Cooperat Fish & Wildlife Res Unit, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, US Geol Survey, Dept Fisheries & Wildlife Sci, Blacksburg, VA 24061 USA. RP Jones, JW (reprint author), Virginia Polytech Inst & State Univ, Dept Fisheries & Wildlife Sci, Coll Nat Resources, Blacksburg, VA 24061 USA. EM vtaquaculture@hotmail.com OI Johnson, Nathan/0000-0001-5167-1988 NR 6 TC 11 Z9 15 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1471-8278 J9 MOL ECOL NOTES JI Mol. Ecol. Notes PD DEC PY 2004 VL 4 IS 4 BP 649 EP 652 DI 10.1111/j.1471-8286.2004.00762.x PG 4 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 876KV UT WOS:000225496600036 ER PT J AU Desai, KV Michalowska, AM Kondaiah, P Ward, JM Shih, JH Green, JE AF Desai, KV Michalowska, AM Kondaiah, P Ward, JM Shih, JH Green, JE TI Gene expression profiling identifies a unique androgen-mediated inflammatory/immune signature and a PTEN (phosphatase and tensin homolog deleted on chromosome 10)-mediated apoptotic response specific to the rat ventral prostate SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; METHYL-N-NITROSOUREA; CANCER CELLS; TESTOSTERONE PROPIONATE; SEQUENTIAL TREATMENT; CYPROTERONE-ACETATE; PROTEIN EXPRESSION; TUMOR PROGRESSION; TRANSGENIC MICE; WISTAR RATS AB Understanding androgen regulation of gene expression is critical for deciphering mechanisms responsible for the transition from androgen-responsive (AR) to androgen-independent ( AI) prostate cancer (PCa). To identify genes differentially regulated by androgens in each prostate lobe, the rat castration model was used. Microarray analysis was performed to compare dorsolateral (DLP) and ventral prostate (VP) samples from sham-castrated, castrated, and testosterone-replenished castrated rats. Our data demonstrate that, after castration, the VP and the DLP differed in the number of genes with altered expression (1496 in VP vs. 256 in DLP) and the nature of pathways modulated. Gene signatures related to apoptosis and immune response specific to the ventral prostate were identified. Microarray and RT-PCR analyses demonstrated the androgen repression of IGF binding protein-3 and -5, CCAAT-enhancer binding protein-delta, and phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) genes, previously implicated in apoptosis. We show that PTEN protein was increased only in the luminal epithelial cells of the VP, suggesting that it may be a key mediator of VP apoptosis in the absence of androgens. The castration-induced immune/inflammatory gene cluster observed specifically in the VP included IL-15 and IL-18. Immunostaining of the VP, but not the DLP, showed an influx of T cells, macrophages, and mast cells, suggesting that these cells may be the source of the immune signature genes. Interestingly, IL-18 was localized mainly to the basal epithelial cells and the infiltrating macrophages in the regressing VP, whereas IL-15 was induced in the luminal epithelium. The VP castration model exhibits immune cell infiltration and loss of PTEN that is often observed in progressive PCa, thereby making this model useful for further delineation of androgen-regulated gene expression with relevance to PCa. C1 NIH, Lab Cell Regulat & Carcinogenesis, Comparat Med Branch, NIAID, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Indian Inst Sci, Dept Mol Reprod Dev & Genet, Bangalore 560012, Karnataka, India. RP Green, JE (reprint author), NIH, Lab Cell Regulat & Carcinogenesis, Comparat Med Branch, NIAID, 41 Medlars Dr,Room C619, Bethesda, MD 20892 USA. EM jegreen@nih.gov NR 42 TC 26 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2004 VL 18 IS 12 BP 2895 EP 2907 DI 10.1210/me.2004-0033 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 873SL UT WOS:000225301100005 PM 15358834 ER PT J AU Buzas, B Belfer, I Hipp, H Lorincz, I Evans, C Phillips, G Taubman, J Max, MB Goldman, D AF Buzas, B Belfer, I Hipp, H Lorincz, I Evans, C Phillips, G Taubman, J Max, MB Goldman, D TI Haplotype block and superblock structures of the alpha 1-adrenergic receptor genes reveal echoes from the chromosomal past SO MOLECULAR GENETICS AND GENOMICS LA English DT Article DE adrenergic receptor; single-nucleotide polymorphism (SNP); haplotype; linkage disequilibrium; recombination ID ALPHA(1B)-ADRENERGIC RECEPTOR; HUMAN GENOME; ALPHA(1)-ADRENERGIC RECEPTOR; LINKAGE DISEQUILIBRIUM; ESSENTIAL-HYPERTENSION; PROTEIN-KINASE; ACTIVATION; POLYMORPHISMS; ADRENOCEPTOR; HYPERTROPHY AB A significant proportion of the human genome is contained within haplotype blocks across which pairwise linkage disequilibrium (LD) is very high. However, LD is also often high between markers at more remote distances, and within different haplotype blocks. Here, we evaluate the origins of haplotype block structure in the three genes for alphal adrenergic receptors (alpha1-AR) in the human genome (ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism (SNP) marker maps, and show that LD signals between distant markers are due to the presence of extended haplotype superblocks in individuals with ancient chromosomes which have escaped historic recombination. ARs mediate the physiological effects of epinephrine and norepinephrine, and are targets of many therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR missense variants, haplotype block structures in US Caucasians and African Americans, and haplotype tag SNPs for each block, and we present strong evidence for ancient haplotype block superstructure at these genes which has been partially disrupted by recombination, and evidence for reinstatement of linkage disequilibrium by subsequent recombination events. ADRA1A is comprised of four haplotype blocks in US Caucasians, while in African Americans Block I is split. ADRA1B has four blocks in US Caucasians, but in African Americans only the first two blocks are present. ADRA1D has two blocks in US Caucasians, and the first block is replaced by two smaller blocks in African Americans. For both A DRA1A and ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy in the human genome, which may reduce redundancy of testing by further aggregation of genotype data. C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Natl Inst Dental & Craniofacial Res, Pain & Neurosensory Mech Branch, Rockville, MD 20852 USA. RP Buzas, B (reprint author), NIAAA, Neurogenet Lab, Pk 5 Bldg,Room 431,12420 Parklawn Dr, Rockville, MD 20852 USA. EM bbuzas@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Hipp, Heather/0000-0002-1089-3928 FU NIAAA NIH HHS [Z01 AA000301] NR 27 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1617-4615 J9 MOL GENET GENOMICS JI Mol. Genet. Genomics PD DEC PY 2004 VL 272 IS 5 BP 519 EP 529 DI 10.1007/s00438-004-1074-9 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 886NP UT WOS:000226235900005 PM 15503142 ER PT J AU Myerowitz, R Mizukami, H Richardson, KL Finn, LS Tifft, CJ Proia, RL AF Myerowitz, R Mizukami, H Richardson, KL Finn, LS Tifft, CJ Proia, RL TI Global gene expression in a type 2 Gaucher disease brain SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Gaucher disease; sphingolipidoses; lysosomal storage disease; gene expression profiling ID INHERITED ENZYME DEFICIENCY; REPLACEMENT THERAPY; ALPHA-SYNUCLEIN; SERIAL ANALYSIS; PARKINSONS-DISEASE; HUMAN MONOCYTES; GLUCOCEREBROSIDASE; MOUSE; MACROPHAGES; COMPLEMENT AB Gaucher disease is a member of a family of inherited disorders called sphingolipidoses that among others includes Tay-Sachs and Sandhoff diseases. It is caused by the accumulation of glucosylceramide (glucocerebroside) due to deficient activity of the enzyme glucosylceramide-p-glucosidase (glucocerebrosidase). As with other glycosphingolipidoses, severe neurodegeneration is present in types 2 and 3 Gaucher disease. We have used Serial Analysis of Gene Expression (SAGE) to characterize the gene expression profiles in brain of patients with glycosphingolipid storage diseases to understand the molecular details of neurodegeneration. In the current study we have determined the gene expression profile from the brain of a patient with type 2 Gaucher disease, the acute neuronopathic form of the disorder. We found that the expression profile of the type 2 Gaucher brain is significantly altered relative to the normal control brain profile. There were also differences when compared with profiles from Tay-Sachs and Sandhoff patients, in particular in levels of genes related to macrophage activation. Intriguingly we found that gamma-synuclein, a family member of proteins involved the pathogenesis of other neurodegenerative disorders, was elevated in the one Gaucher type 2 patient brain we examined. (C) 2004 Elsevier Inc. All rights reserved. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. St Marys Coll Maryland, Dept Biol, St Marys City, MD 20686 USA. Univ Washington, Childrens Hosp & Med Ctr, Dept Pathol, Seattle, WA 98105 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 NR 40 TC 14 Z9 15 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2004 VL 83 IS 4 BP 288 EP 296 DI 10.1016/j.ymgme.2004.06.020 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 883MN UT WOS:000226016700001 PM 15589115 ER PT J AU Walker, LC Teebi, AS Marini, JC De Paepe, A Malfait, F Atsawasuwan, P Yamauchi, M Yeowell, HN AF Walker, LC Teebi, AS Marini, JC De Paepe, A Malfait, F Atsawasuwan, P Yamauchi, M Yeowell, HN TI Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE collagen cross-links; Ehlers-Danlos syndromes; genetic heterogeneity; lysyl hydroxylase2; mutational analysis; skin fibroblasts ID SYNDROME TYPE-VI; CROSS-LINKING; GALACTOSYLTRANSFERASE-I; LYSINE HYDROXYLATION; TISSUE DISTRIBUTION; MOLECULAR PACKING; MESSENGER-RNAS; COLLAGEN; DEFICIENCY; ISOFORM AB The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized by tissue fragility, hyperelasticity of the skin and joint hypermobility. This phenotype, accompanied by kyphoscoliosis and/or ocular fragility, is present in patients with the autosomal recessive type VI form of EDS. These patients have significantly decreased levels of lysyl hydroxylase (LH) activity, due to mutations in the LH1 gene. LH hydroxylates specific lysine residues in the collagen molecule that are precursors for the formation of cross-links which provide collagen with its tensile strength. No disorder has been directly linked to decreased expression of LH2 and LH3, two other isoforms of LH. This study describes 3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 mRNAs, in their skin fibroblasts. In contrast to the effect of LH1 deficiency in EDS VI patients, the decreased expression of LH2 does not affect LH activity, bifunctional collagen cross-links (measured after reduction as dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL)), or helical lysine hydroxylation in these cell lines. Sequence analysis of full length LH2 cDNAs and 1 kb of the promoter region of LH2 does not show mutations that could explain the decreased expression of LH2. These results suggest that the deficiency of LH2 in these fibroblasts may be caused by changes in other factors required for the expression of LH2. (C) 2004 Elsevier Inc. All rights reserved. C1 Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. Univ Toronto, Div Clin Genet, Toronto, ON, Canada. NICHD, Heritable Disorders Branch, Bethesda, MD USA. State Univ Ghent Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. RP Walker, LC (reprint author), Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. RI Malfait, Fransiska/K-7897-2014; OI Atsawasuwan, Phimon/0000-0002-2576-060X FU NIA NIH HHS [AG10215] NR 39 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2004 VL 83 IS 4 BP 312 EP 321 DI 10.1016/j.ymgme.2004.07.013 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 883MN UT WOS:000226016700004 PM 15589118 ER PT J AU Nguyen, DH Taub, DD AF Nguyen, DH Taub, DD TI Targeting lipids to prevent HIV infection SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEMBRANE CHOLESTEROL; T-LYMPHOCYTES; TYPE-1; RAFTS; ENTRY; CD4; MICRODOMAINS; RECEPTOR; DOMAINS C1 Univ Calif San Diego, Sch Med, Glycobiol Res & Training Program, La Jolla, CA 92093 USA. NIA, Immunol Lab, NIH, DHHS,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), Univ Calif San Diego, Sch Med, Glycobiol Res & Training Program, La Jolla, CA 92093 USA. EM dhn002@ucsd.edu; Taubd@grc.nia.ruh.gov NR 28 TC 16 Z9 18 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD DEC PY 2004 VL 4 IS 6 BP 318 EP 320 DI 10.1124/mi4.6.3 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 884AZ UT WOS:000226058300003 PM 15616159 ER PT J AU Szakacs, G Gottesman, MM AF Szakacs, G Gottesman, MM TI Comparing solid tumors with cell lines: Implications for identifying drug resistance genes in cancer SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID DATABASE C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Szakacs, G (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM szakacsg@mail.nih.gov; mgottesman@nih.gov RI Szakacs, Gergely/A-2580-2009 OI Szakacs, Gergely/0000-0002-9311-7827 NR 6 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD DEC PY 2004 VL 4 IS 6 BP 323 EP 325 DI 10.1124/mi.4.6.5 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 884AZ UT WOS:000226058300005 PM 15616161 ER PT J AU Jacobson, KA Kim, SK Costanzi, S Gao, ZG AF Jacobson, KA Kim, SK Costanzi, S Gao, ZG TI Purine receptors: GPCR structure and agonist design SO MOLECULAR INTERVENTIONS LA English DT Review ID PROTEIN-COUPLED RECEPTOR; SITE-DIRECTED MUTAGENESIS; A(3) ADENOSINE RECEPTORS; P2Y(1) RECEPTOR; ADRENERGIC-RECEPTOR; SPECIES-DIFFERENCES; LIGAND RECOGNITION; NUCLEOTIDE ANALOGS; A-3 RECEPTOR; BINDING-SITE AB An integrated approach to the study of drug-receptor interactions has been applied to adenosine receptors (ARs) and P2Y nucleotide receptors. This approach includes probing the receptor structure through site-directed mutagenesis and molecular modeling, in concert with altering the structure of the agonist ligands. Goals of this structural approach are to generate a testable hypothesis for location of the binding site and subsequently to enable the rational design of new agonists and antagonists. In this manner, receptor subtype selectivity has been increased, and agonists have been converted into partial agonists and antagonists. An approach to receptor engineering (neoceptors) has been explored, in which synthetic small molecule agonists (neoligands) are specifically tailored to activate only receptors in which the putative binding sites have been modified. This orthogonal approach to receptor activation, intended for eventual gene therapy, has been demonstrated for A(3) and A(2A) ARs. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [ZIA DK031126-03, Z01 DK031116-20, Z01 DK031117-20, Z99 DK999999] NR 55 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD DEC PY 2004 VL 4 IS 6 BP 337 EP 347 DI 10.1124/mi.4.6.7 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 884AZ UT WOS:000226058300007 PM 15616163 ER PT J AU Seshu, J Boylan, JA Hyde, JA Swingle, KL Gherardini, FC Skare, JT AF Seshu, J Boylan, JA Hyde, JA Swingle, KL Gherardini, FC Skare, JT TI A conservative amino acid change alters the function of BosR, the redox regulator of Borrelia burgdorferi SO MOLECULAR MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; OXYR TRANSCRIPTION FACTOR; FERRIC UPTAKE REGULATOR; OUTER-SURFACE PROTEIN; GENE-EXPRESSION; MAMMALIAN HOST; OXIDATIVE STRESS; RESPONSE REGULATOR; LINEAR PLASMID-25; HYDROGEN-PEROXIDE AB Borrelia burgdorferi, the aetiologic agent of Lyme disease, modulates gene expression in response to changes imposed by its arthropod vector and mammalian hosts. As reactive oxygen species (ROS) are known to vary in these environments, we asked how B. burgdorferi responds to oxidative stress. The B. burgdorferi genome encodes a PerR homologue (recently designated BosR) that represses the oxidative stress response in other bacteria, suggesting a similar function in B. burgdorferi. When we tested the sensitivity of B. burgdorferi to ROS, one clonal non-infectious B. burgdorferi isolate exhibited hypersensitivity to t-butyl hydroperoxide when compared with infectious B. burgdorferi and other non-infectious isolates. Sequence analysis indicated that the hypersensitive non-infectious isolates bosR allele contained a single nucleotide substitution, converting an arginine to a lysine (bosRR39K). Mutants in bosRR39K exhibited an increase in resistance to oxidative stressors when compared with the parental non-infectious strain, suggesting that BosRR39K functioned as a repressor. Complementation with bosRR39K and bosR resulted in differential sensitivity to t-butyl hydroperoxide, indicating that these alleles are functionally distinct. In contrast to BosR, BosRR39K did not activate transcription of a napA promoter-lacZ reporter in Escherichia coli nor bind the napA promoter/operator domain. However, we found that both BosR and BosRR39K bound to the putative promoter/operator region of superoxide dismutase (sodA). In addition, we determined that cells lacking BosRR39K synthesized fourfold greater levels of the decorin binding adhesin DbpA suggesting that BosRR39K regulates genes unrelated to oxidative stress. Based on these data, we propose that the single amino acid substitution, R39K, dramatically alters the activity of BosR by altering its ability to bind DNA at target regulatory sequences. C1 Texas A&M Univ, Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. RP Skare, JT (reprint author), Texas A&M Univ, Hlth Sci Ctr, Dept Med Microbiol & Immunol, 407 Reynolds Med Bldg, College Stn, TX 77843 USA. EM jskare@tamu.edu FU NIAID NIH HHS [AI42345, R01 AI042345] NR 42 TC 36 Z9 36 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2004 VL 54 IS 5 BP 1352 EP 1363 DI 10.1111/j.1365-2958.2004.04352.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 873FI UT WOS:000225264900018 PM 15554974 ER PT J AU Kim, WH Park, WB Gao, B Jung, MH AF Kim, WH Park, WB Gao, B Jung, MH TI Critical role of reactive oxygen species and mitochondrial membrane potential in Korean mistletoe lectin-induced apoptosis in human hepatocarcinoma cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; ALBUM VAR. COLORATUM; VISCUM-ALBUM; PERMEABILITY TRANSITION; AGGLUTININ-I; CASPASES; BCL-2; MECHANISMS; NECROSIS AB Viscum album L. coloratum agglutinin (VCA), isolated from Korean mistletoe, is a strong inducer of apoptosis in a variety of tumor cells; however, the underlying molecular mechanisms responsible are not clear. Here, we show that VCA induces apoptotic killing, as demonstrated by DNA fragmentation, Hoechst 33258 staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and flow cytometry analysis in hepatocarcinoma Hep3B cells. VCA treatment results in a significant increase in reactive oxygen species (ROS) and loss of mitochondrial membrane potential (DeltaPsim). Furthermore, treatment with the antioxidant N-acetyl-L-cysteine reduces ROS induction by VCA, preventing apoptosis in Hep3B cells, indicating that oxidative stress is involved in VCA-mediated cell death. Our results also show rapid changes in mitochondrial transition permeability, Bax translocation, cytochrome c release, caspase-3 activity, and poly(ADP-ribose) polymerase degradation in Hep3B cells occurring in VCA-induced apoptosis. There is much evidence that implicates c-Jun NH2-terminal kinase (JNK) activation with apoptosis in a variety of cellular and animal models. In this study, we show that VCA induces JNK phosphorylation, which is abolished with pretreatment with a JNK inhibitor. Moreover, Hep3B cells overexpressing JNK1 or stress-activated protein kinase kinase (SEK1) seem to be more susceptible to cell death from ROS and loss of DeltaPsim induced by VCA, whereas expression of dominant-negative JNK1 or SEK1 in Hep3B cells do not. These data suggest that JNK phosphorylation may be a major regulator involved in VCA-induced apoptosis. Together, these results suggest that VCA induces apoptosis by inducing ROS production and a loss of DeltaPsim, in which JNK phosphorylation plays a critical role in these events. C1 Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, Seoul 122701, South Korea. Seoul Womens Univ, Coll Nat Sci, Seoul, South Korea. NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Jung, MH (reprint author), Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, 5 Nokbun Dong, Seoul 122701, South Korea. EM jung0603@nih.go.kr NR 40 TC 58 Z9 65 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2004 VL 66 IS 6 BP 1383 EP 1396 DI 10.1124/mol.104.001347 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 873VQ UT WOS:000225309900003 PM 15340045 ER PT J AU Annereau, JP Szakacs, G Tucker, CJ Arciello, A Cardarelli, C Collins, J Grissom, S Zeeberg, BR Reinhold, W Weinstein, JN Pommier, Y Paules, RS Gottesman, MM AF Annereau, JP Szakacs, G Tucker, CJ Arciello, A Cardarelli, C Collins, J Grissom, S Zeeberg, BR Reinhold, W Weinstein, JN Pommier, Y Paules, RS Gottesman, MM TI Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance SO MOLECULAR PHARMACOLOGY LA English DT Article ID GENE-EXPRESSION; CARCINOMA-CELLS; CANCER-CELLS; P-GLYCOPROTEIN; CAMPTOTHECIN RESISTANCE; LUNG-CANCER; SENSITIVITY; PROTEINS; OVEREXPRESSION; ANTICANCER AB Discovery of the multidrug resistance protein 1 (MDR1), an ATP-binding cassette (ABC) transporter able to transport many anticancer drugs, was a clinically relevant breakthrough in multidrug resistance research. Although the overexpression of ABC transporters such as P-glycoprotein/ABCB1, MRP1/ABCC1, and MXR/ABCG2 seems to be a major cause of failure in the treatment of cancer, acquired resistance to multiple anticancer drugs may also be multifactorial, involving alteration of detoxification processes, apoptosis, DNA repair, drug uptake, and overexpression of other ABC transporters. As a tool for the study of such phenomena, we designed and created a microarray platform, the ABC-ToxChip, to evaluate relative levels of transcriptional activation among genes involved in the various mechanisms of resistance. In the ABC-ToxChip, a comprehensive set of genes important in toxicological responses (represented by 2200 cDNA probes) is complemented with probes specifically matching ABC transporters as well as oligonucleotides representing 18,000 unique human genes. By comparing the transcriptional profiles of KB-3-1 and DU-145 parental cells with resistant derivatives selected in colchicine (KB-8-5), and 9-nitro-camptothecin (RCO.1), respectively, we demonstrate that ABC transporters (ABCB1/MDR1 and ABCC2/MRP2, respectively) show dramatic overexpression, whereas the glutathione S-transferase gene GST-Pi shows the strongest decrease in expression among the 20,000 genes studied. The results were confirmed by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The custom-designed ABC-Tox microarray presented here will be helpful to elucidate mechanisms leading to anticancer drug resistance. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Szakacs, Gergely/A-2580-2009 OI Szakacs, Gergely/0000-0002-9311-7827 NR 45 TC 64 Z9 68 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2004 VL 66 IS 6 BP 1397 EP 1405 DI 10.1124/mol.104.005009 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 873VQ UT WOS:000225309900004 PM 15342794 ER PT J AU Yokochi, T Robertson, KD AF Yokochi, T Robertson, KD TI Doxorubicin inhibits DNMT1, resulting in conditional apoptosis SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN CANCER-CELLS; DNA METHYLTRANSFERASE; DE-NOVO; METHYLATION; ADRIAMYCIN; ACTIVATION; EXPRESSION; TOXICITY; GENES AB Chemotherapy using DNA intercalators is one of the most successful approaches to cancer treatment. Although DNA intercalators are believed to inhibit DNA polymerases and topoisomerases, resulting in the induction of apoptosis in tumor cells, other factors potentially inhibited by the anthracycline antibiotics remain to be elucidated. Herein, we show that the enzymatic activity of DNMT1, the primary DNA methyltransferase in mammalian cells, is inhibited by DNA intercalators, such as doxorubicin, in an in vitro assay. Enzymatic analyses indicate that doxorubicin inhibits the catalytic activity of DNMT1 via DNA intercalation. We also found that apoptosis was induced in DNMT1(+/+) HCT116 cells by only a limited range of doxorubicin dose, meaning that apoptotic cell death is "conditional" with respect to the concentration of the DNA intercalating drug. It is noteworthy that conditional apoptosis is not observed in human colorectal cancer cells lacking DNMT1 but can be induced in DNMT1(+/+) cells by transfection of a plasmid expressing DNMT1. Our results suggest that DNMT1 is one of the major targets of doxorubicin resulting in drug-induced apoptosis in human cancer cells. We propose that expression levels of DNMT1 in tumor cells may affect the effectiveness of doxorubicin in chemotherapy. C1 NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bethesda, MD 20892 USA. RP Robertson, KD (reprint author), Univ Florida, Dept Biochem & Mol Biol, Box 100245, Gainesville, FL 32610 USA. EM keithr@ufl.edu FU NCI NIH HHS [1K22-CA84535-01] NR 30 TC 53 Z9 58 U1 2 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2004 VL 66 IS 6 BP 1415 EP 1420 DI 10.1124/mol.104.002634 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 873VQ UT WOS:000225309900006 PM 15340041 ER PT J AU Kel, A Reymann, S Matys, V Nettesheim, P Wingender, E Borlak, J AF Kel, A Reymann, S Matys, V Nettesheim, P Wingender, E Borlak, J TI A novel computational approach for the prediction of networked transcription factors of aryl hydrocarbon-receptor-regulated genes SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROMOTER MODULE; BINDING-SITES; EXPRESSION; ELEMENTS; RECOGNITION; CELLS; IDENTIFICATION; SEQUENCES; SYSTEM AB A novel computational method based on a genetic algorithm was developed to study composite structure of promoters of coexpressed genes. Our method enabled an identification of combinations of multiple transcription factor binding sites regulating the concerted expression of genes. In this article, we study genes whose expression is regulated by a ligand-activated transcription factor, aryl hydrocarbon receptor (AhR), that mediates responses to a variety of toxins. AhR-mediated change in expression of AhR target genes was measured by oligonucleotide microarrays and by reverse transcription-polymerase chain reaction in human and rat hepatocytes. Promoters and long-distance regulatory regions (>10 kb) of AhR-responsive genes were analyzed by the genetic algorithm and a variety of other computational methods. Rules were established on the local oligonucleotide context in the flanks of the AhR binding sites, on the occurrence of clusters of AhR recognition elements, and on the presence in the promoters of specific combinations of multiple binding sites for the transcription factors cooperating in the AhR regulatory network. Our rules were applied to search for yet unknown Ah-receptor target genes. Experimental evidence is presented to demonstrate high fidelity of this novel in silico approach. C1 Ctr Drug Res & Med Biotechnol, Fraunhofer Inst Toxicol & Expt Med, D-30625 Hannover, Germany. BIOBASE GmbH, Wolfenbuttel, Germany. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. NIEHS, Res Triangle Pk, NC 27709 USA. Hannover Med Sch, Ctr Pharmacol & Toxicol, D-3000 Hannover, Germany. RP Borlak, J (reprint author), Ctr Drug Res & Med Biotechnol, Fraunhofer Inst Toxicol & Expt Med, Nikolai Fuchs Str 1, D-30625 Hannover, Germany. EM borlak@item.fraunhofer.de OI Wingender, Edgar/0000-0002-7729-8453 NR 29 TC 24 Z9 25 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2004 VL 66 IS 6 BP 1557 EP 1572 DI 10.1124/mol.104.001677 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 873VQ UT WOS:000225309900020 PM 15342792 ER PT J AU Xiao, YF Ke, QG Seubert, JM Bradbury, JA Graves, J DeGraff, LM Falck, JR Krausz, K Gelboin, HV Morgan, JP Zeldin, DC AF Xiao, YF Ke, QG Seubert, JM Bradbury, JA Graves, J DeGraff, LM Falck, JR Krausz, K Gelboin, HV Morgan, JP Zeldin, DC TI Enhancement of cardiac L-type Ca2+ currents in transgenic mice with cardiac-specific overexpression of CYP2J2 SO MOLECULAR PHARMACOLOGY LA English DT Article ID ARACHIDONIC-ACID METABOLISM; SENSITIVE K+ CHANNELS; DEPENDENT PROTEIN-KINASE; RAT VENTRICULAR MYOCYTES; EPOXYEICOSATRIENOIC ACIDS; CALCIUM-CHANNELS; SMOOTH-MUSCLE; HUMAN CYTOCHROME-P450; MOLECULAR-CLONING; HUMAN PLATELETS AB CYP2J2 is abundant in cardiomyocytes and is involved in the metabolism of arachidonic acid ( AA) to epoxyeicosatrienoic acids (EETs), which affect multiple cell functions. In this study, we investigated the effect of overexpression of CYP2J2 on cardiac L-type Ca2+ currents (I-Ca) in adult transgenic mice. Cardiac-specific overexpression of CYP2J2 was achieved using the alpha-myosin heavy chain promoter. I-Ca was recorded from isolated ventricular cardiomyocytes. Compared with the wildtype cardiomyocytes (n = 60), the density of I-Ca was significantly increased by 40 +/- 9% in the CYP2J2 transgenic cardiomyocytes ( n = 71; P < 0.001). N-Methylsulfonyl-6-(2-proparglyloxyphenyl) hexanamide (MS-PPOH), a specific inhibitor of EET biosynthesis, and clotrimazole, a cytochrome P450 inhibitor, significantly reduced I-Ca in both wild-type and transgenic cardiomyocytes; however, MS-PPOH inhibited I-Ca to a greater extent in the CYP2J2 transgenic cells ( n = 10) than in the wild-type cells ( n = 10; P < 0.01). Addition of 11,12-EET significantly restored I-Ca in MS-PPOH-treated cells. Intracellular dialysis with either of two inhibitory monoclonal antibodies against CYP2J2 significantly reduced I-Ca in both wild-type and transgenic mice. Membrane-permeable 8-bromo-cAMP and the beta-adrenergic agonist isoproterenol significantly reversed the monoclonal antibody-induced inhibition of I-Ca. In addition, the total protein level of the alpha1 subunit of the Ca-v 1.2 L-type Ca2+ channel was not altered in CYP2J2 transgenic hearts, but the phosphorylated portion was markedly increased. In conclusion, overexpression of CYP2J2 increases I-Ca in CYP2J2 transgenic cardiomyocytes via a mechanism that involves cAMP-protein kinase A-dependent phosphorylation of the L-type Ca2+ channel. C1 Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Div Cardiovasc, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Univ Texas SW, Dept Biochem, Dallas, TX USA. NCI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Xiao, YF (reprint author), Medtronic Inc, 7000 Cent Ave NE,B252, Minneapolis, MN 55432 USA. EM yong-fu.xiao@medtronic.com OI Falck, John/0000-0002-9219-7845 FU NIGMS NIH HHS [GM31278] NR 39 TC 37 Z9 39 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2004 VL 66 IS 6 BP 1607 EP 1616 DI 10.1124/mol.104.004150 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 873VQ UT WOS:000225309900026 PM 15361551 ER PT J AU Hempel, N Wang, HB LeCluyse, EL McManus, ME Negishi, M AF Hempel, N Wang, HB LeCluyse, EL McManus, ME Negishi, M TI The human sulfotransferase SULT1A1 gene is regulated in a synergistic manner by Sp1 and GA binding protein SO MOLECULAR PHARMACOLOGY LA English DT Article ID THERMOLABILE PHENOL SULFOTRANSFERASE; TRANSCRIPTION FACTOR GABP; STRUCTURAL-CHARACTERIZATION; HUMAN HEPATOCYTES; THYROID-HORMONE; RECEPTOR CAR; ETS FAMILY; EXPRESSION; CLONING; CDNA AB Human sulfotransferase SULT1A1 is an important phase II xenobiotic metabolizing enzyme that is highly expressed in the liver and mediates the sulfonation of drugs, carcinogens, and steroids. Until this study, the transcriptional regulation of the SULT1A subfamily had been largely unexplored. Preliminary experiments in primary human hepatocytes showed that SULT1A mRNA levels were not changed in response to nuclear receptor activators, such as dexamethasone and 3-methylcolanthrene, unlike other metabolizing enzymes. Using HepG2 cells, the high activity of the TATA-less SULT1A1 promoter was shown to be dependent on the presence of Sp1 and Ets transcription factor binding sites (EBS), located within - 112 nucleotides from the transcriptional start site. The homologous promoter of the closely related SULT1A3 catecholamine sulfotransferase, which is expressed at negligible levels in the adult liver, displayed 70% less activity than SULT1A1. This was shown to be caused by a two-base pair difference in the EBS. The Ets transcription factor GA binding protein (GABP) was shown to bind the SULT1A1 EBS and could transactivate the SULT1A1 promoter in Drosophila melanogaster S2 cells. Cotransfection of Sp1 could synergistically enhance GABP-mediated activation by 10-fold. Although Sp1 and GABP alone could induce SULT1A3 promoter activity, the lack of the EBS on this promoter prevented a synergistic interaction between the two factors. This study reports the first insight into the transcriptional regulation of the SULT1A1 gene and identifies a crucial difference in regulation of the closely related SULT1A3 gene, which accounts for the two enzymes' differential expression patterns observed in the adult liver. C1 Univ Queensland, Fac Biol & Chem Sci, Sch Biomed Sci, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia. Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC USA. NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, Res Triangle Pk, NC 27709 USA. RP McManus, ME (reprint author), Univ Queensland, Fac Biol & Chem Sci, Sch Biomed Sci, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia. EM m.mcmanus@uq.edu.au RI Hempel, Nadine/F-1700-2014; OI Hempel, Nadine/0000-0002-5574-8783; LeCluyse, Edward/0000-0002-2149-8990 NR 40 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2004 VL 66 IS 6 BP 1690 EP 1701 DI 10.1124/mol.104.003350 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 873VQ UT WOS:000225309900035 PM 15383623 ER PT J AU Patterson, GH AF Patterson, GH TI A new harvest of fluorescent proteins SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Patterson, GH (reprint author), NIH, Cell Biol & Metab Branch, Bldg 18T Rm 101,18 Lib Dr, Bethesda, MD 20892 USA. EM pattersg@mail.nih.gov NR 11 TC 18 Z9 19 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2004 VL 22 IS 12 BP 1524 EP 1525 DI 10.1038/nbt1204-1524 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 878HX UT WOS:000225638600019 PM 15583657 ER PT J AU Lee, JS Chu, IS Mikaelyan, A Calvisi, DF Heo, J Reddy, JK Thorgeirsson, SS AF Lee, JS Chu, IS Mikaelyan, A Calvisi, DF Heo, J Reddy, JK Thorgeirsson, SS TI Application of comparative functional genomics to identify best-fit mouse models to study human cancer SO NATURE GENETICS LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; GROWTH-FACTOR-ALPHA; ACYL-COA OXIDASE; PEROXISOME PROLIFERATOR; HEPATOCELLULAR-CARCINOMA; C-MYC; TRANSGENIC MICE; CELL LYMPHOMA; LIVER-TUMORS; HEPATOCARCINOGENESIS AB Genetically modified mice have been extensively used for analyzing the molecular events that occur during tumor development. In many, if not all, cases, however, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions(1-3). This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. Here we use global gene expression patterns of 68 hepatocellular carcinomas (HCCs) from seven different mouse models and 91 human HCCs from predefined subclasses(4) to obtain direct comparison of the molecular features of mouse and human HCCs. Gene expression patterns in HCCs from Myc, E2f1 and Myc E2f1 transgenic mice were most similar to those of the better survival group of human HCCs, whereas the expression patterns in HCCs from Myc Tgfa transgenic mice and in diethylnitrosamine-induced mouse HCCs were most similar to those of the poorer survival group of human HCCs. Gene expression patterns in HCCs from Acox1(-/-) mice and in ciprofibrate-induced HCCs were least similar to those observed in human HCCs. We conclude that our approach can effectively identify appropriate mouse models to study human cancers. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 30 TC 262 Z9 267 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2004 VL 36 IS 12 BP 1306 EP 1311 DI 10.1038/ng1481 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 874MI UT WOS:000225354100019 PM 15565109 ER PT J AU Mocellin, S Mandruzzato, S Bronte, V Marincola, FM AF Mocellin, S Mandruzzato, S Bronte, V Marincola, FM TI Cancer vaccines: pessimism in check SO NATURE MEDICINE LA English DT Letter ID TUMOR-CELL VACCINE; IMMUNOTHERAPY; MELANOMA; ANTIGEN; CARCINOMA; RESPONSES; TRIAL C1 Univ Padua, Dept Oncol & Surg Sci, Surg Sect, I-35128 Padua, Italy. Univ Padua, Dept Oncol & Surg Sci, Oncol Sect, I-35128 Padua, Italy. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Mocellin, S (reprint author), Univ Padua, Dept Oncol & Surg Sci, Surg Sect, Via Giustiniani, I-35128 Padua, Italy. EM mocellins@hotmail.com RI Bronte, Vincenzo/K-7902-2016 OI Bronte, Vincenzo/0000-0002-3741-5141 NR 15 TC 39 Z9 42 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2004 VL 10 IS 12 BP 1278 EP 1279 DI 10.1038/nm1204-1278 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 876MK UT WOS:000225500900012 PM 15580242 ER PT J AU Rosenberg, SA Yang, JC Restifo, NP AF Rosenberg, SA Yang, JC Restifo, NP TI Cancer vaccines: pessimism in check - Reply SO NATURE MEDICINE LA English DT Letter ID ANTITUMOR LYMPHOCYTES; T-CELLS; REGRESSION; AUTOIMMUNITY C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, CRC Room 3-3940,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. EM sar@mail.nih.gov RI Restifo, Nicholas/A-5713-2008 NR 8 TC 8 Z9 8 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2004 VL 10 IS 12 BP 1279 EP 1280 DI 10.1038/nm1204-1279b PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 876MK UT WOS:000225500900014 ER PT J AU Wood, A Grady, C Emanuel, EJ AF Wood, A Grady, C Emanuel, EJ TI Regional ethics organizations for protection of human research participants SO NATURE MEDICINE LA English DT Editorial Material ID MULTICENTER RESEARCH; CLINICAL-TRIALS; BOARDS; COMMITTEES; OVERSIGHT C1 Univ Calif Berkeley, Sch Law, Berkeley, CA 94720 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wood, A (reprint author), Univ Calif Berkeley, Sch Law, Berkeley, CA 94720 USA. EM eemanuel@nih.gov NR 28 TC 18 Z9 18 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2004 VL 10 IS 12 BP 1283 EP 1288 DI 10.1038/nm1204-1283 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 876MK UT WOS:000225500900015 PM 15580245 ER PT J AU Germain, RN AF Germain, RN TI An innately interesting decade of research in immunology SO NATURE MEDICINE LA English DT Review ID REGULATORY T-CELLS; TOLL-LIKE RECEPTORS; NATURAL-KILLER-CELLS; PLASMACYTOID DENDRITIC CELLS; ECTODERMAL DYSTROPHY PATIENTS; SECONDARY LYMPHOID ORGANS; ADAPTIVE IMMUNE-RESPONSES; CLASS-I; NK CELLS; ANTIGEN PRESENTATION AB Nature has provided, in the white corpuscles as you call them - in the phagocytes as we call them - a natural means of devouring and destroying all disease germs. There is at bottom only one genuinely scientific treatment for all diseases, and that is to stimulate the phagocytes." So opined B. B. in G. B. Shaw's The Doctor's Dilemma(1) in a dramatic restatement of a key portion of Ilya Metchnikoff's Nobel Prize address: "Whenever the organism enjoys immunity, the introduction of infectious microbes is followed by the accumulation of mobile cells, of white corpuscles of the blood in particular which absorb the microbes and destroy them. The white corpuscles and the other cells capable of doing this have been designated 'phagocytes,' (i.e., devouring cells) and the whole function that ensures immunity has been given the name of 'phagocytosis('"2). Based on these insights into the foundation of resistance to infectious disease, Metchnikoff was awarded the 1908 Nobel Prize in Physiology or Medicine together with Paul Ehrlich ( Fig. 1). Although both were cited for discoveries in immunity, the contributions of the two men seem worlds apart. Ehrlich's studies did not deal with generic responses to infection, but rather with the highly specific nature of antibodies and their relationship to the cells producing them: "As the cell receptor is obviously preformed, and the artificially produced antitoxin only the consequence, i.e. secondary, one can hardly fail to assume that the antitoxin is nothing else but discharged components of the cell, namely receptors discharged in excess("3). But biological systems are just that - systems - and the parts need to work together. And so we arrive, a century later, at an appreciation for just how intimately related these two seemingly disparate aspects of host defense really are. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 299 TC 81 Z9 87 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2004 VL 10 IS 12 BP 1307 EP 1320 DI 10.1038/nm1159 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 876MK UT WOS:000225500900024 PM 15580257 ER PT J AU Woods, C Montcouquiol, M Kelley, MW AF Woods, C Montcouquiol, M Kelley, MW TI Math1 regulates development of the sensory epithelium in the mammalian cochlea SO NATURE NEUROSCIENCE LA English DT Article ID HAIR CELL-DIFFERENTIATION; INNER-EAR DEVELOPMENT; MIND-BOMB MUTANT; GAMMA-SECRETASE; ORGAN DEVELOPMENT; EXPRESSION; NOTCH; ZEBRAFISH; CORTI; PROTEINS AB The transcription factor Math1 (encoded by the gene Atoh1, also called Math1) is required for the formation of mechanosensory hair cells in the inner ear; however, its specific molecular role is unknown. Here we show that absence of Math1 in mice results in a complete disruption of formation of the sensory epithelium of the cochlea, including the development of both hair cells and associated supporting cells. In addition, ectopic expression of Math1 in nonsensory regions of the cochlea is sufficient to induce the formation of sensory clusters that contain both hair cells and supporting cells. The formation of these clusters is dependent on inhibitory interactions mediated, most probably, through the Notch pathway, and on inductive interactions that recruit cells to develop as supporting cells through a pathway independent of Math1. These results show that Math1 functions in the developing cochlea to initiate both inductive and inhibitory signals that regulate the overall formation of the sensory epithelia. C1 NIDCD, Sect Dev Neurosci, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Kelley, MW (reprint author), NIDCD, Sect Dev Neurosci, NIH, Porter Neurosci Res Ctr, Bldg 35, Bethesda, MD 20892 USA. EM kelleymt@nidcd.nih.gov OI montcouquiol, mireille/0000-0001-8739-6519 NR 46 TC 215 Z9 227 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2004 VL 7 IS 12 BP 1310 EP 1318 DI 10.1038/nn1349 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 874MG UT WOS:000225353900011 PM 15543141 ER PT J AU Sutter, NB Ostrander, EA AF Sutter, NB Ostrander, EA TI Dog star rising: The canine genetic system SO NATURE REVIEWS GENETICS LA English DT Review ID RADIATION HYBRID MAP; MULTIFOCAL RENAL CYSTADENOCARCINOMAS; PROGRESSIVE RETINAL ATROPHY; COMPARATIVE CHROMOSOME MAP; COPPER TOXICOSIS LOCUS; GERMAN-SHEPHERD DOG; HOGG-DUBE-SYNDROME; LINKAGE DISEQUILIBRIUM; DOMESTIC DOG; NODULAR DERMATOFIBROSIS AB Purebred dogs are providing invaluable information about morphology, behaviour and complex diseases, both of themselves and humans, by supplying tractable populations in which to map genes that control those processes. The diversification of dog breeds has led to the development of breeds enriched for particular genetic disorders, the mapping and cloning of which have been facilitated by the availability of the canine genome map and sequence. These tools have aided our understanding of canine population genetics, linkage disequilibrium and haplotype sharing in the dog, and have informed ongoing efforts of the need to identify quantitative trait loci that are important in complex traits. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, 50 South Dr,MSC8002,Bldg 50,Room 5222, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 NR 101 TC 130 Z9 138 U1 7 U2 48 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD DEC PY 2004 VL 5 IS 12 BP 900 EP 910 DI 10.1038/nrg1492 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 875JQ UT WOS:000225416800012 PM 15573122 ER PT J AU Waters, MD Fostel, JM AF Waters, MD Fostel, JM TI Toxicogenomics and systems toxicology: Aims and prospects SO NATURE REVIEWS GENETICS LA English DT Review ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION ANALYSIS; DNA MICROARRAYS; RISK-ASSESSMENT; MOUSE-LIVER; PROTEIN EXPRESSION; RAT-LIVER; SACCHAROMYCES-CEREVISIAE; INDUCED HEPATOTOXICITY; MASS-SPECTROMETRY AB Toxicogenomics combines transcript, protein and metabolite profiling with conventional toxicology to investigate the interaction between genes and environmental stress in disease causation. The patterns of altered molecular expression that are caused by specific exposures or disease outcomes have revealed how several toxicants act and cause disease. Despite these success stories, the field faces noteworthy challenges in discriminating the molecular basis of toxicity. We argue that toxicology is gradually evolving into a systems toxicology that will eventually allow us to describe all the toxicological interactions that occur within a living system under stress and use our knowledge of toxicogenomic responses in one species to predict the modes-of-action of similar agents in other species. C1 NIEHS, Natl Ctr Toxicogen, Res Triangle Pk, NC 27709 USA. RP Waters, MD (reprint author), NIEHS, Natl Ctr Toxicogen, POB 12233,MD F1-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waters2@niehs.nih.gov NR 128 TC 208 Z9 230 U1 5 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD DEC PY 2004 VL 5 IS 12 BP 936 EP 948 DI 10.1038/nrg1493 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 875JQ UT WOS:000225416800015 PM 15573125 ER PT J AU Sodhi, A Montaner, S Gutkind, JS AF Sodhi, A Montaner, S Gutkind, JS TI Viral hijacking of G-protein-coupled-receptor signalling networks SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID SARCOMA-ASSOCIATED HERPESVIRUS; IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE-BINDING-PROTEIN; CD4(+) T-CELLS; HIGH CONSTITUTIVE ACTIVITY; EFFUSION LYMPHOMA-CELLS; FOCAL ADHESION KINASE; FRAME U12 ENCODES; NF-KAPPA-B; KAPOSIS-SARCOMA AB Viruses use a surprising diversity of approaches to hijack G-protein-coupled receptors and harness their activated intracellular signalling pathways. All of these approaches ultimately function to ensure viral replicative success and often contribute to their pathogenesis. Indeed, a single virus might deploy a repertoire of these strategies to regulate key intracellular survival, proliferative and chemotactic pathways. Understanding the contribution of these biochemical routes to viral pathogenesis might facilitate the development of effective target-specific therapeutic strategies against viral diseases. C1 Natl Inst Dent & Craniofacial Res, Cell Growth Regulat & Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Montaner, S (reprint author), Natl Inst Dent & Craniofacial Res, Cell Growth Regulat & Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 211, Bethesda, MD 20892 USA. EM silvia.montaner@nih.gov; sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 131 TC 96 Z9 98 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD DEC PY 2004 VL 5 IS 12 BP 998 EP 1012 DI 10.1038/nrm1529 PG 15 WC Cell Biology SC Cell Biology GA 879IV UT WOS:000225711100013 PM 15573137 ER PT J AU Swartz, KJ AF Swartz, KJ TI Towards a structural view of gating in potassium channels SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID SHAKER-K+ CHANNEL; VOLTAGE-DEPENDENT K+; GATED SODIUM-CHANNELS; X-RAY-STRUCTURE; CHARGE MOVEMENT; SKELETAL-MUSCLE; S4 SEGMENT; TRANSMEMBRANE SEGMENTS; CRYSTAL-STRUCTURE; MOLECULAR-BASIS AB Voltage-activated cation channels have pores that are selective for K+, Na+ or Ca2+. Neurons use these channels to generate and propagate action potentials, release neurotransmitters at synaptic terminals and integrate incoming signals in dendrites. Recent X-ray and electron microscopy studies of an archaebacterial voltage-activated K+ (Kv) channel have provided the first atomic resolution images of the voltage-sensing domains in Kv channels. Although these structures are consistent with previous biophysical analyses of eukaryotic channels, they also contain surprises, which have provoked new ideas about the structure and movements of these proteins during gating. This review summarizes our current understanding of these intriguing membrane proteins and highlights the open questions. C1 NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, 35 Convent Dr,MSC 3701, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov FU Intramural NIH HHS [ZIA NS002945-13] NR 143 TC 116 Z9 120 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD DEC PY 2004 VL 5 IS 12 BP 905 EP 916 DI 10.1038/nrn1559 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 875YO UT WOS:000225459300013 PM 15550946 ER PT J AU Klann, E Dever, TE AF Klann, E Dever, TE TI Biochemical mechanisms for translational regulation in synaptic plasticity SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID LONG-TERM POTENTIATION; X MENTAL-RETARDATION; LOCAL PROTEIN-SYNTHESIS; INITIATION-FACTOR 4E; FACTOR 2-ALPHA KINASE; ELONGATION FACTOR-II; RAPAMYCIN-SENSITIVE MANNER; MESSENGER-RNA TRANSLATION; ELEMENT-BINDING PROTEIN; MAMMALIAN-CELLS AB Changes in gene expression are required for long-lasting synaptic plasticity and long-term memory in both invertebrates and vertebrates. Regulation of local protein synthesis allows synapses to control synaptic strength independently of messenger RNA synthesis in the cell body. Recent reports indicate that several biochemical signalling cascades couple neurotransmitter and neurotrophin receptors to translational regulatory factors in protein synthesis-dependent forms of synaptic plasticity and memory. In this review, we highlight these translational regulatory mechanisms and the signalling pathways that govern the expression of synaptic plasticity in response to specific types of neuronal stimulation. C1 Baylor Coll Med, Dept Physiol & Mol Biophys, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Klann, E (reprint author), Baylor Coll Med, Dept Physiol & Mol Biophys, 1 Baylor Plaza BCM 335, Houston, TX 77030 USA. EM eklann@bcm.tmc.edu OI Dever, Thomas/0000-0001-7120-9678 NR 130 TC 220 Z9 224 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD DEC PY 2004 VL 5 IS 12 BP 931 EP 942 DI 10.1038/nrn1557 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 875YO UT WOS:000225459300015 PM 15550948 ER PT J AU Collingridge, GL Isaac, JTR Wang, YT AF Collingridge, GL Isaac, JTR Wang, YT TI Receptor trafficking and synaptic plasticity SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID LONG-TERM POTENTIATION; METABOTROPIC GLUTAMATE RECEPTORS; CULTURED HIPPOCAMPAL-NEURONS; ACTIVITY-DEPENDENT REGULATION; DOMAIN-CONTAINING PROTEINS; CELL-SURFACE EXPRESSION; D-ASPARTATE RECEPTORS; AMPA RECEPTOR; KAINATE RECEPTORS; NMDA RECEPTORS AB Long-term potentiation and long-term depression are processes that have been widely studied to understand the molecular basis of information storage in the brain. Glutamate receptors are required for the induction and expression of these forms of plasticity, and GABA (gamma-aminobutyric acid) receptors are involved in their modulation. Recent insights into how these receptors are rapidly moved into and out of synaptic membranes has profound implications for our understanding of the mechanisms of long-term potentiation and long-term depression. C1 Univ Bristol, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada. Univ British Columbia, Vancouver Hosp, Dept Med, Vancouver, BC V6T 1Z3, Canada. Univ British Columbia, Hlth Sci Ctr, Vancouver, BC V6T 1Z3, Canada. NIH, Bethesda, MD 20892 USA. RP Collingridge, GL (reprint author), Univ Bristol, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Univ Walk, Bristol BS8 1TD, Avon, England. EM g.l.collingridge@bris.ac.uk RI Wang, Yu Tian/A-4729-2008; Collingridge, Graham/C-4605-2015; Wang, Yu Tian/J-8255-2015 OI Collingridge, Graham/0000-0002-9572-5359; Wang, Yu Tian/0000-0001-8592-0698 NR 132 TC 563 Z9 590 U1 2 U2 67 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD DEC PY 2004 VL 5 IS 12 BP 952 EP 962 DI 10.1038/nrn1556 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 875YO UT WOS:000225459300017 PM 15550950 ER PT J AU Volkow, ND Li, TK AF Volkow, ND Li, TK TI Science and society - Drug addiction: the neurobiology of behaviour gone awry SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; COCAINE-SEEKING BEHAVIOR; SUBSTANCE USE DISORDERS; ALCOHOL DEPENDENCE; IN-VIVO; ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS; MONOAMINE-OXIDASE; DOUBLE-BLIND AB Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad 'choices' that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction. C1 NIDA, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 79 TC 256 Z9 262 U1 8 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD DEC PY 2004 VL 5 IS 12 BP 963 EP 970 DI 10.1038/nrn1539 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 875YO UT WOS:000225459300018 PM 15550951 ER PT J AU Lee, CJ Lee, SM Mukhopadhyay, P Kim, SJ Lee, SC Ahn, WS Yu, MH Storz, G Ryu, SE AF Lee, CJ Lee, SM Mukhopadhyay, P Kim, SJ Lee, SC Ahn, WS Yu, MH Storz, G Ryu, SE TI Redox regulation of OxyR requires specific disulfide bond formation involving a rapid kinetic reaction path SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; PROTEIN; ACTIVATION; OXIDATION; STRESS; MECHANISM; SWITCH AB The Escherichia coli OxyR transcription factor is activated by cellular hydrogen peroxide through the oxidation of reactive cysteines. Although there is substantial evidence for specific disulfide bond formation in the oxidative activation of OxyR, the presence of the disulfide bond has remained controversial. By mass spectrometry analyses and in vivo labeling assays we found that oxidation of OxyR results in the formation of a specific disulfide bond between Cys199 and Cys208 in the wild-type protein. In addition, using time-resolved kinetic analyses, we determined that OxyR activation occurs at a rate of 9.7 s(-1). The disulfide bond-mediated conformation switch results in a metastable form that is locally strained by 3 kcal mol(-1). On the basis of these observations we conclude that OxyR activation requires specific disulfide bond formation and that the rapid kinetic reaction path and conformation strain, respectively, drive the oxidation and reduction of OxyR. C1 Korea Res Inst Biosci & Biotechnol, Ctr Cellular Switch Prot Struct, Taejon 305806, South Korea. Korea Res Inst Biosci & Biotechnol, System Proteom Res Ctr, Taejon 305806, South Korea. Korea Inst Sci & Technol, Div Life Sci, Seoul 130650, South Korea. Korea Inst Sci & Technol, Functional Proteom Ctr, Seoul 130650, South Korea. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ryu, SE (reprint author), Korea Res Inst Biosci & Biotechnol, Ctr Cellular Switch Prot Struct, 52 Euh Eun Dong, Taejon 305806, South Korea. EM ryuse@kribb.re.kr RI MUKHOPADHYAY, PARTHA/G-3890-2010; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Storz, Gisela/0000-0001-6698-1241 NR 25 TC 145 Z9 153 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2004 VL 11 IS 12 BP 1179 EP 1185 DI 10.1038/nsmb856 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 876FU UT WOS:000225482700011 PM 15543158 ER PT J AU Busby, J O'Brien, KK Gibson, AM McKeith, IG Perry, RH Hardy, JA Singleton, AB Morris, CM AF Busby, J O'Brien, KK Gibson, AM McKeith, IG Perry, RH Hardy, JA Singleton, AB Morris, CM TI Dementia with Lewy bodies: no association of polymorphisms in the human synphilin gene SO NEUROGENETICS LA English DT Letter ID PARKINSONS-DISEASE; ALPHA-SYNUCLEIN C1 Univ Newcastle Upon Tyne, Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Newcastle Gen Hosp, Inst Ageing & Hlth, Dept Neuropathol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Newcastle Upon Tyne, Wolfson Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Busby, J (reprint author), Univ Newcastle Upon Tyne, Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD DEC PY 2004 VL 5 IS 4 BP 251 EP 252 DI 10.1007/s10048-004-0188-x PG 2 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 887DI UT WOS:000226285100009 PM 15490287 ER PT J AU Knutson, KM Wood, JN Grafman, J AF Knutson, KM Wood, JN Grafman, J TI Brain activation in processing temporal sequence: an fMRI study SO NEUROIMAGE LA English DT Article DE prefrontal cortex; scripts; SECs; semantic; structured event complex; temporal order ID INFERIOR PREFRONTAL CORTEX; FUNCTIONAL MAGNETIC-RESONANCE; FRONTAL-LOBE LESIONS; CINGULATE CORTEX; RETRIEVAL; KNOWLEDGE; MEMORY; MRI; BOUNDARIES; SENTENCE AB Structured event complexes (SECs) are stored representations of sequential event knowledge, and represent sequences of activities that have been described elsewhere as scripts or schemas. Previous studies have shown that the prefrontal cortex is involved in temporal sequencing. The present study investigates the involvement of the prefrontal cortex in temporal order and membership judgments of script and category items by using functional magnetic resonance imaging. In this experiment, stimuli were either script events or category items. In experimental trials, subjects classified stimuli according to temporal order or membership category. Results show that the script order task and the chronological order task (relative to their respective memberships tasks) were associated with different patterns of PFC activation. Both order tasks activated the middle frontal gyrus bilaterally; however, script order tasks showed additional activation in right inferior frontal gyros, and the chronological order tasks in left inferior frontal gyrus. These results suggest that while the middle frontal gyri are activated bilaterally in both script and chronological temporal ordering tasks, there are different, though largely overlapping, neural substrates for script and chronological representations during temporal ordering. Published by Elsevier Inc. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Room 5C205,Bldg 10,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Knutson, Kristine/0000-0003-4626-4514; Grafman, Jordan H./0000-0001-8645-4457 NR 54 TC 45 Z9 46 U1 4 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2004 VL 23 IS 4 BP 1299 EP 1307 DI 10.1016/j.neuroimage.2004.08.012 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 883US UT WOS:000226041800006 PM 15589094 ER PT J AU Zhan, W Stein, EA Yang, Y AF Zhan, W Stein, EA Yang, Y TI Mapping the orientation of intravoxel crossing fibers based on the phase information of diffusion circular spectrum SO NEUROIMAGE LA English DT Article DE diffusion circular spectrum mapping; diffusion MRI; diffusion tensor imaging; fiber crossing; high angular resolution diffusion; phase ID HUMAN BRAIN; WEIGHTED MRI; TENSOR DATA; SPIN-ECHO; ANISOTROPY; TRACKING; TISSUES; NMR AB A new method is presented to map the orientation of intravoxel crossing fibers by using the phase of the diffusion circular spectrum harmonies. In a previous study [Zhan, W., Go, H., Xu, S., Silbersweig, D.A., Stern, E., Yang, Y., 2003. Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients. Magn. Reson. Med. 49, 1077-1088], we demonstrated that the magnitude of the 4th-order harmonic of the diffusion circular spectrum can be used to identify the existence of fiber crossings. However, the orientation of the intravoxel crossing fibers remained unknown. This study extends the diffusion circular spectrum mapping method so that it is able to identify the orientation of the intravoxel crossing fibers by utilizing the phase information of the circular spectrum. In general, the phase of the circular harmonic determines the rotation of the apparent diffusion coefficient (ADC) profile on the sampling circle that is spanned by the major and medium eigenvector of the diffusion tensor and thus can be used to determine the orientation of the crossing fibers. Simulation results show that the regular tensor-based major eigenvector maps have obvious artifacts in the fiber-crossing area, whereas the estimated crossing fibers by the proposed method are much more consistent with the orientation of the actual intravoxel fibers. Diffusion MRI experiments were performed on five healthy human brains using a 3T scanner. The brain regions with fiber crossings were selected by thresholding the magnitudes of the 4th-order circular spectrum map. Intravoxel crossing fibers were estimated by the phase of the 4th-order harmonic for each voxel within these areas. The estimated intravoxel crossing fibers demonstrated a clear consistency with the orientations of fiber tracks in the surrounding tissues, reducing the fiber orientation discontinuity of the regular major eigenvector map. Published by Elsevier Inc. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Yang, Y (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr,Room 383, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov RI Stein, Elliot/C-7349-2008 NR 25 TC 20 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2004 VL 23 IS 4 BP 1358 EP 1369 DI 10.1016/j.neuroimage.2004.07.062 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 883US UT WOS:000226041800012 PM 15589100 ER PT J AU Hummel, F Saur, R Lasogga, S Plewnia, C Erb, M Wildgruber, D Grodd, W Gerloff, C AF Hummel, F Saur, R Lasogga, S Plewnia, C Erb, M Wildgruber, D Grodd, W Gerloff, C TI To act or not to act. Neural correlates of executive control of learned motor behavior SO NEUROIMAGE LA English DT Article DE learned motor behavior; negative BOLD; inhibition; fMRI ID INFERIOR PREFRONTAL CORTEX; RESPONSE SELECTION; INHIBITORY CONTROL; BLOOD OXYGENATION; FUNCTIONAL MRI; HUMAN BRAIN; CORTICAL ACTIVATION; COGNITIVE CONTROL; FINGER MOVEMENTS; FOCAL DYSTONIA AB Successful behavior requires contextual modulation of learned "programs", that is, the retrieval or nonretrieval (inhibition) of behavioral elements depending on situative context. Here we report neural correlates of these elementary aspects of behavior as identified with functional magnetic resonance imaging (fMRI). Inhibition of a "ready-to-go" behavioral program was represented in the brain by reduction of net synaptic activity in the cerebro-cerebellar pathway. The metabolic correlate of inhibition was a multifocal (premotor, primary sensorimotor, superior parietal, cingulate cortex, and cerebellum) decrease of the blood oxygenation level-dependent (BOLD) signal to below the resting state (negative BOLD) with a concomitant decrease of motor cortical excitability. The reverse was true for retrieval. We propose that contextual modulation of learned behavioral programs depends on an interplay of focal increases and decreases of neural activity and that the inhibitory changes are reflected by negative BOLD responses in an extended cerebro-cerebellar network of sensorimotor structures. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Tubingen, Sch Med, Cort Physiol Res Grp, Dept Neurol,Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Sect Magnet Resonance Imaging Cent Nervous Syst, Dept Neuroradiol, D-72076 Tubingen, Germany. Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany. RP Gerloff, C (reprint author), Univ Tubingen, Sch Med, Cort Physiol Res Grp, Dept Neurol,Hertie Inst Clin Brain Res, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM christian.gerloff@uni-tuebingen.de RI Wildgruber, Dirk/A-3481-2012; Plewnia, Christian/D-1652-2015; OI Erb, Michael/0000-0002-9311-4693 NR 59 TC 30 Z9 31 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2004 VL 23 IS 4 BP 1391 EP 1401 DI 10.1016/j.neuroimage.2004.07.070 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 883US UT WOS:000226041800015 PM 15589103 ER PT J AU Holmes, A Lachowicz, JE Sibley, DR AF Holmes, A Lachowicz, JE Sibley, DR TI Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes SO NEUROPHARMACOLOGY LA English DT Review DE dopamine; receptor; gene; behavior; knockout; mouse ID TARGETED GENE DELETION; LONG-TERM POTENTIATION; OROFACIAL MOVEMENT TOPOGRAPHIES; ETHOLOGICALLY BASED RESOLUTION; CONDITIONED PLACE PREFERENCE; INDUCED LOCOMOTOR-ACTIVITY; RAT PREFRONTAL CORTEX; C-FOS RESPONSES; WILD-TYPE MICE; DEFICIENT MICE AB The functional specificity of dopamine receptor subtypes remains incompletely understood. in part due to the absence of highly selective agonists and antagonists. Phenotypic analysis of dopamine receptor knockout mice has been instumental in identifying the role of dopamine receptor subtypes in mediating dopamine's effects on motor function. cognition. reward, and emotional behaviors. In this article, we provide an update of recent studies in dopamine receptor knockout mice and discuss the limitations and future promise of this approach. Published by Elsevier Ltd. C1 NIAAA, Sect Behav Sci & Genet, NIH, Bethesda, MD 20892 USA. Schering Plough Res Inst, CNS CV Biol Res, Kenilworth, NJ 07033 USA. NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, NIH, Bldg 10,Room 3C217, Bethesda, MD 20892 USA. EM holmesan@mail.nih.gov NR 222 TC 81 Z9 82 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 2004 VL 47 IS 8 BP 1117 EP 1134 DI 10.1016/j.neuropharm.2004.07.034 PG 18 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 879ZK UT WOS:000225757900001 PM 15567422 ER PT J AU Akbar, N Apud, JA Egan, MF Straub, RE Goldberg, TE Weinberger, DR AF Akbar, N Apud, JA Egan, MF Straub, RE Goldberg, TE Weinberger, DR TI Catechol-o-methyltransferase (COMT) polymorphism and anxiety susceptibility in persons with schizophrenia and normal controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S181 EP S181 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000526 ER PT J AU Barr, CS Newman, TK Dvoskin, RL Suomi, SJ Lipsky, RH Goldman, D Higley, JD AF Barr, CS Newman, TK Dvoskin, RL Suomi, SJ Lipsky, RH Goldman, D Higley, JD TI Asssoication of a CRH gene haplotype with HPA axis activity in rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIAAA, NIH, Clin Studies Lab, Poolesville, MD USA. NIAAA, NIH, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S118 EP S119 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000345 ER PT J AU Basselin, M Chang, L Bell, J Rapoport, SI AF Basselin, M Chang, L Bell, J Rapoport, SI TI Chronic ithium treatment of rats reduces brain Nmda-initiated arachidonic acid signaling by downregulating Ca2 dependent cytosolic phospholipid A2 SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S181 EP S181 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000524 ER PT J AU Callicott, J Straub, RE Pezawas, L Egan, MF Mattay, VS Hariri, AR Verchinski, BA Meyer-Lindenberg, A Balkissoon, R Kolachana, B Goldberg, TE Weinberger, DR AF Callicott, J Straub, RE Pezawas, L Egan, MF Mattay, VS Hariri, AR Verchinski, BA Meyer-Lindenberg, A Balkissoon, R Kolachana, B Goldberg, TE Weinberger, DR TI Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, IRP, NIH, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 0 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S55 EP S56 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000165 ER PT J AU Cannon, DM Nugent, A Erickson, K Carson, RE Eckelman, WC Kieswetter, DO Bain, EE Solorio, G Charney, D Drevets, WC AF Cannon, DM Nugent, A Erickson, K Carson, RE Eckelman, WC Kieswetter, DO Bain, EE Solorio, G Charney, D Drevets, WC TI Muscarinic cholinergic2 receptor binding in bipolar disorder: Relation to saliency of affective words SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, NIH, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009; Carson, Richard/H-3250-2011 OI Cannon, Dara/0000-0001-7378-3411; Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S93 EP S93 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000274 ER PT J AU Drevets, W AF Drevets, W TI Functional neuroimaging abnormalities to unipolar and bipolar depression: Relationship to neuropathological changes and treatment outcome SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S66 EP S66 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000196 ER PT J AU Du, J Gray, N Falke, C Wei, YL Chen, WX Szabo, S Manji, H AF Du, J Gray, N Falke, C Wei, YL Chen, WX Szabo, S Manji, H TI Regulation of synaptic localization and trafficking of AMPA glutamate receptor subunit GluR2 by mood stabilizers and antidepressants: Avenues for the development of novel therapeutics SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, LMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S152 EP S153 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000445 ER PT J AU Egan, M Straub, R Goldberg, TE Callicott, J Hariri, A Mattay, V Bertolino, A Hyde, T Weickert, CS Akil, M Kleinman, J Weinberger, D AF Egan, M Straub, R Goldberg, TE Callicott, J Hariri, A Mattay, V Bertolino, A Hyde, T Weickert, CS Akil, M Kleinman, J Weinberger, D TI Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S56 EP S56 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000167 ER PT J AU Einat, H AF Einat, H TI Animals models for bipolar disorder: New understanding and new possibilities SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA. NIMH, LMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S13 EP S13 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000038 ER PT J AU Engel, S Creson, T Shen, Y Hao, YL Nekrasova, T Manji, HK Landreth, GE Chen, G AF Engel, S Creson, T Shen, Y Hao, YL Nekrasova, T Manji, HK Landreth, GE Chen, G TI Behavioral deficits of ERK1 knockout mice in mood disorder related animal tests SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, LMP, MAP,IRP, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S94 EP S95 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000278 ER PT J AU Enoch, MA Schwartz, L Virkkunen, M Goldman, D AF Enoch, MA Schwartz, L Virkkunen, M Goldman, D TI GABRA2 haplotype frequencies differ significantly between high anxiety alcoholics, low anxiety alcoholics and non-alcoholics in two ethnically diverse populations SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S74 EP S75 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000220 ER PT J AU Freed, WJ Chen, J Errico, S Becker, KG AF Freed, WJ Chen, J Errico, S Becker, KG TI Changes in 14-3-3 protein expression mediates NMDA-induced neurotoxicity and the neuroprotective effect of Delta 9-tetrahydrocannabinol SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Cellular Neurobiol Branch,IRP, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S75 EP S75 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000223 ER PT J AU Gardner, E Ashby, CR Xi, ZX Pak, AC Gilbert, J Newman, AH Heidbreder, CA AF Gardner, E Ashby, CR Xi, ZX Pak, AC Gilbert, J Newman, AH Heidbreder, CA TI The dopamine D3 receptor and drug addiction: Studies with preclinical animal models SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S18 EP S18 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000053 ER PT J AU Ghelardoni, S Bazinet, RP Rapoport, SI Bosetti, F AF Ghelardoni, S Bazinet, RP Rapoport, SI Bosetti, F TI Administration of topiramate to rats for two weeks does not alter brain arachidonic acid release and its cyclooxygenase-mediated metabolism SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIA, BPMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S91 EP S91 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000267 ER PT J AU Giedd, JN Lenroot, R AF Giedd, JN Lenroot, R TI XXY (Klinefelter syndrome): A pediatric quantitative magnetic resonance imaging study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S81 EP S82 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000240 ER PT J AU Gingrich, J Goldman, D Mann, JJ Hariri, A AF Gingrich, J Goldman, D Mann, JJ Hariri, A TI Novel serotonin transporter gene promoter variants and psychiatric illness SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIAA, Neurogenet Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S45 EP S46 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000135 ER PT J AU Gogtay, N Herman, D Ordonez, A Giedd, J Hayashi, K Greenstein, D Vaitiuzis, C Nugent, TF Classen, L Thompson, P Rapoport, J AF Gogtay, N Herman, D Ordonez, A Giedd, J Hayashi, K Greenstein, D Vaitiuzis, C Nugent, TF Classen, L Thompson, P Rapoport, J TI Dynamic mapping of cortical brain development in pediatric bipolar illness SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S82 EP S82 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000241 ER PT J AU Goldman, AL Pezawas, L Mattay, VS Chen, G Meyer-Lindenberg, A Weinberger, DR AF Goldman, AL Pezawas, L Mattay, VS Chen, G Meyer-Lindenberg, A Weinberger, DR TI Top-down vs. bottom-up regulation of frontal cortical memory networks in the context of emotion SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 ID PREFRONTAL CORTEX; COGNITION C1 NIMH, GCAP, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S144 EP S145 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000421 ER PT J AU Hall, FS Xu, F Caron, MG Murphy, DL Lesch, KP Uhl, GR AF Hall, FS Xu, F Caron, MG Murphy, DL Lesch, KP Uhl, GR TI Nociception in NET, SERT and NET/SERT double knockout mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Mol Neurobiol Branch, NIH, DHHS, Baltimore, MD USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S131 EP S132 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000381 ER PT J AU Hardin, M Jazbec, S Pine, D Ernst, M AF Hardin, M Jazbec, S Pine, D Ernst, M TI Incentive motivation influences saccadic eye movements in healthy, anxious, and depressed adolescents SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S100 EP S101 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000294 ER PT J AU Hasler, G Neumeister, A Van der Veen, JW Tumonis, T Bain, EE Shen, J Drevets, WC Charney, DS AF Hasler, G Neumeister, A Van der Veen, JW Tumonis, T Bain, EE Shen, J Drevets, WC Charney, DS TI Proton magnetic resonance spectroscopy of the prefrontal cortex in remitted depressed patients SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract 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 Psychiat, Amer Coll Neuropsychopharmacol C1 NIMH, 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 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S146 EP S147 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000427 ER PT J AU Hasler, G Gregen, PJ Gamma, A Ajdacic, V Eich, D Rossler, W Angst, J AF Hasler, G Gregen, PJ Gamma, A Ajdacic, V Eich, D Rossler, W Angst, J TI The longitudinal associations between panic and asthma. The Zurich cohort study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract 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 Psychiat, Amer Coll Neuropsychopharmacol C1 NIMH, MADP, Bethesda, MD 20892 USA. Psychiat Univ Hosp, Zurich, Switzerland. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S146 EP S146 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000426 ER PT J AU Holmes, A Millstein, RA Boyce-Rustay, JM Wiedholz, L Izquierdo, A AF Holmes, A Millstein, RA Boyce-Rustay, JM Wiedholz, L Izquierdo, A TI Genetic modulation of early life trauma and neglect in mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIAAA, Sect Behav Sci & Genet, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S6 EP S6 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000019 ER PT J AU Innis, RB AF Innis, RB TI PET imaging of rodents to examine treatment with stem cells and traditional medications SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S25 EP S25 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000076 ER PT J AU Iudicello, JE Apud, JA Egan, MF Straub, RE Goldberg, TE Weinberger, DR AF Iudicello, JE Apud, JA Egan, MF Straub, RE Goldberg, TE Weinberger, DR TI The effects of the COMT-inhibitor tolcapone on cognition in healthy human subjects: Modulation by the COMTVal(108/158)Met polymorphism SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S123 EP S123 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000358 ER PT J AU Le Foll, B Goldberg, SR AF Le Foll, B Goldberg, SR TI Rimonabant, a CB1 antagonist, blocks nicotine conditioned place preferences without altering nicotine discrimination SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Preclin Pharmacol Sect, Baltimore, MD USA. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S135 EP S135 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000393 ER PT J AU Lehrmann, E Colantuoni, C Gallegos, G Deep-Soboslay, A Becker, KG Wood, WH Huestis, MA Kleinman, JE Weinberger, DR Hyde, TM Freed, WJ AF Lehrmann, E Colantuoni, C Gallegos, G Deep-Soboslay, A Becker, KG Wood, WH Huestis, MA Kleinman, JE Weinberger, DR Hyde, TM Freed, WJ TI Patterns of transcriptoin in human orbitofrontal cortex in drug abuse: Changes in the CCK-B receptor SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, IRP, NIH,DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S135 EP S136 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000394 ER PT J AU Leibenluft, E Pine, D AF Leibenluft, E Pine, D TI Prefrontal-striatal-amygdala dysfunction in bipolar disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S19 EP S19 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000057 ER PT J AU Lipska, BK Peters, T Horowitz, C Shannon, C Straub, WR Hyde, TM Egan, MF Callicott, J Kleinman, JE Weinberger, DR AF Lipska, BK Peters, T Horowitz, C Shannon, C Straub, WR Hyde, TM Egan, MF Callicott, J Kleinman, JE Weinberger, DR TI Expression of DISC1 in development and in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, CBDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S170 EP S170 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000494 ER PT J AU Lupica, C Riegel, A Hoffman, A AF Lupica, C Riegel, A Hoffman, A TI Cellular substrates of Delta(9)-THC and endogenous cannabinoid effects on brain drug reward circuitry SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Cellular Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S63 EP S64 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000190 ER PT J AU Manji, H Gray, N Szabo, ST Du, L AF Manji, H Gray, N Szabo, ST Du, L TI Regulation of cellular plasticity and resilience by mood stabilizers: The role of AMPA receptor synaptic trafficking SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, LMP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S57 EP S57 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000171 ER PT J AU Marenco, S Pierpaoli, C Rohde, GK Honea, RA Barnett, AS Apud, J Egan, MF Weinberger, DR AF Marenco, S Pierpaoli, C Rohde, GK Honea, RA Barnett, AS Apud, J Egan, MF Weinberger, DR TI DTI measures are insensitive to the effect of neuroleptics SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, CBDB, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011 OI Marenco, Stefano/0000-0002-2488-2365; NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S172 EP S172 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000498 ER PT J AU Meyer-Lindenberg, A McInerney-Leo, A Koch, P Kohn, PD Sarpal, D Carson, R Lichter-Konecki, U Nussbaum, RL Berman, KF AF Meyer-Lindenberg, A McInerney-Leo, A Koch, P Kohn, PD Sarpal, D Carson, R Lichter-Konecki, U Nussbaum, RL Berman, KF TI A multitracer PET study of dopaminergic function and regional cerebral blood flow in human aging SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, NIH, DHHS, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011; Sarpal, Deepak/O-5630-2014 OI Carson, Richard/0000-0002-9338-7966; NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S128 EP S128 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000372 ER PT J AU Monk, CS Nelson, EE McClure, EB Mogg, K Bradley, BP Leibenluft, E Blair, JR Cheng, G Charney, DS Ernst, M Pine, DS AF Monk, CS Nelson, EE McClure, EB Mogg, K Bradley, BP Leibenluft, E Blair, JR Cheng, G Charney, DS Ernst, M Pine, DS TI Attention to threat in adolescents with anxiety disorders: Evidence for abnormal behavioral and ventrolateral prefrontal cortex function SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, NIH, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S5 EP S5 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000013 ER PT J AU Murray, EA AF Murray, EA TI Role of macaque orbital prefrontal cortex in affective processing and response selection SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S20 EP S20 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000059 ER PT J AU Newman, TK Barr, CS Babb, PL Champoux, M Suomi, SJ Lesch, KP Higley, JD AF Newman, TK Barr, CS Babb, PL Champoux, M Suomi, SJ Lesch, KP Higley, JD TI MAOA gene promoter polymorphism influences aggression and impulsivity in male rhesus macaques (Macaca mulatta) SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIAAA, Lab Clin Studies & Neurogenet, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S233 EP S233 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000671 ER PT J AU Perlman, WR Webster, MJ Kleinman, JE Weickert, CS AF Perlman, WR Webster, MJ Kleinman, JE Weickert, CS TI Reduction in estrogen receptor alpha rnRNA levels in the anterior hippocampus of patients with schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Clin Brain Disorders Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S220 EP S221 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000636 ER PT J AU Pezawas, L Goldman, AL Verchinski, BA Mattay, VS Callicott, JH Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR AF Pezawas, L Goldman, AL Verchinski, BA Mattay, VS Callicott, JH Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR TI Interaction of SERT & BDNF: Susceptibility for depression is reflected in morphometric changes of critical limbic circuits in humans SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S200 EP S200 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000579 ER PT J AU Rogawski, MA AF Rogawski, MA TI Molecular mechanisms of action of aintiepileptic drugs in the treatment of bipolar disorder: How can more effective agents be developed? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NINDS, 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 NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S13 EP S14 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000040 ER PT J AU Rothman, R Clark, RD Baumann, MH AF Rothman, R Clark, RD Baumann, MH TI Substituted amphetamines increase the concentration of free serotonin in the bloodstream of conscious rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Clin Pharmacol Sect, IRP, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S186 EP S186 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000538 ER PT J AU Russo, CR Goldberg, TE Iudicello, JE Elvevaag, BE Straub, R Egan, MF Weinberger, DR AF Russo, CR Goldberg, TE Iudicello, JE Elvevaag, BE Straub, R Egan, MF Weinberger, DR TI Effects of the BDNF Val66met polymorphism on verbal episodic memory: Hits, false alarms, delay, and depth of encoding SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 Cognit & Psychosis Program, Bethesda, MD USA. Clin Brain Disorders Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S236 EP S236 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000680 ER PT J AU Schmidt, PJ Khine, K Palladino-Negro, P Rubinow, DR AF Schmidt, PJ Khine, K Palladino-Negro, P Rubinow, DR TI Gonadal steroids and mood: Phenotypic antecedents to the search for genes SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, BEB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S62 EP S62 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000186 ER PT J AU Schwandt, ML Shannon, C Lindell, SG Suomi, SJ Higley, JD AF Schwandt, ML Shannon, C Lindell, SG Suomi, SJ Higley, JD TI Birthweight and hypothalamic-pituitary-adrenal (HPA) axis function in young rhesus macaques (Macaca mulatta) SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIAAA, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S143 EP S143 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000417 ER PT J AU Shurtleff, D Hanson, G AF Shurtleff, D Hanson, G TI NIDA's division of Basic Neuroscience and Behavioral Research: Overview of current directions and future research opportunities SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Div Basic Neurosci & Behav Res, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S187 EP S187 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000542 ER PT J AU Sibley, DR Free, RB Cabrera, DM Kim, OJ AF Sibley, DR Free, RB Cabrera, DM Kim, OJ TI Identification of D1 dopamine receptor interacting proteins using co-immunoprecipitation-based proteomics SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. RI Cabrera, David/I-1013-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S181 EP S181 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000525 ER PT J AU Sokolov, BP Jiang, LX Aston, C AF Sokolov, BP Jiang, LX Aston, C TI Evidence for multiple deficits in intracellular signal transduction pathways and myelination-related abnormalities in the temporal cortex of patients with bipolar SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S210 EP S210 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000607 ER PT J AU Sporn, AL AF Sporn, AL TI Clozapine treatment of childhood onset schizophrenia: Evaluation of efficacy, adverse effects, and long-term outcome SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S226 EP S227 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000651 ER PT J AU Steele, SU Marenco, S Barnett, AS Van der Veen, JW Goldberg, TE Straub, RE Egan, MF Weinberger, DR AF Steele, SU Marenco, S Barnett, AS Van der Veen, JW Goldberg, TE Straub, RE Egan, MF Weinberger, DR TI GRM3 genotype is associated with reduced N-acetyl aspartate levels in the frontal cortex SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S194 EP S195 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000565 ER PT J AU Szabo, ST Einat, H Chen, WX Falke, C Du, J Manji, HK AF Szabo, ST Einat, H Chen, WX Falke, C Du, J Manji, HK TI Neurogranin: A critical molecule at the nexus of 3 major signaling pathways and mood modulation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Mood & Anxiety Disorders Program, Mol Pathophysiol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S211 EP S211 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000611 ER PT J AU Vitiello, B AF Vitiello, B TI The Treatment of Adolescents with Depression Study (TADS): Efficacy results SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, DSIR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S20 EP S20 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000061 ER PT J AU Volkow, ND Wang, GJ Ma, J Fowler, JS Wong, C Logan, J Ding, YS AF Volkow, ND Wang, GJ Ma, J Fowler, JS Wong, C Logan, J Ding, YS TI Activation of the rectal gyrus by intravenous methylphenidate in cocaine addicted subjects but not in controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 Natl Inst Drug Abuse, Bethesda, MD USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S2 EP S2 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000005 ER PT J AU Vythilingam, M Lawley, M Collin, C Bonne, O Hadd, K Charney, DS Grillon, C AF Vythilingam, M Lawley, M Collin, C Bonne, O Hadd, K Charney, DS Grillon, C TI Hydrocortisone impairs hippocampal-dependent trace eyeblink conditioning in posttraumatic stress disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S215 EP S215 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000620 ER PT J AU Wang, G Engel, S Shen, Y Zhou, RL Yuan, PX Einat, H Manji, HK Chen, G AF Wang, G Engel, S Shen, Y Zhou, RL Yuan, PX Einat, H Manji, HK Chen, G TI A new animal model of depression that includes an anhedonic measure and gene expression changes in the brains of modeled animals SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, LMP, MAP, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S94 EP S94 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000277 ER PT J AU Weiss, S Condon, TP Resnick, S Oslin, DW Blow, FC AF Weiss, S Condon, TP Resnick, S Oslin, DW Blow, FC TI Substance abuse in the 21st century: What problems lie ahead for the baby boomers? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S12 EP S12 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000036 ER PT J AU Zarate, CA Singh, JB Quiroz, JA Denicoff, KK De Jesus, G Luckenbaugh, D Manji, HK Charney, DS AF Zarate, CA Singh, JB Quiroz, JA Denicoff, KK De Jesus, G Luckenbaugh, D Manji, HK Charney, DS TI Memantine in major depression: A double-blind, placebo-controlled study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S218 EP S218 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000628 ER PT J AU Zhang, L Barrett, J Manji, H AF Zhang, L Barrett, J Manji, H TI Are oligodendrocytes under-appreciated targets for longterm mood stabilization? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 USUHS, Bethesda, MD USA. NIMH, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S217 EP S218 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000627 ER PT J AU Zhou, RL Gray, NA Yuan, PX Du, J Zhang, L Li, XX Chen, JS Chen, G Damschroder-Williams, PJ Manji, H AF Zhou, RL Gray, NA Yuan, PX Du, J Zhang, L Li, XX Chen, JS Chen, G Damschroder-Williams, PJ Manji, H TI Genomic studies identify a novel plasticity regulating glucorticoid receptor (Gr) chaperone protein as a target for mood stabilization: from microarray to functional studies SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 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 C1 NIMH, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2004 VL 29 SU 1 BP S218 EP S218 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 877RO UT WOS:000225588000629 ER PT J AU Koretsky, AP Silva, AC AF Koretsky, AP Silva, AC TI Manganese-enhanced magnetic resonance imaging (MEMRI) SO NMR IN BIOMEDICINE LA English DT Editorial Material DE manganese; imaging; brain; heart; neuronal-tract tracer; neuroarchitecture; contrast agents ID WATER EXCHANGE; BRAIN; MRI; HEARTS; NMR; RELAXATION; ACTIVATION; INJECTION; ION AB Manganese ion (Mn2+) is in essential metal that participates as a cofactor in a number of critical biological functions. such as electron transport. detoxification of free radicals and synthesis of neurotransmitters. Mn2+ can enter excitable cells using some of the same transport systems as Ca2+ and it can bind to a number of intracellular sites because it has high affinity for Ca2+ and Mg2+ binding sites on proteins and nucleic acids. Paramagnetic forms of manganese ions are potent MR1 relaxation agents. Indeed, Mn2+ was the first contrast agent proposed for use in MRI. Recently, there has been renewed interest in combining the strong MRI relaxation effects of Mn2+ with its unique biology. in order to further the already broad assortment Of useful information that can be measured by MRI. Such an approach has been continuously developed in the past several years to provide unique tissue contrast. to assess tissue viability. to act as a surrogate marker of calcium influx into cells and to trace neuronal connections. This special issue of NMR in Biomedicine on manganese-enhanced MRI (MEMRI) is aimed at providing the readers of this journal with an extensive review of some of the most prominent applications of MEMRI in biological systems. Written by several of the leaders in the field, the reviews and original research articles featured in this special issue are likely to offer an exciting and inspiring view of the broad range of applications of MEMRI. Copyright (C) 2004 John Wiley Sons. Ltd. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr Bldg 10,Room B1D728, Bethesda, MD 20892 USA. EM KoretskyA@ninds.nih.gov RI Silva, Afonso/A-7129-2009; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 31 TC 148 Z9 152 U1 1 U2 23 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2004 VL 17 IS 8 BP 527 EP 531 DI 10.1002/nbm.940 PG 5 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 886XM UT WOS:000226266400001 PM 15617051 ER PT J AU Silva, AC Lee, JH Aoki, L Koretsky, AR AF Silva, AC Lee, JH Aoki, L Koretsky, AR TI Manganese-enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations SO NMR IN BIOMEDICINE LA English DT Review DE manganese; animal models; brain; heart; contrast-algents; rat; mouse; imaging ID PERFUSED RAT-HEART; IN-VIVO; CONTRAST AGENTS; INFARCTED MYOCARDIUM; T-1-WEIGHTED MRI; BASAL GANGLIA; MOUSE-BRAIN; CA CHANNELS; 3D MRI; INJECTION AB Manganese-enhanced MRI (MEMRI) is being increasingly used for MRI in animals due to the unique T-1 contrast that is sensitive to a number of biological processes. Three specific uses of MEMRI have been demonstrated: to visualize activity in the brain and the heart; to trace neuronal specific connections in the brain: and to enhance the brain cytoarchitecture after a systemic dose. Based on an ever-growing number of applications, MEMR1 is proving useful as a new molecular imaging method to visualize functional neural circuits and anatomy as well as function in the brain in vivo. Paramount to the successful application of MEMR1 is the ability to deliver Mn2+ to the site of interest at an appropriate dose and in a time-efficient manner. A major drawback to the use of Mn2+ as a contrast agent is its cellular toxicity. Therefore. it is critical to use as low a dose as possible. In the present work the different approaches to MEMRI are reviewed from a practical standpoint. Emphasis is given to the experimental methodology of how to achieve significant, yet safe. amounts of Mn2+ to the target areas of interest. Copyright (C) 2004 John Wiley Sons. Ltd. C1 NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Meiji Univ Oriental Med, Dept Med Informat, Kyoto, Japan. RP Silva, AC (reprint author), NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Room B1D106, Bethesda, MD 20892 USA. EM SilvaA@ninds.nih.gov RI Silva, Afonso/A-7129-2009; Aoki, Ichio/G-2529-2011; Koretsky, Alan/C-7940-2015 OI Aoki, Ichio/0000-0002-4429-5053; Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 63 TC 291 Z9 305 U1 4 U2 70 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2004 VL 17 IS 8 BP 532 EP 543 DI 10.1002/nbm.945 PG 12 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 886XM UT WOS:000226266400002 PM 15617052 ER PT J AU Guo, Y Franks, PW Brookshire, T Tataranni, PA AF Guo, Y Franks, PW Brookshire, T Tataranni, PA TI The intra- and inter-instrument reliability of DXA based on ex vivo soft tissue measurements SO OBESITY RESEARCH LA English DT Article DE phantom; DXA; comparison; percentage of fat; reliability ID X-RAY ABSORPTIOMETRY; BODY-COMPOSITION; FAN-BEAM; DENSITOMETERS; PENCIL AB Objective: Comparison of ex-vivo soft tissue measurements using the GE/Lunar pencil (DPX-L; GE/Lunar Co., Madison, WI) and fan beam (Prodigy dual-energy X-ray absorptiometers (DXA) GE/Lunar Co.). Research Methods and Procedures: Intra-instrument reliability was assessed by repeatedly scanning soft tissue phantoms for lean tissue (water) and fat tissue (methanol) using one DPX-L and two identical Prodigy DXAs at fast, medium, and slow scan modes. For each machine, 10 scans of each phantom were performed at each scan speed. The number of scans per instrument totaled 60. Data were analyzed using ANOVA to ascertain whether scan speed affected the intra-instrument reliability and to test whether soft tissue measurements differed among instruments. Percentage fat (phantom density) was the outcome variable. Results: Intra-instrument reliability, expressed as coefficient of variation, ranged between 0.7% and 5.2% for the DPX-L and 0.4% and 4.5% for the Prodigy, with the lowest coefficients of variation observed when scanning the fat tissue phantom. Scan speed also affected the intra-instrument reliability (p < 0.01). Furthermore, differences in the measurement of percentage body fat for both the lean and fat tissue phantoms were observed among all three absorptiometers (all p < 0.01). After adjusting for scan speed, differences persisted for all three instruments. Discussion: Intra- and inter-instrument reliability of DXA machines, even those from the same manufacturer, remains unpredictable. Thus, when measuring body composition using DXA, it is important to consider that even in the absence of measurement bias, the use of different DXA machines, particularly when using a variety of speed settings, will increase the residual error around the true value. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Guo, Y (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. EM yanguo@phx.niddk.nih.gov NR 7 TC 40 Z9 40 U1 0 U2 3 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2004 VL 12 IS 12 BP 1925 EP 1929 DI 10.1038/oby.2004.241 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 892VS UT WOS:000226678700004 PM 15687392 ER PT J AU Stevens, J Suchindran, C Ring, K Baggett, CD Jobe, JB Story, M Thompson, J Going, SB Caballero, B AF Stevens, J Suchindran, C Ring, K Baggett, CD Jobe, JB Story, M Thompson, J Going, SB Caballero, B TI Physical activity as a predictor of body composition in American Indian children SO OBESITY RESEARCH LA English DT Article DE accelerometry; BMI; body fat; longitudinal; overweight status ID ENERGY-EXPENDITURE; WHITE-CHILDREN; OBESITY; SCHOOLCHILDREN; PREVENTION; OVERWEIGHT; ADIPOSITY; CHILDHOOD; IMPEDANCE; PATHWAYS AB Objective: To examine physical activity in second grade American Indian children as a predictor of percentage body fat 3 years later. Research Methods and Procedures: Physical activity was assessed as average vector magnitude (AVM) counts from an accelerometer in 454 second grade children as part of the Pathways study. BMI was assessed, and skinfolds and bioelectrical impedance were used to estimate fat mass, fat-free body mass, and percentage body fat in validated prediction equations. Associations were examined using mixed models regression controlling for baseline body composition. Results: In normal-weight children, higher AVM counts were significantly associated with decreases in percentage body fat. Among overweight children, higher AVM counts were significantly associated with increases in BMI, fat mass, and fat-free mass but not percentage body fat. Discussion: Higher physical activity levels in second grade were associated with lower levels of percentage body fat in fifth grade in normal-weight but not in overweight children. C1 Univ N Carolina, Sch Publ Hlth, Dept Nutr & Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ Minnesota, Div Epidemiol, NHLBI, Minneapolis, MN USA. Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Stevens, J (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr & Epidemiol, CB 7461, Chapel Hill, NC 27599 USA. EM June_Stevens@unc.edu FU NHLBI NIH HHS [HL-50885, HL-50905, HL-50869, HL-50907, HL-50867] NR 30 TC 42 Z9 42 U1 0 U2 10 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2004 VL 12 IS 12 BP 1974 EP 1980 DI 10.1038/oby.2004.248 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 892VS UT WOS:000226678700011 PM 15687399 ER PT J AU Bumbaca, D Littlejohn, JE Nayakanti, H Rigden, DJ Galperin, MY Jedrzejas, MJ AF Bumbaca, D Littlejohn, JE Nayakanti, H Rigden, DJ Galperin, MY Jedrzejas, MJ TI Sequence analysis and characterization of a novel fibronectin-binding repeat domain from the surface of Streptococcus pneumoniae SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; PROTEIN MODELS; STAPHYLOCOCCUS-AUREUS; SECONDARY STRUCTURE; GENE; PREDICTION; PYOGENES; STRAIN; IDENTIFICATION; PATHOGEN AB Streptococcus pneumoniae open reading frame SP0082 encodes a surface protein that contains four copies of a novel conserved repeat domain that bears no significant sequence similarity to proteins of known function. Homologous sequences from other streptococci contain two to six of these repeats, designated the SSURE (streptococcal surface repeat) domain. To investigate the functional role(s) of this domain, the third SSURE repeat of SP0082 sequence has been expressed in Escherichia coli, purified to homogeneity and characterized by biochemical and immunological methods. The expressed protein fragment was found to bind to fibronectin, but not to collagen or submaxillary mucin. Anti-SSURE antibodies recognized the corresponding protein on the surface of pneumococcal cells. These data identify S. pneumoniae SP0082 protein and its homologs in other streptococci as fibronectin-binding surface adhesins. The SSURE domain is likely to contain a novel protein fold, which was tentatively modeled using ab initio modeling methods. C1 Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Jedrzejas, MJ (reprint author), Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM MJedrzejas@chori.org RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 FU NIAID NIH HHS [AI44079] NR 57 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1536-2310 J9 OMICS JI OMICS PD WIN PY 2004 VL 8 IS 4 BP 341 EP 356 DI 10.1089/omi.2004.8.341 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 899KX UT WOS:000227144400006 PM 15703481 ER PT J AU Colevas, AD Scharf, O Schoenfeldt, M AF Colevas, A. Dimitrios Scharf, Orit Schoenfeldt, Mason TI Current clinical trials of cilengitide, an alpha(v) antagonist in clinical development as an anticancer agent SO ONCOLOGY-NEW YORK LA English DT Article ID V INTEGRINS; BLOOD-VESSELS; IN-VIVO; EXPRESSION; TUMORS; ALPHA-V-BETA-3; CARCINOMA; MELANOMA; MIGRATION; CELLS C1 NCI, Investigat Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. PSI Inc, Bethesda, MD USA. Emmes Corp, Rockville, MD USA. RP Colevas, AD (reprint author), NCI, Investigat Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2004 VL 18 IS 14 BP 1778 EP + PG 4 WC Oncology SC Oncology GA 052DY UT WOS:000238212800012 PM 15700626 ER PT J AU Christen, WG Glynn, RJ Sperduto, RD Chew, EY Buring, JE AF Christen, WG Glynn, RJ Sperduto, RD Chew, EY Buring, JE TI Age-related cataract in a randomized trial of beta-carotene in women SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE beta-carotene; cataract incidence; age-related cataract; Women's Health Study; randomized trial ID CIGARETTE-SMOKING; SERUM CAROTENOIDS; ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; VITAMIN-A; NUCLEAR CATARACT; LENS OPACITIES; MALE SMOKERS; LUNG-CANCER; RISK AB PURPOSE To examine the development of age-related cataract in a trial of beta-carotene supplementation in women. METHODS The Women's Health Study is a randomized, doublemasked, placebo-controlled trial originally designed to test the balance of benefits and risks of beta-carotene (50 mg on alternate days), vitamin E, and aspirin in the primary prevention of cancer and cardiovascular disease among 39,876 female health professionals aged 45 years or older. The beta-carotene component of the trial was terminated early after a median treatment duration Of 2.1 years. Main outcome measures were visually-significant cataract and cataract extraction, based on selfreport confirmed by medical record review. RESULTS There were 129 cataracts in the beta-carotene group and 133 in the placebo group (relative risk [RR] = 0.95, 95 % CI 0.75-1.2 1). For cataract extraction, there were 94 cases in the beta-carotene group and 89 cases in the placebo group (RR = 1.04, 95 % CI 0.78-1-39). Subgroup analyses suggested a possible beneficial effect of beta-carotene in smokers. CONCLUSIONS These randomized trial data from a large population of apparently healthy female health professionals indicate that two years of beta-carotene treatment has no large beneficial or harmful effect on the development of cataract during the treatment period. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulat Care & Prevent, Boston, MA USA. NEI, Bethesda, MD 20892 USA. RP Christen, WG (reprint author), 900 Commonwealth Ave E, Boston, MA 02215 USA. EM wchristen@rics.bwh.harvard.edu FU Intramural NIH HHS [Z99 EY999999]; NCI NIH HHS [CA 47988]; NEI NIH HHS [EY 06633]; NHLBI NIH HHS [HL 43851] NR 35 TC 25 Z9 25 U1 0 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD DEC PY 2004 VL 11 IS 5 BP 401 EP 412 DI 10.1080/09286580490515152 PG 12 WC Ophthalmology SC Ophthalmology GA 887SF UT WOS:000226325100007 PM 15590586 ER PT J AU Wang, XB Manner, PA Horner, A Shum, L Tuan, RS Nuckolls, GH AF Wang, XB Manner, PA Horner, A Shum, L Tuan, RS Nuckolls, GH TI Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE osteoarthritis; matrix metalloproteinase; fibroblast growth factor; RUNX2 ID FIBROBLAST-GROWTH-FACTOR; RAT COLLAGENASE-3 PROMOTER; INTERSTITIAL COLLAGENASE; PARATHYROID-HORMONE; ARTICULAR-CARTILAGE; CHONDROCYTE DIFFERENTIATION; ACTIVATOR PROTEIN-1; BONE-DEVELOPMENT; GENE-EXPRESSION; MESSENGER-RNA AB Objective: To understand the molecular mechanisms that lead to increased MMP-13 expression and cartilage degeneration during the progression of osteoarthritis (OA), we have investigated the expression of the transcription factor RUNX2 in OA cartilage and the regulation of MMP-13 expression by RUNX2 and FGF2 in articular chondrocytes. Design: RUNX2 and MMP-13 expression in human OA and control cartilage was analyzed by immunohistochemistry. The effects of RUNX2 over-expression, with or without FGF2 treatment, on MMP-13 promoter activity and enzyme accumulation were measured in articular chondrocytes. Inhibitors of MEK/ERK were assayed for their ability to block FGF2 and RUNX2 up-regulation of the MMP-13 promoter. We analyzed RUNX2 phosphorylation in response to FGF2. Results: Fibirillated OA cartilage exhibited increased RUNX2 immunoreactivity when compared to control cartilage. RUNX2 co-localized with MMP-13 in clusters of chondrocytes in fibrillated OA cartilage. RUNX2 over-expression in cultured chondrocytes increased their responsiveness to FGF2 treatment, which led to increased MMP-13 expression. Inhibitors of MEK/ERK signaling blocked up-regulation of the MMP-13 promoter by RUNX2 and FGF2, and also blocked the activation of RUNX2 by FGF2. FGF2 treatment of articular chondrocytes increased RUNX2 phosphorylation approximately 2-fold. Conclusions: Increased expression of RUNX2 in OA cartilage may contribute to increased expression of MMP-13. FGF2, which is present in OA synovial fluid, activated RUNX2 via the MEK/ERK pathway and increased MMP-13 expression. However, it is unlikely that RUNX2 is a substrate of ERK1/2. RUNX2 expression and activation may be a significant step in the progression of OA by promoting changes in gene expression and chondrocyte differentiation. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept HHS, Bethesda, MD 20892 USA. George Washington Univ, Dept Orthopaed Surg, Washington, DC USA. RP Nuckolls, GH (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept HHS, 1 Democracy Plaza,Suite 800,6701 Democracy Blvd,M, Bethesda, MD 20892 USA. EM glen_nuckolls@nih.gov FU NIAMS NIH HHS [Z01-AR41114] NR 54 TC 128 Z9 136 U1 5 U2 9 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD DEC PY 2004 VL 12 IS 12 BP 963 EP 973 DI 10.1016/j.joca.2004.08.008 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 878BT UT WOS:000225622200004 PM 15564063 ER PT J AU He, D Veiersted, KB Hostmark, AT Medbo, JI AF He, D Veiersted, KB Hostmark, AT Medbo, JI TI Letter to the editor regarding He et al., "Effect of acupuncture treatment on chronic neck and shoulder pain in sedentary female workers: a 6-month and 3-year follow-up study" (Pain 109:299-307)* - Reply to Miller and Lie SO PAIN LA English DT Letter C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP He, D (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dong.he@medisin.uio.no NR 7 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2004 VL 112 IS 3 BP 411 EP 412 DI 10.1016/j.pain.2004.09.024 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 877VH UT WOS:000225601500026 ER PT J AU Miller, FG Lie, RK AF Miller, FG Lie, RK TI Letter to the editor regarding He et al., "Effect of acupuncture treatment on chronic neck and shoulder pain in sedentary female workers: a 6-month and 3-year follow-up study" (Pain 109:299-307)* SO PAIN LA English DT Letter C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 3 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2004 VL 112 IS 3 BP 411 EP 411 DI 10.1016/j.pain.2004.09.025 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 877VH UT WOS:000225601500025 PM 15561400 ER PT J AU Odio, CM Araya, R Pinto, LE Castro, CE Vasquez, S Alfaro, B Saenz, A Herrera, ML Walsh, TJ AF Odio, CM Araya, R Pinto, LE Castro, CE Vasquez, S Alfaro, B Saenz, A Herrera, ML Walsh, TJ TI Caspofungin therapy of neonates with invasive candidiasis SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE caspofungin; amphotericin B; neonatal; candidiasis; candidemia; endocarditis; meningitis; neonatal intensive care unit; prematures ID INTENSIVE-CARE-UNIT; DISSEMINATED FUNGAL-INFECTIONS; ANTIFUNGAL MK-0991 L-743,872; LOW-BIRTH-WEIGHT; AMPHOTERICIN-B; PEDIATRIC-PATIENTS; DISSEMINATED ASPERGILLOSIS; RANDOMIZED TRIAL; CANDIDEMIA; MULTICENTER AB Background: Invasive candidiasis is an increasing problem in neonatal intensive care units worldwide and is an important cause of morbidity, mortality and prolongation of hospital stay. Despite administration of amphotericin B, invasive candidiasis in neonates is sometimes complicated by persistent fungemia and refractory invasive candidiasis. The problem has been augmented by the increasing prevalence of non-albicans species that often are resistant to fluconazole and to amphotericin B. Population and Methods: The population consisted of 1 term and 9 premature neonates with invasive candidiasis caused by Candida albicans (n = 4), Candida parapsilosis (n = 3), Candida tropicalis (n = 2) and Candida glabrata (n = 1). Despite initial therapy with deoxycholate amphotericin B, blood cultures remained positive in all patients for 13-49 days. Invasive candidiasis progressed to meningitis and enlarging renal Candida bezoars in the kidney of one patient and an enlarging atrial vegetation in another. Another patient developed severe hypokalemia refractory to potassium supplementation. Two of the C. albicans and all of the non-albicans Candida isolates were resistant to fluconazole; the C. glabrata isolate was resistant to amphotericin B. Amphotericin B was discontinued and caspofungin initiated in all patients in a dosage of 1 mg/kg/d for 2 days followed by 2 mg/kg/d. Results: All positive blood cultures cleared between 3 and 7 days after initiation of caspofungin, the atrial vegetation resolved and the renal Candida bezoars disappeared. Renal and hepatic function tests did not show any values above normal throughout caspofungin therapy. There were no attributable clinical adverse events during the administration of caspofungin in any of the patients. Conclusions: Caspofungin was effective, safe and well-tolerated as an alternative therapy for persistent and progressive candidiasis in those neonates who were unresponsive to or intolerant of deoxycholate amphotericin B. C1 Sch Med Sci, San Jose, Costa Rica. Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD USA. Hosp Nacl Ninos Dr Carlos Saenz Herrera, Div Infect Dis & Neonatol, San Jose, Costa Rica. RP Odio, CM (reprint author), Hosp Nacl Ninos Dr Carlos Saenz Herrera, Div Infect Dis & Neonatol, Apartado 1654-1000, San Jose, Costa Rica. EM Codio@hnn.sa.cr NR 35 TC 116 Z9 125 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 2004 VL 23 IS 12 BP 1093 EP 1097 DI 10.1097/01.inf.0000145408.51526.0a PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 881MT UT WOS:000225872300004 PM 15626944 ER PT J AU Prevots, DR Pascual, FB Angellili, ML Brayden, R Irigoyen, M Larussa, P Sawyer, M Baughman, AL Pallansch, MA AF Prevots, DR Pascual, FB Angellili, ML Brayden, R Irigoyen, M Larussa, P Sawyer, M Baughman, AL Pallansch, MA TI Population immunity to polioviruses among preschool children from four urban underserved low income communities, United States, 1997-2001 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE polio; seroprevalence; vaccines ID IMMUNIZATION; VACCINE; POLIOMYELITIS; IMPACT; ERADICATION; CHILDHOOD; RATES; AREAS AB Background: In 1997, the Advisory Committee for Immunization Practices (ACIP) recommended a change in polio vaccination policy, the first in 30 years, from the oral poliovirus vaccine (OPV) to a combined OPV/inactivated poliovirus vaccine (IPV) sequential schedule for routine childhood vaccination. To evaluate the impact of the change in polio vaccination schedule on population immunity, we conducted a seroprevalence survey among low income preschool children from selected urban areas. Methods: A repeat cross-sectional serosurvey was conducted during 1997-2001. Children 19-35 months of age receiving well-child care were recruited from outpatient clinics of academic medical centers. Serum samples were obtained and tested for neutralizing antibodies to polioviruses types 1, 2 and 3. A standardized questionnaire was administered to the parents or guardians of enrolled children. Results: Seroprevalence remained high and stable during the study period. Among children sampled in the last study year (initiating their vaccinations from August 1997 through September 2000), seroprevalence was greater than or equal to95% to poliovirus serotypes 1 and 2 and greater than or equal to94% to serotype 3. Overall coverage with greater than or equal to3 doses of polio vaccine was 82-95% across sites during this period. The proportion initiating their vaccination schedule with IPV increased from 2.6% in study year 1 (children born October 1994-January 1997) to 80% in study year 4 (children born October 1997-January 2000). Conclusions: Children in these underserved low income communities are well-protected against the spread of polioviruses; the introduction of IPV did not adversely impact coverage or seroprevalence. Continued monitoring is needed to evaluate population immunity in the absence of OPV circulation. C1 Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Resp & Enter Viruses Branch, Atlanta, GA USA. Univ Colorado, Hlth Sci Ctr, Childrens Hosp Denver, Denver, CO USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. New York Presbyterian Hosp, New York, NY USA. Univ Calif San Diego, Ctr Med, San Diego, CA 92103 USA. RP Prevots, DR (reprint author), NIAID, NIH, 6610 Rockledge Dr,Room 2029,MSC 6613, Bethesda, MD 20892 USA. EM rprevots@niaid.nih.gov NR 23 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 2004 VL 23 IS 12 BP 1130 EP 1136 DI 10.1097/01.inf.0000143641.27336.2e PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 881MT UT WOS:000225872300012 PM 15626951 ER PT J AU Snider, LA Sachdev, V MacKaronis, JE St Peter, M Swedo, SE AF Snider, LA Sachdev, V MacKaronis, JE St Peter, M Swedo, SE TI Echocardiographic findings in the PANDAS subgroup SO PEDIATRICS LA English DT Article DE autoimmunity; streptococcal infection; echocardiography; obsessive-compulsive disorder; tics ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; VALVULAR REGURGITATION; SYDENHAMS CHOREA; DOPPLER-ECHOCARDIOGRAPHY; RHEUMATIC-FEVER; HEART-DISEASE; FOLLOW-UP; DIAGNOSIS; SYMPTOMS; CHILDREN AB Background. Sydenham's chorea is the neurologic manifestation of rheumatic fever and is a diagnosis of exclusion requiring only the presence of frank chorea in the absence of another neurologic disorder. Two thirds of children with Sydenham's chorea also have rheumatic carditis (pathologic mitral valve regurgitation). Although there are similar neuropsychiatric symptoms and preceding group A beta-hemolytic streptococcal infection associated with both Sydenham's chorea and the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) subgroup, it is unknown whether patients in the PANDAS subgroup have any cardiac involvement. Methods. Sixty children meeting the criteria for PANDAS were entered into protocols at National Institute of Mental Health between 1993 and 2002. Doppler and 2-dimensional echocardiograms were performed on these subjects to assess valvular heart disease. Results. Of these 60 children, no echocardiographic evidence of significant mitral or aortic valve regurgitation was found. One patient was found to have mild mitral regurgitation, and all patients had normal left atrial size and normal left ventricular size and function. Follow-up echocardiograms on 20 children showed no significant valvular regurgitation. Conclusion. The evidence of a clear lack of rheumatic carditis in these children supports the hypothesis that PANDAS is a distinct neuropsychiatric diagnosis separate from Sydenham's chorea. C1 NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Snider, LA (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room 4N208,MSC 1255, Bethesda, MD 20892 USA. EM sniderl@intra.nimh.nih.gov NR 22 TC 12 Z9 12 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2004 VL 114 IS 6 BP E748 EP E751 DI 10.1542/peds.2004-0308 PG 4 WC Pediatrics SC Pediatrics GA 875WN UT WOS:000225453000066 PM 15545618 ER PT J AU Lin, ZC Walther, D Yu, XY Drgon, T Uhl, GR AF Lin, ZC Walther, D Yu, XY Drgon, T Uhl, GR TI The human serotonin receptor 213: coding region polymorphisms and association with vulnerability to illegal drug abuse SO PHARMACOGENETICS LA English DT Article DE 5-HT2B receptor (HTR2B); association study; double-mutant; genome scan; neuropsychiatric genetics; reward; single nucleotide polymorphism (SNP) ID SEROTONIN 5-HT2B RECEPTOR; NICOTINE DEPENDENCE; ALCOHOL DEPENDENCE; GENOME SCAN; 2B RECEPTOR; WIDE SCAN; LINKAGE; GENES; LOCI; EXPRESSION AB Objective and methods 5-Hydroxytryptamine (serotonin) receptor 2B (HTR2B) is involved in brain development. Although expressed in the human brain, HTR2B has not been investigated much for its role in higher brain functions. Here we describe a genome-scan with 391 simple sequence repeat markers in 300 Caucasians, identifying HTR2B gene as a candidate for drug abuse vulnerability. Results From DNA re-sequencing of 110 subjects, we discovered three novel single nucleotide polymorphisms (SNPs), two of which confer a double-mutant of the receptor protein in a drug-abusing population. Arg6, a conserved basic residue, and the conserved acidic Glu42 are mutated simultaneously into Gly, termed R6G/E42G. Furthermore, this double-mutant tends to associate with drug abuse (P = 0.08 by chi(2) test). The third SNP that is a synonymous mutation in the codon of Gln11 showed significant association with drug abuse (P = 0.0335 by Fisher's exact test). Conclusion Our data are the first suggesting that HTR2B contributes to brain architecture and pathways that are involved in illegal drug reward. (C) 2004 Lippincott Williams Wilkins. C1 NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. RP Lin, ZC (reprint author), NIDA, Mol Neurobiol Branch, NIH, IRP, 5500 Nathan Schock Dr, Baltimore, MD 21224 USA. EM zlin@intra.nida.nih.gov NR 37 TC 21 Z9 23 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 2004 VL 14 IS 12 BP 805 EP 811 DI 10.1097/00008571-200412000-00003 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 886HZ UT WOS:000226218900003 PM 15608559 ER PT J AU Oroszi, G Goldman, D AF Oroszi, G Goldman, D TI Alcoholism: genes and mechanisms SO PHARMACOGENOMICS LA English DT Review DE alcoholism; ADH; ALDH; COMT; GABA(A alpha 6); genetics; HTTLPR; NPY; OPRM1; treatment response ID OPIOID RECEPTOR GENE; SEROTONIN TRANSPORTER GENE; NEUROPEPTIDE-Y POLYMORPHISM; AMERICAN-INDIAN POPULATION; GENOME-WIDE SEARCH; GABA(A) RECEPTOR; LINKAGE DISEQUILIBRIUM; PREPRONEUROPEPTIDE-Y; ETHANOL-CONSUMPTION; METABOLISM GENES AB Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor mu1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC9412, Rockville, MD 20852 USA. EM dgneuro@box-d.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 90 TC 80 Z9 86 U1 6 U2 14 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD DEC PY 2004 VL 5 IS 8 BP 1037 EP 1048 DI 10.1517/14622416.5.8.1037 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881YM UT WOS:000225905400004 PM 15584875 ER PT J AU Devan, BD Sierra-Mercado, D Jimenez, M Bowker, JL Duffy, KB Spangler, EL Ingram, DK AF Devan, BD Sierra-Mercado, D Jimenez, M Bowker, JL Duffy, KB Spangler, EL Ingram, DK TI Phosphodiesterase inhibition by sildenafil citrate attenuates the learning impairment induced by blockade of cholinergic muscarinic receptors in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE phosphodiesterase inhibition; acetylcholine; muscarinic receptors; aging; animal model; Alzheimer's disease; learning and memory; cognitive performance; stone maze; rats ID LONG-TERM POTENTIATION; 14-UNIT T-MAZE; D-ASPARTATE RECEPTOR; NITRIC-OXIDE; ALZHEIMERS-DISEASE; IMMUNOHISTOCHEMICAL LOCALIZATION; COGNITIVE ENHANCEMENT; TREATMENT STRATEGIES; RECOGNITION MEMORY; NERVOUS-SYSTEM AB We examined whether treatment with sildenafil citrate (the active compound of Viagra), a cyclic nucleotide phosphodiesterase type 5 inhibitor (PDE5), would reverse the learning impairment induced by cholinergic muscarinic (mACh) receptor blockade [0.75 mg/kg scopolamine HCl, intraperitoneal (i.p.) injections]. Rats were pretrained in a one-way active avoidance of foot shock in a straight runway and the next day received 15 training trials in a 14-unit T-maze. Performance in this maze paradigm requires accurate responding to avoid mild foot shock and has been shown to be sensitive to aging and to impairment in central cholinergic systems. Intraperitoneal (i.p.) injections of scopolamine or saline and sildenafil or vehicle were given 30 and 15 min before training, respectively. The combined treatment conditions were as follows: saline+vehicle (control), scopolamine (0.75 mg/kg)+vehicle, and scopolamine (0.75 mg/kg)+sildenafil (1.5, 3.0, or 4.5 mg/ kg). Behavioral measures of performance included deviations from the correct pathway (errors), run time from start to goal, shock frequency, and duration. Statistical analysis revealed that scopolamine impaired maze performance and that sildenafil (3.0 mg/kg) significantly attenuated this impairment in a dose-dependent manner. These results suggest that sildenafil citrate may serve as a cognitive enhancer for therapeutic treatment of cholinergic dysfunction in age-related cognitive decline and Alzheimer's dementia (AD). (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, Behav Neurosci Sect, Lab Expt Gerontol, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Devan, BD (reprint author), NIA, Behav Neurosci Sect, Lab Expt Gerontol, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM DevanBr@grc.nia.nih.gov FU NIGMS NIH HHS [GM 08253, GM 07717] NR 49 TC 58 Z9 60 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 2004 VL 79 IS 4 BP 691 EP 699 DI 10.1016/j.pbb.2004.09.019 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 881YV UT WOS:000225906400010 PM 15582676 ER PT J AU Isaac, JTR Mellor, J Hurtado, D Roche, KW AF Isaac, JTR Mellor, J Hurtado, D Roche, KW TI Kainate receptor trafficking: physiological roles and molecular mechanisms SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE kainate receptor; glutamate; hippocampus; ER retention motif; receptor targeting; synaptic plasticity ID MOSSY-FIBER SYNAPSES; EXCITATORY SYNAPTIC-TRANSMISSION; CELL-SURFACE EXPRESSION; ER RETENTION SIGNAL; HIPPOCAMPAL INTERNEURONS; THALAMOCORTICAL SYNAPSES; ENDOPLASMIC-RETICULUM; RAT HIPPOCAMPUS; GLUR6-DEFICIENT MICE; PROTEIN INTERACTIONS AB Recently, there has been intense interest in the mechanisms regulating the trafficking and synaptic targeting of kainate receptors in neurons. This topic is still in its infancy when compared with studies of trafficking of other ionotropic glutamate receptors; however, it is already clear that mechanisms exist for subunit- and splice variant-specific trafficking of kainate receptors. There is also enormous diversity of kainate receptor targeting, with the best-studied neurons in this regard being hippocampal CA3 pyramidal neurons and CA1 GABAergic interneurons. This review summarizes the current state of knowledge on this topic, focusing on the molecular mechanisms of kainate receptor trafficking and the potential for these mechanisms to regulate neuronal kainate receptor function. (C) 2004 Elsevier Inc. All rights reserved. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Bristol, Dept Anat, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. RP Isaac, JTR (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM isaacj@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 NR 74 TC 29 Z9 29 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD DEC PY 2004 VL 104 IS 3 BP 163 EP 172 DI 10.1016/j.pharmthera.2004.08.006 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 876PD UT WOS:000225508500001 PM 15556673 ER PT J AU Alexander, E Susla, GM Burstein, AH Brown, DT Ognibene, FP AF Alexander, E Susla, GM Burstein, AH Brown, DT Ognibene, FP TI Retrospective evaluation of commonly used equations to predict energy expenditure in mechanically ventilated, critically ill patients SO PHARMACOTHERAPY LA English DT Article DE energy expenditure; critically ill; mechanically ventilated; predictive equations; indirect calorimetry; severity of illness ID AGREEMENT; NUTRITION AB Study Objective. To determine which of four commonly used equations to estimate energy expenditure is precise and unbiased compared with energy expenditure as measured by indirect calorimetry. Design. Retrospective, observational study. Setting. Adult medical intensive care unit in a research hospital of the National Institutes of Health Clinical Center. Patients. Seventy-six adult, mechanically ventilated, critically ill patients. Intervention. Indirect calorimetry reports generated by the National Institutes of Health Critical Care Medicine Department's Metabolic Cart Consult Service were reviewed. Bias and precision of resting energy expenditure (REE) estimated by equations were computed using mean prediction error (ME) and root mean squared prediction error (MSE). Equations were considered precise if the 95% confidence interval for MSE was within 15% of the measured energy expenditure (MEE) determined by indirect calorimetry. Equations were considered unbiased if the 95% confidence interval for ME included zero. Paired t tests were used to compare estimated REE values for each predictive equation with MEE values determined by indirect calorimetry. Data were stratified into regions of bias using classification and regression tree analysis, as well as visual inspection of estimated REE-versus-MEE curves for each equation. Measurements and Main Results. The Harris-Benedict equation multiplied by an activity factor of 1.2 was unbiased and precise. The Ireton-Jones equation was precise but biased. The American College of Chest Physicians' consensus recommendation was biased and imprecise. The Harris-Benedict equation without an activity factor also demonstrated bias and imprecision. Conclusions. The Harris-Benedict equation multiplied by an activity factor of 1.2 is suitable for predicting REE and may be used in the absence of indirect calorimetry. C1 Tampa Gen Hosp, Dept Pharm Serv, Tampa, FL 33601 USA. VHA, Serv Pharm, N Potomac, MD USA. Pfizer Global Res & Dev, Clin Sci, Groton, CT USA. Natl Inst Hlth, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD USA. RP Alexander, E (reprint author), Tampa Gen Hosp, Dept Pharm Serv, Box 1289,Room F226, Tampa, FL 33601 USA. EM ealexander@tgh.org NR 21 TC 27 Z9 29 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 2004 VL 24 IS 12 BP 1659 EP 1667 DI 10.1592/phco.24.17.1659.52342 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 876EE UT WOS:000225478100002 PM 15585435 ER PT J AU Ma, BY Nussinov, R AF Ma, BY Nussinov, R TI From computational quantum chemistry to computational biology: experiments and computations are (full) partners SO PHYSICAL BIOLOGY LA English DT Article ID DESIGN; PROTEINS; STATE AB Computations are being integrated into biological research at an increasingly fast pace. This has not only changed the way in which biological information is managed; it has also changed the way in which experiments are planned in order to obtain information from nature. Can experiments and computations be full partners? Computational chemistry has expanded over the years, proceeding from computations of a hydrogen molecule toward the challenging goal of systems biology, which attempts to handle the entire living cell. Applying theories from ab initio quantum mechanics to simplified models, the virtual worlds explored by computations provide replicas of real-world phenomena. At the same time, the virtual worlds can affect our perception of the real world. Computational biology targets a world of complex organization, for which a unified theory is unlikely to exist. A computational biology model, even if it has a clear physical or chemical basis, may not reduce to physics and chemistry. At the molecular level, computational biology and experimental biology have already been partners, mutually benefiting from each other. For the perception to become reality, computation and experiment should be united as full partners in biological research. C1 SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI Frederick, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI Frederick, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 14 TC 2 Z9 2 U1 1 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD DEC PY 2004 VL 1 IS 4 BP P23 EP P26 AR PII S1478-3967(04)87961-0 DI 10.1088/1478-3967/1/4/P01 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 997EF UT WOS:000234227100001 PM 16204832 ER PT J AU Wobus, CE Karst, SM Thackray, LB Chang, KO Sosnovtsev, SV Belliot, G Krug, A Mackenzie, JM Green, KY Virgin, HW AF Wobus, CE Karst, SM Thackray, LB Chang, KO Sosnovtsev, SV Belliot, G Krug, A Mackenzie, JM Green, KY Virgin, HW TI Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages SO PLOS BIOLOGY LA English DT Article ID MURINE CYTOMEGALOVIRUS-INFECTION; NORWALK VIRUS CAPSIDS; FELINE CALICIVIRUS; MONOCLONAL-ANTIBODIES; TARGETED DISRUPTION; INNATE IMMUNITY; INTERFERON; DISEASE; EXPRESSION; POLIOVIRUS AB Noroviruses are understudied because these important enteric pathogens have not been cultured to date. We found that the norovirus murine norovirus 1 (MNV-1) infects macrophage-like cells in vivo and replicates in cultured primary dendritic cells and macrophages. MNV-1 growth was inhibited by the interferon-alphabeta receptor and STAT-1, and was associated with extensive rearrangements of intracellular membranes. An amino acid substitution in the capsid protein of serially passaged MNV-1 was associated with virulence attenuation in vivo. This is the first report of replication of a norovirus in cell culture. The capacity of MNV-1 to replicate in a STAT-1-regulated fashion and the unexpected tropism of a norovirus for cells of the hematopoietic lineage provide important insights into norovirus biology. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Royal Childrens Hosp, Sir Albert Sakzewski Virus Res Ctr, Brisbane, Qld, Australia. Univ Queensland, Clin Med Virol Ctr, Brisbane, Qld, Australia. RP Virgin, HW (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. EM virgin@wustl.edu OI Mackenzie, Jason/0000-0001-6613-8350 FU NCI NIH HHS [T32 CA009547, T32-CA09547]; NIAID NIH HHS [R01 AI54483, AI007163, R01 AI054483, T32 AI007163, T32-AI07163] NR 35 TC 446 Z9 456 U1 4 U2 43 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2004 VL 2 IS 12 BP 2076 EP 2084 AR e432 DI 10.1371/journal.pbio.0020432 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 884QA UT WOS:000226099600010 PM 15562321 ER PT J AU Hematti, P Hong, BK Ferguson, C Adler, R Hanawa, H Sellers, S Holt, IE Eckfeldt, CE Sharma, Y Schmidt, M von Kalle, C Persons, DA Billings, EM Verfaillie, CM Nienhuis, AW Wolfsberg, TG Dunbar, CE Calmels, B AF Hematti, P Hong, BK Ferguson, C Adler, R Hanawa, H Sellers, S Holt, IE Eckfeldt, CE Sharma, Y Schmidt, M von Kalle, C Persons, DA Billings, EM Verfaillie, CM Nienhuis, AW Wolfsberg, TG Dunbar, CE Calmels, B TI Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells SO PLOS BIOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN TRANSCRIPTOME MAP; MEDIATED GENE-TRANSFER; RETROVIRAL INSERTIONS; REPOPULATING CELLS; NONHUMAN-PRIMATES; EXPRESSED GENES; CD34(+) CELLS; THERAPY; LEUKEMIA AB Murine leukemia virus (MLV)-derived vectors are widely used for hematopoietic stem cell (HSC) gene transfer, but lentiviral vectors such as the simian immunodeficiency virus (SIV) may allow higher efficiency transfer and better expression. Recent studies in cell lines have challenged the notion that retroviruses and retroviral vectors integrate randomly into their host genome. Medical applications using these vectors are aimed at HSCs, and thus large-scale comprehensive analysis of MLV and SIV integration in long-term repopulating HSCs is crucial to help develop improved integrating vectors. We studied integration sites in HSCs of rhesus monkeys that had been transplanted 6 mo to 6 y prior with MLV- or SIV-transduced CD34(+) cells. Unique MLV ( 491) and SIV ( 501) insertions were compared to a set of in silico-generated random integration sites. While MLV integrants were located predominantly around transcription start sites, SIV integrants strongly favored transcription units and gene-dense regions of the genome. These integration patterns suggest different mechanisms for integration as well as distinct safety implications for MLV versus SIV vectors. C1 NIH, Hematol Branch, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Expt Hematol Div, Memphis, TN 38105 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Stem Cell Inst, Minneapolis, MN USA. NHLBI, Bioinformat Core Facil, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Dept Internal Med, D-7800 Freiburg, Germany. Childrens Hosp Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA. RP Dunbar, CE (reprint author), NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov RI calmels, boris/R-2538-2016; OI Verfaillie, Catherine/0000-0001-7564-4079; Eckfeldt, Craig/0000-0003-2834-0421 NR 53 TC 185 Z9 191 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2004 VL 2 IS 12 BP 2183 EP 2190 AR e423 DI 10.1371/journal.pbio.0020423 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 884QA UT WOS:000226099600019 PM 15550989 ER PT J AU Luo, SJ Kim, JH Johnson, WE van der Welt, J Martenson, J Yuhki, N Miquelle, DG Uphyrkina, O Goodrich, JM Quigley, HB Tilson, R Brady, G Martelli, P Subramaniam, V McDougal, C Hean, S Huang, SQ Pan, WS Karanth, UK Sunquist, M Smith, JLD O'Brien, SJ AF Luo, SJ Kim, JH Johnson, WE van der Welt, J Martenson, J Yuhki, N Miquelle, DG Uphyrkina, O Goodrich, JM Quigley, HB Tilson, R Brady, G Martelli, P Subramaniam, V McDougal, C Hean, S Huang, SQ Pan, WS Karanth, UK Sunquist, M Smith, JLD O'Brien, SJ TI Phylogeography and genetic ancestry of tigers (Panthera tigris) SO PLOS BIOLOGY LA English DT Article ID CAT FELIS-CATUS; DOMESTIC CAT; MITOCHONDRIAL-DNA; VOLCANIC WINTER; NUCLEAR GENOME; CONSERVATION; MICROSATELLITES; PURIFICATION; POLYMORPHISM; ISTHMUS AB Eight traditional subspecies of tiger (Panthera tigris), of which three recently became extinct, are commonly recognized on the basis of geographic isolation and morphological characteristics. To investigate the species' evolutionary history and to establish objective methods for subspecies recognition, voucher specimens of blood, skin, hair, and/or skin biopsies from 134 tigers with verified geographic origins or heritage across the whole distribution range were examined for three molecular markers: (1) 4.0 kb of mitochondrial DNA (mtDNA) sequence; (2) allele variation in the nuclear major histocompatibility complex class II DRB gene; and (3) composite nuclear microsatellite genotypes based on 30 loci. Relatively low genetic variation with mtDNA, DRB, and microsatellite loci was found, but significant population subdivision was nonetheless apparent among five living subspecies. In addition, a distinct partition of the Indochinese subspecies P. t. corbetti into northern Indochinese and Malayan Peninsula populations was discovered. Population genetic structure would suggest recognition of six taxonomic units or subspecies: (1) Amur tiger P. t. altaica; (2) northern Indochinese tiger P. t. corbetti; (3) South China tiger P. t. amoyensis; (4) Malayan tiger P. t. jacksoni, named for the tiger conservationist Peter Jackson; (5) Sumatran tiger P. t. sumatrae; and (6) Bengal tiger P. t. tigris. The proposed South China tiger lineage is tentative due to limited sampling. The age of the most recent common ancestor for tiger mtDNA was estimated to be 72,000-108,000 y, relatively younger than some other Panthera species. A combination of population expansions, reduced gene flow, and genetic drift following the last genetic diminution, and the recent anthropogenic range contraction, have led to the distinct genetic partitions. These results provide an explicit basis for subspecies recognition and will lead to the improved management and conservation of these recently isolated but distinct geographic populations of tigers. C1 NCI, Lab Genom Divers, Frederick, MD 21701 USA. Univ Minnesota, Conservat Biol Grad Program, St Paul, MN 55108 USA. Wildlife Conservat Soc, Russian Far E Program, Bronx, NY USA. Wildlife Conservat Soc, Hornocker Wildlife Inst, Bozeman, MT USA. Minnesota Zoo, Apple Valley, MN USA. Potter Pk Zoo, Lansing, MI USA. Singapore Zool Gardens, Singapore, Singapore. Zoo Negara, Hulu Kelang, Selangor, Malaysia. Tiger Tops, Kathmandu, Nepal. Minist Agr Forestry & Fisheries, Int Cooperat Off, Phnom Penh, Cambodia. Beijing Zoo, Beijing, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. Wildlife Conservat Soc, India Program, Bangalore, Karnataka, India. Univ Florida, Dept Wildlife Ecol & Conservat, Gainesville, FL USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21701 USA. EM obrien@ncifcrf.gov RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 69 TC 116 Z9 134 U1 17 U2 141 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2004 VL 2 IS 12 BP 2275 EP 2293 AR e442 DI 10.1371/journal.pbio.0020442 PG 19 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 884QA UT WOS:000226099600027 PM 15583716 ER PT J AU Naftanel, MA Harlan, DM AF Naftanel, MA Harlan, DM TI Pancreatic islet transplantation SO PLOS MEDICINE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INTENSIVE TREATMENT; COMPLICATIONS; INTERVENTIONS; EPIDEMIOLOGY; PROGRESSION; LANGERHANS; TRENDS C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDKD, Islet & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Harlan, DM (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. EM davidmh@intra.niddk.nih.gov NR 17 TC 31 Z9 33 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2004 VL 1 IS 3 BP 198 EP 201 AR e58 DI 10.1371/journal.pmed.0010058 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 902TH UT WOS:000227378900016 PM 15630467 ER PT J AU Moolchan, EI Schroeder, JR AF Moolchan, EI Schroeder, JR TI Quit attempts among African American teenage smokers seeking treatment: gender differences SO PREVENTIVE MEDICINE LA English DT Article DE adolescent; smoking; addiction; quit attempts; ethnicity; gender ID NICOTINE PATCH THERAPY; SMOKING-CESSATION; ADOLESCENT SMOKERS; PREDICTORS; DEPENDENCE; INITIATION; PATTERNS; HEALTH AB Background. African Americans experience disproportionate smoking-related mortality. Because established smoking during youth predisposes to adult smoking and serious health consequences, characterizing ethnic differences in adolescent smokers' self-quit attempts may inform ethnic-specific approaches to youth smoking cessation. Methods. African American and European American teenage smokers applying to a teenage smoking cessation study (2000-2003) provided smoking-related data, including characteristics of previous cessation attempts and prior use of nicotine replacement therapy (NRT). Tobacco dependence was assessed using the Fagerstrom Test of Nicotine Dependence (FTND). Results. Of 980 (15.5 +/- 1.3 years, 41.8% African American, 59.9% female) participants, African Americans boys were significantly less likely than European American boys to report a prior quit attempt (OR = 0.35, 95% CI 0.17-0.73, P = 0.0049) or to have used NRT (OR = 0.60, 95% CI 0.36-0.998, P = 0.049) after adjusting for years smoked and FTND score. African American girls were more likely to report a prior request for cessation treatment than European American girls after adjusting for FTND and years smoked (OR = 2.19, 95% CI 1.37-3.48, P = 0.001). Conclusions. While increasing education and outreach to African American boys and enhancing access to formal cessation programs for African American girls who smoke may be beneficial, our findings warrant extension to non-treatment-seeking teenage smokers. Published by The Institute For Cancer Prevention and Elsevier Inc. C1 NIDA, Intramural Res Program,Dept HHS, Teen Tobacco Addict Treatment Res Clin, Clin Pharmacol & Therapeut Res Branch,NIH, Baltimore, MD 21224 USA. RP Moolchan, EI (reprint author), NIDA, Intramural Res Program,Dept HHS, Teen Tobacco Addict Treatment Res Clin, Clin Pharmacol & Therapeut Res Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 35 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2004 VL 39 IS 6 BP 1180 EP 1186 DI 10.1016/j.ypmed.2004.04.050 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 876KR UT WOS:000225496200017 PM 15539053 ER PT J AU Xiao, WH Hodge, DR Wang, LH Yang, XY Zhang, XH Farrar, WL AF Xiao, WH Hodge, DR Wang, LH Yang, XY Zhang, XH Farrar, WL TI Co-operative functions between nuclear factors NF kappa B and CCAT/enhancer-binding protein-beta (C/EBP-beta) regulate the IL-6 promoter in autocrine human prostate cancer cells SO PROSTATE LA English DT Article DE prostate cancer; IL-6; NF-kappa B; C/EBP-beta; autocrine ID INTERLEUKIN-6 EXPRESSION; AUTOIMMUNE-DISEASE; LNCAP; RECEPTOR; LINES; ALPHA; MICE; GENE; TRANSCRIPTION; LOCALIZATION AB BACKGROUND. IL-6 is a growth and survival factor for prostate cancer cells through autocrine pathways. Here, we have systematically examined the transcriptional regulation mechanisms of IL-6 in autocrine prostate cancer cells. METHODS. RT-PCR and immunohistochemical staining were used to determine IL-6 production in the cells. Serial mutant IL-6 promoter luciferase reporters were generated and their transcriptional activities were examined. The transcription factors involved in IL-6 regulation were identified with super-shift EMSA. Overexpression of NFKB p65 and C/EBP-P, and blockade of NFKB with IKBalpha or CAPE were performed to demonstrate the cooperation between NFKB p65 and C/EBP-beta in activation of IL-6. RESULTS. Transcription factor regulatory sites IL6-NFKB, IL6-C/EBP, IL6-CREB, and IL6AP1, are responsive to constitutively activated IL-6 production in autocrine prostate cancer cell lines. Among these sites, IL6-AP1 and IL6-C/EBP appear most important, while IL6-NFKB shows the least effect for IL-6 promoter activity as determined by mutant IL-6 promoter luciferase reporter assay. Nevertheless, nuclear factor NFKB is activated and required. Such activation is minimally dependent upon the IL6-NFKB site, occurring through cooperation with other transcription factors that bind the IL-6 promoter. Cooperation between NFKB p65 and C/ EBP-beta did not require a functional IL6-NFKB binding site. C1 NCI, Basic Res Program, SAIC Frederick, Mol Immunoregulat Lab,Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. NCI, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP Farrar, WL (reprint author), NCI, Basic Res Program, SAIC Frederick, Mol Immunoregulat Lab,Canc Res & Dev Ctr,NIH, POB B,Bldg 560,Rm 31-76, Frederick, MD 21702 USA. EM farrar@ncifcrf.gov RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 FU NCI NIH HHS [N01-CO-12400] NR 35 TC 61 Z9 64 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2004 VL 61 IS 4 BP 354 EP 370 DI 10.1002/pros.20113 PG 17 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 871SI UT WOS:000225153200006 PM 15389813 ER PT J AU Pinsky, PF AF Pinsky, PF TI Labrie et al. SO PROSTATE LA English DT Letter C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2004 VL 61 IS 4 BP 371 EP 371 DI 10.1002/pros.20165 PG 1 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 871SI UT WOS:000225153200007 PM 15503321 ER PT J AU Steinbach, PJ AF Steinbach, PJ TI Exploring peptide energy landscapes: A test of force fields and implicit solvent models SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; GENERALIZED BORN MODEL; SCREENED COULOMB POTENTIALS; ANTIPARALLEL BETA-SHEET; TRP-CAGE; FOLDING SIMULATIONS; NUCLEIC-ACIDS; CONTINUUM ELECTROSTATICS; MINIMIZATION PROCEDURE; MACROMOLECULAR ENERGY AB A biased Monte Carlo-minimization/annealing conformational search was used to characterize five descriptions of the energy landscape for each of three model systems: the 20-residue "trp-cage" miniprotein, the 20-residue "BS1" peptide, and the 17-residue "U(1-17)T9D" peptide. The EEF1 and SASA energy landscapes were studied as well as those defined by using the GB/ACE implicit water model with one of three protein force fields: CHARMM19, CHARMM22, and CHARMM22/ CMAP. The lowest-energy structures of the trp-cage and BSI peptides found for the EEF1 landscape have main-chain root-mean-square deviations (rmsds) from the respective NMR structures of less than 2 Angstrom; for U(1-17)T9D, the deviation is less than 3 A using EEF1. The main-chain rmsd of the minimum-energy trp-cage conformation obtained for the GB/ ACE/CHARAM22/CMAP landscape is less than 1 Angstrom. However, this energy function strongly favored helical structures for the two peptides shown by NMR to form beta-sheet structures. Brief annealing of the system following main-chain conformational changes was found to enhance the exploration of low-energy states. The thousands of simulations reported here suggest that the prediction of protein structure might be improved by the simultaneous use of a CMAP-like description of the main chain and an EEF1-like description of the solvent. (C) 2004 Wiley-Liss, Inc. C1 NIH, Ctr Mol Modeling, Ctr Informat Technol, DHHS, Bethesda, MD 20892 USA. RP Steinbach, PJ (reprint author), NIH, Ctr Mol Modeling, Ctr Informat Technol, DHHS, Bg 12A-Rm 2051,12 S Dr, Bethesda, MD 20892 USA. EM steinbac@helix.nih.gov NR 81 TC 35 Z9 36 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2004 VL 57 IS 4 BP 665 EP 677 DI 10.1002/prot.20247 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 874LE UT WOS:000225351100003 PM 15390266 ER PT J AU Krieger, E Darden, T Nabuurs, SB Finkelstein, A Vriend, G AF Krieger, E Darden, T Nabuurs, SB Finkelstein, A Vriend, G TI Making optimal use of empirical energy functions: Force-field parameterization in crystal space SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; PROTEIN STRUCTURES; DATABASE; MODELS; BOND AB Today's energy functions are not able yet to distinguish reliably between correct and almost correct protein models. Improving these near-native models is currently a major bottle-neck in homology modeling or experimental structure determination at low resolution. Increasingly accurate energy functions are required to complete the "last mile of the protein folding problem," for example during a molecular dynamics simulation. We present a new approach to reach this goal. For 50 high resolution X-ray structures, the complete unit cell was reconstructed, including disordered water molecules, counter ions, and hydrogen atoms. Simulations were then run at the pH at which the crystal was solved, while force-field parameters were iteratively adjusted so that the damage done to the structures was minimal. Starting with initial parameters from the AMBER force field, the optimization procedure converged at a new force field called YAMBER (Yet Another Model Building and Energy Refinement force field), which is shown to do significantly less damage to X-ray structures, often move homology models in the right direction, and occasionally make them look like experimental structures. Application of YAMBER during the CASP5 structure prediction experiment yielded a model for target 176 that was ranked first among 150 submissions. Due to its compatibility with the well-established AMBER format, YAMBER can be used by almost any molecular dynamics program. The parameters are freely available from www.yasara.org/ yamber. (C) 2004 Wiley-Liss, Inc. C1 Univ Nijmegen, CMBI, NL-6525 ED Nijmegen, Netherlands. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. Russian Acad Sci, Inst Prot Res, Pushchino, Moscow Region, Russia. RP Krieger, E (reprint author), Univ Nijmegen, CMBI, Toernooiveld 1, NL-6525 ED Nijmegen, Netherlands. EM elmar.krieger@yasara.org RI Vriend, Gert/D-6730-2011; Vriend, G./H-8112-2014; OI Finkelstein, Alexei/0000-0002-2138-4803 NR 31 TC 383 Z9 386 U1 4 U2 22 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2004 VL 57 IS 4 BP 678 EP 683 DI 10.1002/prot.20251 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 874LE UT WOS:000225351100004 PM 15390263 ER PT J AU Chang, CS Pluckthun, A Wlodawer, A AF Chang, CS Pluckthun, A Wlodawer, A TI Crystal structure of a truncated version of the phage lambda protein gpD SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article ID BACTERIOPHAGE-LAMBDA; DISPLAY; SURFACE C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI Pluckthun, Andreas/C-2746-2009 OI Pluckthun, Andreas/0000-0003-4191-5306 NR 11 TC 4 Z9 5 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2004 VL 57 IS 4 BP 866 EP 868 DI 10.1002/prot.20254 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 874LE UT WOS:000225351100026 PM 15317025 ER PT J AU Elliott, ST Crider, DG Garham, CP Boheler, KR Van Eyk, JE AF Elliott, ST Crider, DG Garham, CP Boheler, KR Van Eyk, JE TI Two-dimensional gel electrophoresis database of cultured murine R1 embryonic stem cells SO PROTEOMICS LA English DT Article DE database; embryonic stern cell; mouse; two-dimensional gel electrophoresis ID TYROSINE-PHOSPHORYLATION; DIFFERENTIATION; IDENTIFICATION; PROTEINS; KINASE; CARDIOMYOCYTES; PROLIFERATION; ISOFORM; THERAPY; BINDING AB Embryonic stem (ES) cell lines represent a population of undifferentiated pluripotent cells capable of multilineage differentiation in vitro. Although very useful for studying developmental processes, human ES cell lines have also been suggested as a potential and unlimited source for cellular transplantation and the treatment of human disease. The proteomic basis of embryonic sternness (pluripotentiality and multilineage differentiation) and the transitions that lead to specific cell lineages however, remain to be defined. As an important first step in defining these processes, we have performed a proteomic analysis of undifferentiated mouse R1 ES cell lines using pH 3-10, 4-7 and 6-11 two-dimensional electrophoresis gels, matrix-assisted laser desorption/ionization and tandem mass spectrometry. Of the 700 gel spots analyzed, 241 distinct protein species were identified corresponding to 218 unique proteins, with a significant proportion functionally related to protein expression. C1 Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. Queens Univ, Dept Physiol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD USA. RP Van Eyk, JE (reprint author), Johns Hopkins Univ, Dept Med, 602 Ctr Tower,Mason Lord Bldg,Bayview Med Campus, Baltimore, MD 21224 USA. EM ivaneyk1@jhmi.edu NR 30 TC 42 Z9 44 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD DEC PY 2004 VL 4 IS 12 BP 3813 EP 3832 DI 10.1002/pmic.200300820 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880PH UT WOS:000225801200013 PM 15378706 ER PT J AU Bonne, O Charney, DS AF Bonne, O Charney, DS TI Neuropathology of stress: Prospects and caveats SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Editorial Material ID MAJOR DEPRESSION; TRAUMA EXPOSURE; PRENATAL STRESS; LIFE EVENTS; DISORDER; PTSD; TWIN; SCHIZOPHRENIA; PSYCHOPATHOLOGY; DYSFUNCTION C1 Hebrew Univ Jerusalem, Hadassah Univ Hosp, Dept Psychiat, IL-91905 Jerusalem, Israel. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Bonne, O (reprint author), Hadassah Med Ctr, Dept Psychiat, POB 12000, IL-91120 Jerusalem, Israel. EM bonne@hadassah.org NR 39 TC 2 Z9 2 U1 5 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2004 VL 67 IS 4 BP 407 EP 411 DI 10.1521/psyc.67.4.407.56561 PG 5 WC Psychiatry SC Psychiatry GA 890GJ UT WOS:000226499400009 PM 15801382 ER PT J AU Deep-Soboslay, A Martin, CE Kleinman, JE AF Deep-Soboslay, A Martin, CE Kleinman, JE TI The development of a posttraumatic stress disorder brain collection SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Editorial Material ID RISK-FACTORS; DEPRESSION C1 NIMH, Sect Neuropathol, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Kleinman, JE (reprint author), NIMH, Sect Neuropathol, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM kleinmaj@intra.nimh.nih.gov NR 11 TC 2 Z9 2 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 2004 VL 67 IS 4 BP 416 EP 418 DI 10.1521/psyc.67.4.416.56568 PG 3 WC Psychiatry SC Psychiatry GA 890GJ UT WOS:000226499400011 PM 15801384 ER PT J AU Zhu, GS Lipsky, RH Xu, K Ali, S Hyde, T Kleinman, J Akhtar, LA Mash, DC Goldman, D AF Zhu, GS Lipsky, RH Xu, K Ali, S Hyde, T Kleinman, J Akhtar, LA Mash, DC Goldman, D TI Differential expression of human COMT alleles in brain and lymphoblasts detected by RT-coupled 5 ' nuclease assay SO PSYCHOPHARMACOLOGY LA English DT Article DE COMT; allele-specific expression; single nucleotide polymorphism; haplotype; lymphoblast; brain; human ID CATECHOL-O-METHYLTRANSFERASE; FUNCTIONAL POLYMORPHISM; GENE-EXPRESSION; HUMAN GENOME; SCHIZOPHRENIA; GENOTYPE; HAPLOTYPE; FREQUENCIES; RISK AB Rationale: A common polymorphism, Val158-Met, alters catechol-O-methyltransferase ( COMT) enzyme activity and has been linked to psychiatric phenotypes. Bray et al. ( 2003) reported that COMT is subject to differential allele expression in brain, finding modest ( 13 - 22%) underexpression of a haplotype containing Val158. However, disparate findings by another group who used the same method, but in lymphoblasts, raise the issues of tissue specificity, magnitude of differential expression, and identity of loci altering expression. Objectives: We measured COMT allele expression ratios in heterozygous human lymphoblast cell lines and brains. Methods: Using transcribed single nucleotide polymorphisms as endogenous reporters, we developed an RT-coupled 5' nuclease assay for allele expression ratios and applied it to 63 COMT rs4818( C> G) heterozygotes and 68 Val158Met [rs4680( G> A)] heterozygotes. Results: For rs4818 ( C> G), the C allele was overexpressed relative to the G allele in 18 of 27 lymphoblast lines and 23 of 36 brains. For Val158Met, Met158 was overexpressed relative to Val158 in all ( 29 of 29) lymphoblast lines and all ( 39 of 39) brains. Each of the 22 rs4818 heterozygotes without differential allele expression was a Val158/Val158 homozygote. The Met158 allele was overexpressed by 65 - 77% when compared with Val158 in lymphoblasts and brain. Haplotype augmented ability to predict expression in brain only. However, the expression of the Val158 allele on the high-expressing haplotype was only 19% higher than Val158 alleles on the other haplotype background. Conclusions: COMT alleles are differentially expressed. The Met158 allele predicts higher mRNA expression in both brain and lymphoblasts. As exemplified here, the RT-coupled 5' nuclease assay is a reliable method for the quantitative evaluation of cis-acting regulatory effects. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Changhai Hosp, Shanghai 200433, Peoples R China. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Miami, Dept Neurol, Miami, FL 33136 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 12420 Parklawn Dr, Rockville, MD 20852 USA. EM dgneuro@box-d.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 32 TC 43 Z9 45 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2004 VL 177 IS 1-2 BP 178 EP 184 DI 10.1007/s00213-004-1938-z PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 876BT UT WOS:000225471300020 PM 15290009 ER PT J AU Thompson, FE Midthune, D Subar, AF Kahle, LL Schatzkin, A Kipnis, V AF Thompson, FE Midthune, D Subar, AF Kahle, LL Schatzkin, A Kipnis, V TI Performance of a short tool to assess dietary intakes of fruits and vegetables, percentage energy from fat and fibre SO PUBLIC HEALTH NUTRITION LA English DT Article DE diet; epidemiological methods; surveillance; validation study; data collection; questionnaires ID FOOD-FREQUENCY QUESTIONNAIRE; DOUBLY LABELED WATER; INTAKE DISTRIBUTIONS; BEHAVIORAL-APPROACH; RELIABILITY; VALIDATION; POPULATION; CANCER; WOMEN; CONSUMPTION AB Objectives: We describe the methods used to develop and score a 17-item 'screener' designed to estimate intake of fruit and vegetables, percentage energy from fat and fibre. The ability of this screener and a food-frequency questionnaire (FFQ) to measure these exposures is evaluated. Design: Using US national food consumption data, stepwise multiple regression was used to identify the foods to be included on the instrument; multiple regression analysis was used to develop scoring algorithms. The performance of the screener was evaluated in three different studies. Estimates of intakes measured by the screener and the FFQ were compared with true usual intake based on a measurement error model. Setting: US adult population. Subjects: For development of instrument, n=9323 adults. For testing of instrument, adult men and women in three studies completing multiple 24-hour dietary recalls, FFQ and screeners, n=484, 462 and 416, respectively. Results: Median recalled intakes for examined exposures were generally estimated closely by the screener. In the various validation studies, the correlations between screener estimates and estimated true intake were 0.5-0.8. In general, the performances of the screener and the full FFQ were similar; estimates of attenuation were lower for screeners than for full FFQs. Conclusions: When coupled with appropriate reference data, the screener approach described may yield useful estimates of intake, for both surveillance and epidemiological purposes. C1 NCI, Risk Factor Surveillance & Methodol Branch, Appl Res Program, Div Canc Control & Populat Sci,EPN 4016, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Thompson, FE (reprint author), NCI, Risk Factor Surveillance & Methodol Branch, Appl Res Program, Div Canc Control & Populat Sci,EPN 4016, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM ThompsoF@mail.nih.gov NR 31 TC 94 Z9 95 U1 3 U2 14 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD DEC PY 2004 VL 7 IS 8 BP 1097 EP 1106 DI 10.1079/PHN2004642 PG 10 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 873GT UT WOS:000225268600016 PM 15548349 ER PT J AU Stone, HB Moulder, JE Coleman, CN Ang, KK Anscher, MS Barcellos-Hoff, MH Dynan, WS Fike, JR Grdina, DJ Greenberger, JS Hauer-Jensen, M Hill, RP Kolesnick, RN MacVittie, TJ Marks, C McBride, WH Metting, N Pellmar, T Purucker, M Robbins, ME Schiestl, RH Seed, TM Tomaszewski, JE Travis, EL Wallner, PE Wolpert, M Zaharevitz, D AF Stone, HB Moulder, JE Coleman, CN Ang, KK Anscher, MS Barcellos-Hoff, MH Dynan, WS Fike, JR Grdina, DJ Greenberger, JS Hauer-Jensen, M Hill, RP Kolesnick, RN MacVittie, TJ Marks, C McBride, WH Metting, N Pellmar, T Purucker, M Robbins, ME Schiestl, RH Seed, TM Tomaszewski, JE Travis, EL Wallner, PE Wolpert, M Zaharevitz, D TI Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries - Report of the NCI workshop, December 3-4, 2003 SO RADIATION RESEARCH LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; CENTRAL-NERVOUS-SYSTEM; KERATINOCYTE GROWTH-FACTOR; HEMATOPOIETIC STEM-CELLS; MARROW TRANSPLANT NEPHROPATHY; PROTEASE-ACTIVATED RECEPTOR-1; CHRONIC OXIDATIVE STRESS; TOTAL-BODY IRRADIATION; INDUCED LUNG TOXICITY; NORMAL TISSUE-INJURY AB To develop approaches to prophylaxis/protection, mitigation and treatment of radiation injuries, appropriate models are needed that integrate the complex events that occur in the radiation-exposed organism. While the spectrum of agents in clinical use or preclinical development is limited, new research findings promise improvements in survival after whole-body irradiation and reductions in the risk of adverse effects of radiotherapy. Approaches include agents that act on the initial radiochemical events, agents that prevent or reduce progression of radiation damage, and agents that facilitate recovery from radiation injuries. While the mechanisms of action for most of the agents with known efficacy are yet to be fully determined, many seem to be operating at the tissue, organ or whole animal level as well as the cellular level. Thus research on prophylaxis/protection, mitigation and treatment of radiation injuries will require studies in whole animal models. Discovery, development and delivery of effective radiation modulators will also require collaboration among researchers in diverse fields such as radiation biology, inflammation, physiology, toxicology, immunology, tissue injury, drug development and radiation oncology. Additional investment in training more scientists in radiation biology and in the research portfolio addressing, radiological and nuclear terrorism would benefit the general population in case of a radiological terrorism event or a large-scale accidental event as well as benefit patients treated with radiation. (C) 2004 by Radiation Research Society. C1 NCI, Bethesda, MD USA. Med Coll Wisconsin, Milwaukee, WI USA. MD Anderson Cancer Ctr, Houston, TX USA. Duke Univ, Med Ctr, Durham, NC USA. Lawrence Berkely Natl Lab, Berkeley, CA USA. Med Coll Georgia, Augusta, GA USA. Univ Calif San Francisco, San Francisco, CA USA. Univ Chicago, Chicago, IL USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Arkansas Med Sci, Little Rock, AR USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON, Canada. Mem Sloan Kettering Canc Ctr, New York, NY USA. Univ Maryland, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Dept Energy, Germantown, MD USA. Uniformed Serv Univ Hlth Sci, AFRRI, Bethesda, MD USA. US FDA, Rockville, MD USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Catholic Univ Amer, Washington, DC USA. RP Stone, HB (reprint author), EPN 6015A,6130 Executive Blvd,MSC 7440, Bethesda, MD 20892 USA. EM stoneh@mail.nih.gov RI Moulder, John/E-6799-2012 FU NCI NIH HHS [R01 CA098239, R01 CA098239-01A2] NR 197 TC 155 Z9 160 U1 3 U2 10 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2004 VL 162 IS 6 BP 711 EP 728 DI 10.1667/RR3276 PG 18 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 873ED UT WOS:000225261400014 PM 15548121 ER PT J AU Baldridge, MG Stahl, RL Gerstenberger, SL Tripoli, V Hutz, RJ AF Baldridge, MG Stahl, RL Gerstenberger, SL Tripoli, V Hutz, RJ TI In utero and lactational exposure of Long-Evans rats to ammonium perchlorate (AP) disrupts ovarian follicle maturation SO REPRODUCTIVE TOXICOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OH SP Soc Study Reprod DE ammonium perchlorate; follicle; ovary; thyroid hormones ID PORCINE GRANULOSA-CELLS; THYROID-HORMONE RECEPTORS; DEVELOPING DEER MICE; STIMULATING-HORMONE; AROMATASE-ACTIVITY; DRINKING-WATER; POSTNATAL DAY-21; HYPOTHYROIDISM; THYROXINE; STEROIDOGENESIS AB Ammonium perchlorate (AP) is a powerful oxidizer manufactured almost exclusively for the aerospace industry. AP salts are also used in airbags, flares, fertilizers, enamels and paints. As a result of widespread industrial use, AP has become a persistent environmental contaminant of drinking water in several U.S. states. AP ion disrupts the trapping of iodide as well as facilitates the discharge of unorganified iodide from the thyroid gland. Such disturbances in thyroid hormone concentrations during critical periods of development are then known to cause profound reproductive and developmental defects, since thyroid hormones modulate both follicular development and steroidogenesis and affect estrogen metabolism and receptor. This study was designed (1) to determine whether exposure to a low or high concentration of AP (LAP, HAP) exerts detrimental effects on follicle maturation in the Long-Evans hooded rat and (2) to determine whether the modulatory effects of AP can be ameliorated by levo-thyroxine sodium (T-4) supplementation. Animals were treated via deionized drinking water on GD 7-21 with LAP (0.4 mg/kg/day) or HAP (4.0 mg/kg/day). Half of each group was also given T-4 supplements via drinking water on GD 7-21. Female pups were sacrificed on postnatal days 24/25, and the ovaries were excised, fixed for histology and analyzed. The analysis included a count, measurement and classification of preantral and antral follicles in the greatest cross-sectional area of the ovary. The results indicated that treatment with the HAP significantly reduced the number of preantral follicles <50,000 mum(2) and the total number of antral follicles in the <50,000, 50-100,000 and >100,000 mum(2) size classes. In ovaries treated with the LAP, we observed no significant decrease in preantral follicles of any size class and only a significant reduction in the largest antral follicles. T-4 only circumvented the effect on the number of small preantral and antral follicles; however, a significant diminution in the antral follicle number persisted in the mid-sized (HAP) and large (LAP, HAP)-sized classes. These data support the hypothesis that AP reduces the number of preantral and antral follicles in certain size classes in rats exposed during a critical period of development, and that T-4 can attenuate the effects of AP on small preantral and antral follicles, but not on medium or large antral follicles. (T35ES007292 & ES08342.) (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. Univ Wisconsin, NIEHS, Biomed Sci Ctr, Milwaukee, WI 53204 USA. Univ Nevada, Dept Environm Studies, Las Vegas, NV 89154 USA. RP Baldridge, MG (reprint author), Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. EM rjhutz@uwm.edu FU NIEHS NIH HHS [T35ES007292, ES08342] NR 50 TC 16 Z9 21 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD DEC PY 2004 VL 19 IS 2 BP 155 EP 161 DI 10.1016/j.reprotox.2004.07.002 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 871HT UT WOS:000225121800002 PM 15501380 ER PT J AU Lyubimov, AV Smith, JA Rousselle, SD Mercieca, MD Tomaszewski, JE Smith, AC Levine, BS AF Lyubimov, AV Smith, JA Rousselle, SD Mercieca, MD Tomaszewski, JE Smith, AC Levine, BS TI The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE tetrathiomolybdate; copper depletion; reproduction; ceruloplasmin; sperm abnormalities; epididymis; early development ID NEUROLOGICALLY AFFECTED PATIENTS; WILSONS-DISEASE; INITIAL THERAPY; DEFICIENT RATS; AMMONIUM TETRATHIOMOLYBDATE; METASTATIC CANCER; SEMEN PARAMETERS; OXIDASE ACTIVITY; DIETARY COPPER; CERULOPLASMIN AB Based on its ability to chelate copper, TTM is being studied as an antiangiogenic agent for cancer therapy. The purpose of this study was to evaluate the toxicity of TTM and the protection of copper supplementation on the reproductive capability of male and female CD(R) rats. Doses of 0, 1, 4, and 12 mg/kg/day with copper supplementation (110 mg/kg of diet) were given by gavage. There were no effects on the estrous cycle or reproductive indices, or maternal toxicity in any female dose group. Male rats given 12 mg/kg/day showed significant decreases in body weight gains and food consumption, and anemia. Serum ceruloplasmin levels were dose-dependently decreased in all male dose groups. Reduced epididymal weights, sperm counts, and sperm motility, sperm morphologic abnormalities and histopathologic changes in testis and epididymis occurred only at 12 mg/kg/day. Dietary copper supplementation prevented the adverse sperm effects produced by 12 mg/kg/day of TTM. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Illinois, Toxicol Res Lab, Chicago, IL 60612 USA. Pathol Associates Inc, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. RP Lyubimov, AV (reprint author), Univ Illinois, Toxicol Res Lab, 1940 W Taylor St, Chicago, IL 60612 USA. EM lyubimov@uic.edu FU NCI NIH HHS [N01-CM-87103] NR 51 TC 20 Z9 20 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD DEC PY 2004 VL 19 IS 2 BP 223 EP 233 DI 10.1016/j.reprotox.2004.07.006 PG 11 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 871HT UT WOS:000225121800010 PM 15501388 ER PT J AU Palacio, LG Sanchez, JL Jimenez, ME Rivera-Valencia, D Jimenez-Ramirez, I Arcos-Burgos, M AF Palacio, LG Sanchez, JL Jimenez, ME Rivera-Valencia, D Jimenez-Ramirez, I Arcos-Burgos, M TI Linkage analysis of the 15q25-15q22 region in an extended multigenerational family segregating for idiopathic epilepsy SO REVISTA DE NEUROLOGIA LA English DT Article DE antioquia; chromosome 15; Colombia; epilepsy; generalised idiopathic epilepsy; genetics; linkage; microsatellites ID MYOCLONIC EPILEPSY; GENE-CLUSTER; COLOMBIA; POPULATION; ANTIOQUIA; MUTATION; LOCUS AB Introduction. Linkage analyses provide strong evidence of how genetic factors influence epilepsy, due to the fact that they involve the determination of the cosegregation of specific marker alleles with epilepsy within families. Aims. Our aim was to determine whether there was some kind of propensity to develop generalised idiopathic epilepsy (GIE) in the 15q22.1-q25.1 region in an extended multigenerational family from the Paisa de Antioquia community, which is a genetic isolate located in Colombia that segregates for GIE and has a strong capacity to detect linkage. Patients and methods. We selected a family containing a number of individuals suffering from epilepsy who visited the Antioquia Neurological Institute. Each affected individual had to have been diagnosed by a neurologist as suffering from non-myoclonic idiopathic epilepsy or from partial idiopathic epilepsy. All patients suspected of suffering from idiopathic epilepsy were submitted to video monitoring in order to characterise seizures electroencephalographically. Results. Of the 106 individuals in this family who were included in the family tree, 76 were genotyped; 15 of them suffered from generalised clonic tonic seizures and six were considered as being possibly affected. Lod score results were significantly negative for all the markers in relation to each of the models under consideration. Conclusions. The possibility of the genes that code for the alpha-3, alpha-5 and beta-4 subunits of the neuronal nicotinic acetylcholine receptor (CHRNA3, CHRNA5 and CHRNB4) situated in the 15q region being responsible for the familial aggregation of GIE in this family, as has been suggested in previous studies in other families, was ruled out. C1 Univ Antioquia, Inst Neurol Antioquia, Medellin, Colombia. Univ Antioquia, Grp Genet Poblac Mutacarcinogenesis & Epidemiol G, Inst Biol, Medellin, Colombia. NHGRI, NIH, Bethesda, MD 20892 USA. RP Arcos-Burgos, M (reprint author), Calle 55,N 46-36, Medellin, Colombia. EM marcosbu@mail.nih.gov NR 18 TC 1 Z9 1 U1 0 U2 1 PU REVISTA DE NEUROLOGIA PI BARCELONA PA C/O CESAR VIGUERA, EDITOR, APDO 94121, 08080 BARCELONA, SPAIN SN 0210-0010 J9 REV NEUROLOGIA JI Rev. Neurologia PD DEC 1 PY 2004 VL 39 IS 11 BP 1021 EP 1025 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 881OC UT WOS:000225875800005 PM 15597263 ER PT J AU Dagdug, L Young, L AF Dagdug, L Young, L TI Theoretical basis for the study of the effect of base composition on DNA melting SO REVISTA MEXICANA DE FISICA LA English DT Article DE DNA; melting temperature; stochastic matrix method ID STOCHASTIC MATRIX-METHOD; THERMAL-DENATURATION; GEL-ELECTROPHORESIS; TEMPERATURE; POLYMERASE; TRANSITION; ACID AB We extend the ideas used to describe the glass transition in strong glasses employing the stochastic matrix method, giving a theoretical framework for the study of the configurational changes and the melting temperature of DNA. Our theoretical model enables a systematic study of the melting transition and the melting temperature dependence on the sequence differences in vertical stacking. Taking into account the fractional composition in a single strand, exact analytic results are given for the fraction of bonds intact and denatured at a particular temperature. This method is applicable to long DNA as well as RNA. C1 Univ Autonoma Metropolitana Iztapalapa, Mexico City 09340, DF, Mexico. NIH, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Dagdug, L (reprint author), Univ Autonoma Metropolitana Iztapalapa, Apartado Postal 55-534, Mexico City 09340, DF, Mexico. NR 21 TC 1 Z9 1 U1 0 U2 0 PU SOCIEDAD MEXICANA DE FISICA PI COYOACAN PA APARTADO POSTAL 70-348, COYOACAN 04511, MEXICO SN 0035-001X J9 REV MEX FIS JI Rev. Mex. Fis. PD DEC PY 2004 VL 50 IS 6 BP 594 EP 600 PG 7 WC Physics, Multidisciplinary SC Physics GA 883AW UT WOS:000225982800007 ER PT J AU Morgen, K McFarland, HF Pillemer, SR AF Morgen, K McFarland, HF Pillemer, SR TI Central nervous system disease in primary Sjogren's syndrome: The role of magnetic resonance imaging SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE Sjogren's syndrome; magnetic resonance imaging; central nervous system ID ATTENUATED INVERSION-RECOVERY; WHITE-MATTER LESIONS; MIMICKING MULTIPLE-SCLEROSIS; CONVENTIONAL SPIN-ECHO; LUPUS-ERYTHEMATOSUS; CEREBRAL INVOLVEMENT; NEUROPSYCHIATRIC DYSFUNCTION; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; NEUROLOGICAL INVOLVEMENT AB OBJECTIVES To examine the frequency of central nervous system (CNS) disease in primary Sjogren's syndrome (pSS) and indicate ways in which cerebral magnetic resonance imaging (MRI) may help determine the significance of CNS involvement. METHODS The current review was based on a Medline (Pubmed) literature search through May 2003, focused on Sjogren's syndrome, other vasculitides, multiple sclerosis (MS), specific MRI techniques, and MRI findings with regard to the above-mentioned diseases. Additional literature was identified in the reference sections of articles listed in Medline. RESULTS Severe CNS manifestations reminiscent of MS have been described in pSS patients. Moreover, the prevalence of nonfocal neuropsychological abnormalities has been found to be elevated in some pSS patient populations. MRI studies suggest discrete cerebral tissue damage even in neurologically asymptomatic patients. However, small white matter lesions are nonspecific and may be related to age or cerebrovascular risk factors such as hypertension. A large controlled study, complementing established T2-weighted MRI with fluid-attenuated inversion recovery (FLAIR) to achieve high sensitivity in lesion detection, could indicate the disease specificity of white matter lesions in pSS. Newer MR techniques, such as spectroscopy and magnetization transfer imaging, applied, for example, in MS and systemic lupus erythematosus (SLE) to evaluate CNS tissue injury, could help determine the extent and mechanisms of macroscopic and microscopic CNS lesions in pSS. CONCLUSIONS Future controlled studies will be necessary to more precisely estimate the prevalence of CNS lesions in pSS, specifically of discrete white matter abnormalities. Newer MRI techniques have the potential to provide information on the severity and pathophysiological mechanisms of CNS tissue damage. C1 Univ Giessen, Dept Neurol, D-35385 Giessen, Germany. Bender Inst Neuroimaging, Giessen, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. RP Morgen, K (reprint author), Univ Giessen, Dept Neurol, Steg 14, D-35385 Giessen, Germany. EM Katrin.Morgen@neuro.med.uni-giessen.de NR 67 TC 39 Z9 42 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 2004 VL 34 IS 3 BP 623 EP 630 DI 10.1016/j.semarthrit.2004.07.005 PG 8 WC Rheumatology SC Rheumatology GA 885XM UT WOS:000226190600009 PM 15609267 ER PT J AU Carbone, M Gruber, J Wong, M AF Carbone, M Gruber, J Wong, M TI Modern criteria to establish human cancer etiology SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material C1 Loyola Univ, Cardinal Bernardin Canc Ctr, Dept Pathol, Maywood, IL 60302 USA. NCI, Canc Etiol Branch, Div Canc Biol, Bethesda, MD 20892 USA. RP Carbone, M (reprint author), Loyola Univ, Cardinal Bernardin Canc Ctr, Dept Pathol, Room 205,2160 S 1st Ave, Maywood, IL 60302 USA. EM mcarbon@lumc.edu NR 2 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2004 VL 14 IS 6 BP 397 EP 398 DI 10.1016/j.semcancer.2004.06.001 PG 2 WC Oncology SC Oncology GA 867MS UT WOS:000224847300001 PM 15489131 ER PT J AU Parker, GC Anastassova-Kristeva, M Broxmeyer, HE Dodge, WH Eisenberg, LM Gehling, UM Guenin, LM Huss, R Moldovan, NI Rao, M Srour, EF Yoder, MC AF Parker, GC Anastassova-Kristeva, M Broxmeyer, HE Dodge, WH Eisenberg, LM Gehling, UM Guenin, LM Huss, R Moldovan, NI Rao, M Srour, EF Yoder, MC TI Stem cells: Shibboleths of development SO STEM CELLS AND DEVELOPMENT LA English DT Editorial Material ID PLASTICITY C1 Wayne State Univ, Sch Med, Carman & Ann Adams Dept Pediat, Childrens Res Ctr Michigan, Detroit, MI 48201 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Hosp Hamburg Eppendorf, Transplant Ctr, Hamburg, Germany. Med Univ S Carolina, Charleston, SC 29425 USA. Bulgarian Acad Sci, BG-1040 Sofia, Bulgaria. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. USC, Los Angeles, CA USA. Univ Munich, Inst Pathol, D-8000 Munich, Germany. NIA, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Med, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Parker, GC (reprint author), Wayne State Univ, Sch Med, Carman & Ann Adams Dept Pediat, Childrens Res Ctr Michigan, 3901 Beaubien, Detroit, MI 48201 USA. EM gparker@med.wayne.edu NR 8 TC 22 Z9 23 U1 0 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD DEC PY 2004 VL 13 IS 6 BP 579 EP 584 DI 10.1089/scd.2004.13.579 PG 6 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 883PD UT WOS:000226024700001 PM 15684825 ER PT J AU Brimble, SN Zeng, XM Weiler, DA Luo, YQ Liu, Y Lyons, IG Freed, WJ Robins, AJ Rao, MS Schulz, TC AF Brimble, SN Zeng, XM Weiler, DA Luo, YQ Liu, Y Lyons, IG Freed, WJ Robins, AJ Rao, MS Schulz, TC TI Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001 SO STEM CELLS AND DEVELOPMENT LA English DT Article ID HUMAN BLASTOCYSTS; PARKINSONS-DISEASE; FREE CULTURE; IN-VITRO; SIGNATURE; TRANSPLANTATION; THERAPY AB The number of human embryonic stem cell (hESC) lines available to federally funded U. S. researchers is currently limited. Thus, determining their basic characteristics and disseminating these lines is important. In this report, we recovered and expanded the earliest available cryopreserved stocks of the BG01, BG02, and BG03 hESC lines. These cultures exhibited multiple definitive characteristics of undifferentiated cells, including long-term self-renewal, expression of markers of pluripotency, maintenance of a normal karyotype, and differentiation to mesoderm, endoderm, and ectoderm. Each cell line exhibited a unique genotype and human leukocyte antigen (HLA) isotype, confirming that they were isolated independently. BG01, BG02, and BG03 maintained in feeder-free conditions demonstrated self-renewal, maintenance of normal karyotype, and gene expression indicative of undifferentiated pluripotent stem cells. A survey of gene expression in BG02 cells using massively parallel signature sequencing generated a digital read-out of transcript abundance and showed that this line was similar to other hESC lines. BG01, BG02, and BG03 hESCs are therefore independent, undifferentiated, and pluripotent lines that can be maintained without accumulation of karyotypic abnormalities. C1 BresaGen Inc, Athens, GA 30605 USA. NIDA, Cellular Neurobiol Branch, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Schulz, TC (reprint author), BresaGen Inc, 111 Riverbend Rd, Athens, GA 30605 USA. EM tschulz@novocell.com FU NIDDK NIH HHS [R24DK063689] NR 28 TC 144 Z9 152 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD DEC PY 2004 VL 13 IS 6 BP 585 EP 597 DI 10.1089/scd.2004.13.585 PG 13 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 883PD UT WOS:000226024700002 PM 15684826 ER PT J AU Suon, S Jin, H Donaldson, AE Caterson, EJ Tuan, RS Deschennes, G Marshall, C Iacovitti, L AF Suon, S Jin, H Donaldson, AE Caterson, EJ Tuan, RS Deschennes, G Marshall, C Iacovitti, L TI Transient differentiation of adult human bone marrow cells into neuron-like cells in culture: Development of morphological and biochemical traits is mediated by different molecular mechanisms SO STEM CELLS AND DEVELOPMENT LA English DT Article ID STEM-CELLS; STROMAL CELLS; TYROSINE-HYDROXYLASE; PROGENITOR CELLS; IN-VIVO; DOPAMINERGIC TRAITS; GROWTH-FACTORS; BRAIN NEURONS; EXPRESSION; RAT AB Studies on rodent bone marrow stromal cells (MSCs) have revealed a capacity, for at least a portion of cells, to express neuron-like traits after differentiation in culture. Little, however, is known about the ability of human MSCs in this regard. We show here that incubation with certain differentiation cocktails, particularly those that include reagents that increase cellular cAMP levels, produces a rapid (1-4 h) and transient (24-48 h) transformation of nearly all hMSCs into neuron-like cells displaying a complex network of processes using phase or scanning electron microscopic optics. In addition, differentiated human (h) MSCs express increased quantities of neuron-[beta-tubulin III, neurofilament (NF), neuronal-specific enolase (NSE)] and glial- [glial fibrillary acidic protein (GFAP)] specific proteins and mRNAs, which are also expressed in low levels in undifferentiated MSCs. In contrast, the mesenchymal marker, fibronectin, which is highly expressed in the undifferentiated state, is reduced following differentiation. These biochemical changes, but not the acquisition of a neuron- like appearance, are partially inhibited by incubation of hMSCs with protein ( cycloheximide) and mRNA (actinomycin D) synthesis inhibitors with differentiating reagents. Only incubation with 100 ng/ml colchicine, which disrupts the microtubular cytoskeleton, prevents the conversion of hMSCs into neuron-like cells. These results demonstrate that hMSCs acquire the morphological appearance and the biochemical makeup typical of neurons by independently regulated mechanisms. C1 Thomas Jefferson Univ, Coll Med, Farber Inst Neurosci, Dept Neurol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Natl Inst Musculoskeletal & Skin Dis, Cartilage Biol & Orthopaed Branch, Natl Inst Hlth & Human Sci, Bethesda, MD 20892 USA. RP Iacovitti, L (reprint author), Thomas Jefferson Univ, Coll Med, Farber Inst Neurosci, Dept Neurol, 900 Walnut St,JHN 462, Philadelphia, PA 19107 USA. EM lorraine.iacovitti@jefferson.edu FU NINDS NIH HHS [R01 NS043309-01, R01 NS043309, R01 NS032519-11A1, R01 NS024204-13, NS32519, NS24204, NS 43309, R01 NS024204, R01 NS024204-14, R01 NS032519, R01 NS032519-10, R01 NS043309-02] NR 46 TC 38 Z9 49 U1 0 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD DEC PY 2004 VL 13 IS 6 BP 625 EP 635 DI 10.1089/scd.2004.13.625 PG 11 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 883PD UT WOS:000226024700006 PM 15684830 ER PT J AU Miura, T Luo, YQ Khrebtukova, I Brandenberger, R Zhou, DX Thies, RS Vasicek, T Young, H Lebkowski, J Carpenter, MK Rao, MS AF Miura, T Luo, YQ Khrebtukova, I Brandenberger, R Zhou, DX Thies, RS Vasicek, T Young, H Lebkowski, J Carpenter, MK Rao, MS TI Monitoring early differentiation events in human embryonic stem cells by massively parallel signature sequencing and expressed sequence tag scan SO STEM CELLS AND DEVELOPMENT LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; GENE-EXPRESSION; MOUSE EMBRYOS; IN-VITRO; TRANSCRIPTION FACTOR; PREIMPLANTATION EMBRYOS; CAENORHABDITIS-ELEGANS; DNA METHYLTRANSFERASES; MOLECULAR SIGNATURE; HUMAN BLASTOCYSTS AB To identify genes that may be involved in the process of human embryonic stem cell (hESC) differentiation, we profiled gene expression by expressed sequenced tag ( EST) enumeration and massively parallel signature sequencing (MPSS) using RNA samples from feeder-free cultures of undifferentiated ( passages 40-50) and differentiated (day 14) H1, H7, and H9 lines. MPSS and EST scan analysis showed good concordance and identified a large number of genes that changed rapidly as cultures transition from a pluripotent to a differentiated state. These included known and unknown ES cell-specific genes as well as a large number of known genes that were altered as cells differentiate. A subset of genes that were either up- or down-regulated were selected and their differential expression confirmed by a variety of independent methods, including comparison of expression after further differentiation, publicly available databases, and direct assessments by reverse transcriptase (RT)-PCR and immunocytochemistry. The analysis identified markers unique to the hESC and embryoid bodies (hEBs) stage as well as signaling pathways that likely regulate differentiation. The data generated can be used to monitor the state of hESC isolated by different laboratories using independent methods and maintained under differing culture conditions. C1 NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Lab Neurosci,NIH, Baltimore, MD 21224 USA. Geron Corp, Menlo Pk, CA 94025 USA. Lynx Therapeut Inc, Hayward, CA 94545 USA. John P Robarts Res Inst, Krembil Ctr Stem Cell Biol, London, ON N6A 5K8, Canada. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21224 USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Lab Neurosci,NIH, 5600 Nathan Shock Dr,Room 4E02, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov NR 63 TC 68 Z9 72 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD DEC PY 2004 VL 13 IS 6 BP 694 EP 715 DI 10.1089/scd.2004.13.694 PG 22 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 883PD UT WOS:000226024700013 PM 15684837 ER PT J AU DeRose, EF Kirby, TW Mueller, GA Chikova, AK Schaaper, RM London, RE AF DeRose, EF Kirby, TW Mueller, GA Chikova, AK Schaaper, RM London, RE TI Phage like it HOT: Solution structure of the bacteriophage P1-encoded HOT protein, a homolog of the theta subunit of E-coli DNA polymerase III SO STRUCTURE LA English DT Article ID ISOTOPICALLY-ENRICHED PROTEINS; TRIPLE RESONANCE EXPERIMENTS; DIPOLAR COUPLINGS; SIDE-CHAIN; SEQUENTIAL ASSIGNMENT; C-13 MAGNETIZATION; NMR-SPECTROSCOPY; LARGER PROTEINS; CHEMICAL-SHIFTS; SPECTRA AB DNA polymerase III, the main replicative polymerase of E. coli, contains a small subunit, theta, that binds to the epsilon proofreading subunit and appears to enhance the enzyme's proofreading function-especially under extreme conditions. It was recently discovered that E. coli bacteriophage P1 encodes a theta homolog, named HOT. The H-1-N-15 HSQC spectrum of HOT exhibits more uniform intensities and less evidence of conformational exchange than that of theta; this uniformity facilitates a determination of the HOT solution structure by NMR. The structure contains three alpha helices, as reported previously for theta; however, the folding topology of the two proteins is very different. Residual dipolar coupling measurements on labeled theta support the conclusion that it is structurally homologous with HOT. As judged by CD measurements, the melting temperature of HOT was 62degreesC, compared to 56degreesC for theta, consistent with other data suggesting greater thermal stability of the HOT protein. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov NR 51 TC 14 Z9 14 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2004 VL 12 IS 12 BP 2221 EP 2231 DI 10.1016/j.str.2004.09.019 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 880XN UT WOS:000225823600015 PM 15576035 ER PT J AU Ialongo, NS Koenig-McNaught, AL Wagner, BM Pearson, JL McCreary, BK Poduska, J Kellam, S AF Ialongo, NS Koenig-McNaught, AL Wagner, BM Pearson, JL McCreary, BK Poduska, J Kellam, S TI African American children's reports of depressed mood, hopelessness, and suicidal ideation and later suicide attempts SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID HIGH-SCHOOL-STUDENTS; ADOLESCENT SUICIDE; RISK-FACTORS; YOUNG ADOLESCENTS; BEHAVIOR; PREDICTORS; DISORDERS; CHILDHOOD; SAMPLE; ADULTS AB This study attempted to assess whether family demographic characteristics and child aggressive behavior are equal to or better than child self-reported depressive symptoms in predicting suicidal behavior. Participants were a community population of African Americans first recruited at age 6 and followed periodically through age 19-20. Measures included child self-reports of depressed mood, hopelessness, and suicidal ideation, teacher reported child aggression in grades 4-6, 6(th) grade caregiver report of family demographic characteristics, and the participants' report at age 19-20 of suicide attempts. Depressed mood proved the most consistent predictor of adolescent/young adult attempts in our logistic regression analyses of the data from the population as a whole and among females. The relationship between depressed mood and suicide attempts in males was in the expected direction, but was not statistically significant. Teacher-reported youth aggressive behavior did prove to be a significant predictor of attempts in 4(th) and 5(th) grade for the population as a whole, but not in our analyses by gender. The relationships between family demographic characteristics and attempts failed to reach statistical significance, but were, generally, in the expected direction. The study revealed that African American children's self-reports of depressed mood as early as grade 4 may prove useful in predicting adolescent/young adult suicide attempts, particularly among females. Neither family demographics nor teacher-reported child aggressive behavior proved equal to child self-reported depressive symptoms in predicting later suicide attempts. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. Catholic Univ Amer, Washington, DC 20064 USA. NIMH, Bethesda, MD 20892 USA. RP Ialongo, NS (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 N Broadway, Baltimore, MD 21205 USA. FU NIMH NIH HHS [T32 MH18834, R01 MH42968] NR 40 TC 23 Z9 23 U1 2 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD WIN PY 2004 VL 34 IS 4 BP 395 EP 407 DI 10.1521/suli.34.4.395.53743 PG 13 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 882BN UT WOS:000225913600006 PM 15585461 ER PT J AU Grover, AC Libutti, SK Pingpank, JF Helsabeck, C Beresnev, T Alexander, HR AF Grover, AC Libutti, SK Pingpank, JF Helsabeck, C Beresnev, T Alexander, HR TI Isolated hepatic perfusion for the treatment of patients with advanced liver metastases from pancreatic and gastrointestinal neuroendocrine neoplasms SO SURGERY LA English DT Article; Proceedings Paper CT 25th Annua Meeting of the American-Association-of-Endocrine-Surgeons CY APR 04-06, 2004 CL Charlottesville, VA SP Amer Assoc Endocrine Surg ID TUMOR-NECROSIS-FACTOR; HYPERTHERMIA; MELPHALAN; CARCINOMA; MELANOMA; MICE AB Background. We report results of using isolated hepatic Perfusion (IHP) in patients with advanced progressive liver metastases (LM) from pancreatic and gastrointestinal neuroendocrine neoplasms (AENs). Methods. Thirteen patients with LM from NENs (mean percent hepatic replacement, 30; range, 10-60) were treated with a I-hour hyperthermic IHP via a laparotomy with the use of 1.5 or 2.0 mg/kg melphalan and/or I mg tumor necrosis factor. An oxygenated extracorporeal circuit with inflow through the gastroduodenal artery and common hepatic artery, and outflow to a segment of the inferior vena cava was used. Portal flow and inferior vena cava flow were shunted to the axillary vein. Radiographic response, recurrence pattern, and survival were assessed. Results. Mean operative time was 9 hours (8-11 hours), and a median hospital stay was 10 days (6-64 days). Fifty percent of evaluable patients had a radiographic partial response in the liver (mean duration, 15 months; range, 6-26 months; 2 ongoing). Four had a marginal response (25%-49% reduction in the neoplasm). The median, hepatic, progression-free survival was 7 months (range, 3-27 months). The median actuarial survival was 48 months including I treatment mortality (median follow-up, 23 months). Conclusions. For patients with advanced LM from AENs, IHP provides a reasonable response rate and duration with acceptable morbidity; continued clinical evaluation is important. C1 NCI, Canc Res Ctr, Surg Metab Sect, NIH,Surg Branch, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Canc Res Ctr, Surg Metab Sect, NIH,Surg Branch, 10 Ctr Dr,Bldg 10,Rm 2B07, Bethesda, MD 20892 USA. NR 11 TC 20 Z9 20 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2004 VL 136 IS 6 BP 1176 EP 1181 DI 10.1016/j.surg.2004.06.044 PG 6 WC Surgery SC Surgery GA 881NS UT WOS:000225874800020 PM 15657573 ER PT J AU Norton, JA Melcher, ML Gibril, F Jensen, RT AF Norton, JA Melcher, ML Gibril, F Jensen, RT TI Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment SO SURGERY LA English DT Article; Proceedings Paper CT 25th Annua Meeting of the American-Association-of-Endocrine-Surgeons CY APR 04-06, 2004 CL Charlottesville, VA SP Amer Assoc Endocrine Surg ID STOMACH; TYPE-1; CELLS; HYPERGASTRINEMIA; PATHOGENESIS; ANTRECTOMY; MANAGEMENT AB Background. Gastric carcinoid tumors occur in 15% to 50% of patients with multiple endocrine neoplasia-1/Zollinger-Ellison syndrome (MEN-1/ZES) but are thought to be benign. We report 5 patients with MEN-1/ZES with symptomatic, aggressive gastric carcinoid tumors that required surgical procedures. Methods. This was a retrospective chart review. Results. Each patient had MEN-1/ZES. Each patient had innumerable gastric carcinoid tumors with symptoms. The fasting gastrin level was 47, 000 pg/mL (normal, <200 pg/mL); the basal acid output was 79 mEq/hr (n = 3), and the age at surgical exploration was 47 6 years, with a duration of MEN-1 of 21 +/- 3 years and of ZES of 15 +/- 2 years. All patients had elevated 5-HIAA or serotonin levels. Somatostatin receptor scintigraphy showed increased stomach uptake in 4 patients (80%). Four patients had a total gastrectomy; 4 patients had lymph node metastases removed, and 3 patients had liver metastases resected. One patient who did not have a total gastrectomy had liver carcinoid metastases. Conclusions. These results demonstrate that gastric carcinoid tumors in patients with long-standing MEN-1/ZES may be symptomatic, aggressive, and metastasize to the liver. With increased long-term medical treatment and life expectancy, these tumors will become an important determinant of survival. C1 Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Norton, JA (reprint author), Stanford Univ, Med Ctr, Dept Surg, Rm H-3591,300 Pasteur Dr, Stanford, CA 94305 USA. OI Melcher, Marc/0000-0002-7185-4383 NR 25 TC 56 Z9 59 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2004 VL 136 IS 6 BP 1267 EP 1273 DI 10.1016/j.surg.2004.06.057 PG 7 WC Surgery SC Surgery GA 881NS UT WOS:000225874800046 PM 15657586 ER PT J AU Kim, I Oyler, JM Moolchan, ET Cone, EJ Huestis, MA AF Kim, I Oyler, JM Moolchan, ET Cone, EJ Huestis, MA TI Urinary pharmacokinetics of methamphetamine and its metabolite, amphetamine following controlled oral administration to humans SO THERAPEUTIC DRUG MONITORING LA English DT Article DE methamphetamine; amphetamine; urine; pharmacokinetics; excretion ID EXCRETION; COCAINE AB Methamphetamine is widely abused for its euphoric effects. Our objectives were to characterize the urinary pharmacokinetics of methamphetamine and amphetamine after controlled methamphetamine administration to humans and to improve the interpretation of urine drug test results. Participants (n = 8) received 4 daily 10-mg (low) oral doses of sustained-re lease (d)-methamphetamine hydrochloride within 7 days. After 4 weeks, 5 participants received 4 daily 20-mg (high) oral doses. All urine specimens were collected during the study. Methamphetamine and amphetamine were measured by GC-MS/PCI. Maximum excretion rates ranged from 403 to 4919 mug/h for methamphetamine and 59 to 735 mug/h for amphetamine with no relationship between dose and excretion rate. The mean molar percentage of dose in the urine as total methamphetamine and amphetamine were 57.5 +/- 21.7% (low dose) and 40.9 +/- 8.5% (high dose). Mean urinary terminal elimination half-lives across doses were 23.6 +/- 6.6 hours for methamphetamine and 20.7 +/- 7.3 hours for amphetamine. Methamphetamine renal clearance across doses was 175 102 mL/min. The mean amphetamine/methamphetamine percentage ratio based on the area under the urinary excretion-time curve increased over time from 13.4 +/- 6.5% to 35.7 +/- 26.6%. Slow urinary excretion results in drug accumulation and increases in detection time windows. Our findings also support the presence of an active renal excretion mechanism for methamphetamine. C1 NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. ConeChem Res, Severna Pk, MD USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Bldg C,Room 371,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 21 TC 27 Z9 27 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 2004 VL 26 IS 6 BP 664 EP 672 DI 10.1097/00007691-200412000-00013 PG 9 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 877AV UT WOS:000225541100013 PM 15570192 ER PT J AU van der Palen, J Rea, TD Manolio, TA Lumley, T Newman, AB Tracy, RP Enright, PL Psaty, BM AF van der Palen, J Rea, TD Manolio, TA Lumley, T Newman, AB Tracy, RP Enright, PL Psaty, BM TI Respiratory muscle strength and the risk of incident cardiovascular events SO THORAX LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; HEART-FAILURE; PROGNOSTIC-SIGNIFICANCE; RANDOMIZED-TRIAL; REFERENCE VALUES; LUNG-FUNCTION; MORTALITY; WOMEN; MEN; DYSFUNCTION AB Background: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained. Methods: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke. Results: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to 2.15) after adjustment for nonpulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly. Conclusions: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation. C1 Med Spectrum Twente, Dept Epidemiol, Enschede, Netherlands. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Vermont, Dept Pathol, Colchester, VT USA. Univ Arizona, Coll Publ Hlth, Tucson, AZ USA. RP van der Palen, J (reprint author), Med Spectrum Twente, Dept Epidemiol, Enschede, Netherlands. EM vdpalen@euronet.nl RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 NR 25 TC 34 Z9 36 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD DEC PY 2004 VL 59 IS 12 BP 1063 EP 1067 DI 10.1136/thx.2004.021915 PG 5 WC Respiratory System SC Respiratory System GA 874NV UT WOS:000225358000014 PM 15563706 ER PT J AU Jimenez, C Moran, SA Sereti, I Wynne, S Yen, PM Falloon, J Davey, RT Sarlis, NJ AF Jimenez, C Moran, SA Sereti, I Wynne, S Yen, PM Falloon, J Davey, RT Sarlis, NJ TI Graves' disease after interleukin-2 therapy in a patient with human immunodeficiency virus infection SO THYROID LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the Endocrine-Society CY JUN 19-22, 2002 CL SAN FRANCISCO, CA SP Endocrine Soc ID ACTIVE ANTIRETROVIRAL THERAPY; AUTOIMMUNE THYROID-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL-CLONES; IMMUNE RESTORATION; HIV-INFECTION; RECOMBINANT INTERLEUKIN-2; PERIPHERAL-BLOOD; CD4(+); ABNORMALITIES AB Interleukin-2 (IL-2) is a cytokine that regulates the proliferation and differentiation of lymphocytes, and is currently used clinically in the treatment of assorted malignancies. Additionally, IL-2 is being actively investigated in clinical trials for treatment of human immunodeficiency virus (HIV) infection. Patients treated with IL-2 are susceptible to autoimmune thyroid disease (AITD), presenting as thyroiditis, which leads to either thyrotoxicosis or hypothyroidism, if not correctly and promptly identified and treated. IL-2-induced hypothyroidism can also sometimes follow a thyrotoxic phase. However, the development of Graves' disease (GD) in this clinical setting has not been reported to date. Here, we report the case of a 39-year-old HIV-infected man in whom GD developed after IL-2 therapy. We correlated the immunologic parameters pertinent to the patient's HIV infection status with clinical, hormonal, and serologic evidence of GD during its emergence. This revealed an association between peripheral blood cell numbers of specific lymphocyte subpopulations (CD4(+), CD3(+)CD25(+), and naive T-cells) and serum levels of markers for AITD (free thyroxine [T-4] and thyroid-stimulating immunoglobulin). Interestingly, no association was found between natural killer (NK) cell numbers and AITD markers. The immunopathogenesis of GD in this patient may be similar to that hypothesized for the GD that occurs in immune-reconstituted patients after combination antiretroviral therapy. From a practical standpoint, we propose that patients who have received or are receiving treatment with IL-2 who show signs of hyperthyroidism need to be carefully evaluated for GD. C1 Univ Texas, MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Baylor Coll Med, Houston, TX 77030 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX USA. RP Sarlis, NJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Baylor Coll Med, 1515 Holcombe Blvd,Unit 435, Houston, TX 77030 USA. EM njsarlis@mdanderson.org NR 43 TC 11 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 2004 VL 14 IS 12 BP 1097 EP 1102 DI 10.1089/thy.2004.14.1097 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 885AV UT WOS:000226129200015 PM 15650365 ER PT J AU Bucher, JR Portier, C AF Bucher, JR Portier, C TI Human carcinogenic risk evaluation, part V: The National Toxicology Program vision for assessing the human carcinogenic hazard of chemicals SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE carcinogen identification; approach; mechanism-based biological observations ID CANCER; BIOASSAY; ASSAYS; MODELS AB The National Toxicology Program (NTP) has over 25 years of experience in the design, performance, and interpretation of assays for identifying carcinogenic hazards to humans. Through the years we have examined alternative assays and adjunct assays to the standard rodent cancer bioassay including batteries of genetic toxicity tests and genetically modified mouse models. As our collective understanding of carcinogenesis advances, toxicologists and regulatory scientists will at some point begin to rely on mechanism-based biological observations rather than the two-year rodent bioassay to predict human cancer hazards. The goal of the NTP Vision for the 21st Century is to develop the science base that will advance the use of mechanism-based biological observations, eventually providing a replacement for disease-specific toxicology models in the protection of public health. C1 NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 15 TC 20 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 363 EP 366 DI 10.1093/toxsci/kfh293 PG 4 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300002 PM 15456919 ER PT J AU Guo, GL Moffit, JS Ward, JM Aleksunes, LA Slitt, AL Kliewer, SA Manautou, JE Gonzalez, FJ AF Guo, GL Moffit, JS Ward, JM Aleksunes, LA Slitt, AL Kliewer, SA Manautou, JE Gonzalez, FJ TI Enhanced acetaminophen toxicity by activation of the pregnane X receptor SO TOXICOLOGICAL SCIENCES LA English DT Article DE PXR; acetaminophen; hepatotoxicity; nuclear receptor ID CONSTITUTIVE ANDROSTANE RECEPTOR; INDUCED HEPATIC NECROSIS; INDUCED HEPATOTOXICITY; NULL MICE; DRUG-INTERACTIONS; GLUTATHIONE; PREGNENOLONE-16-ALPHA-CARBONITRILE; PROTECTION; RESISTANCE; CYP2E1 AB The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation. C1 NCI, Metab Lab, CCR, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Frederick, MD 21701 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. RP Gonzalez, FJ (reprint author), NCI, Metab Lab, CCR, NIH, Bldg 37,Rm 3106B, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU NIEHS NIH HHS [F32 ES011239-02, F32 ES011239] NR 33 TC 70 Z9 73 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 374 EP 380 DI 10.1093/toxsci/kfh286 PG 7 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300004 PM 15456926 ER PT J AU Martinez, JM Baek, SJ Mays, DM Tithof, PK Eling, TE Walker, NJ AF Martinez, JM Baek, SJ Mays, DM Tithof, PK Eling, TE Walker, NJ TI EGR1 is a novel target for AhR agonists in human lung epithelial cells SO TOXICOLOGICAL SCIENCES LA English DT Article DE early growth response 1; mRNA stabilization; cell transformation; 2,3,7,8-tetrachlorodibenzo-p-dioxin; lung epithelial cells ID ARYL-HYDROCARBON RECEPTOR; POLYCYCLIC AROMATIC-HYDROCARBONS; ACTIVATOR MESSENGER-RNA; EARLY GROWTH RESPONSE-1; TUMOR-NECROSIS-FACTOR; FACTOR-BETA 1; TRANSCRIPTION FACTOR; FIBROSARCOMA CELLS; DIOXIN RECEPTOR; RICH ELEMENT AB The transcription factor early growth response 1 (EGR1) was previously identified as a potential novel target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human lung epithelial cells by toxicogenomic analysis. EGR1 has been implicated in the pathogenesis of vascular disease and is altered by a number of factors that include stress, inflammation, and hypoxia. Depending on its downstream targets or protein interactions, EGR1 regulates important biological processes that include cell growth, apoptosis, and differentiation. The following experiments were conducted to determine if EGR1 is indeed a target of TCDD and polycyclic aromatic hydrocarbons (PAHs) that can act through a similar mechanism. Pulmonary epithelial cells were exposed to TCDD for 24 h and an increase in EGR1 mRNA was measured. In addition, EGR1 protein was increased by TCDD and PAHs that have binding affinity to the aryl hydrocarbon receptor. The transcriptional activity of the EGR1 promoter was measured with a luciferase construct; however, no increases in luciferase activity were detected in TCDD or PAH-treated cells. Using actinomycin to inhibit RNA synthesis, we found that TCDD increased the half-life of EGR1 mRNA from 13 to 22 min. Thus, the increase in EGR1 expression appears to be mediated through a post-transcriptional mechanism that leads to the higher EGR1 protein levels in TCDD and PAH treated cells, compared to vehicle treated cells. Increased expression of a transcription factor EGR1 with tumorigenic and other biological activities could contribute to the deleterious pulmonary effects of exposure to these environmental agents. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Knoxville, TN 37996 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Martinez, JM (reprint author), NIEHS, Lab Computat Biol & Risk Anal, 111 Alexander Dr,POB 12233,ND C4-05, Res Triangle Pk, NC 27709 USA. EM martine2@niehs.nih.gov RI Walker, Nigel/D-6583-2012; OI Walker, Nigel/0000-0002-9111-6855; Baek, Seung/0000-0001-7866-7778 NR 48 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 429 EP 435 DI 10.1093/toxsci/kfh272 PG 7 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300009 PM 15342960 ER PT J AU Germolec, DR Kashon, M Nyska, A Kuper, CF Portier, C Kommineni, C Johnson, KA Luster, MI AF Germolec, DR Kashon, M Nyska, A Kuper, CF Portier, C Kommineni, C Johnson, KA Luster, MI TI The accuracy of extended histopathology to detect immunotoxic chemicals SO TOXICOLOGICAL SCIENCES LA English DT Article DE extended histopathology; immunotoxicity; screening tests; B6C3F1 mice; safety assessment ID FEMALE B6C3F1 MICE; EXOGENOUS CORTICOSTERONE; RESTRAINT STRESS; RISK-ASSESSMENT; IMMUNE; SENSITIVITY; VALIDATION; RESISTANCE; PARAMETERS; THYMUS AB The accuracy of extended histopathology to detect immunotoxic chemicals in female B6C3F1 mice was evaluated under the auspices of the National Toxicology Program (NTP). A workgroup was formed consisting of four pathologists who conducted extended histopathological evaluation of lymphoid tissues obtained from a subset of NTP toxicology studies, in which previously detailed immunotoxicity assessment was performed. In addition, a positive control data set of three known immunosuppressive agents, one negative control data set, and an additional negative control group composed of the vehicle only treated groups were included. Data obtained from extended histopathology evaluations were compared to more traditional immune test results (both functional and nonfunctional) from previously conducted immunotoxicity assessments. Analyses of the data indicated that the ability to identify immunotoxic chemicals using histological endpoints decreased linearly as the level of stringency used to determine significant histopathological changes increased. A relatively high (80%) accuracy level was achieved when histological changes were considered in toto (i.e., any histological abnormality in the three tissues examined), using minimal or mild criteria for scoring. When minimal or mild histological changes were considered significant for a specific tissue, a 60% level of accuracy in identifying immunotoxic chemicals was obtained as compared to a 90% accuracy level that was achieved with this data set using the antibody plaque forming cell response, considered to represent the most predictive functional test. A minimal classification was obtained in the analyses of the negative control groups, suggesting that use of the minimal classification for hazard identification is inappropriate as it will likely result in a high incidence of false positives. This was not the case when mild classifications were used as an indicator of significance, which in most instances allowed the successful identification of negatives. When moderate to marked histopathological changes were used to identify immunotoxic chemicals, the level of accuracy that could be achieved was poor. A considerably higher level of accuracy was obtained for the positive control data set than the test chemical data set suggesting that the ability to detect an immunotoxic agent histologically is proportional to the potency of the immunotoxic agent. Comparison of immune function test results and histopathological results obtained from the high-dose treatment groups and the lower-dose treatment group did not reveal any significant differences between the two endpoints to predict immunotoxicity as a function of dose. Of the three lymphoid organs examined, (i.e., lymph node, thymus, and spleen), the most consistent and discernible histological lesions were observed in the thymus cortical region. These lesions correlated with thymus: body weight ratios and to a slightly lesser extent, the antibody plaque forming cell response. Addition of general toxicological endpoints such as body weight and leukocyte counts did not significantly improve the sensitivity of extended histopathology for this data set. Taken together, these data suggest that, while not as sensitive as functional analyses, extended histopathology may provide a reasonable level of accuracy as a screening test to identify immunotoxic chemicals, provided the level of stringency used to score histological lesions is carefully considered to allow for detection of immunotoxic agents while limiting false positives. C1 NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIOSH, Biostat Branch, Morgantown, WV USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. TNO Nutr & Food Res, Zeist, Netherlands. NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. NIOSH, Pathol & Physiol Res Branch, Morgantown, WV USA. Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV USA. RP Germolec, DR (reprint author), NIEHS, Mol Toxicol Lab, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM germolec@niehs.nih.gov RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Kuper, Frieke/0000-0001-8273-2915 NR 33 TC 39 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 504 EP 514 DI 10.1093/toxsci/kfh271 PG 11 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300018 PM 15342959 ER PT J AU Scallet, AC Divine, RL Newbold, RR Delclos, KB AF Scallet, AC Divine, RL Newbold, RR Delclos, KB TI Increased volume of the calbindin D28k-labeled sexually dimorphic hypothalamus in genistein and nonylphenol-treated male rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE medial preoptic nucleus; hypothalamus; 3-D reconstruction; endocrine disrupters; estrogens; sex differences; calcium binding proteins ID SPRAGUE-DAWLEY RATS; FINCH SONG SYSTEM; GONADOTROPIN-RELEASING-HORMONE; MEDIAL PREOPTIC AREA; CASTRATED ADULT-RAT; PITUITARY-RESPONSIVENESS; DIETARY EXPOSURE; FEMALE RATS; POSTNATAL-DEVELOPMENT; NEONATAL EXPOSURE AB The adult rat brain develops through an interplay of neuronal proliferation and programmed cell death. Steroid hormones and growth factors may alter the balance between these competing processes. "Endocrine disrupters" (EDs) may also alter brain development, by mimicry or modulation of endogenous hormone systems. Under control conditions, the sexually dimorphic nucleus (SDN) of the medial preoptic hypothalamus becomes larger in adult males than females, but its final volume may also reflect the hormonal conditions prevailing during development. Two EDs that have recently been studied in protocols involving lifespan exposures are the phytoestrogen genistein and the weakly estrogenic compound para-nonylphenol, which is used in the production of many surfactants and plastics. Experimental dietary exposure of adult female rats to genistein or p-nonylphenol began 28 days prior to their mating at concentrations of 5 ppm, 100 ppm, and 500 ppm for genistein or 25 ppm, 200 ppm, and 750 ppm for p-nonylphenol. Exposure of the offspring continued throughout gestation and lactation, as well as in their chow after weaning, until they were sacrificed at 140 days of age for immunohistochemical labeling of the calbindin D28k-labeled subdivision of the SDN: the CALB-SDN. Both genistein and nonylphenol were found to increase the volume of the CALB-SDN in male rats (p's < 0.01), but not in female rats. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Charles River Labs, Jefferson, AR 72079 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Dr, Jefferson, AR 72079 USA. EM ascallet@nctr.fda.gov NR 55 TC 22 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 570 EP 576 DI 10.1093/toxsci/kfh297 PG 7 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300025 PM 15456915 ER PT J AU Crowell, JA Korytko, PJ Morrissey, RL Booth, TD Levine, BS AF Crowell, JA Korytko, PJ Morrissey, RL Booth, TD Levine, BS TI Resveratrol-associated renal toxicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE resveratrol; cancer chemoprevention; kidney ID NF-KAPPA-B; ESTROGEN-RECEPTOR; POLYPHENOLIC COMPOUND; INDUCED ACTIVATION; SMALL-INTESTINE; CANCER; RATS; APOPTOSIS; GRAPES; WINE AB Resveratrol, (3,5,4'-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic, antiviral, and beneficial cardiovascular and cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg trans-resveratrol per kilogram body weight per day for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg per kilogram body weight per day. These included increased clinical signs of toxicity; reduced final body weights and food consumption; elevated BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts. Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, were observed. Diffuse epithelial hyperplasia in the bladder was considered, equivocal and of limited biological significance. No histological effects on the liver were observed, despite the clinical chemistry changes and increased liver weights in the females. Effects seen in the group administered 1000 mg resveratrol per kilogram body weight per day included reduced body weight gain (females only) and elevated white blood cell count (males only). Plasma resveratrol concentrations in blood collected 1 h after dose administration during week 4 were dose related but were relatively low given the high dosage levels; conjugates were not measured. Under the conditions of this study, the no observed adverse effect level was 300 mg resveratrol per kilogram body weight per day in rats. C1 NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. Univ Illinois, Toxicol Res Lab, Chicago, IL 60612 USA. Pathol Associates Inc, Chicago, IL 60612 USA. Royalmount Pharmaceut Inc, Montreal, PQ H4P 2T4, Canada. RP Crowell, JA (reprint author), NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, 6130 Execut Blvd,Bldg EPN,Rm 2118, Bethesda, MD 20892 USA. EM jc94h@nih.gov NR 28 TC 151 Z9 161 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 614 EP 619 DI 10.1093/toxsci/kfh263 PG 6 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300030 PM 15329443 ER PT J AU Couse, JF Korach, KS AF Couse, JF Korach, KS TI Estrogen receptor-alpha-mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the murine reproductive tract SO TOXICOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mult-Organic Risk Assessment of Endocrine Disrupters CY MAR 31-APR 01, 2004 CL Mallorca, SPAIN DE uterus; prostate; homeobox; endocrine disruption ID C-FOS PROTOONCOGENE; DEVELOPMENTAL EXPOSURE; MESSENGER-RNA; WNT GENES; ADULT-RAT; NULL MICE; IN-UTERO; EXPRESSION; MOUSE; BETA AB It is generally believed that estrogen receptor-dependent and -independent pathways are involved in mediating the developmental effects of the synthetic estrogen, diethylstilbestrol (DES). However, the precise role and extent to which each pathway contributes to the resulting pathologies remains unknown. We have employed the estrogen receptor knockout (ERKO) mice, which lack either estrogen receptor-alpha (alphaERKO or estrogen receptor-beta (betaERKO), to gain insight into the contribution of each ER-dependent pathway in mediating the effects of neonatal DES exposure in the female and male reproductive tract tissues of the mouse. Estrogen receptor-a female mice exhibited complete resistance to the chronic effects of neonatal DES exposure that were obvious in exposed wild-type animals, including atrophy and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent cornification of the vaginal epithelium. DES-mediated reduction in uterine Hoxa10, Hova11 and Wnt7a expression that occurs wild-type females during the time of exposure was also absent in alphaERKO females. In the male, alphaERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure on the prostate, including decreased androgen receptor levels, epithelial hyperplasia, and increased basal cell proliferation. Although ERbeta is highly expressed in the prostate epithelium, DES-exposed betaERKO males exhibited all of the effects of neonatal DES exposure that were observed in similarly exposed wild-type males. Therefore, the lack of DES-effects on gene expression and tissue differentiation in the alphaERKO uterus and prostate provides unequivocal evidence of an obligatory role for ERalpha in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Korach, KS (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 56 TC 68 Z9 73 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 1 PY 2004 VL 205 IS 1-2 BP 55 EP 63 DI 10.1016/j.tox.2004.06.046 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 864YK UT WOS:000224669100008 PM 15458790 ER PT J AU Kaminski, RM Tochman, AM Dekundy, A Turski, WA Czuczwar, SJ AF Kaminski, RM Tochman, AM Dekundy, A Turski, WA Czuczwar, SJ TI Ethosuximide and valproate display high efficacy against lindane-induced seizures in mice SO TOXICOLOGY LETTERS LA English DT Article DE lindane; pentylenetetrazol; ethosuximide; valproate; seizures; mice ID CONVENTIONAL ANTIEPILEPTICS; PHARMACOLOGICAL FACTORS; ANTICONVULSANT ACTIVITY; LABORATORY EVALUATION; CHILDREN; DRUGS; ANTAGONISTS; VIGABATRIN; MECHANISMS; TOXICITY AB Both lindane (gamma-hexachlorocyclohexane), an organochlorine ectoparasiticide and pentylenetetrazol, used as a model of experimental epilepsy, produce convulsive seizures resulting from the blockade of the gamma-aminobutyric acid (GABA(A)) receptor. In the present study we established the protective effects of ethosuximide and valproate against seizures induced by lindane and compared them with the well-known protective effects of these drugs against pentylenetetrazol-induced seizures in mice. Both ethosuximide and valproate afforded complete and dose-dependent protection against seizures induced by lindane. However, the potencies of these drugs were lower than those obtained against pentylenetetrazol seizures. Nevertheless, the protective efficacy of ethosuximide and valproate against experimentally induced lindane seizures may suggest possible efficacy of these drugs against seizures in lindane-poisoned patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Inst Agr Med, Isotope Lab, PL-20950 Lublin, Poland. Inst Agr Med, Dept Toxicol, PL-20950 Lublin, Poland. Skubiszewski Med Univ Lublin, Dept Pharmacol & Toxicol, PL-20090 Lublin, Poland. Skubiszewski Med Univ Lublin, Dept Pathophysiol, PL-20090 Lublin, Poland. RP Kaminski, RM (reprint author), NINDS, Epilepsy Res Sect, NIH, 35 Lincoln Dr,MSC 3702,Bldg 35,Rm1C1000, Bethesda, MD 20892 USA. EM kaminskr@ninds.nih.gov NR 35 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 1 PY 2004 VL 154 IS 1-2 BP 55 EP 60 DI 10.1016/j.toxlet.2004.07.002 PG 6 WC Toxicology SC Toxicology GA 865DL UT WOS:000224682600006 PM 15475178 ER PT J AU Stevens, WT Pittaluga, S Dunleavy, K Wilson, WH Leitman, SF Bolan, CD AF Stevens, WT Pittaluga, S Dunleavy, K Wilson, WH Leitman, SF Bolan, CD TI Hemophagocytosis and coagulopathy associated with cutaneous gamma-delta T-cell lymphoma SO TRANSFUSION LA English DT Editorial Material C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Stevens, WT (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM wstevens@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2004 VL 44 IS 12 BP 1679 EP 1679 DI 10.1111/j.0041-1132.2004.04230.x PG 1 WC Hematology SC Hematology GA 879FU UT WOS:000225702600001 PM 15584978 ER PT J AU Yakovleva, O Janiak, A McKenzie, C McShane, L Brown, P Cervenakova, L AF Yakovleva, O Janiak, A McKenzie, C McShane, L Brown, P Cervenakova, L TI Effect of protease treatment on plasma infectivity in variant Creutzfeldt-Jakob disease mice SO TRANSFUSION LA English DT Article ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CELLULAR PRION PROTEIN; BLOOD-TRANSFUSION; PRECLINICAL DIAGNOSIS; TONSIL BIOPSY; COMPONENTS; SCRAPIE; CELLS; UK; ACCUMULATION AB BACKGROUND: The emergence of variant Creutzfeldt-Jakob disease (vCJD) and of a probable transmission of the disease through blood transfusion from a presymptomatic case has underlined the need for a reliable, sensitive, and specific screening test. This study was initiated to explain why attempts to identify protease-resistant prion protein (PrPres) following treatment with proteinase K (PK) in blood or blood components have so far failed. STUDY DESIGN AND METHODS: RIII mice were inoculated intracerebrally (i.c.) with vCJD agent. As soon as some mice became ill, blood from all mice was collected, pooled, and separated into components. Aliquots of plasma were treated with either 100 and 500 mug per mL PK or left untreated. Samples were analyzed for total protein and for PrPres by Western blot with 6H4 antibodies. Infectivity in PK-treated and untreated samples was bioassayed by i.c. inoculation into healthy mice. RESULTS: Estimated infectivity in untreated control plasma was 20.6 IU per mL. Treatment of plasma with 100 or 500 pg per mL PK resulted in estimated infectivity levels of 8.4 and 5.2 IU per mL, respectively. Coomassie staining revealed substantial changes in the protein profile after PK treatment, with massive degradation of proteins at 500 pg per mL PK. No PrPres was detected in plasma samples by Western blotting. CONCLUSION: Infectivity in plasma of vCJD-infected mice showed a trend toward reduction following enzymatic treatment with increasing doses of PK, possibly because of activity against proteolysis-sensitive isoforms of abnormal prion protein. It is concluded that the use of PK in protocols for the detection of PrPres may decrease the sensitivity of blood-based assays. C1 Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, Rockville, MD 20855 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NIH, CNS Studies Lab, Bethesda, MD 20892 USA. RP Cervenakova, L (reprint author), Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM cervenakl@usa.redcross.org NR 35 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2004 VL 44 IS 12 BP 1700 EP 1705 DI 10.1111/j.0041-1132.2004.04198.x PG 6 WC Hematology SC Hematology GA 879FU UT WOS:000225702600006 PM 15584983 ER PT J AU McEntyre, JR Gibson, TJ AF McEntyre, JR Gibson, TJ TI Patterns and clusters within the PSM column in TiBS, 1992-2004 SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID MULTIPLE SEQUENCE ALIGNMENT; AMINO-ACID-SEQUENCES; NUCLEIC-ACID; BINDING DOMAIN; PROTEIN; MOTIF; SUPERFAMILY; DATABASE; KINASE; COMMON AB Sequence similarities among proteins can infer biological function and evolutionary relationships - a powerful approach for investigating new proteins and suggesting future experiments. The availability of public sequence databases and freely distributed tools for sequence analysis has meant that researchers from all over the world can use this approach. For the past 12 years, the Protein Sequence Motif column in TiBS has provided a platform for documenting interesting discoveries from sequence analyses. As the column comes to an end, we look at the published contributions over the years and reflect on sequence analysis through the beginning of the genomic era. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. European Mol Biol Lab, D-96117 Heidelberg, Germany. RP McEntyre, JR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr,MSC 6510,Bldg 45,Room 5AN,45B, Bethesda, MD 20892 USA. EM mcentyre@ncbi.nlm.nih.gov OI Gibson, Toby James/0000-0003-0657-5166; McEntyre, Jo/0000-0002-1611-6935 NR 60 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 2004 VL 29 IS 12 BP 627 EP 633 DI 10.1016/j.tibs.2004.10.006 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880UE UT WOS:000225814300001 PM 15544947 ER PT J AU Sakai, K Hikosaka, O Nakamura, K AF Sakai, Katsuyuki Hikosaka, Okihide Nakamura, Kae TI Emergence of rhythm during motor learning SO TRENDS IN COGNITIVE SCIENCES LA English DT Review AB Complex motor skill often consists of a fixed sequence of movements. Recent studies show that a stereotyped temporal pattern or rhythm emerges as we learn to perform a motor sequence. This is because the sequence is reorganized during learning as serial chunks of movements in both a sequence-specific and subject-specific manner. On the basis of human imaging studies we propose that the formation of chunk patterns is controlled by the cerebellum, its posterior and anterior lobes contributing, respectively, to the temporal patterns before and after chunk formation. The motor rhythm can assist the motor networks in the cerebral cortex to control automatic movements within chunks and the cognitive networks to control non-automatic movements between chunks, respectively. In this way, organized motor skill can be performed automatically and flexibly. C1 Univ Tokyo, Grad Sch Med, Dept Cognit Neurosci, Tokyo 1330033, Japan. NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Sakai, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Cognit Neurosci, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1330033, Japan. EM ksakai@m.u-tokyo.ac.jp NR 68 TC 61 Z9 61 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD DEC PY 2004 VL 8 IS 12 BP 547 EP 553 DI 10.1016/j.tics.2004.10.005 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA V43QO UT WOS:000202949800007 PM 15556024 ER PT J AU Murphy, WJ Pevzner, PA O'Brien, SJ AF Murphy, WJ Pevzner, PA O'Brien, SJ TI Mammalian phylogenomics comes of age SO TRENDS IN GENETICS LA English DT Review ID ENDEMIC AFRICAN MAMMALS; MITOCHONDRIAL GENOMES; PLACENTAL MAMMALS; GENE ORDER; ANCESTRAL KARYOTYPE; PHYLOGENETIC TREE; WEB SERVER; EVOLUTION; SEQUENCE; REARRANGEMENTS AB The relatively new field of phylogenomics is beginning to reveal the potential of genomic data for evolutionary studies. As the cost of whole genome sequencing falls, anticipation of complete genome sequences from divergent species, reflecting the major lineages of modern mammals, is no longer a distant dream. In this article, we describe how comparative genomic data from mammals is progressing to resolve long-standing phylogenetic controversies, to refine dogma on how chromosomes evolve and to guide annotation of human and other vertebrate genomes. C1 NCI, Lab Genom Divers, SAIC Frederick, Basic Res Lab, Frederick, MD 21702 USA. Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. EM wmurphy@cvm.tamu.edu FU NCI NIH HHS [N01 CO 12400] NR 86 TC 211 Z9 220 U1 4 U2 22 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 2004 VL 20 IS 12 BP 631 EP 639 DI 10.1016/j.tig.2004.09.005 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 876WE UT WOS:000225528400009 PM 15522459 ER PT J AU McBride, AA McPhillips, MG Oliveira, JG AF McBride, AA McPhillips, MG Oliveira, JG TI Brd4: tethering, segregation and beyond SO TRENDS IN MICROBIOLOGY LA English DT Review ID SARCOMA-ASSOCIATED HERPESVIRUS; PAPILLOMAVIRUS E2 PROTEIN; NUCLEAR ANTIGEN; MITOTIC CHROMOSOMES; BROMODOMAIN PROTEIN; EPISOMAL MAINTENANCE; HOST CHROMOSOMES; VIRAL-DNA; CHROMATIN; ATTACHMENT AB Papillomaviruses segregate their genomes in dividing cells by tethering them to mitotic chromosomes via the viral E2 protein. A recent report has shown that this interaction is mediated by the cellular bromodomain protein Brd4. This discovery provides new insight into the mechanism of viral genome segregation and raises many exciting questions about the regulation and nature of the interaction of this complex with mitotic chromosomes. C1 NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI McBride, Alison/0000-0001-5607-5157 NR 18 TC 33 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD DEC PY 2004 VL 12 IS 12 BP 527 EP 529 DI 10.1016/j.tim.2004.10.002 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 880GY UT WOS:000225778200001 PM 15539109 ER PT J AU Bennink, JR Palmore, TN AF Bennink, JR Palmore, TN TI The promise of siRNAs for the treatment of influenza SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID RNA INTERFERENCE; VIRUS REPLICATION; MAMMALIAN-CELLS; INHIBITION; STRATEGIES; CHANNEL AB Current WHO reports on the Asian avian influenza virus outbreaks are poignant reminders of the potential for the emergence of highly virulent strains of influenza A virus (IAV) and the fact that it remains a scourge on human health. As IAV drifts and shifts its genetic and antigenic composition, it presents an ever-changing challenge for vaccines and antiviral medications. Short-interfering RNAs (siRNAs) are the latest class of potential antiviral therapeutics to be developed. Recent reports using siRNAs in mice suggest that they hold great promise for the prevention and treatment of IAV infections. C1 NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. RP Bennink, JR (reprint author), NIAID, NIH, Viral Dis Lab, 4 Ctr Dr, Bethesda, MD 20892 USA. EM jbennink@nih.gov NR 29 TC 17 Z9 20 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD DEC PY 2004 VL 10 IS 12 BP 571 EP 574 DI 10.1016/j.molmed.2004.10.004 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 883NG UT WOS:000226018900001 PM 15567323 ER PT J AU Baum, BJ Voutetakis, A Wang, JH AF Baum, BJ Voutetakis, A Wang, JH TI Salivary glands: novel target sites for gene therapeutics SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID REGULATED SECRETORY PATHWAY; RAT SUBMANDIBULAR-GLANDS; SYSTEMIC DELIVERY; IN-VIVO; ENDOCRINE SECRETION; INNATE IMMUNITY; GROWTH-HORMONE; ORAL MUCOSITIS; PROTEINS; VECTOR AB Directing the local or systemic expression of therapeutic proteins is a potentially important clinical application of gene transfer technology. Gene-based therapeutics theoretically offer many advantages over protein therapeutics. Numerous tissues have been evaluated for this purpose in animal models, most commonly the liver and skeletal muscle. Based on pre-clinical studies, we suggest that salivary glands are a valuable, yet underappreciated, target tissue for both systemic and upper gastrointestinal tract gene therapeutic applications. C1 Natl Inst Dental & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dental & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov NR 44 TC 42 Z9 42 U1 1 U2 32 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD DEC PY 2004 VL 10 IS 12 BP 585 EP 590 DI 10.1016/j.molmed.2004.10.003 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 883NG UT WOS:000226018900006 PM 15567328 ER PT J AU Roche, KW AF Roche, KW TI The expanding role of PSD-95: a new link to addiction SO TRENDS IN NEUROSCIENCES LA English DT Article ID NMDA RECEPTOR SUBUNITS; LONG-TERM POTENTIATION; POSTSYNAPTIC DENSITY-95; C-TERMINUS; PROTEIN; PLASTICITY; DESENSITIZATION; TRAFFICKING; MEMBRANE; KINASES AB One feature of addiction is the enhanced locomotor response known as behavioral sensitization that occurs with prolonged exposure to psychostimulants. In a recent study, Yao et al. have analyzed four distinct animal models that share this common phenotype. Evaluation of gene expression in the striatum reveals that postsynaptic density (PSD)-95, a synaptic scaffolding protein, is downregulated in each model, suggesting an essential role for this protein in addiction. C1 NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Roche, KW (reprint author), NINDS, Natl Inst Hlth, Bldg 35,Room 2C903, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 2004 VL 27 IS 12 BP 699 EP 700 DI 10.1016/j.tins.2004.09.002 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 877AK UT WOS:000225540000001 PM 15541508 ER PT J AU Carucci, DJ AF Carucci, DJ TI Plasmodium post-genomics: an update SO TRENDS IN PARASITOLOGY LA English DT Review ID PROTEIN IDENTIFICATION TECHNOLOGY; MASS-SPECTROMETRY; FALCIPARUM; SEQUENCE; PROTEOMICS; MIXTURES; DATABASE AB The concept behind the first Molecular Approaches to Malaria meeting, held 1-5 February 2000 in Lorne, Australia, was ahead of its time; to convene a meeting of malaria researchers, database developers and genomics scientists, and to discuss how genomic sciences and their relevant disciplines could be applied to solve important problems in malaria research. The success of the second Molecular Approaches to Malaria meeting, held 1-5 February 2004 in the same place, together with the influence of genomics on malaria research, is testament to the vision that the organizers had at the first meeting. This review attempts to capture some of the current efforts in the post-genomics era of malaria research and highlights the approaches discussed at the Molecular Approaches to Malaria 2004 meeting. C1 Fdn Natl Inst Hlth, Grand Challenges Global Hlth Initia, Bethesda, MD 20892 USA. RP Carucci, DJ (reprint author), Fdn Natl Inst Hlth, Grand Challenges Global Hlth Initia, 45 Ctr Dr,3AN-44, Bethesda, MD 20892 USA. EM dcarucci@fnih.org NR 24 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD DEC PY 2004 VL 20 IS 12 BP 558 EP 561 DI 10.1016/j.pt.2004.09.007 PG 4 WC Parasitology SC Parasitology GA 874WW UT WOS:000225382300004 PM 15522664 ER PT J AU Lee, W Deter, RL McNie, B Goncalves, LF Espinoza, J Chaiworapongsa, T Romero, R AF Lee, W Deter, RL McNie, B Goncalves, LF Espinoza, J Chaiworapongsa, T Romero, R TI Individualized growth assessment of fetal soft tissue using fractional thigh volume SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE 3D ultrasonography; fetal growth; IUGR; Rossavik growth model ID BIRTH-WEIGHT PREDICTION; TO-CHEEK DIAMETER; MENSTRUAL AGE; 3-DIMENSIONAL ULTRASOUND; CURVE STANDARDS; ABDOMINAL CIRCUMFERENCE; HEAD CIRCUMFERENCE; ASSESSMENT SCORE; NORMAL FETUSES; FEMUR LENGTH AB Objectives The main goals of this study were to introduce fractional thigh volume (TVol) as a new soft tissue parameter for fetal growth evaluation, define its relationship to menstrual age, and develop individualized fetal growth standards based on Rossavik growth models. Methods A prospective, longitudinal study of 22 fetuses was conducted with conventional biometry and TVol measurements by three-dimensional ultrasonography. Infant growth outcomes were determined from modified neonatal growth assessment scores. Rossavik functions (p = c(t)(k+s(t))) were used to fit complete datasets to examine relationships between TVol and model coefficients. Second-trimester models were subsequently specified from the linear slopes of growth curves before 28.0 menstrual weeks with each fetus acting as its own control. Third-trimester trajectories and birth measurements were predicted for standard growth parameters and TVol. Observed and predicted measurements were compared using percent deviations and growth potential realization index values. Four additional infants, with serial prenatal scans and postnatal evidence of intrauterine growth restriction (IUGR), were also evaluated. Results All 22 fetuses bad no evidence of growth abnormalities after delivery. Accelerated soft tissue deposition occurred in the fetal thigh by 28 menstrual weeks. A mean TVol start point of 9.0 +/- 1.4 menstrual weeks was consistent with embryological studies of thigh development. Rossavik functions fitted all TVol trajectories well (mean R-2 = 0.998 +/- 0.002). By fixing the coefficient k at its mean value (2.976), the fit did not change and the variabilities of coefficients c and s were reduced. The mean percent deviation between observed and predicted third-trimester TVol measurements was -0.048 +/- 7.5%. Relatively early pathological deviations were observed for TVol in all four fetuses with IUGR; in these cases the abdominal circumference was abnormal in only one fetus and thigh circumference in none. Conclusions Individualized growth assessment can be used to accurately predict TVol during the third trimester of pregnancy and at birth. Expected growth trajectories, from second-trimester data, do not rely on population-based standards because each fetus serves as its own control. This new parameter may allow earlier detection and improved monitoring of fetal soft tissue abnormalities such as IUGR. Copyright (C) 2004 ISUOG. Published by John Wiley Sons, Ltd. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu NR 51 TC 33 Z9 36 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD DEC PY 2004 VL 24 IS 7 BP 766 EP 774 DI 10.1002/uog.1779 PG 9 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 884IE UT WOS:000226077300013 PM 15586365 ER PT J AU Espinoza, J Kalache, K Goncalves, LF Lee, W Chaiworapongsa, T Schoen, ML Devers, P Treadwell, M Mazor, M Romero, R AF Espinoza, J Kalache, K Goncalves, LF Lee, W Chaiworapongsa, T Schoen, ML Devers, P Treadwell, M Mazor, M Romero, R TI Prenatal diagnosis of membranous ventricular septal aneurysms and their association with absence of atrioventricular valve 'offsetting' SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE aneurysm; AV canal; AV valve offsetting; fetus; prenatal diagnosis; ultrasound; VSD ID MUSCULAR INTERVENTRICULAR SEPTUM; OUTFLOW TRACT OBSTRUCTION; CONGENITAL ANEURYSM; PULMONARY VALVE; DOWNS-SYNDROME; SPONTANEOUS CLOSURE; TRICUSPID-VALVE; HUMAN-HEART; DEFECT; DELETION AB Congenital aneurysm of the membranous portion of the ventricular septum in association with absence of atrioventricular valve 'offsetting' was diagnosed in two fetuses at 29 and 34 weeks. In the first case the fetus bad a normal karyotype and no other structural heart defects, whereas in the second case there was a partial deletion of the long arm of chromosome 5 and an absent pulmonary valve syndrome. The association of absence of 'offsetting' with aneurysms of the membranous ventricular septum may represent spontaneous closure of ventricular septal defects initially extended to the inlet. Copyright (C) 2004 ISUOG. Published by John Wiley Sons, Ltd. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Univ Hosp Berlin, Charite, Dept Obstet & Gynecol, Berlin, Germany. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. William Beaumont Hosp, Dept Fetal Imaging, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 47 TC 6 Z9 10 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD DEC PY 2004 VL 24 IS 7 BP 787 EP 792 DI 10.1002/uog.1769 PG 6 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 884IE UT WOS:000226077300016 PM 15543526 ER PT J AU Zeliadt, SB Potosky, AL Etzioni, R Ramsey, SD Penson, DF AF Zeliadt, SB Potosky, AL Etzioni, R Ramsey, SD Penson, DF TI Racial disparity in primary and adjuvant treatment for nonmetastatic prostate cancer: Seer-medicare trends 1991 to 1999 SO UROLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; UNITED-STATES; MEN; CARCINOMA; POPULATION; PATTERNS; CLAIMS; TIME AB Objectives. To assess trends in the initial care of nonmetastatic prostate cancer, including the use of primary and adjuvant androgen deprivation therapy (ADT), using population-based treatment claims from 1991 to 1999. Methods. We used a database linking the Surveillance, Epidemiology, and End Results (SEER) registry with Medicare claims to extract treatment information for 90,128 men aged 65 years and older, who were newly diagnosed with nonmetastatic prostate cancer. Results. The use of aggressive therapy has increased among white men over time; but aggressive therapy has recently declined among African-American men. Accounting for age, grade, socioeconomic status, and comorbidity, African-American men were 26% less likely to receive aggressive therapy than white men (odds ratio 0.74; 95% confidence interval 0.70 to 0.79). The use of ADT has increased substantially in both the primary and the adjuvant settings. By 1999, 45.6% of white men and 35.8% of African-American men who selected conservative management received primary ADT; among men treated with external beam radiotherapy, the proportion receiving adjuvant ADT was 53.7% for white men and 42.4% for African-American men (P < 0.001). Conclusions. Racial differences in the use of aggressive and conservative therapies are increasing. ADT is becoming a widely adopted component of initial treatment for localized prostate cancer. It is crucial to understand the impact of treatment patterns, including the increased use of ADT, on patient survival, morbidity, and costs of care. (C) 2004 Elsevier Inc. C1 Fred Hutchinson Canc Res Ctr, Dept Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. Univ So Calif, Keck Sch Med, Dept Urol & Prevent Med, Los Angeles, CA USA. Norris Canc Ctr, Los Angeles, CA USA. RP Zeliadt, SB (reprint author), Fred Hutchinson Canc Res Ctr, Dept Publ Hlth Sci, POB 19024,M2-230, Seattle, WA 98109 USA. EM szeliadt@fhcrc.org FU NCI NIH HHS [CA-88160, CA-92408] NR 30 TC 73 Z9 73 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD DEC PY 2004 VL 64 IS 6 BP 1171 EP 1176 DI 10.1016/j.urology.2004.07.037 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 884OI UT WOS:000226094500023 PM 15596192 ER PT J AU Glaser, V Miller, L AF Glaser, V Miller, L TI An interview with Louis Miller, MD SO VECTOR-BORNE AND ZOONOTIC DISEASES LA English DT Editorial Material C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1530-3667 J9 VECTOR-BORNE ZOONOT JI Vector-Borne Zoonotic Dis. PD WIN PY 2004 VL 4 IS 4 BP 384 EP 390 DI 10.1089/vbz.2004.4.384 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 888MW UT WOS:000226379700014 ER PT J AU Freed, EO AF Freed, EO TI Mechanisms of enveloped virus release SO VIRUS RESEARCH LA English DT Editorial Material C1 NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Bg 535,RM 124, Frederick, MD 21702 USA. EM efreed@nih.gov NR 0 TC 11 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 2004 VL 106 IS 2 BP 85 EP 86 DI 10.1016/j.virusres.2004.08.006 PG 2 WC Virology SC Virology GA 879WZ UT WOS:000225751200001 PM 15567489 ER PT J AU Demirov, DG Freed, EO AF Demirov, DG Freed, EO TI Retrovirus budding SO VIRUS RESEARCH LA English DT Review DE retrovirus; L domains; multivesicular ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; LATE ASSEMBLY DOMAIN; ROUS-SARCOMA-VIRUS; MURINE LEUKEMIA-VIRUS; PFIZER MONKEY VIRUS; UBIQUITIN-PROTEASOME SYSTEM; VESICULAR STOMATITIS-VIRUS; RECEPTOR DOWN-REGULATION; VIRAL PARTICLE RELEASE AB The release of retrovirus particles from the infected cell is greatly stimulated by short motifs, known as "late" or "L" domains, present within the Gag precursor protein. Three distinct classes of L domains have been identified; these bear the core sequence: Pro-Thr/Ser-Ala-Pro [P(T/S)AP]. Pro-Pro-x-Tyr (PPxY), or Tyr-Pro-x-Leu (YPxL). A number of recent studies have demonstrated that L domains function by interacting with components of the machinery responsible for sorting cellular proteins into the multivesicular body (MVB) pathway. This review traces the history of L domain discovery and characterization, and highlights the relationship between L domain activity, retrovirus release. and the host endosomal sorting machinery. Published by Elsevier B.V. C1 NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Bldg 535,Rm 124, Frederick, MD 21702 USA. EM efreed@mail.nih.gov NR 154 TC 218 Z9 225 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 2004 VL 106 IS 2 BP 87 EP 102 DI 10.1016/j.virusres.2004.08.007 PG 16 WC Virology SC Virology GA 879WZ UT WOS:000225751200002 PM 15567490 ER PT J AU Optican, LM Miura, K AF Optican, LM Miura, K TI Tenotorny and congenital nystagmus: a null result is not a failure, for "it is not the answer that enlightens, but the question" SO VISION RESEARCH LA English DT Letter ID EXTRAOCULAR-MUSCLE TENOTOMY; MACAQUE MONKEYS; ADULT PATIENTS; WAVE-FORMS; SURGERY C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Kyoto Univ, NEI, Kyoto, Japan. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, 49 Convent Dr, Bethesda, MD 20892 USA. EM lanceoptican@nih.gov NR 13 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD DEC PY 2004 VL 44 IS 26 BP 3095 EP 3098 DI 10.1016/j.visres.2004.07.009 PG 4 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 864JZ UT WOS:000224631100013 ER PT J AU Hoyo, C Cousins, DS Bisgrove, EZ Gaines, MM Schwingl, PJ Fortney, JA AF Hoyo, C Cousins, DS Bisgrove, EZ Gaines, MM Schwingl, PJ Fortney, JA TI Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under SO WEST INDIAN MEDICAL JOURNAL LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; RISK-FACTORS; CANCER RISK; COSTA-RICA; ASSOCIATION; NEOPLASIA; HPV AB Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long term users. Increased risk in some groups, however, warrant further study. C1 Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hoyo, C (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, 347 Hanes House,Box 2914, Durham, NC 27710 USA. EM hoyo0001@mc.duke.edu NR 21 TC 2 Z9 5 U1 0 U2 2 PU UNIV WEST INDIES FACULTY MEDICAL SCIENCES PI KINGSTON PA MONA CAMPUS, KINGSTON 7, JAMAICA SN 0043-3144 J9 W INDIAN MED J JI West Ind. Med. J. PD DEC PY 2004 VL 53 IS 6 BP 406 EP 412 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 917IZ UT WOS:000228455600009 PM 15816269 ER PT J AU Figg, WD Franks, ME Venzon, D Duray, P Cox, MC Linehan, WM Van Bingham, W Eastham, JA Reed, E Sartor, O AF Figg, WD Franks, ME Venzon, D Duray, P Cox, MC Linehan, WM Van Bingham, W Eastham, JA Reed, E Sartor, O TI Gleason score and pretreatment prostate-specific antigen in survival among patients with stage D2 prostate cancer SO WORLD JOURNAL OF UROLOGY LA English DT Article DE prostate; carcinoma; Gleason; differentiation ID LONG-TERM SURVIVAL; RADICAL PROSTATECTOMY; RADIATION-THERAPY; PROGNOSTIC-SIGNIFICANCE; ENDOCRINE TREATMENT; PROTEOMIC ANALYSIS; NEEDLE-BIOPSY; FOLLOW-UP; CARCINOMA; GRADE AB Although multiple studies have addressed the prognostic importance of tumor differentiation in patients with clinically localized prostate cancer, few data are available in patients with metastatic disease. We evaluated and compared survival data in two groups of men with Whitmore stage D2 metastatic prostate cancer initially treated with hormonal therapy. A series of 76 patients with D2 metastatic disease were evaluated and treated at the National Cancer Institute (NCI) in conjunction with an additional cohort of 141 patients from the Louisiana State University School of Medicine (LSU). Pathological specimens were classified according to the Gleason score. Fifty-two (25%) of the combined NCI/LSU specimens had a Gleason score of 6 or less, 71 (34%) had a value of 7, and remaining 87 (41%) had scores between 8 and 10. The median PSA at the time of diagnosis for the NCI patients was 294.2 ng/ml. Time to treatment failure was defined as the time that a greater than 50% increase above nadir PSA was noted. In neither group was Gleason score correlated with overall survival. There was no association between the time to progression following hormone therapy and primary tumor Gleason score. The PSA concentration at the time of diagnosis was not correlated with the Gleason score for the NCI patients; however, there was an inverse correlation between pretreatment PSA level and time to progression following hormonal ablation. Gleason score does not appear to impact survival in metastatic prostate cancer. PSA as a marker of the biological behavior in metastatic disease may also be limited. These findings should be reevaluated in larger, better matched cohorts. Novel techniques such as serum proteomics, microarrays, and metastatic cell isolation methods may better predict outcome in advanced prostate cancer. C1 NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Sch Med, Shreveport, LA 71130 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.gov RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 46 TC 10 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD DEC PY 2004 VL 22 IS 6 BP 425 EP 430 DI 10.1007/s00345-004-0443-7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 894CK UT WOS:000226767400004 PM 15592675 ER PT J AU Mertz, EL Leikin, S AF Mertz, EL Leikin, S TI Interactions of inorganic phosphate and sulfate anions with collagen SO BIOCHEMISTRY LA English DT Article ID X-RAY-DIFFRACTION; AMINO-ACID SEQUENCE; I COLLAGEN; FIBRIL-FORMATION; HYDROPHOBIC INTERACTIONS; RECONSTITUTED COLLAGEN; MOLECULAR PACKING; STAINING PATTERN; NATIVE COLLAGEN; TRIPLE HELICES AB We use direct infrared measurements to determine the number of binding sites, their dissociation constants, and preferential interaction parameters for inorganic phosphate and sulfate anions in collagen fibrils from rat tail tendons. In contrast to previous reports of up to 150 bound phosphates per collagen molecule, we find only 1-2 binding sites for sulfate and divalent phosphate under physiological conditions and similar to10 binding sites at low ionic strength. The corresponding dissociation constants depend on NaCl concentration and pH and vary from similar to50 muM to similar to1-5 mM in the physiological range of pH. In fibrils, bound anions appear to form salt bridges between positively charged amino acid residues within regions of high excess positive charge. In solution, we found no evidence of appreciable sulfate or phosphate binding to isolated collagen molecules. Although sulfate and divalent phosphate bind to fibrillar collagen at physiological concentrations, our X-ray diffraction and in vitro fibrillogenesis experiments suggest that this binding plays little role in the formation, stability and structure of fibrils. In particular, we demonstrate that the previously reported increase in the critical fibrillogenesis concentration of collagen is caused by preferential exclusion of "free" (not bound to specific sites) sulfate and divalent phosphate from interstitial water in fibrils rather than by anion binding. Contrary to divalent phosphate, monovalent phosphate does not bind to collagen. It is preferentially excluded from interstitial water in fibrils, but it has no apparent effect on critical fibrillogenesis concentration at physiological NaCl and pH. C1 NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Mertz, EL (reprint author), NICHHD, Dept Hlth & Human Serv, NIH, Bldg 9,Room 1E125, Bethesda, MD 20892 USA. EM mertze@mail.nih.gov RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 40 TC 38 Z9 38 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 30 PY 2004 VL 43 IS 47 BP 14901 EP 14912 DI 10.1021/bi048788b PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MA UT WOS:000225353300004 PM 15554697 ER PT J AU Berman, JJ AF Berman, JJ TI Tumor taxonomy for the developmental lineage classification of neoplasms SO BMC CANCER LA English DT Article ID INFORMATICS; DATABASE AB Background: The new "Developmental lineage classification of neoplasms" was described in a prior publication. The classification is simple (the entire hierarchy is described with just 39 classifiers), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. A taxonomy is a list of the instances that populate a classification. The taxonomy of neoplasia attempts to list every known term for every known tumor of man. Methods: The taxonomy provides each concept with a unique code and groups synonymous terms under the same concept. A Perl script validated successive drafts of the taxonomy ensuring that: 1) each term occurs only once in the taxonomy; 2) each term occurs in only one tumor class; 3) each concept code occurs in one and only one hierarchical position in the classification; and 4) the file containing the classification and taxonomy is a well-formed XML (eXtensible Markup Language) document. Results: The taxonomy currently contains 122,632 different terms encompassing 5,376 neoplasm concepts. Each concept has, on average, 23 synonyms. The taxonomy populates "The developmental lineage classification of neoplasms," and is available as an XML file, currently 9+ Megabytes in length. A representation of the classification/taxonomy listing each term followed by its code, followed by its full ancestry, is available as a flat-file, 19+ Megabytes in length. The taxonomy is the largest nomenclature of neoplasms, with more than twice the number of neoplasm names found in other medical nomenclatures, including the 2004 version of the Unified Medical Language System, the Systematized Nomenclature of Medicine Clinical Terminology, the National Cancer Institute's Thesaurus, and the International Classification of Diseases Oncolology version. Conclusions: This manuscript describes a comprehensive taxonomy of neoplasia that collects synonymous terms under a unique code number and assigns each tumor to a single class within the tumor hierarchy. The entire classification and taxonomy are available as open access files (in XML and flat-file formats) with this article. C1 NCI, Canc Diag Program, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Canc Diag Program, Bethesda, MD 20892 USA. EM bermanj@mail.nih.gov NR 16 TC 9 Z9 11 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD NOV 30 PY 2004 VL 4 AR 88 DI 10.1186/1471-2407-4-88 PG 6 WC Oncology SC Oncology GA 891VX UT WOS:000226610200001 PM 15571625 ER PT J AU O'Sullivan, TN Wu, XFS Rachel, RA Huang, JD Swing, DA Matesic, LE Hammer, JA Copeland, NG Jenkins, NA AF O'Sullivan, TN Wu, XFS Rachel, RA Huang, JD Swing, DA Matesic, LE Hammer, JA Copeland, NG Jenkins, NA TI dsu functions in a MYO5A-independent pathway to suppress the coat color of dilute mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE melanosome transfer; myosin 5A; vesicle transport ID KINESIN-RELATED PROTEIN; MYOSIN-VA; SACCHAROMYCES-CEREVISIAE; MELANOSOME TRANSPORT; MOUSE MELANOCYTES; POLARIZED GROWTH; GENE DSU; MUTATIONS; DEFECTS; SMY1P AB MYO5A is a major actin-based vesicle transport motor that binds to one of its cargos, the melanosome, by means of a RAB27A/MLPH receptor. When one of the members of this receptor-motor complex is mutated, the melanosomes clump in the perinuclear region of the melanocyte and are transferred unevenly to the developing hair, leading to a dilution of coat color. Mutation of a fourth gene, dilute suppressor (dsu), suppresses this coat color dilution. MYO5A is required for the peripheral accumulation of melanosomes in melanocytes, but its role in melanosome transfer to neighboring keratinocytes and the hair is unknown. Here, we show that MYO5A is nonessential for melanosome transfer, although pigment incorporation into the hair in MYO5A-deficient mice is uneven, probably due to the clumping of melanosomes that occurs in the perinuclear region of mutant melanocytes. We also show that dsu is caused by a loss-of-function mutation in a unique vertebrate-specific protein that appears to function in an MYO5A-independent pathway to alter pigment incorporation into the hair. Therefore, dsu identifies a unique protein involved in pigmentation of the mammalian hair. C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. RP Jenkins, NA (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM jenkins@ncifcrf.gov RI Huang, Jiandong/C-4277-2009 NR 33 TC 23 Z9 24 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 30 PY 2004 VL 101 IS 48 BP 16831 EP 16836 DI 10.1073/pnas.0407339101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 876PC UT WOS:000225508400024 PM 15550542 ER PT J AU Yoshimitsu, M Sato, T Tao, KS Walia, JS Rasaiah, VI Sleep, GT Murray, GJ Poeppi, AG Underwood, J West, L Brady, RO Medin, JA AF Yoshimitsu, M Sato, T Tao, KS Walia, JS Rasaiah, VI Sleep, GT Murray, GJ Poeppi, AG Underwood, J West, L Brady, RO Medin, JA TI Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; lentivirus; luciferase marking; lysosomal storage disorder ID MUCOPOLYSACCHARIDOSIS-VII DOGS; MEDIATED GENE-TRANSFER; BONE-MARROW-CELLS; ALPHA-GALACTOSIDASE; REPLACEMENT THERAPY; RETROVIRAL VECTOR; MULTIPLE ORGANS; DISEASE; EXPRESSION; TRANSDUCTION AB Successful therapy for many inherited disorders could be improved if the intervention were initiated early. This is especially true for lysosomal storage disorders. Earlier intervention may allow metabolic correction to occur before lipid buildup has irreversible consequences and/or before the immune system mounts limiting responses. We have been developing gene therapy to treat lysosornal storage disorders, especially Fabry disease. We describe studies directed toward metabolic correction in neonatal animals mediated by recombinant lentiviral vectors. To develop this method, we first injected a marking lentiviral vector that engineers expression of luciferase into the temporal vein of recipient neonatal animals. The use of a cooled charged-coupled device camera allowed us to track transgene expression over time in live animals. We observed intense luciferase expression in many tissues, including the brain, that did not diminish over 24 weeks. Next, we injected neonatal Fabry mice a single time with a therapeutic lentiviral vector engineered to express human a-galactosiclase A. The injection procedure was well tolerated. We observed increased plasma levels of alpha-galactosiclase A activity starting at our first plasma collection point (4 weeks). Levels of a-galactosiclase A activity were found to be significantly elevated in many tissues even after 28 weeks. No immune response was observed against the corrective transgene product. Increased levels of enzyme activity also led to significant reduction of globotriaosylceramicle in the liver, spleen, and heart. This approach provides a method to treat lysosomal storage disorders and other disorders before destructive manifestations occur. C1 Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. Univ Toronto, Dept Cardiol, Toronto, ON M5G 1X8, Canada. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Infect Immun Injury & Repair Program, Toronto, ON M5G 1X8, Canada. Univ Hlth Network, Ontario Canc Inst, Div Expt Therapeut, Toronto, ON M5G 2M1, Canada. RP Yoshimitsu, M (reprint author), Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. EM jmedin@uhnres.utoronto.ca FU NHLBI NIH HHS [HL70569-03, R01 HL070569] NR 29 TC 66 Z9 67 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 30 PY 2004 VL 101 IS 48 BP 16909 EP 16914 DI 10.1073/pnas.0407572101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 876PC UT WOS:000225508400037 PM 15550536 ER PT J AU Dushoff, J Plotkin, JB Levin, SA Earn, DJD AF Dushoff, J Plotkin, JB Levin, SA Earn, DJD TI Dynamical resonance can account for seasonality of influenza epidemics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE demographic stochasticity; disease dynamics; susceptible infectious recovered (SIR); immunity ID EVOLUTION; TIME AB influenza incidence exhibits strong seasonal fluctuations in temperate regions throughout the world, concentrating the mortality and morbidity burden of the disease into a few months each year. The cause of influenza's seasonality has remained elusive. Here we show that the large oscillations in incidence may be caused by undetectably small seasonal changes in the influenza transmission rate that are amplified by dynamical resonance. C1 Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Harvard Soc Fellows, Cambridge, MA 02138 USA. McMaster Univ, Dept Math & Stat, Hamilton, ON L8S 4K1, Canada. RP Dushoff, J (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. EM dushoff@eno.princeton.edu RI Plotkin, Joshua/E-6947-2013; OI Earn, David/0000-0002-7562-1341 FU NIGMS NIH HHS [1-R01-GM60729-01] NR 14 TC 192 Z9 198 U1 2 U2 26 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 30 PY 2004 VL 101 IS 48 BP 16915 EP 16916 DI 10.1073/pnas.0407293101 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 876PC UT WOS:000225508400038 PM 15557003 ER PT J AU Egland, PG Palmer, RJ Kolenbrander, PE AF Egland, PG Palmer, RJ Kolenbrander, PE TI Interspecies communication in Streptococcus gordonii-Veillonella atypica biofilms: Signaling in flow conditions requires juxtaposition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bacterial communities; interspecies cell-cell signaling; oral bacteria ID GRAM-POSITIVE BACTERIA; ORAL STREPTOCOCCI; ALPHA-AMYLASE; COAGGREGATION; MYXOBACTERIA; SEQUENCE; STRAINS; CHALLIS; SYSTEM; MUTANS AB During the development of human oral biofilm communities, the spatial arrangement of the bacteria is thought to be driven by metabolic interactions between them. Streptococcus gordonii and Veillonella atypica, two early colonizing members of the dental plaque biofilm, have been postulated to participate in metabolic communication; S. gordonii ferments carbohydrates to form lactic acid, which is a preferred fermentation substrate for V. atypica. We found that, during agar-plate coculture of these organisms, a signaling event occurs that results in increased expression of the S. gordonii a-amylase-encoding gene amyB. Confocal scanning laser microscopy of coculture flowcell-grown biofilms using human saliva as the sole nutrient showed that V. atypica caused S. gordonii to increase expression of a PamyB-'gfp transcriptional fusion in a spatially resolved fashion. In this open system, only those streptococci in mixed-species microcolonies containing V. atypica expressed GFP; nearby S. gordonii colonies that lacked V. atypica did not express GFP. In a closed system containing S. gordonii and V. atypica, flow cytometric analysis showed that S. gordonii containing the PamyB-'gfp reporter plasmid exhibited mean fluorescence levels 20-fold higher than did S. gordonii that had not been incubated with V. atypica. Thus, in a closed system where a diffusible signal can accumulate above a required threshold, interspecies signaling mediates a change in gene expression. We provide evidence that, in open systems like those that predominate in natural biofilms, diffusible signals between species are designed to function over short distances, on the order of 1 mum. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov NR 30 TC 128 Z9 137 U1 3 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 30 PY 2004 VL 101 IS 48 BP 16917 EP 16922 DI 10.1073/pnas.0407457101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 876PC UT WOS:000225508400039 PM 15546975 ER PT J AU Bremner, JD Vythilingam, M Vermetten, E Afzal, N Nazeer, A Newcomer, JW Charney, DS AF Bremner, JD Vythilingam, M Vermetten, E Afzal, N Nazeer, A Newcomer, JW Charney, DS TI Effects of dexamethasone on declarative memory function in posttraumatic stress disorder SO PSYCHIATRY RESEARCH LA English DT Article DE PTSD; memory; dexamethasone; cortisol; glucocorticoids; hippocampus ID CORTICOTROPIN-RELEASING HORMONE; URINARY CORTISOL EXCRETION; CHILDHOOD SEXUAL-ABUSE; SHORT-TERM-MEMORY; HIPPOCAMPAL VOLUME; COMBAT VETERANS; RAT HIPPOCAMPUS; WORKING-MEMORY; MESSENGER-RNA; PTSD SCALE AB Alterations in the hypothalamic pituitary-adrenal (HPA) axis and hippocampal-based memory have been associated with posttraurnatic stress disorder (PTSD), and the administration of exogenous glucocorticoids has been shown to result in a transient verbal declarative memory impairment in healthy human subjects. The purpose of this study was to assess the effects of the glucocorticoid dexamethasone on verbal declarative memory function in patients with PTSD. Forty-two men and women with (n=14) and without (n=28) PTSD received placebo or dexamethasone (1 and 2 mg on two successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall related to a relative detrimental effect of dexamethasone on memory function in healthy subjects, but not those with PTSD. These findings are consistent with an altered sensitivity of declarative memory function in PTSD to regulation by glucocorticoids, possibly explainable by alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Emory Univ, Emory Ctr Positron Emiss Tomog, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA 30306 USA. Emory Univ, Emory Ctr Positron Emiss Tomog, Dept Radiol, Sch Med, Atlanta, GA 30306 USA. Atlanta VAMC, Decatur, GA USA. NIMH, Program Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Cent Mil Hosp, Dept Psychiat, Utrecht, Netherlands. Univ Utrecht, Ctr Med, Utrecht, Netherlands. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Bremner, JD (reprint author), Emory Univ, Emory Ctr Positron Emiss Tomog, Dept Psychiat & Behav Sci, Sch Med, 1256 Briarcliff Rd, Atlanta, GA 30306 USA. EM jdbremn@emory.edu RI Bremner, James/B-1632-2013; OI Vermetten, Eric/0000-0003-0579-4404 FU NIMH NIH HHS [1P50 MH58922, K02 MH01510, R01 MH56120, R01 MH60395] NR 92 TC 25 Z9 25 U1 4 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 30 PY 2004 VL 129 IS 1 BP 1 EP 10 DI 10.1016/j.psychres.2004.08.004 PG 10 WC Psychiatry SC Psychiatry GA 881GN UT WOS:000225851500001 PM 15572179 ER PT J AU Cauchemez, S Carrat, F Viboud, C Valleron, AJ Boelle, PY AF Cauchemez, S Carrat, F Viboud, C Valleron, AJ Boelle, PY TI A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data SO STATISTICS IN MEDICINE LA English DT Article DE infectious diseases; influenza; household transmission; Bayesian inference; Markov chain Monte Carlo methods ID STATISTICAL-ANALYSIS; CONTROLLED TRIAL; PARAMETERS; MODEL; FRANCE; OSELTAMIVIR; CONTACTS; EPIDEMIC; EFFICACY; SAFETY AB We propose a transmission model to estimate the main characteristics of influenza transmission in households. The model details the risks of infection in the household and in the community at the individual scale. Heterogeneity among subjects is investigated considering both individual susceptibility and infectiousness. The model was applied to a data set consisting of the follow-up of influenza symptoms in 334 households during 15 days after an index case visited a general practitioner with virologically confirmed influenza. Estimating the parameters of the transmission model was challenging because a large part of the infectious process was not observed: only the dates when new cases were detected were observed. For each case, the data were augmented with the unobserved dates of the start and the end of the infectious period. The transmission model was included in a 3-levels hierarchical structure: (i) the observation level ensured that the augmented data were consistent with the observed data, (ii) the transmission level described the underlying epidemic process, (iii) the prior level specified the distribution of the parameters. From a Bayesian perspective, the joint posterior distribution of model parameters and augmented data was explored by Markov chain Monte Carlo (MCMC) sampling. The mean duration of influenza infectious period was estimated at 3.8 days (95 per cent credible interval, 95 per cent Cl [3.1,4.6]) with a standard deviation of 2.0 days (95 per cent Cl [1.1,2.8]). The instantaneous risk of influenza transmission between an infective and a susceptible within a household was found to decrease with the size of the household, and established at 0.32 person day(-1) (95 per cent Cl [0.26,0.39]); the instantaneous risk or infection from the community was 0.0056 day(-1) (95 per cent Cl (0.0029,0.0087]). Focusing on the differences in transmission between children (less than 15 years old) and adults, we estimated that the former were more likely to transmit than adults (posterior probability larger than 99 per cent), but that the mean duration of the infectious period was similar in children (3.6 days, 95 per cent Cl [2.3,5.2]) and adults (3.9 days, 95 per cent Cl [3.2.4.9]). The posterior probability that children had a larger community risk was 76 per cent and the posterior probability that they were more susceptible than adults was 79 per cent. Copyright (C) 2004 John Wiley Sons, Ltd. C1 INSERM, U444, F-75571 Paris 12, France. Univ Paris 06, F-75252 Paris, France. Assistance Publ Hop Paris, Paris, France. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Cauchemez, S (reprint author), INSERM, U444, 27 Rue Chaligny, F-75571 Paris 12, France. EM simon.cauchemez@u444.jussieu.fr OI CARRAT, fabrice/0000-0002-8672-7918 NR 27 TC 175 Z9 179 U1 1 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 2004 VL 23 IS 22 BP 3469 EP 3487 DI 10.1002/sim.1912 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 867US UT WOS:000224868600006 PM 15505892 ER PT J AU Konwinski, RR Haddad, R Chun, JA Klenow, S Larson, SC Haab, BB Furge, LL AF Konwinski, RR Haddad, R Chun, JA Klenow, S Larson, SC Haab, BB Furge, LL TI Oltipraz, 3H-1,2-dithiole-3-thione, and sulforaphane induce overlapping and protective antioxidant responses in murine microglial cells SO TOXICOLOGY LETTERS LA English DT Article DE oltipraz; 3H-1,2-dithiole-3-thione; sulforaphane; cDNA microarrays; gene expression profiling; microglial cells; reactive oxygen species ID NITRIC-OXIDE SYNTHASE; CANCER CHEMOPREVENTIVE AGENTS; TRANSCRIPTION FACTOR NRF2; REPUBLIC-OF-CHINA; OXIDATIVE STRESS; OLIGONUCLEOTIDE MICROARRAY; CHEMOPROTECTIVE AGENT; ACTIVATION; ENZYMES; IDENTIFICATION AB Oltipraz (OPZ) is a known inducer of glutathione S-transferases and a mechanism-based inhibitor of cytochrome P450 1A2. Given the detoxification characteristics of this compound, the transcriptional effects of OPZ, along with the related naturally occurring compounds 3H-1,2-dithiole-3-thione (D3T) and sulforaphane (SF), were examined by gene expression profiling in murine BV-2 microglial cells, a neuronal macrophage cell type that mediates inflammatory responses in the brain. We show that the three compounds generate largely overlapping transcriptional changes in genes that are associated with detoxification and antioxidant responses. In addition, induction of an antioxidant/detoxification response in the microglial cells by OPZ, D3T, or SF was also able to protect cells from H2O2-induced toxicity and to attenuate the production of reactive oxygen species in response to lipopolysaccharide treatment of cells. These results show that OPZ, D3T, and SF activate overlapping changes in gene expression and that they can regulate detoxification/antioxidant responses in multiple cells types, including cell types known to have a role in the production of oxidative stress. (C) 2004 Published by Elsevier Ltd. C1 Kalamazoo Coll, Dept Chem, Kalamazoo, MI 49006 USA. Van Andel Res Inst, Lab Microarray Technol, Grand Rapids, MI 49503 USA. RP Furge, LL (reprint author), Wayne State Univ, Sch Med, NICHD, Perinatol Res Branch,Funct Genomics Lab, 3258 Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. EM lfurge@kzoo.edu NR 43 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 28 PY 2004 VL 153 IS 3 BP 343 EP 355 DI 10.1016/j.toxlet.2004.06.006 PG 13 WC Toxicology SC Toxicology GA 865OW UT WOS:000224713400006 PM 15454310 ER PT J AU Waalkes, MP Liu, J Kasprzak, KS Diwan, BA AF Waalkes, MP Liu, J Kasprzak, KS Diwan, BA TI Minimal influence of metallothionein over-expression on nickel carcinogenesis in mice SO TOXICOLOGY LETTERS LA English DT Article DE nickel; carcinogenesis; metallothionein; mice; sarcoma ID I-TRANSGENIC MICE; STRAIN-A MICE; OXIDATIVE STRESS; GENE-EXPRESSION; INDUCTION; TOXICITY; CADMIUM; CELLS; CULTURES; ACETATE AB Metallothionein (MT) is a metal-binding protein associated with tolerance to metals and oxidative stress. Nickel is a metal carcinogen potentially acting through oxidative attack on critical biomolecules. We investigated the role of NIT in nickel carcinogenesis using MT-transgenic mice that constitutively over-express MT-I in all tissues tested. Groups of 25 male MT-transgenic and wild type (C57BL/6; WT) mice received intramuscular injections of nickel subsulfide (Ni3S2) in both thighs at doses of 0 (control), 0.5, or 1.0 mg/site at 12 weeks of age and were observed for 104 weeks. Injection site tumors (ISTs; primarily fibrosarcomas) started occurring 45 weeks after nickel injection and IST incidence was similar in the WT (control - 0%, 0.5 mg/site 20%, 1.0 mg/site - 40%) and NIT-transgenic mice (control - 0%, 0.5 mg/site - 28%, 1.0 mg/site - 29%). At the 0.5 mg/site dose the average time to IST in MT-transgenic mice was similar to13 weeks shorter than in WT mice. Spontaneous lung tumors developed in 25% of control WT mice but none developed in control MT-transgenic mice. A nickel dose-related trend for increased lung tumors occurred in MT-transgenic mice but not in WT mice. Thus, the over-expression of NIT did not significantly mitigate the carcinogenic response to nickel. Published by Elsevier Ireland Ltd. C1 NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, NIEHS,NIH, Res Triangle Pk, NC 27709 USA. NCI, Comparat Carcinogenesis Lab, Metals Sect, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick, Intramurla Res Support Program, Ft Detrick, MD 21702 USA. RP Waalkes, MP (reprint author), NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, NIEHS,NIH, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 35 TC 8 Z9 9 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 28 PY 2004 VL 153 IS 3 BP 357 EP 364 DI 10.1016/j.toxlet.2004.06.003 PG 8 WC Toxicology SC Toxicology GA 865OW UT WOS:000224713400007 PM 15454311 ER PT J AU Bailo, M Soncini, M Vertua, E Signoroni, PB Sanzone, S Lombardi, G Arienti, D Calamani, F Zatti, D Paul, P Albertini, A Zorzi, F Cavagnini, A Candotti, F Wengler, GS Parolini, O AF Bailo, M Soncini, M Vertua, E Signoroni, PB Sanzone, S Lombardi, G Arienti, D Calamani, F Zatti, D Paul, P Albertini, A Zorzi, F Cavagnini, A Candotti, F Wengler, GS Parolini, O TI Engraftment potential of human amnion and chorion cells derived from term placenta SO TRANSPLANTATION LA English DT Article DE amnion; chorion; transplantation; mesenchymal cells; tolerance ID MESENCHYMAL STEM-CELLS; EPITHELIAL-CELLS; MEMBRANE TRANSPLANTATION; EXPRESSION; MARKERS; XENOTRANSPLANTATION; DIFFERENTIATION; RECONSTRUCTION; IMPLANTATION; GENES AB Background. Fetal membranes are tissues of particular interest for several reasons, including their role in preventing rejection of the fetus and their early embryologic origin. which may entail progenitor potential. The immunologic reactivity and the transplantation potential of amnion and chorion cells, however, remain to be elucidated. Methods. Amnion and chorion cells were isolated from human term placenta and characterized by immunohistochemistry, flow cytometric analysis, and expression profile of relevant genes. The immunomodulatory characteristics of these cells were studied in allogeneic and xenogeneic mixed lymphocyte reactions and their engraftment potential analyzed by transplantation into neonatal swine and rats. Posttransplant chimerism was determined by polymerase chain reaction analysis with probes specific for human DNA. Results. Phenotypic and gene expression studies indicated mesenchymal stem cell-like profiles in both amnion and chorion cells that were positive for neuronal, pulmonary, adhesion, and migration markers. In addition, cells isolated both from amnion and chorion did not induce allogeneic nor xenogeneic lymphocyte proliferation responses and were able to actively suppress lymphocyte responsiveness. Transplantation in neonatal swine and rats resulted in human microchimerism in various organs and tissues. Conclusions. Human amnion and chorion cells from term placenta can successfully engraft neonatal swine and rats. These results may be explained by the peculiar immunologic characteristics and mesenchymal stem cell-like phenotype of these cells. These findings suggest that amnion and chorion cells may represent an advantageous source of progenitor cells with potential applications in a variety of cell therapy and transplantation procedures. C1 Osped Poliambulanza, Ctr Ric Parco Sci E Menni, I-25124 Brescia, Italy. Univ Milan, Dipartimento Sci & Tecnol Biomed, Milan, Italy. Ist Zooprofilatt Sperimentale Lombardia & Emilia, Brescia, Italy. CNR, Ist Tecnol Biomed, Milan, Italy. Osped Poliambulanza, Serv Anat Patol, Brescia, Italy. Osped Poliambulanza, Serv Ginecol & Ostetr, Brescia, Italy. Natl Inst Hlth, Disorders Immun Sect, Genet & Mol Biol Branch, Natl Human Genome Res Inst, Bethesda, MD USA. RP Parolini, O (reprint author), Osped Poliambulanza, Ctr Ric Parco Sci E Menni, Via Romiglia 4, I-25124 Brescia, Italy. EM ornella.parolini@tin.it OI albertini, alberto/0000-0002-7989-649X; Parolini, Ornella/0000-0002-5211-6430 NR 41 TC 172 Z9 208 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2004 VL 78 IS 10 BP 1439 EP 1448 DI 10.1097/01.TP.0000144606.84234.49 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 874GY UT WOS:000225340100006 PM 15599307 ER PT J AU Seltzer, A Bregonzio, C Armando, I Baiardi, G Saavedra, JM AF Seltzer, A Bregonzio, C Armando, I Baiardi, G Saavedra, JM TI Oral administration of an AT(1) receptor antagonist prevents the central effects of angiotensin II in spontaneously hypertensive rats SO BRAIN RESEARCH LA English DT Article DE AT(1) receptor antagonist; angiotensin II; spontaneously hypertensive rat ID CORTICOTROPIN-RELEASING-HORMONE; GENE-DISRUPTED MICE; BLOOD-BRAIN-BARRIER; PARAVENTRICULAR NUCLEUS; TYROSINE-HYDROXYLASE; AT(2) RECEPTOR; QUANTITATIVE AUTORADIOGRAPHY; SUBFORNICAL ORGAN; MESSENGER-RNA; ADRENAL-GLAND AB Peripheral and brain angiotensin II AT(1) receptor blockade decreases high blood pressure, stress, and neuronal injury. To clarify the effects of long-term brain Ang II receptor blockade, the AT(1) blocker, candesartan, was orally administered to spontaneously hypertensive rats (SHRs) for 40 days, followed by intraventricular injection of 25 ng of Ang II. Before Ang II injection, AT(1) receptor blockade normalized blood pressure and decreased plasma adrenocorticotropic hormone (ACTH) and corticosterone. After central administration of excess Ang II, the reduction of ACTH and corticosterone release induced by AT(1) receptor blockade no longer occurred. Central Ang II administration to vehicle-treated SHRs further increased blood pressure, provoked drinking, increased tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus, and stimulated sympathoadrenal catecholamine release. Pretreatment with the AT(1) receptor antagonist eliminated Ang II-induced increases in blood pressure, water intake, and sympathoadrenal catecholamine release; inhibited peripheral and brain AT(1) receptors; increased AT(2) receptor binding in the locus coeruleus, inferior olive, and adrenal cortex; and decreased AT(2) receptor binding in the adrenal medulla. Inhibition of brain AT, receptors correlated with decreased TH transcription in the locus coeruleus, indicating a decreased central sympathetic drive. This, and the diminished adrenomedullary AT(1) and AT2 receptor stimulation, result in decreased sympathoadrenomedullary stimulation. Oral administration of AT(1) antagonists can effectively block central actions of Ang II, regulating blood pressure and reaction to stress, and selectively and differentially modulating sympathoadrenal response and the hypothalamic-pituitary-adrenal stimulation produced by brain Ang II-effects of potential therapeutic importance. Published by Elsevier B.V. C1 NIMH, Dept Hlth & Human Serv, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Dept Hlth & Human Serv, Pharmacol Sect, NIH, Bldg 10,Rm 2D57,10 Ctr Dr,MSC-1514, Bethesda, MD 20892 USA. EM saavedrj@intra.nimb.nih.gov NR 54 TC 46 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 26 PY 2004 VL 1028 IS 1 BP 9 EP 18 DI 10.1016/j.brainres.2004.06.079 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 871ZQ UT WOS:000225175700002 PM 15518636 ER PT J AU Ohtsubo, T Rovira, II Starost, MF Liu, CY Finkel, T AF Ohtsubo, T Rovira, II Starost, MF Liu, CY Finkel, T TI Xanthine oxidoreductase is an endogenous regulator of cyclooxygenase-2 SO CIRCULATION RESEARCH LA English DT Article DE kidney; cyclooxygenase ID FAMILIAL ADENOMATOUS POLYPOSIS; URIC-ACID; CARDIOVASCULAR-DISEASE; HOMINOID EVOLUTION; GENE DISRUPTION; IMMUNE-SYSTEM; URATE OXIDASE; RENAL-DISEASE; MICE; CELLS AB Xanthine oxidoreductase (XOR) is the enzyme responsible for the final step in purine degradation resulting in the generation of uric acid. Here we have generated mice deficient in XOR. As expected, these animals lack tissue XOR activity and have low to undetectable serum levels of uric acid. Although normal at birth, XOR-/- mice fail to thrive after 10 to 14 days, and most die within the first month. The cause of death appears to be a form of severe renal dysplasia, a phenotype that closely resembles what has been observed previously in cyclooxygenase-2 (COX-2) deficient mice. We further demonstrate that in the first month of life, a period in which the mouse kidney is undergoing rapid maturation and remodeling, wild-type mice exhibit an approximate to30-fold increase in renal XOR activity, with a corresponding induction of COX-2 expression. In contrast, during this same period, XOR-/- animals fail to augment renal COX-2 expression. Finally, we show that in vitro and in vivo, uric acid can stimulate basal COX-2 expression. These results demonstrate that XOR activity is an endogenous physiological regulator of COX-2 expression and thereby provide insight into previous epidemiological evidence linking elevated serum uric levels with systemic hypertension and increased mortality from cardiovascular diseases. In addition, these results suggest a novel molecular link between cellular injury and the inflammatory response. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Transgen Core Facil, NIH, Bethesda, MD 20892 USA. OD, Div Vet Resources, NIH, Bethesda, MD USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10-6N-240,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 42 TC 50 Z9 52 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 26 PY 2004 VL 95 IS 11 BP 1118 EP 1124 DI 10.1161/01.RES.0000149571.96304.36 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 874MY UT WOS:000225355700010 PM 15528468 ER PT J AU Yamaguchi, K Lee, SH Eling, TE Baek, SJ AF Yamaguchi, K Lee, SH Eling, TE Baek, SJ TI Identification of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) as a novel downstream target of phosphatidylinositol 3-kinase/AKT/GSK-3 beta pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; BETA SUPERFAMILY MEMBER; COLON-CANCER CELLS; GROWTH-FACTOR-BETA; 3-KINASE INHIBITOR; MOLECULAR-CLONING; SIGNALING PATHWAY; CARCINOMA CELLS; KINASE 3-BETA; TUMOR-CELLS AB The signaling pathway of phosphatidylinositol 3-kinase (PI3K)/AKT, which is involved in cell survival, proliferation, and growth, has become a major focus in targeting cancer therapeutics. Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) was previously identified as a gene induced by several anti-tumorigenic compounds including nonsteroidal anti-inflammatory drugs, peroxisome proliferator-activated receptor gamma ligands, and dietary compounds. NAG-1 has been shown to exhibit anti-tumorigenic and/or pro-apoptotic activities in vivo and in vitro. In this report, we showed a PI3K/AKT/glycogen synthase kinase-3beta (GSK-3beta) pathway regulates NAG-1 expression in human colorectal cancer cells as assessed by the inhibition of PI3K, AKT, and GSK-3beta. PI3K inhibition by LY294002 showed an increase in NAG-1 protein and mRNA expression, and 1L-6-hydroxymethyl-chiroinositol 2(R)-2-O-methyl-3-O-octadecylcarbonate (AKT inhibitor) also induced NAG-1 expression. LY294002 caused increased apoptosis, cell cycle, and cell growth arrest in HCT-116 cells. Inhibition of GSK-3beta, which is negatively regulated by AKT, using AR-A014418 and lithium chloride completely abolished LY294002-induced NAG-1 expression as well as the NAG-1 promoter activity. Furthermore, the down-regulation of GSK-3 gene using small interference RNA resulted in a decline of the NAG-1 expression in the presence of LY294002. These data suggest that expression of NAG-1 is regulated by PI3K/AKT/GSK-3beta pathway in HCT-116 cells and may provide a further understanding of the important role of PI3K/AKT/GSK-3beta pathway in tumorigenesis. C1 Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogensis, Knoxville, TN 37996 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogensis, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu OI Baek, Seung/0000-0001-7866-7778 FU NIEHS NIH HHS [K22ES011657] NR 42 TC 73 Z9 79 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 2004 VL 279 IS 48 BP 49617 EP 49623 DI 10.1074/jbc.M408796200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 872SU UT WOS:000225229500011 PM 15377673 ER PT J AU Wessells, J Baer, M Young, HA Claudio, E Brown, K Siebenlist, U Johnson, PF AF Wessells, J Baer, M Young, HA Claudio, E Brown, K Siebenlist, U Johnson, PF TI BCL-3 and NF-kappa B p50 attenuate lipopolysaccharide-induced inflammatory responses in macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; CANDIDATE PROTOONCOGENE BCL-3; IL-10 GENE-EXPRESSION; ONCOPROTEIN BCL-3; NUCLEAR TRANSLOCATION; TRANSCRIPTION FACTORS; TARGETED DISRUPTION; THERAPEUTIC TARGET; IMMUNE-RESPONSES AB Lipopolysaccharide (LPS) induces expression of tumor necrosis factor alpha (TNFalpha) and other pro-inflammatory cytokines in macrophages. Following its induction, TNFalpha gene transcription is rapidly attenuated, in part due to the accumulation of NF-kappaB p50 homodimers that bind to three kappaB sites in the TNFalpha promoter. Here we have investigated the inhibitory role of BCL-3, an IkappaB-like protein that interacts exclusively with p50 and p52 homodimers. BCL-3 was induced by LPS with delayed kinetics and was associated with p50 in the nucleus. Forced expression of BCL-3 suppressed LPS-induced transcription from the TNFalpha promoter and inhibited two artificial promoters composed of TNFalpha kappaB sites that preferentially bind p50 dimers. BCL-3-mediated repression was reversed by trichostatin A and was enhanced by overexpression of HDAC-1, indicating that transcriptional attenuation involves recruitment of histone deacetylase. Analysis of macrophages from p50 and BCL-3 knock-out mice revealed that both transcription factors negatively regulate TNFalpha expression and that BCL-3 inhibits IL-1alpha and IL-1beta. In contrast, induction of the anti-inflammatory cytokine IL-10 was reduced in BCL-3 null macrophages. BCL-3 was not required for the production of p50 homodimers but BCL-3 expression was severely diminished in p50-deficient cells. Together, these findings indicate that p50 and BCL-3 function as anti-inflammatory regulators in macrophages by attenuating transcription of pro-inflammatory cytokines and activating IL-10 expression. C1 NCI Frederick, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. NCI Frederick, Expt Immunol Lab, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Johnson, PF (reprint author), NCI Frederick, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 45 TC 126 Z9 132 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 2004 VL 279 IS 48 BP 49995 EP 50003 DI 10.1074/jbc.M404246200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 872SU UT WOS:000225229500056 PM 15465827 ER PT J AU Daelemans, D Costes, SV Cho, EH Erwin-Cohen, RA Lockett, S Pavlakis, GN AF Daelemans, D Costes, SV Cho, EH Erwin-Cohen, RA Lockett, S Pavlakis, GN TI In vivo HIV-1 rev multimerization in the nucleolus and cytoplasm identified by fluorescence resonance energy transfer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR EXPORT SIGNAL; VIRAL MESSENGER-RNA; TYPE-1 REV; LIVING CELLS; RESPONSE ELEMENT; GENE-PRODUCT; INTRACELLULAR TRAFFICKING; PHOTOBLEACHING RECOVERY; FUNCTIONAL-ANALYSIS AB Nuclear export of intron-containing human immunodeficiency virus type 1 RNA is mediated by the viral Rev protein. Rev is a nucleocytoplasmic transport protein that directly binds to its cis-acting Rev-responsive element RNA. Rev function depends on its ability to multimerize. The in vivo dynamics and the subcellular dependence of this process are still largely unexplored. To visualize and quantitatively analyze the mechanism of Rev multimeric assembly in live cells, we used high resolution in vivo fluorescence resonance energy transfer ( FRET) and fluorescence recovery after photobleaching. By using two different dynamic FRET approaches ( acceptor photobleaching and donor bleaching time measurements), we observed a strong Rev-Rev interaction in the nucleoli of living cells. Most interestingly, we could also detect Rev multimerization in the cytoplasm; however, FRET efficiency in the cytoplasm was significantly lower than in the nucleolus. By using fluorescence recovery after photobleaching, we investigated the mobility of Rev within the nucleolus. Mathematical modeling of the fluorescence recovery after photobleaching recoveries enabled us to extract relative association and dissociation constants and the diffusion coefficient of Rev in the nucleolus. Our results show that Rev multimerizes in the nucleolus of living cells, suggesting an important role of the nucleolus in nucleocytoplasmic transport. C1 NCI, Human Retrovirus Sect, Basic Res Lab, Frederick, MD 21702 USA. NCI, Image Anal Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Daelemans, D (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium. EM dirk.daelemans@uz.kuleuven.ac.be RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 FU NCI NIH HHS [N01-CO-12400] NR 63 TC 40 Z9 42 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 2004 VL 279 IS 48 BP 50167 EP 50175 DI 10.1074/jbc.M407713200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 872SU UT WOS:000225229500076 PM 15294891 ER PT J AU Zhu, YX Li, XM Kyazike, J Zhou, Q Thurberg, BL Raben, N Mattaliano, RJ Cheng, SH AF Zhu, YX Li, XM Kyazike, J Zhou, Q Thurberg, BL Raben, N Mattaliano, RJ Cheng, SH TI Conjugation of mannose 6-phosphate-containing oligosaccharides to acid alpha-glucosidase improves the clearance of glycogen in Pompe mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISEASE TYPE-II; ENZYME REPLACEMENT THERAPY; GROWTH-FACTOR-II; MALTASE DEFICIENCY; HANSENULA-HOLSTII; RABBIT MILK; STORAGE; ADULT; INFANTILE; EXPRESSION AB Clinical studies of enzyme replacement therapy for Pompe disease have indicated that relatively high doses of recombinant human acid alpha-glucosidase (rhGAA) may be required to reduce the abnormal glycogen storage in cardiac and skeletal muscles. This may be because of inefficient cation-independent mannose 6-phosphate receptor (CI-MPR)-mediated endocytosis of the enzyme by the affected target cells. To address this possibility, we examined whether the addition of a high affinity ligand to rhGAA would improve its delivery to these cells. Chemical conjugation of high mannose oligosaccharides harboring mono- and bisphosphorylated mannose 6-phosphates onto rhGAA (neo-rhGAA) significantly improved its uptake characteristics by muscle cells in vitro. Infusion of neo-rhGAA into Pompe mice also resulted in greater delivery of the enzyme to muscle tissues when compared with the unmodified enzyme. Importantly, this increase in enzyme levels was associated with significantly improved clearance of glycogen (similar to5-fold) from the affected tissues. These results suggest that CI-MPR-mediated endocytosis of rhGAA is an important pathway by which the enzyme is delivered to the affected lysosomes of Pompe muscle cells. Hence, the generation of rhGAA containing high affinity ligands for the CI-MPR represents a strategy by which the potency of rhGAA and therefore the clinical efficacy of enzyme replacement therapy for Pompe disease may be improved. C1 Genzyme Corp, Framingham, MA 01701 USA. NIH, Bethesda, MD 20892 USA. RP Cheng, SH (reprint author), Genzyme Corp, 31 New York Ave, Framingham, MA 01701 USA. EM seng.cheng@genzyme.com NR 47 TC 35 Z9 37 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 2004 VL 279 IS 48 BP 50336 EP 50341 DI 10.1074/jbc.M409676200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 872SU UT WOS:000225229500097 PM 15383547 ER PT J AU Sordet, O Khan, QA Plo, I Pourquier, P Urasaki, Y Yoshido, A Antony, S Kohlhagen, G Solary, E Saparbaev, M Laval, J Pommier, Y AF Sordet, O Khan, QA Plo, I Pourquier, P Urasaki, Y Yoshido, A Antony, S Kohlhagen, G Solary, E Saparbaev, M Laval, J Pommier, Y TI Apoptotic topoisomerase I-DNA complexes induced by staurosporine-mediated oxygen radicals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; MAMMALIAN-CELLS; FILTER ELUTION; HL-60 CELLS; INDUCTION; DAMAGE; CLEAVAGE; FRAGMENTATION; INHIBITORS; MECHANISM AB Topoisomerase I (Top1), an abundant nuclear enzyme expressed throughout the cell cycle, relaxes DNA supercoiling by forming transient covalent DNA cleavage complexes. We show here that staurosporine, a ubiquitous inducer of apoptosis in mammalian cells, stabilizes cellular Top1 cleavage complexes. These complexes are formed indirectly as staurosporine cannot induce Top1 cleavage complexes in normal DNA with recombinant Top1 or nuclear extract from normal cells. In treated cells, staurosporine produces oxidative DNA lesions and generates reactive oxygen species (ROS). Quenching of these ROS by the antioxidant N-acetyl-L-cysteine or inhibition of the mitochondrial dependent production of ROS by the caspase inhibitor benzyloxycarbonyl-VAD prevents staurosporine-induced Top1 cleavage complexes. Down-regulation of Top1 by small interfering RNA decreases staurosporine-induced apoptotic DNA fragmentation. We propose that Top1 cleavage complexes resulting from oxidative DNA lesions generated by ROS in staurosporine-treated cells contribute to the full apoptotic response. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. CEA, Lab Recombinat Mech, F-92265 Fontenay Aux Roses, France. Inst Bergonie, INSERM, E347, Mol Pharmacol Grp, F-33076 Bordeaux, France. Fac Med, INSERM, U517, F-21033 Dijon, France. Inst Gustave Roussy, F-94805 Villejuif, France. Fukui Med Univ, Dept Med 1, Fukui, Japan. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014; Saparbaev, Murat/N-3225-2015 OI Saparbaev, Murat/0000-0002-4630-1074 NR 40 TC 44 Z9 46 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 26 PY 2004 VL 279 IS 48 BP 50499 EP 50504 DI 10.1074/jbc.M410277200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 872SU UT WOS:000225229500115 PM 15448130 ER PT J AU Roy, S Semsey, S Liu, MF Gussin, GN Adhya, S AF Roy, S Semsey, S Liu, MF Gussin, GN Adhya, S TI GaIR represses gaIP1 by inhibiting the rate-determining open complex formation through RNA polymerase contact: A GaIR negative control mutant SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE repression; fluorescence; transcription; contact; mutation ID LAMBDA-PRM PROMOTER; COLI GALACTOSE OPERON; TRANSCRIPTION INITIATION; ESCHERICHIA-COLI; GAL REPRESSOR; BACTERIOPHAGE-LAMBDA; ACTIVATION; PROTEIN; DNA; HU AB Ga1R represses the galP1 promoter by a DNA looping-independent mechanism. Equilibrium binding of Ga1R and RNA polymerase to DNA, and real-time kinetics of base-pair distortion (isomerization) showed that the equilibrium dissociation constant of RNA polymerase-P1 closed complexes is largely unaffected in the presence of saturating Ga1R, indicating that mutual antagonism (steric hindrance) of the regulator and the RNA polymerase does not occur at this promoter. In fluorescence kinetics with 2-AP labeled P1 DNA, Ga1R inhibited the slower of the two-step base-pair distortion process. We isolated a negative control Ga1R mutant, S29R, which while bound to the operator DNA was incapable of repression of P1. Based on these results and previous demonstration that repression requires the C-terminal domain of the alpha subunit (alpha-CTD) of RNA polymerase, we propose that Ga1R establishes contact with alpha-CTD at the last resolved isomerization. intermediate, forming a kinetic trap. Published by Elsevier Ltd. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Bose Inst, Dept Biophys, Kolkata 700054, W Bengal, India. Univ Iowa, Dept Sci Biol, Iowa City, IA 52246 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov RI Semsey, Szabolcs/L-6329-2013 NR 50 TC 23 Z9 23 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 26 PY 2004 VL 344 IS 3 BP 609 EP 618 DI 10.1016/j.jmb.2004.09.070 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 873TR UT WOS:000225304500002 PM 15533432 ER PT J AU Li, X Keskin, O Ma, BY Nussinov, R Liang, J AF Li, X Keskin, O Ma, BY Nussinov, R Liang, J TI Protein-protein interactions: Hot spots and structurally conserved residues often locate in complemented pockets that pre-organized in the unbound states: Implications for docking SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein-protein interactions; residue hot spots; protein docking; residue conservation; binding and folding ID PANCREATIC TRYPSIN-INHIBITOR; VISION-BASED TECHNIQUE; COMPUTATIONAL METHODS; BINDING SURFACES; FREE-ENERGY; INTERFACES; RECOGNITION; COMPLEXES; SEQUENCE; PRINCIPLES AB Energetic hot spots account for a significant portion of the total binding free energy and correlate with structurally conserved interface residues. Here, we map experimentally determined hot spots and structurally conserved residues to investigate their geometrical organization. Unfilled pockets are pockets that remain unfilled after protein-protein complexation, while complemented pockets are pockets that disappear upon binding, representing tightly fit regions. We find that structurally conserved residues and energetic hot spots are strongly favored to be located in complemented pockets, and are disfavored in unfilled pockets. For the three available protein-protein complexes with complemented pockets where both members of the complex were alanine-scanned, 62% of all hot spots (DeltaDeltaG > 2 kcal/mol) are within these pockets, and 60% of the residues in the complemented pockets are hot spots. 93% of all red-hot residues (DeltaDeltaG greater than or equal to 4 kcal/mol) either protrude into or are located in complemented pockets. The occurrence of hot spots and conserved residues in complemented pockets highlights the role of local tight packing in protein associations, and rationalizes their energetic contribution and conservation. Complemented pockets and their corresponding protruding residues emerge among the most important geometric features in protein-protein interactions. By screening the solvent, this organization shields backbone hydrogen bonds and charge-charge interactions. Complemented pockets often pre-exist binding. For 18 protein-protein complexes with complemented pockets whose unbound structures are available, in 16 the pockets are identified to pre-exist in the unbound structures. The root-mean-squared deviations of the atoms lining the pockets between the bound and unbound states is as small as 0.9 Angstrom, suggesting that such pockets constitute features of the populated native state that may be used in docking. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA. Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Liang, J (reprint author), Univ Illinois, Dept Bioengn, MC-063, Chicago, IL 60607 USA. EM jliang@uic.edu RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NIGMS NIH HHS [GM68958] NR 56 TC 125 Z9 127 U1 2 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 26 PY 2004 VL 344 IS 3 BP 781 EP 795 DI 10.1016/j.jmb.2004.09.051 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 873TR UT WOS:000225304500015 PM 15533445 ER PT J AU Zhang, MJ Vedantham, P Flynn, DL Hanson, PR AF Zhang, MJ Vedantham, P Flynn, DL Hanson, PR TI High-load, soluble oligomeric carbodiimide: Synthesis and application in coupling reactions SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Review ID SOLID-SUPPORTED REAGENTS; COMPLEMENTARY MOLECULAR REACTIVITY; OLEFIN METATHESIS REACTIONS; CHEMICAL LIBRARY SYNTHESIS; ORGANIC-SYNTHESIS; RECOVERABLE CATALYSTS; CONVENIENT METHOD; PURIFICATION; SCAVENGERS; PRODUCTS AB A facile preparation of a high-load, soluble oligomeric alkyl cyclohexylcarbodiimide (OACC) reagent via ROM polymerization from commercially available starting materials is described. This reagent is exploited as a coupling reagent for esterification, amidation, and dehydration of carboxylic acids (aliphatic and aromatic) with an assortment of alcohols (aliphatic primary, secondary, and benzylic), thiols, phenols, and amines (aliphatic primary, secondary, benzylic, and aromatic/anilines), respectively. Following the coupling event, precipitation with an appropriate solvent (Et2O, MeOH, or EtOAc), followed by filtration through a SPE provides the products in good to excellent yield and purity. C1 Neogenesis, Cambridge, MA 02139 USA. Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Univ Kansas, NIH, Ctr Excellence Combinatorial Methodol & Lib Dev, KUCMLD, Lawrence, KS 66047 USA. RP Flynn, DL (reprint author), Neogenesis, 840 Mem Dr, Cambridge, MA 02139 USA. EM dflynn@deciphera.com; phanson@ku.edu FU NCRR NIH HHS [P20 RR15563]; NIGMS NIH HHS [1P50 GM069663-01] NR 43 TC 34 Z9 34 U1 4 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 26 PY 2004 VL 69 IS 24 BP 8340 EP 8344 DI 10.1021/jo048870c PG 5 WC Chemistry, Organic SC Chemistry GA 874HK UT WOS:000225341300022 PM 15549805 ER PT J AU Eiden, LE AF Eiden, LE TI A two-way bioinformatic street SO SCIENCE LA English DT Editorial Material C1 NIMH, Intramural Res Program, Mol Neurosci Sect, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, Bioinformat Users Grp, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIMH, Intramural Res Program, Mol Neurosci Sect, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 26 PY 2004 VL 306 IS 5701 BP 1437 EP 1437 DI 10.1126/science.1107196 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 875ST UT WOS:000225442700001 PM 15567816 ER PT J AU Soucek, P Skjelbred, CF Svendsen, M Kristensen, T Kure, EH Kristensen, VN AF Soucek, P Skjelbred, CF Svendsen, M Kristensen, T Kure, EH Kristensen, VN TI Single-track sequencing for genotyping of multiple SNPs in the N-acetyltransferase 1 (NAT1) gene SO BMC BIOTECHNOLOGY LA English DT Article ID N-ACETYLTRANSFERASE TYPE-1; AMINE METABOLISM; POLYMORPHISMS; CANCER; SUSCEPTIBILITY; RISK; NAT1-ASTERISK-10; ACETYLATION; ASSOCIATION; ACTIVATION AB Background: Fast, cheap and reliable methods are needed to identify large populations, which may be at risk in relation to environmental exposure. Polymorphisms in NAT1 (N-acetyl transferase) may be suitable markers to identify individuals at risk. Results: A strategy allowing to address simultaneously 24 various genetic variants in the NAT1 gene using the single sequencing reaction method on the same PCR product is described. A modified automated DNA sequencing using only one of the sequence terminators was used to genotype PCR products in single-track sequencing reactions of NAT1 and was shown to be universal for both DNA sequencing using labeled primers and labeled nucleotides. By this method we detected known SNPs at site T640G, which confers the NAT1*11 allele with frequency of 0.036, further T1088A and C1095A with frequency of 0.172 and 0.188, respectively and a deletion of TAATAATAA in the poly A signal area with a frequency 0.031. All observed frequencies were in Hardy Weinberg equilibrium and comparable to those in Caucasian population. The single-track signatures of the variant genotypes were verified on samples previously genotyped by RLFP. Conclusions: The method could be of great help to scientists in the field of molecular epidemiology of screening of large populations for known informative biomarkers of susceptibility, such as NAT1. C1 Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway. Natl Inst Publ Hlth, Ctr Occupat Dis, Grp Biotransformat, Prague 10, Czech Republic. Telemark Univ Coll, Fac Arts & Sci, Dept Environm & Hlth Studies, Porsgrunn, Norway. Telemark Cent Hosp, Dept Occupat & Environm Med, N-3710 Skien, Norway. Univ Oslo, Dept Biochem, Oslo, Norway. Ullevaal Univ Hosp, Dept Pathol, Oslo, Norway. NCI, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. RP Kristensen, VN (reprint author), Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway. EM psoucek@szu.cz; skcf@sthf.no; Svendsen@hit.no; tom.kristensen@biokjemi.uio.no; Elin.Kure@hit.no; vessela@ulrik.uio.no NR 24 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD NOV 25 PY 2004 VL 4 AR 28 DI 10.1186/1472-6750-4-28 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 887EB UT WOS:000226287000001 PM 15563733 ER PT J AU Tohnya, TM Hwang, K Lepper, ER Fine, HA Dahut, WL Venitz, J Sparreboom, A Figg, WD AF Tohnya, TM Hwang, K Lepper, ER Fine, HA Dahut, WL Venitz, J Sparreboom, A Figg, WD TI Determination of CC-5013, an analogue of thalidomide, in human plasma by liquid chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE CC-5013; LC-MS; pharmacokinetics; angiogenesis inhibitor ID ANTIANGIOGENIC ACTIVITY; ANGIOGENESIS; CANCER AB A high-performance liquid chromatographic assay with MS detection has been developed for the quantitative determination of the anti-angiogenic agent CC-5013 in human plasma. Sample pretreatment involved liquid-liquid extraction with acetonitrile/1-chlorobutane (4:1, v/v) solution containing the internal standard, umbelliferone. Separation of the compounds of interest was achieved on a column packed with Waters C-18 Nova-Pak material (4 mum particle size; 300 mm x 3.9 mm internal diameter) using acetonitrile, de-ionized water, and glacial acetic acid in ratios of 20:80:0.1 (v/v/v) (pH 3.5) delivered at an isocratic flow rate of 1.00 ml/min. Simultaneous MS detection was performed at m/z 260.3 (CC-5013) and m/z 163.1 (umbelliferone). The calibration curve was fit to a linear response-concentration data over a range of 5-1000 ng/ml using a weighting factor of 1/x. Values for accuracy and precision, obtained from four quality controls analyzed on three different days in replicates of five, ranged from 98 to 106% and from 5.5 to 15.5%, respectively. The method was successfully applied to study the pharmacokinetics of CC-5013 in a cancer patient receiving the drug as single daily dose. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, NINDS, Bethesda, MD 20892 USA. NCI, Genitourinary Clin Res Sect, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA 23298 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Ctr Canc Res, 9000 Rockville Pike,Bldg10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 11 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 25 PY 2004 VL 811 IS 2 BP 135 EP 141 DI 10.1016/j.chromb.2004.08.022 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 870JE UT WOS:000225052600005 PM 15522712 ER PT J AU La Montagne, JR Fauci, AS AF La Montagne, JR Fauci, AS TI Intradermal influenza vaccination - Can less be more? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DENDRITIC CELLS; VIRUS C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 12 TC 35 Z9 36 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 2004 VL 351 IS 22 BP 2330 EP 2332 DI 10.1056/NEJMe048314 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 873RH UT WOS:000225298100015 PM 15525715 ER PT J AU Guttmacher, AE Collins, FS Carmona, RH AF Guttmacher, AE Collins, FS Carmona, RH TI The family history - More important than ever SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OVARIAN-CANCER; RISK; BREAST C1 NHGRI, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Off Surg Gen, Washington, DC USA. RP Guttmacher, AE (reprint author), NHGRI, NIH, Bldg 31,Rm 4B09, Bethesda, MD 20892 USA. NR 20 TC 252 Z9 260 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 2004 VL 351 IS 22 BP 2333 EP 2336 DI 10.1056/NEJMsb042979 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 873RH UT WOS:000225298100016 PM 15564550 ER PT J AU Nolan, MF Malleret, G Dudman, JT Buhl, DL Santoro, B Gibbs, E Vronskaya, S Buzsaki, G Siegelbaum, SA Kandel, ER Morozov, A AF Nolan, MF Malleret, G Dudman, JT Buhl, DL Santoro, B Gibbs, E Vronskaya, S Buzsaki, G Siegelbaum, SA Kandel, ER Morozov, A TI A behavioral role for dendritic integration: HCN1 channels constrain spatial inputs to distal dendrites memory and plasticity at of CA1 pyramidal neurons SO CELL LA English DT Article ID LONG-TERM POTENTIATION; HIPPOCAMPAL GAMMA OSCILLATIONS; CURRENT I-H; SYNAPTIC MODIFICATIONS; PACEMAKER CHANNELS; THETA OSCILLATIONS; CATION CURRENTS; MICE LACKING; CELLS; MOUSE AB The importance of long-term synaptic plasticity as a cellular substrate for learning and memory is well established. By contrast, little is known about how learning and memory are regulated by voltage-gated ion channels that integrate synaptic information. We investigated this question using mice with general or forebrain-restricted knockout of the HCN1 gene, which we find encodes a major component of the hyperpolarization-activated inward current (I-h) and is an important determinant of dendritic integration in hippocampal CA1 pyramidal cells. Deletion of HCN1 from forebrain neurons enhances hippocampal-dependent learning and memory, augments the power of theta oscillations, and enhances long-term potentiation (LTP) at the direct perforant path input to the distal dendrites of CA1 pyramidal neurons, but has little effect on LTP at the more proximal Schaffer collateral inputs. We suggest that HCN1 channels constrain learning and memory by regulating dendritic integration of distal synaptic inputs to pyramidal cells. C1 Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. Columbia Univ, Dept Physiol, New York, NY 10032 USA. Columbia Univ, Dept Biochem & Biophys, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Columbia Univ, Kavli Inst Brain Sci, New York, NY 10032 USA. NIMH, Hlth Behav Genet, Bethesda, MD 20892 USA. RP Kandel, ER (reprint author), Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. EM erk5@columbia.edu RI Nolan, Matthew/A-1356-2009 OI Nolan, Matthew/0000-0003-1062-6501 FU NIMH NIH HHS [MH045923, MH54671]; NINDS NIH HHS [NS34994, NS36658] NR 52 TC 248 Z9 255 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 24 PY 2004 VL 119 IS 5 BP 719 EP 732 DI 10.1016/S0092-8674(04)01055-4 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 874ZP UT WOS:000225389500016 PM 15550252 ER PT J AU Rane, NS Yonkovich, JL Hegde, RS AF Rane, NS Yonkovich, JL Hegde, RS TI Protection from cytosolic prion protein toxicity by modulation of protein translocation SO EMBO JOURNAL LA English DT Article DE cytotoxicity; prion protein; proteasomal degradation; protein aggregation; protein translocation ID ENDOPLASMIC-RETICULUM MEMBRANE; UBIQUITIN-PROTEASOME SYSTEM; VIRUS PRECORE PROTEIN; NEURONAL CELL-DEATH; ALZHEIMERS-DISEASE; SIGNAL PEPTIDE; NEURODEGENERATIVE DISEASES; TRANSMEMBRANE FORM; PRP; TRANSPORT AB Failure to promptly dispose of undesirable proteins is associated with numerous diseases. In the case of cellular prion protein (PrP), inhibition of the proteasome pathway can generate a highly aggregation-prone, cytotoxic form of PrP implicated in neurodegeneration. However, the predominant mechanisms that result in delivery of PrP, ordinarily targeted to the secretory pathway, to cytosolic proteasomes have been unclear. By accurately measuring the in vivo fidelity of protein translocation into the endoplasmic reticulum (ER), we reveal a slight inefficiency in PrP signal sequence function that generates proteasomally degraded cytosolic PrP. Attenuating this source of cytosolic PrP completely eliminates the dependence on proteasomes for PrP degradation. This allows cells to tolerate both higher expression levels and decreased proteasomal capacity without succumbing to the adverse consequences of misfolded PrP. Thus, the generation of potentially toxic cytosolic PrP is controlled primarily during its initial translocation into the ER. These results suggest that a substantial proportion of the cell's constitutive proteasomal burden may consist of proteins that, like PrP, fail to cotranslationally enter the secretory pathway with high fidelity. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X NR 44 TC 86 Z9 88 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 24 PY 2004 VL 23 IS 23 BP 4550 EP 4559 DI 10.1038/sj.emboj.7600462 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 877CW UT WOS:000225546400003 PM 15526034 ER PT J AU Suzuki, Y Yang, HF Craigie, R AF Suzuki, Y Yang, HF Craigie, R TI LAP2 alpha and BAF collaborate to organize the Moloney murine leukemia virus preintegration complex SO EMBO JOURNAL LA English DT Article DE barrier-to-autointegration factor; integration; lamina-associated polypeptide 2 alpha; moloney murine leukemia virus; preintegration complex ID TO-AUTOINTEGRATION FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR-STRUCTURE DYNAMICS; RETROVIRAL DNA; LEM-DOMAIN; NUCLEOPROTEIN COMPLEX; CELLULAR FACTOR; POLYPEPTIDE 2; INTEGRATION; PROTEIN AB Integration of viral DNA into the host genome is an essential step in retroviral replication. The viral DNA made by reverse transcription is a component of the preintegration complex (PIC) that also contains the viral integrase protein, the enzyme that integrates the viral DNA. Several other viral and cellular proteins are present in the PIC, but their functional roles are less well established. Barrier-to-autointegration factor (BAF) is a cellular protein component of the PIC that blocks autointegration of the viral DNA and stimulates intermolecular integration. In uninfected cells, BAF interacts with members of the LEM family of inner nuclear membrane and nucleoplasmic proteins. Here, we demonstrate that one of the LEM proteins, lamina-associated polypeptide 2alpha (LAP2alpha), is a component of the PIC. LAP2alpha stabilizes the association of BAF with the PIC to stimulate intermolecular integration and suppress autointegration. To further understand the role of LAP2alpha, we established LAP2alpha-knockdown cell lines. Depletion of LAP2alpha significantly inhibited viral replication. Our results demonstrate a critical contribution of LAP2alpha to the nucleoprotein organization of the PIC and to viral replication. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 301,MSC 0560, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov NR 42 TC 45 Z9 48 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 24 PY 2004 VL 23 IS 23 BP 4670 EP 4678 DI 10.1038/sj.emboj.7600452 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 877CW UT WOS:000225546400014 PM 15510219 ER PT J AU Wang, TJ Parise, H Levy, D Dagostino, RB Wolf, PA Vasan, RS Benjamin, EJ AF Wang, TJ Parise, H Levy, D Dagostino, RB Wolf, PA Vasan, RS Benjamin, EJ TI Obesity and the risk of new-onset atrial fibrillation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CORONARY-HEART-DISEASE; NATURAL-HISTORY; FRAMINGHAM; HYPERTENSION; SIZE; PREVALENCE; POPULATION; ECHOCARDIOGRAPHY; PREDICTORS AB Context Obesity is associated with atrial enlargement and ventricular diastolic dysfunction, both known predictors of atrial fibrillation (AF). However, it is unclear whether obesity is a risk factor for AF. Objective. To examine the association between body mass index (BMI) and the risk of developing AF. Design, Setting, and Participants Prospective, community-based observational cohort in Framingham, Mass. We studied 5282 participants (mean age, 57 [SD, 13] years; 2898 women [55%]) without baseline AF (electrocardiographic AF or arterial flutter). Body mass index (calculated as weight in kilograms divided by square of height in meters) was evaluated as both a continuous and a categorical variable (normal defined as <25.0; overweight, 25.0 to <30.0; and obese, greater than or equal to30.0). In addition to adjusting for clinical confounders by multivariable techniques, we also examined models including echocardiographic left atrial diameter to examine whether the influence of obesity was mediated by changes in left atrial dimensions. Main Outcome Measure Association between BMI or BMI category and risk of developing new-onset AF. Results During a mean follow-up of 13.7 years, 526 participants (234 women) developed AF. Age-adjusted incidence rates for AF increased across the 3 BMI categories in men (9.7,10.7, and 14.3 per 1000 person-years) and women (5.1, 8.6, and 9.9 per 1000 person-years). In multivariable models adjusted for cardiovascular risk factors and interim myocardial infarction or heart failure, a 4% increase in AF risk per 1-unit increase in BMI was observed in men (95% confidence interval [Cl], 1 %-7%; P=.02) and in women (95% Cl, 1%-7%; P=.009). Adjusted hazard ratios for AF associated with obesity were 1.52 (95% Cl, 1.09-2.13; P=.02) and 1.46 (95% Cl, 1.03-2.07; P=.03) for men and women, respectively, compared with individuals with normal BMI. After adjustment for echocardiographic left atrial diameter in addition to clinical risk factors, BMI was no longer associated with AF risk (adjusted hazard ratios per 1-unit increase in BMI, 1.00 [95% Cl, 0.97-1.04], P=.84 in men; 0.99 [95% Cl, 0.96-1.02], P=.56 in women). Conclusions Obesity is an important, potentially modifiable risk factor for AF. The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population. burden of AF. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston Med Ctr, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Prevent Med Sect, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23-HL074077-01, K24-HL-04334, N01-HC-25195]; NINDS NIH HHS [6R01-NS-17950] NR 35 TC 502 Z9 522 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 2004 VL 292 IS 20 BP 2471 EP 2477 DI 10.1001/jama.292.20.2471 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 873TD UT WOS:000225303000021 PM 15562125 ER PT J AU Fox, CS Coady, S Sorlie, PD Levy, D Meigs, JB D'Agostino, RB Wilson, PWF Savage, PJ AF Fox, CS Coady, S Sorlie, PD Levy, D Meigs, JB D'Agostino, RB Wilson, PWF Savage, PJ TI Trends in cardiovascular complications of diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; UNITED-STATES; DEATH CERTIFICATES; TEMPORAL TRENDS; SEX-DIFFERENCES; MEDICAL-CARE; EVENT RATES; US ADULTS; MORTALITY AB Context Despite reductions in cardiovascular disease (CVD) mortality over the past few decades, it is unclear whether adults with and without diabetes have experienced similar declines in CVD risk. Objective To determine whether adults with and without diabetes experienced similar declines in incident CVD in 1950-1995. Design, Setting, and Participants Participants aged 45-64 years from the Framingham Heart Study original and offspring cohorts who attended examinations in 1950-1966 ("earlier" time period; 4118 participants, 113 with diabetes) and 1977-1995 ("later" time period; 4063 participants, 317 with diabetes). Incidence rates of CVD among those with and without diabetes were compared between the earlier and later periods. Main Outcome Measures Myocardial infarction, coronary heart disease death, and stroke. Results Among participants with diabetes, the age- and sex-adjusted CVD incidence rate was 286.4 per 10000 person-years in the earlier period and 146.9 per 10000 in the later period, a 49.3% (95% confidence interval [Cl], 16.7%-69.4%) decline. Among participants without diabetes, the age- and sex-adjusted incidence rate was 84.6 per 10000 person-years in the earlier period and 54.3 per 10000 person-years in the later period, a 35.4% (95% Cl, 25.3%-45.4%) decline. Hazard ratios for diabetes as a predictor of incident CVD were not different in the earlier vs later periods. Conclusions We report a 50% reduction in the rate of incident CVD events among adults with diabetes, although the absolute risk of CVD is 2-fold greater than among persons without diabetes. Adults with and without diabetes have benefited similarly during the decline in CVD rates over the last several decades. More aggressive treatment of CVD risk factors and further research on diabetes-specific factors contributing to CVD, risk are needed to further reduce the high absolute risk of CVD still experienced by persons with diabetes. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Diabet & Hypertens, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 45 TC 273 Z9 291 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 2004 VL 292 IS 20 BP 2495 EP 2499 DI 10.1001/jama.292.20.2495 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 873TD UT WOS:000225303000025 PM 15562129 ER PT J AU Huang, KP Huang, FL Jager, T Li, JF Reymann, KG Balschun, D AF Huang, KP Huang, FL Jager, T Li, JF Reymann, KG Balschun, D TI Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurogranin; calmodulin; water maze; learning; LTP; calcium signaling ID PROTEIN-KINASE-C; CALMODULIN-BINDING PROTEIN; RELATIONAL MEMORY DEFICIT; RAT-BRAIN NEUROGRANIN/RC3; NITRIC-OXIDE MODIFICATION; VITAMIN-A-DEFICIENCY; D-ASPARTATE RECEPTOR; DISULFIDE S-OXIDE; SYNAPTIC PLASTICITY; THYROID-HORMONE AB In neurons, neurogranin (Ng) binds calmodulin (CaM), and its binding affinity is reduced by increasing Ca2+, phosphorylation by PKC, or oxidation by oxidants. Ng concentration in the hippocampus of adult mice varied broadly (Ng(+/+), similar to160-370 and Ng(+/-), similar to70-230 pmol/mg); the level in Ng(+/+) mice is one of the highest among all neuronal CaM-binding proteins. Among Ng(+/-) mice, but less apparent in Ng(+/+), a significant relationship existed between their hippocampal levels of Ng and performances in the Morris water maze. Ng(-/-) mice performed poorly in this task; they also displayed deficits in high-frequency-induced long-term potentiation (LTP) in area CA1 of hippocampal slices, whereas low-frequency-induced long-term depression was enhanced. Thus, compared with Ng(+/+) mice, the frequency-response curve of Ng(-/-) shifted to the right. Paired-pulse facilitation and synaptic fatigue during prolonged stimulation at 10 Hz (900 pulses) were unchanged in Ng(-/-) slices, indicating their normal presynaptic function. Measurements of Ca2+ transients in CA1 pyramidal neurons after weak and strong tetanic stimulations (100 Hz, 400 and 1000 msec, respectively) revealed a significantly greater intracellular Ca2+([Ca2+](i)) response in Ng(+/+) compared with Ng(-/-) mice, but the decay time constants did not differ. The diminished Ca2+ dynamics in Ng(-/-) mice are a likely cause of their decreased propensity to undergo LTP. Thus, Ng may promote a high [Ca2+](i) by a "mass-action" mechanism; namely, the higher the Ng concentration, the more Ng-CaM complexes will be formed, which effectively raises [Ca2+](i) at any given Ca2+ influx. This mechanism provides potent signal amplification in enhancing synaptic plasticity as well as learning and memory. C1 NICHHD, Metab Regulat Sect, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Leibniz Inst Neurobiol, D-39008 Magdeburg, Germany. RP Huang, KP (reprint author), NICHHD, Metab Regulat Sect, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36, Bethesda, MD 20892 USA. EM kphuang@helix.nih.gov RI yu, yan/C-2322-2012; Reymann, Klaus/J-8507-2013; OI Li, Junfa/0000-0002-1930-9724 NR 50 TC 98 Z9 112 U1 4 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 24 PY 2004 VL 24 IS 47 BP 10660 EP 10669 DI 10.1523/JNEUROSCI.2213-04.2004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 874EG UT WOS:000225333100011 PM 15564582 ER PT J AU Bossert, JM Liu, SY Lu, L Shaham, Y AF Bossert, JM Liu, SY Lu, L Shaham, Y TI A role of ventral tegmental area glutamate in contextual cue-induced relapse to heroin seeking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE drug environment; extinction; opiate self-administration; reinstatement; renewal; relapse; substantia nigra ID RECEPTOR AGONIST LY379268; COCAINE-SEEKING; CONDITIONED-STIMULUS; DRUG-SEEKING; DOPAMINE; SENSITIZATION; REINSTATEMENT; EXTINCTION; ADDICTION; BEHAVIOR AB The environmental context previously associated with opiate use plays an important role in human relapse, but the neuronal mechanisms involved in context-induced drug relapse are not known. Using a rat relapse model, we determined the effect of a group II metabotropic glutamate receptor agonist [LY379268 ((-)-2-oxa-4-aminobicylco hexane-4,6-dicarboxylic acid)] on contextual cue-induced reinstatement of heroin seeking. LY379268, which acts centrally to reduce evoked glutamate release, was injected systemically or directly into the ventral tegmental area (VTA), a brain area involved in opiate reward and conditioned drug effects. Rats were trained to self-administer intravenous heroin for 12 d; drug infusions were paired with a discrete tone - light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of lever responding, LY379268 was injected systemically or into the VTA, and nonreinforced responding was determined in the extinction context or the drug context. Exposure to the heroin-associated context induced robust reinstatement of drug seeking, and this effect was attenuated by systemic or intra-VTA injections of LY379268. Results indicate that glutamate transmission in the VTA plays an important role in contextual cue-induced relapse to heroin seeking. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept HHS, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 NR 34 TC 150 Z9 154 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 24 PY 2004 VL 24 IS 47 BP 10726 EP 10730 DI 10.1523/JNEUROSCI.3207-04.2004 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 874EG UT WOS:000225333100019 PM 15564590 ER PT J AU Park, KC Lee, SJ Reno, PW AF Park, KC Lee, SJ Reno, PW TI Normal rainbow trout serum (RTS)-resistant variants of the infectious pancreatic necrosis virus (IPNV)-Jasper differ with respect to inhibition by RTS, serotype and cDNA sequence SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE IPNV-Jasper variants; RTS inhibition; serotype; cDNA sequence ID AMINO-ACID-SEQUENCES; MOUTH-DISEASE VIRUS; AQUATIC BIRNAVIRUSES; STRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; GENOME SEGMENT; MONOCLONAL-ANTIBODIES; SALMO-GAIRDNERI; RNA; POPULATION AB In order to determine if the infectious pancreatic necrosis virus isolate IPNV-Jasper (Ja-ATCC) is homogeneous or heterogeneous with respect to inhibition by normal rainbow trout serum (RTS), 50 clones were tested for sensitivity to RTS. The initial isolate was very sensitive to RTS, losing from 10(4) to 10(8) 50% tissue culture infection dose (TCID50) ml(-1) with a 1: 100 dilution of RTS. The sensitivity of the clones ranged from highly sensitive to completely resistant (0 to 10(8) TCID50 ml(-1) reduction). Eight percent of clones (4/50) were very sensitive to RTS (Ja-S) and 84% of clones (42/50) showed a mid-range of sensitivity to RTS. The final 8% of clones (4/50) were resistant to RTS (Ja-R). Enzyme immunodot assay revealed that Ja-S clones showed a monoclonal reaction identical to the parents, Ja-ATCC; however, Ja-R clones differed by several epitopes from the parental strain. Analysis of Ja-S and Ja-R revealed that there were significant differences in their nucleic acid sequences for the capsid protein VP2. These 2 strains shared 80.7 and 86.5% identity in nucleic acid and in amino acid sequences, respectively. Ja-S had 99.7 and 91.0% identity in nucleic acid sequences, and 99.5 and 95.9% in amino acid sequences with Ja-ATCC and Jasper-Dobos (Ja-D), respectively, while Ja-R showed 80.6 and 79.8% identity in nucleic acid sequences and 86.5 and 87.0% in amino acid sequences,with Ja-ATCC and Ja-D, respectively. In conclusion, the Ja-ATCC population was heterogeneous in terms of RTS sensitivity, serotype and cDNA sequences from the VP2 coding region. C1 Oregon State Univ, Hatfield Marine Sci Ctr, Dept Microbiol, Newport, OR 97365 USA. NIEHS, Human Metab Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Oregon State Univ, Hatfield Marine Sci Ctr, Coastal Oregon Marine Expt Stn, Newport, OR 97365 USA. RP Park, KC (reprint author), Natl Res Council Canada, Inst Marine Biosci, 1411 Oxford St, Halifax, NS B3H 3Z1, Canada. EM kyoung.park@nrc.ca NR 52 TC 0 Z9 0 U1 0 U2 0 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD NOV 23 PY 2004 VL 62 IS 1-2 BP 45 EP 55 DI 10.3354/dao062045 PG 11 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 892WO UT WOS:000226680900005 PM 15648830 ER PT J AU Shih, JJ Cohen, LG AF Shih, JJ Cohen, LG TI Cortical reorganization in the human brain - How the old dog learns depends on the trick SO NEUROLOGY LA English DT Editorial Material ID MOTOR; STIMULATION; PLASTICITY C1 Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA. NINDS, Human Cort Physiol Sect, Bethesda, MD USA. RP Shih, JJ (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Neurol MSC10 5620, Albuquerque, NM 87131 USA. EM jshih@salud.unm.edu FU NCRR NIH HHS [P20 RR015636]; NINDS NIH HHS [R01NS42372] NR 10 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 23 PY 2004 VL 63 IS 10 BP 1772 EP 1773 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 873JE UT WOS:000225275000003 PM 15557488 ER PT J AU Kappos, L Weinshenker, B Pozzilli, C Thompson, AJ Dahlke, F Beckmann, K Polman, C McFarland, H AF Kappos, L Weinshenker, B Pozzilli, C Thompson, AJ Dahlke, F Beckmann, K Polman, C McFarland, H CA EU-SPMs NA-SPMS TI Interferon beta-1b in secondary progressive MS - A combined analysis of the two trials SO NEUROLOGY LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; RANDOMIZED CONTROLLED TRIAL; STATUS SCALE EDSS; MAGNETIC-RESONANCE; DOUBLE-BLIND; MULTICENTER; DISABILITY; IMPAIRMENT; MRI AB Background: A European (EU) and a North American (NA) placebo-controlled study with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis (SPMS)showed divergent results with regard to their primary outcome of sustained Expanded Disability Status Scale (EDSS) progression, while effects were similar on relapse and MRI-related endpoints. Reasons for this discrepancy were explored in the combined dataset. Methods: Baseline characteristics and variability in EDSS assessments were compared. Retrospective combined analyses for time to confirmed progression were performed to assess treatment effects overall and in subgroups defined by pre-study disease activity criteria and other key baseline variables. Results: The variance of EDSS measurements was 6.5% higher in the NA-SPMS study. The EU study included patients in an earlier phase of SPMS and with more active disease both pre-study (relapses, MRI) as well as on study (EDSS, relapses, and MRI variables as assessed in the placebo groups). The pooled analysis showed an overall risk reduction by about 20% in patients treated with 8 MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p=0.008). Risk reduction by 30% to 40% was found for patients with at least one relapse or change in EDSS by >1 in the 2 years prior to study entry. No other consistent across-studies relation of clinical and MRI variables at baseline to potential treatment response was found. Conclusions: Although post hoc, this combined analysis of the two large studies with IFNB-1b in secondary progressive multiple sclerosis suggests that both pronounced disability progression and continuing relapse activity might help in identifying those patients in the secondary progressive phase of the disease who are more likely to benefit from treatment. C1 Univ Basel Hosp, Outpatient Clin Neurol Neurosurg, CH-4031 Basel, Switzerland. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN USA. Univ Roma La Sapienza, Dept Neurol, Rome, Italy. Natl Hosp, Dept Neurol, London, England. Schering AG, Berlin, Germany. VU Med Ctr, Dept Neurol, Amsterdam, Netherlands. NIH, Neuroimmunol Branch, Bethesda, MD USA. RP Kappos, L (reprint author), Univ Basel Hosp, Outpatient Clin Neurol Neurosurg, Petersgraben 4, CH-4031 Basel, Switzerland. EM lkappos@uhbs.ch RI Thompson, Alan/C-2654-2008 OI Thompson, Alan/0000-0002-4333-8496 FU Multiple Sclerosis Society [748] NR 26 TC 119 Z9 123 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 23 PY 2004 VL 63 IS 10 BP 1779 EP 1787 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 873JE UT WOS:000225275000005 PM 15557490 ER PT J AU Solfrizzi, V Panza, F Colacicco, AM D'Introno, A Capurso, C Torres, F Grigoletto, F Maggi, S Del Parigi, A Reiman, EM Caselli, RJ Scafato, E Farchi, G Capurso, A AF Solfrizzi, V Panza, F Colacicco, AM D'Introno, A Capurso, C Torres, F Grigoletto, F Maggi, S Del Parigi, A Reiman, EM Caselli, RJ Scafato, E Farchi, G Capurso, A CA Italian Longitudinal Study Aging W TI Vascular risk factors, incidence of MCI, and rates of progression to dementia SO NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; DIFFERENT DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; CARDIOVASCULAR HEALTH; DIABETES-MELLITUS; MEMORY IMPAIRMENT; OLDER-PEOPLE; PREVALENCE; POPULATION; AGE AB Objective: To estimate prevalence, incidence, and rate of progression of mild cognitive impairment (MCI) to dementia and correlated vascular risk factors with incident MCI and its progression to dementia. Methods: The authors evaluated 2,963 individuals from the population-based sample of 5,632 subjects 65 to 84 years old, at the first ( 1992 to 1993) and second survey (1995 to 1996) of the Italian Longitudinal Study on Aging (ILSA), with a 3.5-year follow-up. Dementia, Alzheimer disease (AD), vascular dementia (VaD), other types of dementia, and MCI were classified using current clinical criteria. Results: Among the 2,963 participants, 139 MCI patients were diagnosed at the first ILSA survey. During the 3.5-year follow-up, 113 new events of MCI were diagnosed with an estimated incidence rate of 21.5 per 1,000 person-years. We found a progression rate to dementia ( all causes) of 3.8/100 person-years. Specific progression rates for AD, VaD, and other types of dementia were 2.3, 1.3, and 0.3/100 person-years. Furthermore, age was a risk factor for incident MCI (RR: 5.93, 95% CI: 3.17 to 11.10), while education was protective (RR: 0.06, 95% CI: 0.03 to 0.10), and serum total cholesterol evidenced a borderline nonsignificant trend for a protective effect. There was a nonsignificant trend for stroke as a risk factor of progression of MCI to dementia. Conclusions: In this population, among those who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors influence incident mild cognitive impairment and the rate of progression to dementia. C1 Univ Bari, Dept Geriatr, Ctr Aging Brain, Memory Unit, I-70124 Bari, Italy. Univ Foggia, Dept Geriatr, Foggia, Italy. Univ Padua, Inst Hyg, I-35100 Padua, Italy. CNR, Ctr Aging, Natl Res Council Italy, Padua, Italy. NIDDKD, NIH, Phoenix, AZ USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. Mayo Clin, Dept Neurol, Scottsdale, AZ USA. Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. RP Solfrizzi, V (reprint author), Univ Bari, Policlin, Ctr Aging Brain, Dept Geriatr,Memory Unit, Piazza Giulio Cesare 11, I-70124 Bari, Italy. EM v.solfrizzi@geriatria.uniba.it RI Torres, Filipa/G-9742-2016; OI Torres, Filipa/0000-0002-3138-9309; Capurso, Cristiano/0000-0002-1152-3371; Panza, Francesco/0000-0002-7220-0656 NR 57 TC 280 Z9 291 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 23 PY 2004 VL 63 IS 10 BP 1882 EP 1891 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 873JE UT WOS:000225275000021 PM 15557506 ER PT J AU Bonaventura, J Gow, A AF Bonaventura, J Gow, A TI NO and superoxide: Opposite ends of the seesaw in cardiac contractility SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID LIVER XANTHINE DEHYDROGENASE; NITRIC-OXIDE; HEART-FAILURE; PEROXYNITRITE; MECHANISMS; CONVERSION; NITRATION; NAD C1 Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. Univ Puerto Rico, NIH, COBRE, Mayaguez, PR 00681 USA. Univ Penn, Childrens Hosp Philadelphia, Stokes Res Inst, Philadelphia, PA 19104 USA. RP Bonaventura, J (reprint author), Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. EM joeb@duke.edu RI Gow, Andrew/N-8566-2013 OI Gow, Andrew/0000-0003-0876-5158 FU NCRR NIH HHS [5P20 RR016439, P20 RR016439] NR 20 TC 14 Z9 16 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 2004 VL 101 IS 47 BP 16403 EP 16404 DI 10.1073/pnas.0405859101 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 874JT UT WOS:000225347400006 PM 15546989 ER PT J AU Kwon, J Lee, SR Yang, KS Ahn, Y Kim, YJ Stadtman, ER Rhee, SG AF Kwon, J Lee, SR Yang, KS Ahn, Y Kim, YJ Stadtman, ER Rhee, SG TI Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hydrogen peroxide; peptide growth factor receptor; peroxiredoxin ID TYROSINE-PHOSPHATASE 1B; CYSTEINE-SULFINIC ACID; NECROSIS-FACTOR-ALPHA; HYDROGEN-PEROXIDE; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; SACCHAROMYCES-CEREVISIAE; REDOX REGULATION; IN-VIVO; PEROXIREDOXIN AB Stimulation of cells with various peptide growth factors induces the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) through activation of phosphatidylinositol 3-kinase. The action of this enzyme is reversed by that of the tumor suppressor PTEN. With the use of cells overexpressing NADPH oxidase 1 or peroxiredoxin II, we have now shown that H2O2 produced in response to stimulation of cells with epidermal growth factor or platelet-derived growth factor potentiates PIP3 generation and activation of the protein kinase Akt induced by these growth factors. We also show that a small fraction of PTEN molecules is transiently inactivated as a result of oxidation of the essential cysteine residue of this phosphatase in various cell types stimulated with epidermal growth factor, platelet-derived growth factor, or insulin. These results suggest that the activation of phosphatidylinositol 3-kinase by growth factors might not be sufficient to induce the accumulation of PIP3 because of the opposing activity of PTEN and that the concomitant local inactivation of PTEN by H2O2 might be needed to increase the concentration of PIP3 sufficiently to trigger downstream signaling events. Furthermore, together with previous observations, our data indicate that peroxiredoxin likely participates in PIP3 signaling by modulating the local concentration of H2O2. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Div Mol Life Sci, Ctr Cell Signaling Res, Seoul 120750, South Korea. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 33 TC 342 Z9 350 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 2004 VL 101 IS 47 BP 16419 EP 16424 DI 10.1073/pnas.0407396101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 874JT UT WOS:000225347400010 PM 15534200 ER PT J AU Miki, K Qu, WD Goulding, EH Willis, WD Bunch, DO Strader, LF Perreault, SD Eddy, EM O'Brien, DA AF Miki, K Qu, WD Goulding, EH Willis, WD Bunch, DO Strader, LF Perreault, SD Eddy, EM O'Brien, DA TI Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycolysis; gene targeting; infertility ID MOUSE SPERMATOGENIC CELLS; HYPERACTIVATED MOTILITY; MAMMALIAN SPERMATOZOA; TARGETED DISRUPTION; ALPHA-CHLOROHYDRIN; ACROSOME REACTION; ZONA-PELLUCIDA; GENE; TESTIS; GLUCOSE AB Although glycolysis is highly conserved, it is remarkable that several unique isozymes in this central metabolic pathway are found in mammalian sperm. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS) is the product of a mouse gene expressed only during spermatogenesis and, like its human ortholog (GAPD2), is the sole GAPDH isozyme in sperm. It is tightly bound to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum. We disrupted Gapds expression by gene targeting to selectively block sperm glycolysis and assess its relative importance for in vivo sperm function. Gapds(-/-) males were infertile and had profound defects in sperm motility, exhibiting sluggish movement without forward progression. Although mitochondrial oxygen consumption was unchanged, sperm from Gapds(-/-) mice had ATP levels that were only 10.4% of those in sperm from WT mice. These results imply that most of the energy required for sperm motility is generated by glycolysis rather than oxidative phosphorylation. Furthermore, the critical role of glycolysis in sperm and its dependence on this sperm-specific enzyme suggest that GAPDS is a potential contraceptive target, and that mutations or environmental agents that disrupt its activity could lead to male infertility. C1 Univ N Carolina, Sch Med, Reprod Biol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA. NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Shanghai 200032, Peoples R China. US EPA, Reprod Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. RP O'Brien, DA (reprint author), Univ N Carolina, Sch Med, Reprod Biol Lab, Chapel Hill, NC 27599 USA. EM dao@med.unc.edu FU FIC NIH HHS [TW/HD00627]; NICHD NIH HHS [U54 HD035041, U54 HD35041] NR 41 TC 308 Z9 322 U1 2 U2 37 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 2004 VL 101 IS 47 BP 16501 EP 16506 DI 10.1073/pnas.0407708101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 874JT UT WOS:000225347400024 PM 15546993 ER PT J AU Zapata, JM Krajewska, M Morse, HC Choi, Y Reed, JC AF Zapata, JM Krajewska, M Morse, HC Choi, Y Reed, JC TI TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NF-KAPPA-B; INDUCED APOPTOSIS; T-CELLS; EXPRESSION; ACTIVATION; MALIGNANCIES; REGULATOR; SURVIVAL; MOUSE; LKLF AB Transgenic mice overexpressing in B lymphocytes either Bcl-2 or a TNF receptor-associated factor (TRAF)2 mutant lacking the N-terminal RING and zinc finger domains located at the N terminus of the molecule (TRAF2DN), which mimics TRAF1, developed lymphadenopathy and splenomegaly due to polyclonal B cell expansion. Remarkably, TRAF2DN/Bcl-2 double-transgenic mice contained B cell populations similar to those observed in TRAF2DN mice. However, over time, they developed severe splenomegaly and lymphadenopathy, and most animals also developed leukemia, pleural effusion, and, in some cases, ascites associated with monoclonal and oligoclonal B cell neoplasms. The life span of TRAF2DN/Bcl-2 mice was markedly reduced compared with Bcl-2 and TRAF2DN single-transgenics or wild-type littermates. The expanded B cell population of TRAF2DN/Bcl-2 double-transgenic mice was primarily comprised of small/medium-size noncycling B220(M)/IgM(H)/IgD(L)/ CD21(L)/CD23(NULL)/CD11b(+)/CD5(+) cells that were Bcl-6-negative, consistent with a B-1 phenotype. The cells also expressed high levels of CD54 and other adhesion molecules. In vitro, these B cells showed comparable proliferation rates to those of wild-type counterparts but exhibited markedly increased survival and were resistant to apoptosis induced by chemotherapeutic agents and glucocorticoids. Histopathologic features were consistent with mouse small B cell lymphoma progressing to leukemia with many similarities to human chronic lymphocytic leukemia. Given that many human chronic lymphocytic leukemias overexpress TRAF1 and Bcl-2, our findings suggest that cooperation between Bcl-2 and TRAF pathways contributes to the development of this type of leukemia. C1 Burnham Inst, La Jolla, CA 92037 USA. NIAAA, NIH, Rockville, MD 20852 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Zapata, JM (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM jzapata@burnham.org; reedoffice@burnham.org RI Zapata, Juan/J-6304-2014; OI Zapata, Juan/0000-0002-0110-0009; Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA69381, CA81534, P01 CA069381, P01 CA081534] NR 30 TC 47 Z9 49 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 2004 VL 101 IS 47 BP 16600 EP 16605 DI 10.1073/pnas.0407541101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 874JT UT WOS:000225347400041 PM 15545599 ER PT J AU Gwadry-Sridhar, FH Flintoft, V Lee, DS Lee, H Guyatt, GH AF Gwadry-Sridhar, FH Flintoft, V Lee, DS Lee, H Guyatt, GH TI A systematic review and meta-analysis of studies comparing readmission rates and mortality rates in patients with heart failure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID HOME-BASED INTERVENTION; DISEASE MANAGEMENT; ELDERLY-PATIENTS; CARE; HOSPITALIZATION; RATIONALE; PROGRAM; TRIALS AB Background: Heart failure is the leading cause of hospitalization and readmission in many hospitals worldwide. We performed a meta-analysis to evaluate the effectiveness of multidisciplinary heart failure management programs on hospital admission rates. Methods: We identified studies through an electronic search and mortality using 8 distinct methods. Eligible studies met the following criteria: (1) randomized controlled clinical trials of adult inpatients hospitalized for heart failure enrolled either at the time of discharge or within 1 week after discharge; (2) heart failure-specific patient education intervention coupled with a postdischarge follow-up assessment; and (3) unplanned readmission reported. Four reviewers independently assessed each study for eligibility and quality, achieving a weighted kappa of 0.73 for eligibility and 0.77 for quality. For each study we calculated the relative risk for readmissions and mortality for patients receiving enhanced education relative to patients receiving usual care. Results: A total of 529 citation titles were identified, of which 8 randomized trials proved eligible. The pooled relative risk for hospital readmission rates using a random-effects model was 0.79 (95% confidence interval, 0.68-0.91; P<.001; heterogeneity P=.25). There was no apparent effect on mortality (relative risk, 0.98; 95% confidence interval, 0.72-1.34; P=.90; heterogeneity P=.20). Data were insufficient to meaningfully pool intervention effects on quality of life or compliance. Conclusion: This systematic review suggests that specific heart failure-targeted interventions significantly decrease hospital readmissions but do not affect mortality rates. C1 London Hlth Sci Ctr, Dept Med, Div Crit Care, London, ON N6A 4G5, Canada. Univ Western Ontario, Dept Med, Div Crit Care, London, ON N6A 4G5, Canada. Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. Natl Heart Lung & Blood Inst, Framingham, MA USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. RP Gwadry-Sridhar, FH (reprint author), London Hlth Sci Ctr, Dept Med, Div Crit Care, Victoria Campus,375 S St, London, ON N6A 4G5, Canada. EM Femida.GwadrySridhar@lhsc.on.ca RI Lee, Douglas/J-4315-2014 NR 27 TC 99 Z9 104 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 22 PY 2004 VL 164 IS 21 BP 2315 EP 2320 DI 10.1001/archinte.164.21.2315 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 874FV UT WOS:000225337200003 PM 15557409 ER PT J AU Plafker, SM Plafker, KS Weissman, AM Macara, IG AF Plafker, SM Plafker, KS Weissman, AM Macara, IG TI Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ACTIVATING ENZYME; SACCHAROMYCES-CEREVISIAE; NUCLEOLAR-LOCALIZATION; PROTEOLYTIC SYSTEM; TUMOR-SUPPRESSOR; EPITHELIAL NA+; DNA-REPAIR; PROTEIN; P53; IDENTIFICATION AB Ubiquitin is a small polypeptide that is conjugated to proteins and commonly serves as a degradation signal. The attachment of ubiquitin (Ub) to a substrate proceeds through a multi-enzyme cascade involving an activating enzyme a conjugating enzyme (E1) and a protein ligase We previously demonstrated that a murine E2, UbcM2, is imported into nuclei by the transport receptor importin-11. We now show that the import mechanism for l and two other human class III E2s (UbcH6 and UBE2E2) uniquely requires the covalent attachment of Ub to the active site cysteine of these enzymes. This coupling of E2 activation and transport arises from the selective Interaction of importin-11 with the Ub-loaded forms of these enzymes. Together, these findings reveal that Ub charging can function as a nuclear import trigger, and identify a novel link between E2 regulation and karyopherin-mediated transport. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA. NCI, Canc Res Ctr, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Univ Virginia, Ctr Cell Signaling, Charlottesville, VA 22908 USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. RP Plafker, SM (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA. EM scott-plafker@ouhsc.edu FU NIGMS NIH HHS [R01 GM050526, GM50526] NR 56 TC 53 Z9 58 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 22 PY 2004 VL 167 IS 4 BP 649 EP 659 DI 10.1083/jcb.200406001 PG 11 WC Cell Biology SC Cell Biology GA 875HS UT WOS:000225411600008 PM 15545318 ER PT J AU Siegel, RM Muppidi, JR Sarker, M Lobito, A Jen, M Martin, D Straus, SE Lenardo, MJ AF Siegel, RM Muppidi, JR Sarker, M Lobito, A Jen, M Martin, D Straus, SE Lenardo, MJ TI SPOTS: signaling protein oligomeric transduction structures are early mediators of death receptor-induced apoptosis at the plasma membrane SO JOURNAL OF CELL BIOLOGY LA English DT Article ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; CASPASE-8 ACTIVATION; TNF RECEPTORS; CELL-DEATH; FAS; COMPLEX; CD95; MUTATIONS; MODEL AB Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although FADD and caspase-8 have been identified as key intracellular mediators of Fas signaling, it is not clear how recruitment of these proteins to the Fas death domain leads to activation of caspase-8 in the receptor signaling complex. We have used high-resolution confocal microscopy and live cell imaging to study the sequelae of early events in Fas signaling. These studies have revealed a new stage of Fas signaling in which receptor ligation leads to the formation of surface receptor oligomers that we term signaling protein oligomerization transduction structures (SPOTS). Formation of SPOTS depends on the presence of an intact Fas death domain and FADD but is independent of caspase activity. Analysis of cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted by distinct mechanisms in ALPS. C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NIAMSD, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 26 TC 96 Z9 97 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 22 PY 2004 VL 167 IS 4 BP 735 EP 744 DI 10.1083/jcb.200406101 PG 10 WC Cell Biology SC Cell Biology GA 875HS UT WOS:000225411600015 PM 15557123 ER PT J AU Chun, TH Sabeh, F Ota, I Murphy, H McDonagh, KT Holmbeck, K Birkedal-Hansen, H Allen, ED Weiss, SJ AF Chun, TH Sabeh, F Ota, I Murphy, H McDonagh, KT Holmbeck, K Birkedal-Hansen, H Allen, ED Weiss, SJ TI MT1-MMP-dependent neovessel formation within the confines of the three-dimensional extracellular matrix SO JOURNAL OF CELL BIOLOGY LA English DT Article ID IN-VIVO; ENDOTHELIAL-CELLS; GELATINASE-A; INTEGRIN ALPHA-V-BETA-3; METALLOPROTEINASE MMP-2; GROWTH-FACTOR; ANGIOGENESIS; COLLAGEN; MORPHOGENESIS; MICE AB During angiogenesis, endothelial cells initiate a tissue-invasive program within an interstitial matrix comprised largely of type 1 collagen. Extracellular matrix-degradative enzymes, including the matrix metalloproteinases (MMPs) MMP-2 and MMP-9, are thought to play key roles in angiogenesis by binding to docking sites on the cell surface after activation by plasmin- and/or membrane-type (MT) 1-MMP-dependent processes. To identify proteinases critical to neovessel formation, an ex vivo model of angiogenesis has been established wherein tissue explants from gene-targeted mice are embedded within a three-dimensional, type 1 collagen matrix. Unexpectedly, neither MMP-2, MMP-9 their cognate cell-surface receptors (i.e., beta3 integrin and Cl nor plasminogen are essential for collagenolytic activity, endothelial cell invasion, or neovessel formation. Instead, the membrane-anchored MMP, MT1-MMP confers endothelial cells with the ability to express invasive and tubulogenic activity in a collagen-rich milieu, in vitro or in vivo, where it plays an indispensable role in driving neovessel formation. C1 Univ Michigan, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Weiss, SJ (reprint author), Univ Michigan, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. EM sjweiss@umich.edu FU NCI NIH HHS [R01 CA071699, R01 CA088308] NR 65 TC 218 Z9 231 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 22 PY 2004 VL 167 IS 4 BP 757 EP 767 DI 10.1083/jcb.200405001 PG 11 WC Cell Biology SC Cell Biology GA 875HS UT WOS:000225411600017 PM 15545316 ER PT J AU Sabeh, F Ota, I Holmbeck, K Birkedal-Hansen, H Soloway, P Balbin, M Lopez-Otin, C Shapiro, S Inada, M Krane, S Allen, E Chung, D Weiss, SJ AF Sabeh, F Ota, I Holmbeck, K Birkedal-Hansen, H Soloway, P Balbin, M Lopez-Otin, C Shapiro, S Inada, M Krane, S Allen, E Chung, D Weiss, SJ TI Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP SO JOURNAL OF CELL BIOLOGY LA English DT Article ID I COLLAGEN; METALLOPROTEINASE ACTIVITY; PERICELLULAR PROTEOLYSIS; DEFICIENT MICE; GELATINASE-A; INVASION; CANCER; ACTIVATION; MIGRATION; EXPRESSION AB As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)-dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collogenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity. C1 Univ Michigan, Dept Internal Med, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Cornell Univ, Coll Human Ecol, Div Nutr Sci, Ithaca, NY 14853 USA. Univ Oviedo, Inst Univ Oncol, Dept Bioquim, Oviedo 33006, Spain. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weiss, SJ (reprint author), Univ Michigan, Dept Internal Med, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. EM sjweiss@umich.edu RI inada, masaki/D-1581-2013; Balbin, Milagros/I-4206-2015; Lopez-Otin, Carlos/C-6657-2013 OI inada, masaki/0000-0002-5066-8506; Lopez-Otin, Carlos/0000-0001-6964-1904 FU NCI NIH HHS [R01 CA071699, R01 CA088308]; NHLBI NIH HHS [P01 HL029594, P01 HL29594] NR 59 TC 375 Z9 383 U1 2 U2 20 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 22 PY 2004 VL 167 IS 4 BP 769 EP 781 DI 10.1083/jcb.200408028 PG 13 WC Cell Biology SC Cell Biology GA 875HS UT WOS:000225411600018 PM 15557125 ER PT J AU Hatzakis, AE Touloumi, G Pantazis, N Anastassopoulou, CG Katsarou, O Karafoulidou, A Goedert, JJ Kostrikis, LG AF Hatzakis, AE Touloumi, G Pantazis, N Anastassopoulou, CG Katsarou, O Karafoulidou, A Goedert, JJ Kostrikis, LG TI Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral therapy SO AIDS LA English DT Article DE cellular HIV-1 DNA load; HIV-1 RNA rebound; antiretroviral therapy ID VIRUS TYPE-1 DNA; POLYMERASE-CHAIN-REACTION; PLASMA VIRAL LOAD; PCR-BASED ASSAY; VIROLOGICAL RESPONSE; INFECTED PATIENTS; PROVIRAL DNA; DISEASE PROGRESSION; PROTEASE INHIBITOR; IMMUNODEFICIENCY AB Objective: To assess whether cellular HIV-1 DNA prior to highly active antiretroviral therapy (HAART) initiation predicts its outcome. Design and methods: Patients included all 51 hemophiliacs of the Greek component of the Multicenter Hemophilia Cohort Study who had initiated HAART and for whom cryopreserved lymphocyte samples before HAART initiation were available. Cellular HIV-1 DNA quantification was performed by a molecular beacon-based real-time PCR assay in multiple samples per patient with a median (interquartile range) follow-up of 76 (45-102) weeks. Results: The median (range) baseline HIV-1 DNA load was 297 (< 10 to 3468) copies per 1 x 10(6) peripheral blood mononuclear cells. Baseline HIV-1 DNA load did not predict initial virological response (VR). None of the patients with initial VR and baseline HIV-1 DNA load at or below the median experienced a subsequent virological rebound, while the cumulative probability of virological rebound by week 104 was 55% among those with HIV-1 DNA load greater than the median (P<0.008). Cellular HIV-1 DNA load was the only parameter associated with sustained virological response as shown by univariate or multivariate analyses [adjusted odds ratio (95% confidence interval) 0.197 (0.048-0.801) per 1 log(10) increase in DNA copies, P = 0.023]. Conclusion: Low cellular HIV-1 DNA load is a marker of sustained virological response in patients with initial VR and it can reliably predict the long-term success of HAART. (C) 2004 Lippincott Williams Wilkins. C1 Univ Athens, Sch Med, Dept Hyg & Epidemiol, Natl Retrovirus Reference Ctr, GR-11527 Athens, Greece. Laikon Gen Hosp, Hemophilia Ctr, Athens, Greece. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Cyprus, Sch Nat Sci, Dept Biol Sci, Nicosia, Cyprus. RP Hatzakis, AE (reprint author), Univ Athens, Sch Med, Dept Hyg & Epidemiol, Natl Retrovirus Reference Ctr, 75 Mikras Asias St, GR-11527 Athens, Greece. EM ahatzak@med.uoa.gr RI Kostrikis, Leondios/A-5330-2016 OI Kostrikis, Leondios/0000-0002-5340-7109 FU NCI NIH HHS [N01-CP-33002] NR 47 TC 30 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD NOV 19 PY 2004 VL 18 IS 17 BP 2261 EP 2267 DI 10.1097/00002030-200411190-00006 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 878OU UT WOS:000225656900005 PM 15577538 ER PT J AU Chen, R Lim, JH Jono, H Gu, XX Kim, YS Basbaum, CB Murphy, TF Li, JD AF Chen, R Lim, JH Jono, H Gu, XX Kim, YS Basbaum, CB Murphy, TF Li, JD TI Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKK beta-I kappa B alpha-NF-kappa B signaling pathways SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE outer membrane protein P6; mucin MUC5AC; TLR2; p38 MAPK; AP1; NF-kappa B ID OBSTRUCTIVE PULMONARY-DISEASE; OUTER-MEMBRANE PROTEIN; TOLL-LIKE RECEPTORS; EPITHELIAL-CELLS; LIPOOLIGOSACCHARIDE HTRB; OTITIS-MEDIA; RFAD MUTANTS; PATHOGENESIS; ACTIVATION; MUCUS AB Mucin overproduction is a hallmark of nontypeable Haemophilus influenzae (NTHi) infections. The molecular mechanisms underlying up-regulation of mucin in NTHi infections especially during the initial phase remain unknown. Here we show that P6, a 16-kDa outer membrane lipoprotein well conserved in NTHi, up-regulates MUC5AC mucin gene transcription in vitro and in vivo. Moreover, P6 induces MUC5AC transcription via TLR2-MyD88-IRAK1-TRAF6-TAK1-dependent p38 MAPK-AP1 and IKKbeta-IkappaBalpha-NF-kappaB signaling pathways. This study may bring new insights into the molecular pathogenesis of NTHi-induced infections and lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ So Calif, House Ear Inst, Gonda Dept Cell & Mol Biol, Los Angeles, CA 90057 USA. Univ So Calif, Dept Otolaryngol, Los Angeles, CA 90057 USA. Natl Inst Deafness & Other Commun Disorders, Immunol Lab, Rockville, MD 20850 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Gastrointestinal Res Lab, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. SUNY Buffalo, Div Infect Dis, Buffalo, NY 14215 USA. RP Li, JD (reprint author), Univ So Calif, House Ear Inst, Gonda Dept Cell & Mol Biol, Los Angeles, CA 90057 USA. EM jdli@hei.org FU NCI NIH HHS [CA 24321]; NHLBI NIH HHS [HL 070293, HL 073309, HL 075602]; NIAID NIH HHS [AI 019641]; NIDCD NIH HHS [DC 004562, DC 005843] NR 31 TC 88 Z9 95 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 19 PY 2004 VL 324 IS 3 BP 1087 EP 1094 DI 10.1016/j.bbrc.2004.09.157 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 866XX UT WOS:000224807800019 PM 15485666 ER PT J AU Jeffries, NO AF Jeffries, NO TI Performance of a genetic algorithm for mass spectrometry proteomics SO BMC BIOINFORMATICS LA English DT Article ID LASER DESORPTION/IONIZATION-TIME; OVARIAN-CANCER; PROSTATE-CANCER; SERUM; PATTERNS; IDENTIFICATION; BIOMARKERS AB Background: Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. Results: In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. Conclusions: The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated. C1 NINDS, Off Clin Director, Bethesda, MD 20892 USA. RP Jeffries, NO (reprint author), NINDS, Off Clin Director, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM neal.jeffries@nih.gov NR 19 TC 25 Z9 28 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 19 PY 2004 VL 5 AR 180 DI 10.1186/1471-2105-5-180 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 891YX UT WOS:000226618000002 PM 15555060 ER PT J AU Barlic, J McDermott, DH Merrell, MN Gonzales, J Via, LE Murphy, PM AF Barlic, J McDermott, DH Merrell, MN Gonzales, J Via, LE Murphy, PM TI Interleukin (IL)-15 and IL-2 reciprocally regulate expression of the chemokine receptor CX3CR1 through selective NFAT1- and NFAT2-dependent mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; ACTIVATED T-CELLS; PERIPHERAL-BLOOD LYMPHOCYTES; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; IMMUNOSUPPRESSIVE AGENTS; TARGETED DELETION; CYCLOSPORINE-A; NUCLEAR FACTOR; IN-VIVO AB We have recently reported that interleukin (IL)-15 and IL-2, which signal through IL-2Rbetagamma, oppositely regulate expression of the proinflammatory chemokine receptor CX3CR1. Here we delineate molecular mechanisms responsible for this paradox. By using a luciferase reporter plasmid, we identified a 433-bp region spanning the major transcriptional start point of human CX3CR1 that, when expressed in human peripheral blood mononuclear cells (PBMCs), possessed strong constitutive promoter activity. IL-2 and IL-15 treatment increased and abolished this activity, respectively, mimicking their effects on endogenous CX3CR1. IL-2 and IL-15 have been reported to also have opposite effects on the immunoregulatory transcription factor NFAT ( nuclear factor of activated T cells), and the 433-bp region contains a kappaB-like NFAT site. The effects of IL-15 and IL-2 on both CX3CR1 reporter activity and endogenous CX3CR1 transcription in PBMCs were abolished by the NFAT inhibitors cyclosporin A and VIVIT. Moreover, mutation of the kappaB-like NFAT sequence markedly attenuated IL-2 and IL-15 modulation of CX3CR1 promoter-reporter activity in PBMCs. Furthermore, chromatin immunoprecipitation revealed that IL-15 promoted specific recruitment of NFAT1 but not NFAT2 to the CX3CR1 promoter, whereas IL-2 had the converse effect. This appears to be relevant in vivo because mouse CX3CR1 mRNA was expressed in both PBMCs and splenocytes from NFAT1(-/-) mice injected with recombinant IL-15 but was undetectable in cells from IL-15-injected NFAT1(+/+) BALB/c mice; as predicted, IL-2 up-regulated cx3cr1 in both mouse strains to a similar extent. Thus, by pharmacologic, genetic, and biochemical criteria in vitro and in vivo, our results suggest that IL-15 and IL-2 oppositely regulate CX3CR1 gene expression by differentially recruiting NFAT1 and NFAT2 to a kappaB-like NFAT site within the CX3CR1 promoter. We propose that expression of CX3CR1 and possibly other immunoregulatory genes may be determined in part by the balance of NFAT1 and NFAT2 activity in leukocytes. C1 NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, TB Res Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bldg 10,Rm 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov OI McDermott, David/0000-0001-6978-0867; Via, Laura/0000-0001-6074-9521 NR 70 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 48520 EP 48534 DI 10.1074/jbc.M406978200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100007 PM 15347678 ER PT J AU Pawliczak, R Logun, C Madara, P Lawrence, M Woszczek, G Ptasinska, A Kowalski, ML Wu, T Shelhamer, JH AF Pawliczak, R Logun, C Madara, P Lawrence, M Woszczek, G Ptasinska, A Kowalski, ML Wu, T Shelhamer, JH TI Cytosolic phospholipase A(2) group IV alpha but not secreted phospholipase A(2) group IIA, V, or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through peroxisome proliferator-activated receptors gamma 1 and 2 in human lung cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; EPIDERMAL-GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS; ARACHIDONIC-ACID MOBILIZATION; PROSTAGLANDIN E-2 PRODUCTION; COX-2 EXPRESSION; PPAR-GAMMA; P388D(1) MACROPHAGES; SIGNAL-TRANSDUCTION AB It has been reported that interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) expression is regulated by peroxisome proliferator-activated receptor (PPAR)-gamma synthetic ligands. We have shown previously that cytosolic phospholipase A(2) (cPLA(2)) is able to activate gene expression through PPAR-gamma response elements (Pawliczak, R., Han, C., Huang, X. L., Demetris, A. J., Shelhamer, J. H., and Wu, T. (2002) J. Biol. Chem. 277, 33153 - 33163). In this study we investigated the influence of cPLA(2) and secreted phospholipase A(2) (sPLA(2)) Group IIA, Group V, and Group X on IL-8 and COX-2 expression in human lung epithelial cells (A549 cells). We also studied the results of cPLA(2) activation by epidermal growth factor (EGF) and calcium ionophore (A23187) on IL-8 and COX-2 reporter gene activity, mRNA level, and protein synthesis. cPLA(2) overexpression and activation increased both IL-8 and COX-2 reporter gene activity. Overexpression and activation of Group IIA, Group V, or Group X sPLA(2)s did not increase IL-8 and COX-2 reporter gene activity. Methyl arachidonyl fluorophosphate, a cPLA(2) inhibitor, inhibited the effect of A23187 and of EGF on both IL-8 and COX-2 reporter gene activity, steady state levels of IL-8 and COX-2 mRNA, and IL-8 and COX-2 protein expression. Small inhibitory RNAs directed against PPAR-gamma1 and -gamma2 blunted the effect of A23187 and of EGF on IL-8 and COX-2 protein expression. Moreover small inhibitory RNAs directed against cPLA(2) decreased the effect of A23187 and EGF on IL-8 and COX-2 protein expression. These results demonstrate that cPLA(2) has an influence on IL-8 and COX 2 gene and protein expression at least in part through PPAR-gamma. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Allergy & Clin Immunol, PL-92213 Lodz, Poland. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jshelhamer@nih.gov RI Woszczek, Grzegorz/H-5792-2012; Pawliczak, Rafal/S-9649-2016; OI Pawliczak, Rafal/0000-0001-6784-453X NR 48 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 48550 EP 48561 DI 10.1074/jbc.M408926200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100010 PM 15331599 ER PT J AU Lee, M Kim, JY Anderson, WB AF Lee, M Kim, JY Anderson, WB TI Src tyrosine kinase inhibitor PP2 markedly enhances Ras-independent activation of Raf-1 protein kinase by phorbol myristate acetate and H2O2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-REGULATED KINASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; PHOSPHORYLATION SITES; ENDOTHELIAL-CELLS; ERK ACTIVATION; C-EPSILON; B-RAF; TRANSDUCTION; REQUIREMENT AB Recently we reported that simultaneous treatment of NIH 3T3 cells with the combination of phorbol myristate acetate (PMA) and hydrogen peroxide (H2O2) resulted in synergistic activation of Raf-1 kinase ( Lee, M., Petrovics, G., and Anderson, W. B. ( 2003) Biochem. Biophys. Res. Commun. 311, 1026 - 1033). In this study we have demonstrated that PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine), a potent and selective inhibitor of the Src-family tyrosine kinase, greatly potentiated the ability of PMA and/or H2O2 to activate Raf-1 kinase, whereas it blocked the tyrosine phosphorylation of Raf-1. Unlike PMA/H2O2 treatment, which showed transient activation, PP2-mediated Raf-1 activation was sustained and continued to increase through 4 h of treatment. Transient transfection studies with a dominant-negative mutant of Ras (N19Ras) indicated that this PP2-induced activation of Raf-1 was Ras-independent. Moreover, PP2 showed no effect on platelet-derived growth factor-induced Raf-1 activation. Interestingly, mutation of the reported Raf-1 Src family tyrosine kinase phosphorylation site by conversion of tyrosines 340 and 341 to phenylalanine (YY340/341FF Raf) had limited effect on the ability of PP2 to induce significant stimulation of Raf-1 kinase activity. Taken together, our results suggest that a tyrosine phosphorylation event is involved in the negative feedback regulation of Raf-1. Inhibition of a Src family tyrosine kinase by PP2 appears to alleviate this tyrosine kinase-mediated inhibition of Raf-1 and allow activating modification( s) of Raf-1 to proceed. This PP2 effect resulted in significant and sustained Ras-independent activation of Raf-1 by PMA and H2O2. C1 Korea Res Inst Chem Technol, Korea Inst Toxicol, Lab Genet Toxicol, Taejon 305600, South Korea. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Anderson, WB (reprint author), Korea Res Inst Chem Technol, Korea Inst Toxicol, Lab Genet Toxicol, POB 123, Taejon 305600, South Korea. EM mikelee@kitox.re.kr NR 76 TC 22 Z9 24 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 48692 EP 48701 DI 10.1074/jbc.M403132200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100026 PM 15356004 ER PT J AU Swindle, EJ Metcalfe, DD Coleman, JW AF Swindle, EJ Metcalfe, DD Coleman, JW TI Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-EPSILON-RI; HISTAMINE-RELEASE; IFN-GAMMA; GENERATION; DIPHENYLENEIODONIUM; DEGRANULATION; SUPEROXIDE; PHOSPHORYLATION; INHIBITION; INFECTION AB In immunity, reactive oxygen species (ROS) and nitric oxide (NO) are important antimicrobial agents and regulators of cell signaling and activation pathways. However, the cellular sources of ROS and NO are much debated. Particularly, there is contention over whether mast cells, key secretory cells in allergy and immunity, can generate these chemical species, and if so, whether they are of functional significance. We therefore examined directly by flow cytometry the capacity of mast cells to generate intracellular ROS and NO using the respective cell-permeable fluorescent probes dichlorodihydrofluorescein and diaminofluorescein and evaluated the effects of inhibitors of ROS and NO synthesis on cell degranulation. For each of three mast cell types ( rat peritoneal mast cells, mouse bone marrow-derived mast cells, and human blood-derived mast cells), degranulation stimulated by IgE/antigen was accompanied by production of intracellular ROS but not NO. Inhibition of ROS production led to reduced degranulation, indicating a facilitatory role for ROS, whereas NO synthase inhibitors were without effect. Likewise, bacterial lipopolysaccharide and interferon-gamma over a wide range of conditions failed to generate intracellular NO in mast cells, whereas these agents readily induced intracellular NO in macrophages. NO synthase protein, as assessed by Western blotting, was readily induced in macrophages but not mast cells. We conclude that rodent and human mast cells generate intracellular ROS but not NO and that intracellular ROS but not intracellular NO are functionally linked to mast cell degranulation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Liverpool, Dept Pharmacol, Liverpool L69 3GE, Merseyside, England. RP Swindle, EJ (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C 209, Bethesda, MD 20892 USA. EM ejswindle@niaid.nih.gov NR 40 TC 72 Z9 75 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 48751 EP 48759 DI 10.1074/jbc.M409738200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100033 PM 15361524 ER PT J AU Sauna, ZE Nandigama, K Ambudkar, SV AF Sauna, ZE Nandigama, K Ambudkar, SV TI Multidrug resistance protein 4 (ABCC4)-mediated ATP hydrolysis - Effect of transport substrates and characterization of the post-hydrolysis transition state SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN P-GLYCOPROTEIN; NUCLEOTIDE-BINDING DOMAINS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MYOSIN MOTOR DOMAIN; CATALYTIC CYCLE; ABC TRANSPORTER; PROSTAGLANDIN E-2; CRYSTAL-STRUCTURE; 2ND DOMAIN; CELLS AB Multidrug resistance protein 4 (MRP4/ABCC4), transports cyclic nucleoside monophosphates, nucleoside analog drugs, chemotherapeutic agents, and prostaglandins. In this study we characterize ATP hydrolysis by human MRP4 expressed in insect cells. MRP4 hydrolyzes ATP (K-m, 0.62 mM), which is inhibited by orthovanadate and beryllium fluoride. However, unlike ATPase activity of P-glycoprotein, which is equally sensitive to both inhibitors, MRP4-ATPase is more sensitive to beryllium fluoride than to orthovanadate. 8-Azido[alpha-P-32] ATP binds to MRP4 (concentration for half-maximal binding similar to3 muM) and is displaced by ATP or by its nonhydrolyzable analog AMPPNP (concentrations for half-maximal inhibition of 13.3 and 308 muM). MRP4 substrates, the prostaglandins E1 and E2, stimulate ATP hydrolysis 2- to 3-fold but do not affect the K-m for ATP. Several other substrates, azidothymidine, 9-(2-phosphonylmethoxyethyl) adenine, and methotrexate do not stimulate ATP hydrolysis but inhibit prostaglandin E2-stimulated ATP hydrolysis. Although both post-hydrolysis transition states MRP4.8-azido[alpha-P-32] ADP.Vi and MRP4.8-azido[alpha-P-32] ADP.beryllium fluoride can be generated, nucleotide trapping is similar to4-fold higher with beryllium fluoride. The divalent cations Mg2+ and Mn2+ support comparable levels of nucleotide binding, hydrolysis, and trapping. However, Co2+ increases 8-azido[alpha-P-32] ATP binding and beryllium fluoride-induced 8-azido[alpha-P-32] ADP trapping but does not support steady-state ATP hydrolysis. ADP inhibits basal and prostaglandin E2-stimulated ATP hydrolysis (concentrations for half-maximal inhibition 0.19 and 0.25 mM, respectively) and beryllium fluoride-induced 8-azido[alpha-P-32] ADP trapping, whereas P-i has no effect up to 20 mM. In aggregate, our results demonstrate that MRP4 exhibits substrate-stimulated ATP hydrolysis, and we propose a kinetic scheme suggesting that ADP release from the post-hydrolysis transition state may be the rate-limiting step during the catalytic cycle. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Ambudkar, Suresh/B-5964-2008 NR 68 TC 33 Z9 35 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 48855 EP 48864 DI 10.1074/jbc.M408849200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100047 PM 15364914 ER PT J AU Chou, CL Christensen, BM Frische, S Vorum, H Desai, RA Hoffert, JD de Lanerolle, P Nielsen, S Knepper, MA AF Chou, CL Christensen, BM Frische, S Vorum, H Desai, RA Hoffert, JD de Lanerolle, P Nielsen, S Knepper, MA TI Non-muscle myosin II and myosin light chain kinase are downstream targets for vasopressin signaling in the renal collecting duct SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GOLGI-DERIVED VESICLES; BLADDER GRANULAR-CELL; TOAD URINARY-BLADDER; RAT-KIDNEY; F-ACTIN; WATER PERMEABILITY; EPITHELIAL-CELLS; AQUAPORIN-2 TRAFFICKING; ORGANELLE TRANSPORT; INTRACELLULAR CA2+ AB We have previously demonstrated that vasopressin increases the water permeability of the inner medullary collecting duct (IMCD) by inducing trafficking of aquaporin-2 to the apical plasma membrane and that this response is dependent on intracellular calcium mobilization and calmodulin activation. Here, we address the hypothesis that this water permeability response is mediated in part through activation of the calcium/calmodulin-dependent myosin light chain kinase (MLCK) and regulation of non-muscle myosin II. Immunoblotting and immunocytochemistry demonstrated the presence of MLCK, the myosin regulatory light chain (MLC), and the IIA and IIB isoforms of the non-muscle myosin heavy chain in rat IMCD cells. Two-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified two isoforms of MLC, both of which also exist in phosphorylated and non-phosphorylated forms. P-32 incubation of the inner medulla followed by autoradiography of two-dimensional gels demonstrated increased P-32 labeling of both isoforms in response to the V-2 receptor agonist [deamino-Cys(1), D-Arg(8)] vasopressin (DDAVP). Time course studies of MLC phosphorylation in IMCD suspensions ( using immunoblotting with anti-phospho-MLC antibodies) showed that the increase in phosphorylation could be detected as early as 30 s after exposure to vasopressin. The MLCK inhibitor ML-7 blocked the DDAVP-induced MLC phosphorylation and substantially reduced [Arg(8)] vasopressin (AVP)stimulated water permeability. AVP-induced MLC phosphorylation was associated with a rearrangement of actin filaments ( Alexa Fluor 568-phalloidin) in primary cultures of IMCD cells. These results demonstrate that MLC phosphorylation by MLCK represents a downstream effect of AVP-activated calcium/calmodulin signaling in IMCD cells and point to a role for non-muscle myosin II in regulation of water permeability by vasopressin. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC-1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov RI Frische, Sebastian/B-2332-2009; chen, xuanlan/H-4158-2011; OI Frische, Sebastian/0000-0002-0270-3602; Desai, Ravi/0000-0002-4217-3351; Christensen, Birgitte Monster/0000-0002-6140-4629 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-02182-KE] NR 65 TC 69 Z9 71 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 49026 EP 49035 DI 10.1074/jbc.M408565200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100066 PM 15347643 ER PT J AU Kibler, KV Miyazato, A Yedavalli, VSRK Dayton, AI Jacobs, BL Dapolito, G Kim, SJ Jeang, KT AF Kibler, KV Miyazato, A Yedavalli, VSRK Dayton, AI Jacobs, BL Dapolito, G Kim, SJ Jeang, KT TI Polyarginine inhibits gp160 processing by furin and suppresses productive human immunodeficiency virus type 1 infection SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONVERTING ENZYME-INHIBITORS; ENVELOPE GLYCOPROTEIN; PROPROTEIN CONVERTASES; MOLECULAR CLONE; CELLS; HIV-1; ACTIVATION; PROTEIN; PRECURSOR; CLEAVAGE AB Correct endoproteolytic maturation of gp160 is essential for the infectivity of human immunodeficiency virus type 1. This processing of human immunodeficiency virus-1 envelope protein, gp160, into gp120 and gp41 has been attributed to the activity of the cellular subtilisin-like proprotein convertase furin. The prototypic furin recognition cleavage site is Arg-X-Arg/Lys-Arg. Arg-Arg-Arg-Arg- Arg-Arg or longer iterations of polyarginine have been shown to be competitive inhibitors of substrate cleavage by furin. Here, we tested polyarginine for inhibition of productive human immunodeficiency virus-1-infection in T-cell lines, primary peripheral blood mononuclear cells, and macrophages. We found that polyarginine inhibited significantly human immunodeficiency virus-1 replication at concentrations that were benign to cell cultures ex vivo and mice in vivo. Using a fluorogenic assay, we demonstrated that polyarginine potently inhibited substrate-specific proteolytic cleavage by furin. Moreover, we verified that authentic processing of human immunodeficiency virus-1 gp160 synthesized in human cells from an infectious human immunodeficiency virus-1 (HIV-1) molecular clone was effectively blocked by polyarginine. Taken together, our data support that inhibitors of proteolytic processing of gp160 may be useful for combating human immunodeficiency virus-1 and that polyarginine represents a lead example of such inhibitors. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Arizona State Univ, Biodesign Inst, Ctr Infect Dis & Vaccinol, Tempe, AZ 85287 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 47 TC 28 Z9 29 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 49055 EP 49063 DI 10.1074/jbc.M403394200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100069 PM 15371436 ER PT J AU Furumoto, Y Nunomura, S Terada, T Rivera, J Ra, C AF Furumoto, Y Nunomura, S Terada, T Rivera, J Ra, C TI The Fc epsilon RI beta immunoreceptor tyrosine-based activation motif exerts inhibitory control on MAPK and I kappa B kinase phosphorylation and mast cell cytokine production SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY IGE RECEPTOR; IMMUNOGLOBULIN-E RECEPTOR; LYN KINASE; INOSITOL 5'-PHOSPHATASE; NEGATIVE REGULATION; ALLERGIC RESPONSE; SUBUNIT; DOMAIN; SHIP; DEGRANULATION AB The high affinity IgE Fc receptor (FcepsilonRI) beta chain functions as a signal amplifier and has been linked to atopy, asthma, and allergy. Herein, we report on a previously unrecognized negative regulatory role for the nonconventional beta chain immunoreceptor tyrosine-based activation motif that contains three tyrosine residues (YX5YX3Y). Degranulation and leukotriene production was found to be impaired in cells expressing the mutated FcepsilonRIbeta immunoreceptor tyrosine-based activation motifs FYY, YYF, FYF, and FFF. In contrast, cytokine synthesis and secretion were enhanced in the YFY and FFF mutants. FcepsilonRI phosphorylation and Lyn kinase co-immunoprecipitation was intact in the YFY mutant but was lost in the FYF and FFF mutants. The phosphorylation of Syk, LAT, phospholipase gamma1/2, and Src-homology 2 domain-containing protein phosphatase 2 was intact, whereas the phosphorylation of SHIP-1 was significantly reduced in the YFY mutant cells. The FYF and FFF mutants were defective in phosphorylating all of these molecules. In contrast, the phosphorylation of ERK, p38 MAPK, IkappaB kinase beta(IKKbeta), and nuclear NFkappaB activity was enhanced in the YFY and FFF mutants. These findings show that the FcepsilonRIbeta functions to both selectively amplify (degranulation and leukotriene secretion) and dampen (lymphokine) mast cell effector responses. C1 NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Nihon Univ, Grad Sch Med Sci, Adv Med Res Ctr, Div Mol Cell Immunobiol & Allergol,Itabashi Ku, Tokyo 1378610, Japan. RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Rm 9N228, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 52 TC 76 Z9 78 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 49177 EP 49187 DI 10.1074/jbc.M404730200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100083 PM 15355979 ER PT J AU Yang, XL Wang, WG Fan, JS Lal, A Yang, DM Cheng, HP Gorospe, M AF Yang, XL Wang, WG Fan, JS Lal, A Yang, DM Cheng, HP Gorospe, M TI Prostaglandin A(2)-mediated stabilization of p21 mRNA through an ERK-dependent pathway requiring the RNA-binding protein HuR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTORS; SHOCK TRANSCRIPTION FACTOR; HEAT-SHOCK; PROSTAGLANDIN A(2); GENE-EXPRESSION; ANTINEOPLASTIC PROSTAGLANDINS; CYCLOPENTENONE PROSTAGLANDIN; 3'-UNTRANSLATED REGION; BIOLOGICAL-ACTIVITIES; CARCINOMA CELLS AB Treatment with the stress agent prostaglandin A(2) (PGA(2)) induces expression of the cyclin-dependent kinase inhibitor p21. Here, we present evidence that p21 expression increases through PGA(2)-triggered stabilization of the p21 mRNA and further show that these events require the mitogen-activated protein (MAP) kinase ERK. Binding experiments using either endogenous p21 mRNA or in vitro-labeled p21 transcripts revealed a specific PGA(2)-dependent association of the p21 mRNA with the RNA-binding protein HuR. Interestingly, although inhibition of the ERK pathway did not prevent the PGA(2)-triggered increase in cytoplasmic HuR, it did impair the formation of endogenous and in vitro [HuR-p21 mRNA] complexes and further prevented the PGA(2)-mediated stabilization of the p21 mRNA, suggesting that ERK-mediated events were required for binding HuR to the p21 mRNA and preventing its decay. RNA interference-based knockdown of HuR abundance further served to demonstrate the contribution of HuR-mediated p21 mRNA stabilization toward enhancing p21 expression after PGA(2) treatment. Collectively, our results indicate that PGA(2) stabilizes the p21 mRNA through an ERK-independent increase in cytoplasmic HuR levels and an ERK-dependent association of HuR with the p21 mRNA. C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov NR 68 TC 51 Z9 53 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 49298 EP 49306 DI 10.1074/jbc.M407535200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100098 PM 15371446 ER PT J AU Squires, EJ Sueyoshi, T Negishi, M AF Squires, EJ Sueyoshi, T Negishi, M TI Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; ENHANCER MODULE; CYP2B GENE; CAR; PROTEIN; TRANSCRIPTION; IDENTIFICATION AB The pregnane X receptor (PXR) plays an important role in the response to xenobiotics and endogenous toxins. We have used a specific anti-PXR antibody in the Western blotting of mouse liver nuclear extracts to show that PXR is accumulated in the nucleus after treatment with 5-pregnen-3beta-ol-20-one-16alpha-carbonitrile (PCN), followed by an increase in Cyp3a11 mRNA. Expression of wild type PXR and various mutants as green fluorescent fusion proteins in mouse livers showed that PXR was retained in the cytoplasm from where PCN treatment translocated PXR into the nucleus. Furthermore, the xenochemical response signal, the nuclear translocation signal, and the activation function 2 domain were all required for the nuclear translocation to occur. Immunoprecipitation experiments using the hsp90 antibody demonstrated the presence of PXR in a complex with the endogenous cytoplasmic constitutive active/androstane receptor retention protein (CCRP) in HepG2 cells. Fluorescence resonance energy transfer analysis of mouse liver sections after co-expression of cyan fluorescent protein-CCRP and yellow fluorescent protein-PXR also indicated that CCRP and PXR were closely associated in vivo. Overexpression of exogenous CCRP increased the cytoplasmic level of the PXR.CCRP.hsp90 complex, whereas a decrease in endogenous CCRP by treatment with small interfering RNA for CCRP repressed the PXR-mediated reporter activity in HepG2 cells. We conclude that the CCRP mediates the retention of PXR in the cytosol and modulates the activation of PXR in response to PCN treatment. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 27 TC 119 Z9 128 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 49307 EP 49314 DI 10.1074/jbc.M407281200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100099 PM 15347657 ER PT J AU Namkung, Y Sibley, DR AF Namkung, Y Sibley, DR TI Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D-2 dopamine receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AGONIST-INDUCED DESENSITIZATION; HAMSTER OVARY CELLS; COUPLED RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR; D2 RECEPTORS; HETEROLOGOUS-DESENSITIZATION; DEPENDENT PHOSPHORYLATION; DIFFERENTIAL REGULATION; CROSS-TALK; BETA AB Previously, D-2 dopamine receptors (D-2 DARs) have been shown to undergo G-protein-coupled receptor kinase phosphorylation in an agonist-specific fashion. We have now investigated the ability of the second messenger-activated protein kinases, protein kinase A (PKA) and protein kinase C (PKC), to mediate phosphorylation and desensitization of the D-2 DAR. HEK293T cells were transiently transfected with the D-2 DAR and then treated with intracellular activators and inhibitors of PKA or PKC. Treatment with agents that increase cAMP, and activate PKA, had no effect on the phosphorylation state of the D-2 DAR, suggesting that PKA does not phosphorylate the D-2 DAR in HEK293T cells. In contrast, cellular treatment with phorbol 12-myristate 13-acetate (PMA), a PKC activator, resulted in an similar to3-fold increase in D-2 DAR phosphorylation. The phosphorylation was specific for PKC as the PMA effect was mimicked by phorbol 12,13-dibutyrate, but not by 4alpha-phorbol 12,13-didecanoate, active and inactive, phorbol diesters, respectively. The PMA-mediated D-2 DAR phosphorylation was completely blocked by co-treatment with the PKC inhibitor, bisindolylmaleimide II, and augmented by co-transfection with PKCbetaI. In contrast, PKC inhibition had no effect on agonist-promoted phosphorylation, suggesting that PKC is not involved in this response. PKC phosphorylation of the D-2 DAR was found to promote receptor desensitization as reflected by a decrease in agonist potency for inhibiting cAMP accumulation. Most interestingly, PKC phosphorylation also promoted internalization of the D-2 DAR through a beta-arrestin- and dynamin-dependent pathway, a response not usually associated with PKC phosphorylation of G-protein-coupled receptors. Site-directed mutagenesis experiments resulted in the identification of two domains of PKC phosphorylation sites within the third intracellular loop of the receptor. Both of these domains are involved in regulating sequestration of the D-2 DAR, whereas only one domain is involved in receptor desensitization. These results indicate that PKC can mediate phosphorylation of the D-2 DAR, resulting in both functional desensitization and receptor internalization. C1 NINDS, NIH, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. RP Sibley, DR (reprint author), NINDS, NIH, Mol Neuropharmacol Sect, Bldg 10,Rm 5C108,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. EM sibley@helix.nih.gov NR 58 TC 91 Z9 92 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 2004 VL 279 IS 47 BP 49533 EP 49541 DI 10.1074/jbc.M408319200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100124 PM 15347675 ER PT J AU Baumeister, W Bachmair, A Chau, V Cohen, R Coffino, P DeMartino, G Deshaies, R Dohmen, J Emr, S Finley, D Hampton, R Hill, C Hochstrasser, M Huber, R Jackson, P Jentsch, S Johnson, E Kwon, YT Pagano, M Pickart, C Rechsteiner, M Scheffner, M Sommer, T Tansey, W Tyers, M Vierstra, R Weissman, A Wilkinson, KD Wolf, D AF Baumeister, W Bachmair, A Chau, V Cohen, R Coffino, P DeMartino, G Deshaies, R Dohmen, J Emr, S Finley, D Hampton, R Hill, C Hochstrasser, M Huber, R Jackson, P Jentsch, S Johnson, E Kwon, YT Pagano, M Pickart, C Rechsteiner, M Scheffner, M Sommer, T Tansey, W Tyers, M Vierstra, R Weissman, A Wilkinson, KD Wolf, D TI Varshavsky's contributions SO SCIENCE LA English DT Letter C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. Max Planck Inst Plant Breeding Res, D-50829 Cologne, Germany. Penn State Univ Hershey, Hershey, PA 17033 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. CALTECH, Pasadena, CA 91125 USA. Univ Cologne, D-5000 Cologne 41, Germany. Univ Calif San Diego, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Utah, Salt Lake City, UT 84132 USA. Yale Univ, New Haven, CT 06520 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NYU, New York, NY 10016 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Univ Konstanz, D-78457 Constance, Germany. Max Delbruck Ctr Biomed Res, D-13122 Berlin, Germany. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Samuel Lunenfeld Res Inst, Toronto, ON MG5 1X5, Canada. Univ Wisconsin, Madison, WI 53706 USA. NCI, NIH, Frederick, MD 21702 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Stuttgart, D-70569 Stuttgart, Germany. RP Baumeister, W (reprint author), Max Planck Inst Biochem, D-82152 Martinsried, Germany. RI Scheffner, Martin/K-2940-2012; Deshaies, Raymond/B-8354-2014 OI Scheffner, Martin/0000-0003-2229-0128; Deshaies, Raymond/0000-0002-3671-9354 NR 0 TC 2 Z9 2 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 19 PY 2004 VL 306 IS 5700 BP 1290 EP 1292 DI 10.1126/science.306.5700.1290 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 873SP UT WOS:000225301600020 PM 15550643 ER PT J AU Rosen, TC Yoshida, S Frohlich, R Kirk, KL Haufe, G AF Rosen, TC Yoshida, S Frohlich, R Kirk, KL Haufe, G TI Fluorinated phenylcyclopropylamines. 2. Effects of aromatic ring substitution and of absolute configuration on inhibition of microbial tyramine oxidase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SENSITIVE AMINE OXIDASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; TRANYLCYPROMINE ISOMERS; CATALYTIC MECHANISM; TOPA-QUINONE; ACTIVE-SITE; COPPER; RESOLUTION; FLUOROSTYRENES AB A series of para-substituted diastereopure cis- and trans-2-fluoro-2-arylcyclopropylamines were synthesized and these were investigated as inhibitors of microbial tyramine oxidase from Arthrobacter sp. All compounds were shown to be competitive inhibitors of this enzyme. The nature of the para-substituents in the more potent trans-isomer (cis-relationship between fluorine and the amino group) of 2-fluoro-2-arylcyclopropylamine influenced the inhibitory potency in a consistent fashion. Thus, electron-withdrawing groups (F, Cl) slightly decreased the activity, while the methyl group (+ I substituent) increased the activity by a factor of ca. 7 compared to trans-2-fluoro-2-phenylcyclopropylamine and by a factor of 90 compared to tranylcypromine. Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 2-fluoro-2-phenylcyclopropylamine was an excellent inhibitor of tyramine oxidase whereas the (1R,2R)-enantiomer was essentially devoid of activity. C1 Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Haufe, G (reprint author), Univ Munster, Inst Organ Chem, Corrensstr 40, D-48149 Munster, Germany. EM haufe@uni-muenster.de NR 39 TC 26 Z9 26 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 18 PY 2004 VL 47 IS 24 BP 5860 EP 5871 DI 10.1021/jm049957t PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 870YT UT WOS:000225095700007 PM 15537343 ER PT J AU Paisan-Ruiz, C Jain, S Evans, EW Gilks, WP Simon, J van der Brug, M de Munain, AL Aparicio, S Gil, AM Khan, N Johnson, J Martinez, JR Nicholl, D Carrera, IM Pena, AS de Silva, R Lees, A Marti-Masso, JF Perez-Tur, J Wood, NW Singleton, AB AF Paisan-Ruiz, C Jain, S Evans, EW Gilks, WP Simon, J van der Brug, M de Munain, AL Aparicio, S Gil, AM Khan, N Johnson, J Martinez, JR Nicholl, D Carrera, IM Pena, AS de Silva, R Lees, A Marti-Masso, JF Perez-Tur, J Wood, NW Singleton, AB TI Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease SO NEURON LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; FAMILIAL ALZHEIMERS-DISEASE; MISSENSE MUTATIONS; SYNUCLEIN; LOCUS AB Parkinson's disease (PD; OMIM #168600) is the second most common neurodegenerative disorder in the Western world and presents as a progressive movement disorder. The hallmark pathological features of PD are loss of dopaminergic neurons from the substantia nigra and neuronal intracellular Lewy body inclusions. Parkinsonism is typically sporadic in nature; however, several rare familial forms are linked to genetic loci, and the identification of causal mutations has provided insight into the disease process. PARK8, identified in 2002 by Funayama and colleagues, appears to be a common cause of familial PD. We describe here the cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain. Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor. C1 CSIC, Inst Biomed, Dept Genom & Proteom, Unitat Genet Mol, E-46010 Valencia, Spain. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Reta Lila Weston Inst Neurol Studies, London W1T 45F, England. NIA, Mol Genet Unit, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. NIA, Cell Biol & Gene Express Unit, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. Hosp Donostia, Unidad Expt, E-20014 San Sebastian, Spain. Hosp Donostia, Serv Neurol, E-20014 San Sebastian, Spain. Hosp Ntra Str Antigua Zumarraga, E-20700 Guipuzkao, Spain. Hosp Mendaro, E-20850 Guipuzkao, Spain. Queen Elizabeth Hosp, Birmingham Dept Neurol, Birmingham B15 2TH, W Midlands, England. RP Perez-Tur, J (reprint author), CSIC, Inst Biomed, Dept Genom & Proteom, Unitat Genet Mol, E-46010 Valencia, Spain. EM jpereztur@ibv.csic.es; nwood@ion.ucl.ac.uk; singleta@mail.nih.gov RI de Silva, Rohan/C-1734-2008; Paisan-Ruiz, Coro/C-2912-2009; Perez-Tur, Jordi/A-2143-2010; Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009; Aparicio, Silvia/K-8563-2014; Wood, Nicholas/C-2505-2009; Gilks, William/P-9137-2015 OI de Silva, Rohan/0000-0002-5052-5775; Perez-Tur, Jordi/0000-0002-9111-1712; Aparicio, Silvia/0000-0002-6664-3768; Wood, Nicholas/0000-0002-9500-3348; Gilks, William/0000-0001-7814-3173 FU Parkinson's UK [G-4029] NR 16 TC 1207 Z9 1238 U1 5 U2 49 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 18 PY 2004 VL 44 IS 4 BP 595 EP 600 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 874GE UT WOS:000225338100006 PM 15541308 ER PT J AU Dave, SS Wright, G Tan, B Rosenwald, A Gascoyne, RD Chan, WC Fisher, RI Braziel, RM Rimsza, LM Grogan, TM Miller, TP LeBlanc, M Greiner, TC Weisenburger, DD Lynch, JC Vose, J Armitage, JO Smeland, EB Kvaloy, S Holte, H Delabie, J Connors, JM Lansdorp, PM Ouyang, Q Lister, TA Davies, AJ Norton, AJ Muller-Hermelink, HK Ott, G Campo, E Montserrat, E Wilson, WH Jaffe, ES Simon, R Yang, LM Powell, J Zhao, H Goldschmidt, N Chiorazzi, M Staudt, LM AF Dave, SS Wright, G Tan, B Rosenwald, A Gascoyne, RD Chan, WC Fisher, RI Braziel, RM Rimsza, LM Grogan, TM Miller, TP LeBlanc, M Greiner, TC Weisenburger, DD Lynch, JC Vose, J Armitage, JO Smeland, EB Kvaloy, S Holte, H Delabie, J Connors, JM Lansdorp, PM Ouyang, Q Lister, TA Davies, AJ Norton, AJ Muller-Hermelink, HK Ott, G Campo, E Montserrat, E Wilson, WH Jaffe, ES Simon, R Yang, LM Powell, J Zhao, H Goldschmidt, N Chiorazzi, M Staudt, LM TI Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMAS; LOW-GRADE; EXPRESSION PATTERNS; PROGNOSTIC-FACTORS; DENDRITIC CELLS; RITUXIMAB; CLONING; CHEMOTHERAPY; VACCINATION AB Background: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. Methods: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. Results: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. Conclusions: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis. C1 NCI, NIH, Bethesda, MD 20892 USA. Ctr Informat Technol, Bethesda, MD USA. NHLBI, Bethesda, MD 20892 USA. British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. Univ Nebraska, Med Ctr, Omaha, NE USA. SW Oncol Grp, San Antonio, TX USA. Univ Rochester, Sch Med, Rochester, NY USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Arizona, Ctr Canc, Tucson, AZ USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Norwegian Radium Hosp, Oslo, Norway. St Bartholomews Hosp, Canc Res UK, London, England. Univ Wurzburg, Wurzburg, Germany. Univ Barcelona, Barcelona, Spain. RP Staudt, LM (reprint author), NCI, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [UO1-CA84967] NR 30 TC 790 Z9 810 U1 2 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 18 PY 2004 VL 351 IS 21 BP 2159 EP 2169 DI 10.1056/NEJMoa041869 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 871UU UT WOS:000225160600006 PM 15548776 ER PT J AU Neary, CL Nesterova, M Cho, YS Cheadle, C Becker, KG Cho-Chung, YS AF Neary, CL Nesterova, M Cho, YS Cheadle, C Becker, KG Cho-Chung, YS TI Protein kinase A isozyme switching: eliciting differential cAMP signaling and tumor reversion SO ONCOGENE LA English DT Article DE cAMP-dependent protein kinase; cancer; gene therapy; DNA microarray; confocal microscopy ID RI-ALPHA SUBUNIT; RII(BETA) REGULATORY SUBUNIT; CANCER CELL-GROWTH; CYCLIC-AMP; CATALYTIC SUBUNIT; RESPONSE ELEMENT; GENE-EXPRESSION; BREAST-CANCER; AUTOPHOSPHORYLATION SITE; PROSTATE-CANCER AB The cAMP-dependent protein kinase types I (PKA-I) and II (PKA-II), composed of identical catalytic ( C) subunits but distinct regulatory ( R) subunits (RI versus RII), are expressed in a balance of cell growth and differentiation. Distortion of this balance may underlie tumorigenesis and tumor growth. Here, we used PC3M prostate carcinoma cells as a model to overexpress wild type and mutant R and C subunit genes and examined the effects of differential expression of these genes on tumor growth. Only the RIIbeta and mutant RIalpha-P (a functional mimic of RIIbeta) transfectants exhibited growth inhibition in vitro, reverted phenotype, and apoptosis, and inhibited in vivo tumor growth. DNA microarrays demonstrated that RIIbeta and RIalpha-P overexpression upregulated a cluster of differentiation genes, while downregulating transformation and proliferation signatures. Overexpression of RIalpha and Calpha, which upregulated PKA-I, elicited the expression signatures opposite that elicited by RIIbeta overexpression. Total colocalization of Calpha and RIIbeta seen by confocal microscopy in the RIIbeta cell nucleus supports the opposed genomic regulation demonstrated between Calpha and RIIbeta cells. Differential expression of PKA R subunits may therefore serve as a tumor-target-based gene therapy for PC3M prostate and other cancers. C1 NCI, Cellular Biochem Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 5B05, Bethesda, MD 20892 USA. EM yc12b@nih.gov OI Neary, Catherine/0000-0003-0562-7913; Becker, Kevin/0000-0002-6794-6656 FU NCI NIH HHS [N02-BC76512/C2700212] NR 44 TC 42 Z9 43 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 18 PY 2004 VL 23 IS 54 BP 8847 EP 8856 DI 10.1038/sj.onc.1208165 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 871VQ UT WOS:000225165100015 PM 15480415 ER PT J AU Stoll, BJ Hansen, NI Adams-Chapman, I Fanaroff, AA Hintz, SR Vohr, B Higgins, RD AF Stoll, BJ Hansen, NI Adams-Chapman, I Fanaroff, AA Hintz, SR Vohr, B Higgins, RD TI Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID WHITE-MATTER DAMAGE; CEREBRAL-PALSY; BRAIN-DAMAGE; PERIVENTRICULAR LEUKOMALACIA; INTRAUTERINE INFECTION; PERINATAL INFECTION; PRETERM INFANT; NECROTIZING ENTEROCOLITIS; NATIONAL-INSTITUTE; RESEARCH NETWORK AB Context Neonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care. Objective To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood. Design, Setting, and Participants Infants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n=2161), clinical infection alone (n=1538), sepsis (n=1922), sepsis and necrotizing enterocolitis (n=279), or meningitis with or without sepsis (n=193). Main Outcome Measures Cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up. Results The majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome. Conclusions This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored. C1 Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Stanford Univ, Med Ctr, Div Neonatol, Palo Alto, CA 94304 USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. NICHHD, Bethesda, MD 20892 USA. RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Dept Pediat, 2015 Uppergate Dr, Atlanta, GA 30322 USA. FU NICHD NIH HHS [U10 HD27856, U01 HD19897, U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689] NR 51 TC 629 Z9 661 U1 6 U2 34 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 17 PY 2004 VL 292 IS 19 BP 2357 EP 2365 DI 10.1001/jama.292.19.2357 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 870PL UT WOS:000225070100024 PM 15547163 ER PT J AU Jacobs, ET Jiang, RY Alberts, DS Greenberg, ER Gunter, EW Karagas, MR Lanza, E Ratnasinghe, L Reid, ME Schatzkin, A Smith-Warner, SA Wallace, K Martinez, ME AF Jacobs, ET Jiang, RY Alberts, DS Greenberg, ER Gunter, EW Karagas, MR Lanza, E Ratnasinghe, L Reid, ME Schatzkin, A Smith-Warner, SA Wallace, K Martinez, ME TI Selenium and colorectal adenoma: Results of a pooled analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PREDIAGNOSTIC SERUM SELENIUM; NUTRITION EXAMINATION SURVEY; BASE-LINE CHARACTERISTICS; 3RD NATIONAL-HEALTH; CANCER PREVENTION; CLINICAL-TRIAL; RISK; SUPPLEMENTATION; MORTALITY; DESIGN AB Background: Secondary analyses of data from a large randomized clinical trial have suggested that intake of the trace element selenium reduces risk of colorectal neoplasia, but epidemiologic studies have not shown a consistent protective association. Methods: We conducted a combined analysis of data from three randomized trials-the Wheat Bran Fiber Trial, the Polyp Prevention Trial, and the Polyp Prevention Study-which tested the effects of various nutritional interventions for colorectal adenoma prevention among participants who recently had an adenoma removed during colonoscopy. Selenium concentrations were measured from blood specimens from a total of 1763 trial participants, and quartiles of baseline selenium were established from the pooled data. To estimate the association between baseline selenium and colorectal adenoma risk, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression modeling. All statistical tests were two-sided. Results: Individual study results among participants whose blood selenium concentrations were in the highest versus the lowest quartile varied in magnitude (Polyp Prevention Trial: OR = 0.67, 95 % CI = 0.43 to 1.05; P-trend =.21; Wheat Bran Fiber Trial: OR = 0.66,95% CI = 0.40 to 1.10; P-trend =.13, and Polyp Prevention Study: OR = 0.57, 95 % CI = 0.34 to 0.95, P-trend =.04). Analyses of the pooled data showed that individuals whose blood selenium values were in the highest quartile (median = 150 ng/mL) had statistically significantly lower odds of developing a new adenoma compared with those in the lowest quartile (OR = 0.66, 95% CI = 0.50 to 0.87; P-trend =.006). Conclusions: The inverse association between higher blood selenium concentration and adenoma risk supports previous findings indicating that higher selenium status may be related to decreased risk of colorectal cancer. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Arizona, Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NCI, Bethesda, MD 20892 USA. US FDA, Jefferson, AR USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Jacobs, ET (reprint author), Univ Arizona, Arizona Canc Ctr, POB 245024, Tucson, AZ 85724 USA. EM jacobse@u.arizona.edu FU NCI NIH HHS [CA-41108, CA-23074, CA-77145, CA95060] NR 33 TC 100 Z9 104 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 2004 VL 96 IS 22 BP 1669 EP 1675 DI 10.1093/jnci/djh310 PG 7 WC Oncology SC Oncology GA 870VA UT WOS:000225085500008 PM 15547179 ER PT J AU Feng, WH Cohen, JI Fischer, S Li, L Sneller, M Goldbach-Mansky, R Raab-Traub, N Delecluse, HJ Kenney, SC AF Feng, WH Cohen, JI Fischer, S Li, L Sneller, M Goldbach-Mansky, R Raab-Traub, N Delecluse, HJ Kenney, SC TI Reactivation of latent Epstein-Barr virus by methotrexate: A potential contributor to methotrexate-associated lymphomas SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; IMMEDIATE-EARLY GENE; RHEUMATOID-ARTHRITIS; TRANSCRIPTION FACTOR; INFECTED-CELLS; EBV INFECTION; LYTIC SWITCH; MEF2 FAMILY; BZLF1 GENE; ACTIVATION AB Background: Patients with rheumatoid arthritis or polymyositis treated with methotrexate (MTX) develop Epstein-Barr virus (EBV)-positive lymphomas more frequently than patients treated with other, equally immunosuppressive regimens. Here we determined whether MTX, in contrast to other commonly used medications for rheumatoid arthritis or polymyositis, is unique in its ability to induce the release of infectious EBV from latently infected cells. Methods: The effect of MTX and other immunosuppressant drugs on EBV replication in vitro was assessed using latently infected EBV-positive lymphoblastoid and gastric carcinoma cell lines. Inhibitors of signal transduction pathways were used to define requirements for induction of lytic infection. Drug effects on transcription of the two EBV immediate-early promoters (BRLF1 and BZLF1) and on promoter constructs lacking cis-acting sequences required for activation by other effectors was examined using reporter gene assays. EBV viral load in rheumatoid arthritis and polymyositis patients receiving MTX was compared with that in patients receiving other immunosuppressive medications. Statistical tests were two-sided. Results: MTX activated the release of infectious EBV from latently infected cell lines in vitro, and MTX treatment was associated with activation of the two viral immediate-early promoters in reporter gene assays. Induction of lytic EBV infection by MTX required the p38 MAP kinase, PI3 kinase, and MEK pathways and specific cisacting motifs in the two viral immediate-early promoters. Patients treated with MTX-containing regimens had statistically significantly higher mean EBV loads in their blood than patients treated with immunosuppressing regimens that did not include MTX (40 EBV copies per 10(6) cellular genomes versus 5.1 copies; geometric mean fold difference in copies = 10.8, 95%, confidence interval = 3.0 to 38; P =.011). Conclusion: MTX may promote EBV-positive lymphomas in rheumatoid arthritis and polymyositis patients by its immunosuppressive properties as well as by reactivating latent EBV. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIAID, Lab Clin Infect Dis, Bethesda, MD USA. NIAID, Immunoregulat Lab, Bethesda, MD USA. NIAMSD, Off Clin Director, Bethesda, MD USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. German Canc Res Ctr, Dept Virus Associated Tumors, D-6900 Heidelberg, Germany. Univ N Carolina, Dept Med & Microbiol, Chapel Hill, NC 27599 USA. RP Kenney, SC (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB7295, Chapel Hill, NC 27599 USA. EM shann@med.unc.edu OI Delecluse, Henri-Jacques/0000-0002-1744-6274 FU NCI NIH HHS [P01-CA19014, R01-CA 66519, R01-CA58853]; NHLBI NIH HHS [R01 HL 64851] NR 63 TC 129 Z9 131 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 2004 VL 96 IS 22 BP 1691 EP 1702 DI 10.1093/jnci/djh313 PG 12 WC Oncology SC Oncology GA 870VA UT WOS:000225085500011 PM 15547182 ER PT J AU Wacholder, S Chanock, S Garcia-Closas, M Katki, HA El Ghormli, L Rothman, N AF Wacholder, S Chanock, S Garcia-Closas, M Katki, HA El Ghormli, L Rothman, N TI Re: Assessing the probability that a positive report is false: An approach for molecular epidemiology studies - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID GENETIC ASSOCIATIONS C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Core Genotype Facil, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. RP Wacholder, S (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM wacholder@nih.gov RI Katki, Hormuzd/B-4003-2015; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 5 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 2004 VL 96 IS 22 BP 1722 EP 1723 DI 10.1093/jnci/djh327 PG 2 WC Oncology SC Oncology GA 870VA UT WOS:000225085500016 ER PT J AU Zhang, QJ Zulfiqar, F Riazuddin, SA Xiao, XS Ahmad, Z Riazuddin, S Hejtmancik, JF AF Zhang, QJ Zulfiqar, F Riazuddin, SA Xiao, XS Ahmad, Z Riazuddin, S Hejtmancik, JF TI Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation SO MOLECULAR VISION LA English DT Article ID NUCLEOTIDE-GATED CHANNELS; ALPHA-SUBUNIT; RETINAL DYSTROPHY; BETA-SUBUNIT; GENE; LOCUS; STOICHIOMETRY; PHOSPHODIESTERASE; HOMOLOG; PROTEIN AB Purpose: To map the locus for autosomal recessive retinitis pigmentosa in a large Pakistani family and to determine the causative mutation. Methods: A large family with multiple individuals affected by autosomal recessive retinitis pigmentosa was ascertained in the Punjab province of Pakistan as part of an ongoing project between the CEMB, Lahore, Pakistan and the NEI to identify genetic causes of eye diseases. After initial analysis of previously identified autosomal recessive retinitis pigmentosa loci, a genome wide scan was performed using microsatellite markers at about 10 cM intervals. Two point lod scores were calculated and haplotypes were analyzed in order to define disease locus. Bidirectional dideoxynucleotide sequencing was used to screen for mutations in candidate genes. Results: In the genome wide scan, autosomal recessive retinitis pigmentosa in this Pakistani family showed linkage to an 11.7 cM region of chromosome 4p12 between D4S405 and D4S1592 with a maximum lod score of 2.90 with D4S405 at theta=0.01 Sequence analysis of CNGA1 identified a 2 bp deletion in exon 8: c.626_627delTA resulting in a frameshift, p.Ser209fsX26 in the translated protein. This mutation results in deletion of the COOH terminal 482 of 690 total amino acids in CNGA1 and their replacement by 25 novel amino acids before a premature termination. The mutation is found in a homozygous state in all 7 affected individuals and was heterozygous in all 15 unaffected family members examined. The mutant allele of CNGA1 itself shows linkage to the disease with maximum lod score of 4.43 at theta=0. Conclusions: The autosomal recessive retinitis pigmentosa in this family is caused by a mutation in CNGA1 gene. To our knowledge, this is the first report in which both linkage analysis and identification of a mutation support CNGA1 as a cause for autosomal recessive retinitis pigmentosa. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. RP Hejtmancik, JF (reprint author), NEI, OGCSB, NIH, Bldg 10,Room 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov RI SHEIKH, RIAZUDDIN/L-2406-2015 NR 34 TC 11 Z9 12 U1 0 U2 3 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 17 PY 2004 VL 10 IS 105-7 BP 884 EP 889 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 875FT UT WOS:000225406400002 PM 15570217 ER PT J AU Zhang, QJ Guo, XM Xiao, XS Yi, JH Jia, XY Hejtmancik, JF AF Zhang, QJ Guo, XM Xiao, XS Yi, JH Jia, XY Hejtmancik, JF TI Clinical description and genome wide linkage study of Y-sutural cataract and myopia in a Chinese family SO MOLECULAR VISION LA English DT Article ID DOMINANT CONGENITAL CATARACT; POSTERIOR POLAR CATARACT; OCULAR AXIAL LENGTH; X-LINKED CATARACT; MISSENSE MUTATION; CRYSTALLIN GENE; TRANSCRIPTION FACTOR; FORM-DEPRIVATION; REFRACTIVE ERROR; JUVENILE-ONSET AB Purpose: To describe the clinical characteristics of a Y-sutural cataract associated with myopia in a large Chinese family and to identify the causative gene and mutation. Methods: An autosomal dominant Y-sutural cataract and myopia were identified in members of a large family of Han ethnicity living in southern China. Ophthalmological examinations were performed and a medical history was taken. Blood samples were collected for DNA isolation. A genome wide scan was performed using markers spaced at about 10 cM intervals for genotyping and two point linkage analysis. Candidate genes were sequenced. Results: Bilateral lens opacities, the only sign of cataract in early childhood and the most prominent sign in all affected individuals, involved the entire anterior Y and posterior inverted Y sutures, showing a feather duster like appearance. The Y-sutural cataract in this family mapped to an 11.4 cM (13.5 Mb) region between D3S3606 and D3S1309 on chromosome 3q22 with a maximum lod score of 5.7 at theta=0 for D3S1292. Sequence analysis of the beaded filament structural protein 2 (BFSP2) gene identified a previously described c.697_699delGAA (E233del) mutation which was present in all individuals with Y-sutural cataract but not in unaffected individuals and controls. Myopia, observed in 10 out of 12 cataract patients and significantly higher than that in unaffected offspring and siblings (1 out of 8), was independently mapped to a 61.2 cM (59 Mb) region between D3S3606 and D3S1262 on 3q21.3-q27.2 with maximum lod score of 3.79. Conclusions: This Y-sutural cataract is caused by an E233del mutation in BFSP2 which provides additional evidence supporting mutations in BFSP2 as a cause for cataract and demonstrates phenotypic variability in cataracts caused by BFSP2. The Y-sutural opacity in the lens might be the typical and earliest sign for cataract caused by the BFSP2 mutation. In addition, these results demonstrate a myopia susceptibility locus in this region, which might also be associated with the mutation in BFSP2. C1 Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China. NEI, Ophthalmic Genet & Visual Funct Branch, NIH, Bethesda, MD USA. RP Hejtmancik, JF (reprint author), NEI, OGCSB, NIH, Bldg 10,Room 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov NR 69 TC 35 Z9 38 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 17 PY 2004 VL 10 IS 105-7 BP 890 EP 900 PG 11 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 875FT UT WOS:000225406400003 PM 15570218 ER PT J AU Lightfoot, JT Turner, MJ Daves, M Vordermark, A Kleeberger, SR AF Lightfoot, JT Turner, MJ Daves, M Vordermark, A Kleeberger, SR TI Genetic influence on daily wheel running activity level SO PHYSIOLOGICAL GENOMICS LA English DT Article DE genetics; physical activity; mice; inbred strains; weight; sex ID IN-HOUSE MICE; ACCESSORY OLFACTORY-BULB; PHYSICAL-ACTIVITY; MUS-DOMESTICUS; VOLUNTARY ACTIVITY; LABORATORY MICE; HEART-RATE; EXERCISE; BEHAVIOR; SELECTION AB This project was designed to determine the genetic (between-strain) and environmental (within-strain) variance in daily running wheel activity level in inbred mice. Five male and five female mice, 9.7 - 15.3 wk old, from each of 13 strains (A/J, AKR/J, BALB/cJ, C3H/HeJ, C57Bl/6J, C57L/J, C3Heb/FeJ, CBA/J, DBA/2J, SWR/J, MRL/MpJ, SPRET/Ei, and CAST/Ei) as well as five female NZB/ BinJ mice were housed individually. A running wheel in each cage was interfaced with a magnetic sensor to measure total daily distance and exercise time for each animal every 24 h for 21 consecutive days ( 3 wk). Average daily distance ( km), duration (min), and velocity (m/min) for each strain was then calculated. Significant interstrain differences in average daily distance ( P < 0.001), average daily exercise duration ( P < 0.0001), and average daily exercise velocity ( P < 0.0001) were found, with C57L/J mice running farther and faster than the other strains. Sex was a significant factor in daily running wheel activity, with female mice running an average of 20% farther ( P = 0.01) and 38% faster ( P < 0.0001) than male mice. The male mice ran 15% longer duration on a daily basis ( P = 0.0091). Weight was only associated with exercise velocity in the female mice, but this relationship was not significant when subdivided by strain. Broadsense heritability estimates on the physical activity differed by sex ( for distance, male 31 - 48% and female 12 - 22%; for duration, male 44 - 61% and female 12 - 21%; for velocity, male 49 - 66% and female 44 - 61%). In conclusion, these data indicate that daily running wheel activity level in mice is significantly affected by genetic background and sex. C1 Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA. NIEHS, Lab Resp Biol, Durham, NC USA. RP Lightfoot, JT (reprint author), Univ N Carolina, Dept Kinesiol, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM jtlightf@email.uncc.edu FU NIA NIH HHS [AG-22417]; NIDDK NIH HHS [DK-61635] NR 44 TC 130 Z9 131 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD NOV 17 PY 2004 VL 19 IS 3 BP 270 EP 276 DI 10.1152/physiolgenomics.00125.2004 PG 7 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 881CK UT WOS:000225840800005 PM 15383638 ER PT J AU Feng, HQ Vu, ND Zhou, Z Bai, YW AF Feng, HQ Vu, ND Zhou, Z Bai, YW TI Structural examination of Phi-value analysis in protein folding SO BIOCHEMISTRY LA English DT Article ID STATE HYDROGEN-EXCHANGE; TRANSITION-STATE; CHYMOTRYPSIN INHIBITOR-2; BETA-SHEET; NUCLEATION; STABILITY; INTERMEDIATE; DYNAMICS; RESIDUES; MUTANT AB Protein folding intermediates and transition states are commonly characterized using a protein engineering procedure (Phi-value analysis) based on several assumptions, including (1) intermediates and transition states have native-like conformations and (2) single mutations from larger hydrophobic residues to smaller ones do not perturb their structures. Although Phi-value analysis has been widely used, these assumptions have not been tested to date because of the lack of high-resolution structures of intermediates and transition states. We recently have determined the structure of a folding intermediate for a four-helix bundle protein (Rd-apocytochrome b(562)) using NMR. The intermediate has the N-terminal helix unfolded. The other three helices fold in a native-like topology with extensive non-native hydrophobic interactions. Here, we have determined the Phi values for 14 hydrophobic core residues, including those with significant non-native interactions. All of the Phi values are in the normal range from 0 to 1, indicating that these non-native interactions cannot be identified by the common Phi-value analysis, and therefore, the first assumption is not valid for this intermediate. We also determined the structure of a mutant (F65A) of the intermediate and found that the structure of the intermediate is not perturbed by the mutation, supporting the second assumption. Together, these results suggest that Phi-value analysis may be valid for characterizing the energetics of the interactions between the mutated residue and others, but not for determining the detailed structures of intermediates and transition states because non-native interactions may exist and may not be identifiable by the common Phi-value analysis. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov NR 33 TC 21 Z9 21 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 16 PY 2004 VL 43 IS 45 BP 14325 EP 14331 DI 10.1021/bi048126m PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870YO UT WOS:000225095000002 PM 15533036 ER PT J AU Calado, RT Ly, H Yamaguchi, H Baerlocher, GM Kajigaya, S Chanock, SJ Lansdorp, PM Young, NS AF Calado, RT Ly, H Yamaguchi, H Baerlocher, GM Kajigaya, S Chanock, SJ Lansdorp, PM Young, NS TI Mutations in TERT, the gene encoding telomerase reverse transcriptase, in "acquired" aplastic anemia inhibit enzymatic function by a dominant negative mechanism of action. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Univ British Columbia, Terry Fox Lab, Vancouver, BC V5Z 1M9, Canada. NCI, NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3 BP 5A EP 5A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500006 ER PT J AU Gidvani, VK Ramkissoon, SH Wong, EW Mainwaring, L Sloand, EM Young, NS AF Gidvani, VK Ramkissoon, SH Wong, EW Mainwaring, L Sloand, EM Young, NS TI Tumor necrosis factor-alpha and interleukin-6 promoter gene Polymorphisms in acquired bone marrow failure syndromes. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Natl Capital Consortium, Walter Reed Army Med Ctr, Washington, DC USA. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2004 VL 104 IS 11 MA 3707 BP 12B EP 13B PN 2 PG 2 WC Hematology SC Hematology GA 871JO UT WOS:000225127700039 ER PT J AU Onyekwere, OC Kato, GJ Machado, R Coles, W Nichols, J Hunter, L Gladwin, MT Castro, OL AF Onyekwere, OC Kato, GJ Machado, R Coles, W Nichols, J Hunter, L Gladwin, MT Castro, OL TI Severe pulmonary hypertension in sickle cell patients with HIV infection. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC USA. NHLBI, Vasc Therapeut Sect, Bethesda, MD USA. Dept Crit Care Med, NIH, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3757 BP 25B EP 25B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700089 ER PT J AU Cronin, DP Harlan, LC Clegg, LX Stevens, JL Yuan, G Davis, TA AF Cronin, DP Harlan, LC Clegg, LX Stevens, JL Yuan, G Davis, TA TI Patterns of care in a random population-based sample of patients diagnosed with non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Surveillance Res Program, Bethesda, MD 20892 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Informat Management Syst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 85 BP 28A EP 28A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500088 ER PT J AU Davis, TA Clegg, LX Stevens, JL Harlan, LC AF Davis, TA Clegg, LX Stevens, JL Harlan, LC TI Patterns of care in a random population-based sample of patients diagnosed with CLL. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, CTEP, Bethesda, MD 20892 USA. NCI, SRP, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. NCI, ARP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 86 BP 28A EP 28A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500089 ER PT J AU Rao, VK Carrasquillo, JA Dale, JK Bacharach, S Whatley, M Dugan, F Tretler, J Jaffe, ES Wilson, W Avila, N Straus, SE AF Rao, VK Carrasquillo, JA Dale, JK Bacharach, S Whatley, M Dugan, F Tretler, J Jaffe, ES Wilson, W Avila, N Straus, SE TI Whole-body positron emission tomography (PET) using 2-(18)fluoro2-deoxy-D-glucose (FDG) for monitoring lymphadenopathy in autoimmune lymphoproliferative syndrome (ALPS). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIAID, LCID, NIH, Bethesda, MD 20892 USA. NIH, NMD, CC, Bethesda, MD 20892 USA. NCI, CCR, NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3850 BP 49B EP 50B PN 2 PG 2 WC Hematology SC Hematology GA 871JO UT WOS:000225127700182 ER PT J AU Wilson, WH Dunleavy, K Pittaluga, S Grant, N Steinberg, S Raffeld, M Chabner, B Grossbard, M Jaffe, E Staudt, L Janik, J AF Wilson, WH Dunleavy, K Pittaluga, S Grant, N Steinberg, S Raffeld, M Chabner, B Grossbard, M Jaffe, E Staudt, L Janik, J TI Dose-adjusted EPOCH-rituximab is highly effective in the GCB and ABC subtypes of untreated diffuse large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2004 VL 104 IS 11 MA 159 BP 49A EP 49A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500162 ER PT J AU Calado, RT Savage, SA Lansdorp, PM Chanock, SJ Young, NS AF Calado, RT Savage, SA Lansdorp, PM Chanock, SJ Young, NS TI Genes encoding telomere-binding proteins TERF1, TERF2 and TIN2 are mutated in patients with acquired aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. RI Calado, Rodrigo/G-2619-2011; Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 170 BP 53A EP 53A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500173 ER PT J AU Montero, A Kurlander, R Read, E Leitman, S Nlonda, N Young, N Childs, R Solomon, S Barrett, J AF Montero, A Kurlander, R Read, E Leitman, S Nlonda, N Young, N Childs, R Solomon, S Barrett, J TI Favorable impact of T cell depleted PBSCT on transplant outcomes despite delayed donor T cell engraftment. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 182 BP 56A EP 56A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500185 ER PT J AU Holada, K Brouckova, A Simak, J Gahl, WA Vostal, JG AF Holada, K Brouckova, A Simak, J Gahl, WA Vostal, JG TI Platelet cellular prion protein (PRPC) is associated with alpha granules. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Charles Univ, Fac Med 1, Inst Microbiol & Immunol, Prague, Czech Republic. US FDA, CBER, Div Hematol, Bethesda, MD 20014 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3882 BP 57B EP 57B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700214 ER EF