FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Potocnik, U Ferkolj, I Glavac, D Dean, M AF Potocnik, U Ferkolj, I Glavac, D Dean, M TI Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis SO GENES AND IMMUNITY LA English DT Article DE inflammatory bowel diseases; refractory Crohn's disease; P-glycoprotein function; ulcerative colitis; MDR1 polymorphisms; ABCB1; P-glycoprotein; haplotype structure ID INFLAMMATORY-BOWEL-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS; MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN; GLUCOCORTICOID RESISTANCE; FUNCTIONAL POLYMORPHISMS; TRANSPORTER GENE; DRUG-TRANSPORTER; SUSCEPTIBILITY; EXPRESSION AB We used coding and noncoding polymorphisms evenly spaced across the ABCB1/MDR1 gene to perform association analysis in Slovenian patients with inflammatory bowel diseases and to obtain haplotype structure and patterns of linkage disequilibrium (LD) in the MDR1 gene. A disease association study was performed in 307 IBD patients, including 144 patients with ulcerative colitis (UC) and 163 patients with Crohn's disease (CD), and 355 healthy controls. Here we report an association between MDR1 alleles, polymorphisms and haplotypes and refractory CD patients, who do not respond to standard therapy, including patients who develop fistulas. We also report an association with UC and MDR1 polymorphisms in a Slovenian population. Haplotypes significantly associated with diseases were defined by single-nucleotide polymorphisms (SNPs) in exons 12 (1236 C>A), 21(A893S), and 26 (3435 C>T). In addition, two intronic SNPs in LD with the disease haplotype, one in intron 13 (rs2235035) and another in intron 16 (rs1922242), were significantly associated with refractory Crohn (P=0.026, odds ratio (OR) 2.7 and P 0.025, OR 2.8, respectively), as well as with UC (P=0.006, OR 1.8 and P=0.026, OR 1.9, respectively). Our results suggest that MDR1 is a potential target for therapy in refractory CD patients and in patients with UC. C1 NCI, NIH, FCRDC, Lab Genom Divers, Ft Detrick, MD 21702 USA. Univ Ljubljana, Fac Med, Inst Pathol, Genet Mol Lab, Ljubljana, Slovenia. Univ Med Ctr, Div Internal Med, Dept Gastroenterol, Ljubljana, Slovenia. RP Dean, M (reprint author), NCI, NIH, FCRDC, Lab Genom Divers, Bld 560,Rm 21-18, Ft Detrick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Potocnik, Uros/0000-0003-1624-9428 NR 33 TC 116 Z9 122 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 NOV PY 2004 VL 5 IS 7 BP 530 EP 539 DI 10.1038/sj.gene.6364123 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 865VS UT WOS:000224732900002 PM 15505619 ER PT J AU Caretti, G Di Padova, M Micales, B Lyons, GE Sartorelli, V AF Caretti, G Di Padova, M Micales, B Lyons, GE Sartorelli, V TI The Polycomb EA2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation SO GENES & DEVELOPMENT LA English DT Article DE polycomb group; myogenesis; histone methylation; transcription ID SERUM RESPONSE FACTOR; H3 LYSINE-27 METHYLATION; CREATINE-KINASE GENE; GROUP PROTEIN EZH2; HISTONE H3; REPRESSOR COMPLEX; MOUSE DEVELOPMENT; BINDING PROTEIN; CARDIAC-MUSCLE; C-ELEGANS AB The Ezh2 protein endows the Polycomb PRC2 and PRC3 complexes with histone lysine methyltransferase (HKMT) activity that is associated with transcriptional repression. We report that Ezh2 expression was developmentally regulated in the myotome compartment of mouse somites and that its down-regulation coincided with activation of muscle gene expression and differentiation of satellite-cell-derived myoblasts. Increased Ezh2 expression inhibited muscle differentiation, and this property was conferred by its SET domain, required for the HKMT activity. in undifferentiated myoblasts, endogenous Ezh2 was associated with the transcriptional regulator YY1. Both EA2 and YY1 were detected, with the deacetylase HDAC1, at genomic regions of silent muscle-specific genes. Their presence correlated with methylation of K27 of histone H3. YY1 was required for Ezh2 binding because RNA interference of YY1 abrogated chromatin recruitment of Ezh2 and prevented H3-K27 methylation. Upon gene activation, Ezh2, HDAC1, and YY1 dissociated from muscle loci, H3-K27 became hypomethylated and MyoD and SRF were recruited to the chromatin. These findings suggest the existence of a two-step activation mechanism whereby removal of H3-K27 methylation, conferred by an active Ezh2-containing protein complex, followed by recruitment of positive transcriptional regulators at discrete genomic loci are required to promote muscle gene expression and cell differentiation. C1 NIAMS, Muscle Gene Express Grp, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med, Dept Anat, Madison, WI 53706 USA. RP Sartorelli, V (reprint author), NIAMS, Muscle Gene Express Grp, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. EM sartorev@mail.nih.gov OI DI PADOVA, Monica/0000-0003-3808-7159 NR 69 TC 357 Z9 367 U1 0 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2004 VL 18 IS 21 BP 2627 EP 2638 DI 10.1101/gad.1241904 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 867YM UT WOS:000224878900007 PM 15520282 ER PT J AU Nossal, NG Franklin, JL Kutter, E Drake, JW AF Nossal, NG Franklin, JL Kutter, E Drake, JW TI Gisela Mosig SO GENETICS LA English DT Editorial Material ID DNA-BINDING-PROTEIN; BACTERIOPHAGE T4; CHLAMYDOMONAS-REINHARDTII; GENETIC RECOMBINATION; MULTIPLE INTERACTIONS; CHROMOSOME STRUCTURE; COORDINATE VARIATION; REPLICATION FORKS; CHLOROPLAST DNA; GENE-32 PROTEIN C1 NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Dev & Cell Biol, Nashville, TN 37235 USA. Evergreen State Coll, Olympia, WA 98505 USA. RP Drake, JW (reprint author), NIEHS, Genet Mol Lab, NIH, Room E344,111 S Alexander Dr, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov NR 60 TC 0 Z9 0 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2004 VL 168 IS 3 BP 1097 EP 1104 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 880CU UT WOS:000225767400001 PM 15579671 ER PT J AU Schlecht, HB Lichten, M Goldman, ASH AF Schlecht, HB Lichten, M Goldman, ASH TI Compartmentalization of the yeast meiotic nucleus revealed by analysis of ectopic recombination SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; BOUQUET FORMATION; DROSOPHILA-MELANOGASTER; HOMOLOG JUXTAPOSITION; CHROMOSOME SYNAPSIS; CHROMATIN-STRUCTURE; GENE CONVERSION; FISSION YEAST AB As yeast cells enter meiosis, chromosomes move from a centromere-clustered (Rabl) to a telomere-clustered (bouquet) configuration and then to states of progressive homolog pairing where telomeres are more dispersed. It is uncertain at which stage of this process sequences commit to recombine with each other. Previous analyses using recombination between dispersed homologous sequences (ectopic recombination) support the view that, on average, homologs are aligned end to end by the time of commitment to recombination. We have undertaken further analyses incorporating new inserts, chromosome rearrangements, an alternate mode of recombination initiation, and mutants that disrupt nuclear structure or telomere metabolism. Our findings support previous conclusions and reveal that distance from the nearest telomere is an important parameter influencing recombination between dispersed sequences. In general, the farther dispersed sequences are from their nearest telomere, the less likely they are to engage in ectopic recombination. Neither the mode of initiating recombination nor the formation of the bouquet appears to affect this relationship. We suggest that aspects of telomere localization and behavior influence the organization and mobility of chromosomes along their entire length, during a critical period of meiosis I prophase that encompasses the homology search. C1 Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. NIH, Biochem Lab, Bethesda, MD 20892 USA. RP Goldman, ASH (reprint author), Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. EM a.goldman@shef.ac.uk RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 56 TC 27 Z9 29 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2004 VL 168 IS 3 BP 1189 EP 1203 DI 10.1534/genetics.104.029157 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 880CU UT WOS:000225767400009 PM 15579679 ER PT J AU Mason, JM Ransom, J Konev, AY AF Mason, JM Ransom, J Konev, AY TI A deficiency screen for dominant suppressors of telomeric silencing in Drosophila SO GENETICS LA English DT Article ID POSITION-EFFECT VARIEGATION; HETEROCHROMATIN PROTEIN-1; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; P-ELEMENT; CHROMATIN-STRUCTURE; TRYPANOSOMA-BRUCEI; CHROMOSOME ENDS; MELANOGASTER; ORGANIZATION AB Heterochromatin is a specialized chromatin structure in chromosomal regions associated with repeated DNA sequences and low concentrations of genes. Formation of heterochromatin is determined in large part by enzymes that modify histories and structural proteins that bind to these modified histones in a cooperative fashion. In Drosophila, mutations in genes that encode heterochromatic proteins are often dominant and increase expression of genes placed into heterochromatic positions. To find components of telomeric heterochromatin in Drosophila, we screened a collection of autosomal deficiencies for dominant suppressors of silencing of a transgene at the telomere of chromosome 2L. While many deficiency chromosomes are associated with dominant suppressors, in the cases tested on chromosome 2 the suppressor mapped to the 2L telomere, rather than the deficiency. We infer that background effects may hamper the search for genes that play a role in telomeric heterochromatin formation and that either very few genes participate in this pathway or mutations in these genes are not dominant suppressors of telomeric position effect. The data also suggest that the 2L telomere region plays a major role in telomeric silencing. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Mason, JM (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RI Konev, Alexander/J-4401-2015 OI Konev, Alexander/0000-0002-4497-6377 NR 52 TC 20 Z9 20 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2004 VL 168 IS 3 BP 1353 EP 1370 DI 10.1534/genetics.104.030676 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 880CU UT WOS:000225767400020 PM 15579690 ER PT J AU Sarin, S Ross, KE Boucher, L Green, Y Tyers, M Cohen-Fix, O AF Sarin, S Ross, KE Boucher, L Green, Y Tyers, M Cohen-Fix, O TI Uncovering novel cell cycle players through the inactivation of securin in budding yeast SO GENETICS LA English DT Article ID DNA-DAMAGE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; GENETIC-ANALYSIS; PHOSPHORYLATION; ANAPHASE; PDS1; UBIQUITINATION; LOCALIZATION; STABILITY; PATHWAYS AB Budding yeast securin/Pds1p, an inhibitor of the anaphase activator separase/Esp1p, is involved in several checkpoint pathways and in promoting Esp1p's nuclear localization. Using a modified synthetic genetic array (SGA) screen for genes that become essential in the absence of Pds1p, we uncovered roles for uncharacterized genes in cell cycle processes, including Esp1p activation. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5G 1X5, Canada. RP Cohen-Fix, O (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, 8 Ctr Dr,Bldg 8,Room 319, Bethesda, MD 20892 USA. NR 26 TC 19 Z9 20 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2004 VL 168 IS 3 BP 1763 EP 1771 DI 10.1534/genetics.104.029033 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 880CU UT WOS:000225767400052 PM 15579722 ER PT J AU Kimonis, VE Mehta, SG DiGiovanna, JJ Bale, SJ Pastakia, B AF Kimonis, VE Mehta, SG DiGiovanna, JJ Bale, SJ Pastakia, B TI Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome SO GENETICS IN MEDICINE LA English DT Article DE Gorlin syndrome; nevoid basal cell carcinoma syndrome; PTCH1; radiological features ID HUMAN HOMOLOG; AFFECTED INDIVIDUALS; SKELETAL ANOMALIES; CLINICAL FINDINGS; NEVUS SYNDROME; JAW CYSTS; MUTATIONS; MANIFESTATIONS; GENE AB Purpose: Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. NBCCS is due to mutations in PTCH1, the human homologue of the Drosophila segment polarity gene patched. Mutations are detected in approximately 60% to 85% of individuals tested by sequencing of PTCH1; therefore, clinical examination and x-rays remain important in diagnosis of NBCCS. Methods: We studied 82 NBCCS patients and 38 of their unaffected siblings at the NIH between 1985 and 1994. Chest, rib, spine, skull, hand and foot x-rays, brain MRI or CT, and pelvic ultrasound (in females) were obtained in the affected individuals and compared to their unaffected relatives. Results: The following features were significantly more frequent in those with NBCCS: calcification of the falx cerebri, the most frequent radiological feature, was present in 79% of patients > 20 years and in 37% <20 years, calcification of the tentorium cerebellum was present in 20%, bridging of the sella in 68%, and abnormal frontal sinus aeration in 18% of affected individuals. Bifid ribs most often involving the third, fourth, and fifth ribs were seen in 26%; splayed, fused, and misshapen ribs in a further 16%, and widened ends of clavicles in 12%. Spine X-rays revealed calcification of the nuchal ligament in 18%, fusion of vertebrae in 10%, and hemivertebrae in 15%. Flame-shaped lucencies of the metacarpals and/or phalanges were present in 30%, modeling deformities of the phalanges in 14%, and polydactyly of the feet in 4%. The frequency of scoliosis, cervical ribs, absent or rudimentary ribs, spina bifida occulta, or short 4th metacarpal was not higher in the affected individuals as compared to their unaffected relatives. Except for falx calcification, the frequency of radiological manifestations was similar in different age groups. Cranial CT or MRI in 42 affected individuals revealed asymmetric or dilated ventricles in 24%, cerebral atrophy in 10%, cavum septum pellucidum in 19%, dysgenesis or agenesis of the corpus callosum in 10%, and meningioma in 5%. Ovarian fibromas were detected in 17% of females. Conclusions: This study reports the varied radiological manifestations of NBCCS. In the absence of major features such as basal cell carcinomas, jaw cysts, or falx calcification, which is often not evident until the teen years, other radiological manifestations of the disorder can permit early diagnosis of NBCCS in childhood. This will allow optimum surveillance for medulloblastoma and other neoplasms (cardiac fibromas and basal cell carcinomas) associated with NBCCS. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. NIAMS, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD USA. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Dept Dermatol, Dermatopharmacol Div, Providence, RI 02912 USA. RP Kimonis, VE (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Clin Genet & Metab, 300 Longwood Ave,Fegan 10, Boston, MA 02115 USA. NR 31 TC 60 Z9 61 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 2004 VL 6 IS 6 BP 495 EP 502 DI 10.1097/01.GIM.0000145045.17711.1C PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 872BE UT WOS:000225180000006 PM 15545745 ER PT J AU Apse, KA Biesecker, BB Giardiello, FM Fuller, BP Bernhardt, BA AF Apse, KA Biesecker, BB Giardiello, FM Fuller, BP Bernhardt, BA TI Perceptions of genetic discrimination among at-risk relatives of colorectal cancer patients SO GENETICS IN MEDICINE LA English DT Article DE genetic discrimination; genetic testing; legislation; media; colorectal cancer ID HUNTINGTONS-DISEASE; HEALTH INSURERS; SUSCEPTIBILITY; ATTITUDES; INFORMATION; POPULATION; INSURANCE; FEAR; LAWS AB Purpose: To explore the concerns of at-risk relatives of colorectal cancer patients about genetic discrimination and their awareness of current legislative protections. Methods: A questionnaire was sent to unaffected individuals with a family history of colorectal cancer who had enrolled in the Johns Hopkins Hereditary Colorectal Cancer Registry (N = 777). Results: Of the 470 respondents, approximately half rated their level of concern about genetic discrimination as high. The majority of respondents, 79%, learned about genetic discrimination from at least one media source (television, newspapers, magazines, and radio). If they were to pursue genetic testing, respondents with a higher level of concern about genetic discrimination would be significantly more likely to pay out of pocket, use an alias, or ask for test results to be excluded from their medical record. Awareness and understanding of legislation regarding genetic discrimination was found to be minimal. Conclusion: Findings from this study demonstrate the negative effect of concerns about genetic discrimination on decisions about utilization of genetic services. Stronger legislative protections against genetic discrimination and increased public education through the scientific community and media sources are needed. C1 Beth Israel Deaconess Med Ctr, Div Neurogenet, Boston, MA 02215 USA. NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA. NHGRI, Policy & Program Anal Branch, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Div Med Genet, Philadelphia, PA 19104 USA. RP Apse, KA (reprint author), 77 Ave Louis Pasteur,NRB-266, Boston, MA 02115 USA. EM kapse@bidmc.harvard.edu FU NHGRI NIH HHS [02-HG-0163] NR 22 TC 48 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 2004 VL 6 IS 6 BP 510 EP 516 DI 10.1097/01.GIM.0000144013.96456.6C PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 872BE UT WOS:000225180000008 PM 15545747 ER PT J AU Blakesley, RW Hansen, NF Mullikin, JC Thomas, PJ McDowell, JC Maskeri, B Young, AC Benjamin, B Brooks, SY Coleman, BI Gupta, J Ho, SL Karlins, EM Maduro, QL Stantripop, S Tsurgeon, C Vogt, JL Walker, MA Masiello, CA Guan, XB Bouffared, GG Green, ED AF Blakesley, RW Hansen, NF Mullikin, JC Thomas, PJ McDowell, JC Maskeri, B Young, AC Benjamin, B Brooks, SY Coleman, BI Gupta, J Ho, SL Karlins, EM Maduro, QL Stantripop, S Tsurgeon, C Vogt, JL Walker, MA Masiello, CA Guan, XB Bouffared, GG Green, ED CA NISC Comparative Sequencing TI An intermediate grade of finished genomic sequence suitable for comparative analyses SO GENOME RESEARCH LA English DT Article ID SEGMENTAL DUPLICATIONS; ESCHERICHIA-COLI; DNA-SEQUENCES; MOUSE; INSIGHTS; REGIONS; ANNOTATION; PREDICTION; DATABASES; QUALITY AB Although the cost of generating draft-quality genomic sequence continues to decline, refining that sequence by the process of "sequence finishing" remains expensive. Near-perfect finished sequence is an appropriate goal for the human genome and a small set of reference genomes; however, such a high-quality product cannot be cost-justified for large numbers of additional genomes, at least for the foreseeable future. Here we describe the generation and quality of an intermediate grade of finished genomic sequence (termed comparative-grade finished sequence), which is tailored for use in multispecies sequence comparisons. Our analyses indicate that this sequence is very high quality (with the residual gaps and errors mostly falling within repetitive elements) and reflects 99% of the total sequence. Importantly, cornparative-grade sequence finishing requires similar to40-fold less reagents and similar to10-fold less personnel effort compared to the generation of near-perfect finished sequence, such as that produced for the human genome. Although applied here to finishing sequence derived from individual bacterial artificial chromosome (BAC) clones, one could envision establishing routines for refining sequences emanating from whole-genome shotgun sequencing projects to a similar quality level. Our experience to date demonstrates that comparative-grade sequence finishing represents a practical and affordable option for sequence refinement en route to comparative analyses. C1 NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov NR 50 TC 58 Z9 58 U1 0 U2 0 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 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2004 VL 14 IS 11 BP 2235 EP 2244 DI 10.1101/gr.2648404 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 868LC UT WOS:000224914100003 PM 15479945 ER PT J AU Mortlock, DP Portnoy, ME Chandler, RL Green, ED AF Mortlock, DP Portnoy, ME Chandler, RL Green, ED CA NISC Comparative Sequencing Progra TI Comparative sequence analysis of the Gdf6 locus reveals a duplicon-mediated chromosomal rearrangement in rodents and rapidly diverging coding and regulatory sequences SO GENOMICS LA English DT Article DE duplications; synteny; Gdf6; enhancer elements; gene rearrangement; bacterial artificial chromosome ID GENOMIC DNA-SEQUENCES; SEGMENTAL DUPLICATIONS; MOUSE GENOME; GENE; MUTATIONS; REGION; EXPRESSION; EVOLUTION; HYBRIDIZATION; ALIGNMENTS AB Duplicated segments of genomic DNA can catalyze both gene evolution and chromosome evolution. Here we describe a rodent-specific duplication involving the Uqcrb gene, a cis-regulatory element for the Gqf6 gene, and a chromosomal rearrangement. Comparisons of Gdf6 sequences from several placental mammals and platypus revealed many strongly conserved regions flanking Gqf6 and the adjacent Uqcrb gene. However, in rat and mouse a synteny break resides approximately 70 kb upstream of Gdf6, such that Gdf6 and Uqcrb are on separate chromosomes. In rodents, Gdf6 and Uqcrb are both associated with homologous duplicons that may have catalyzed a rearrangement separating the two genes. However, the duplicon spanned both Uqcrb and a cis-regulatory element that controls Gdf6 transcription in limb skeletal joints. In mouse and rat, one duplicon now contains a degrading Uqcrb pseudogene but retains strongly conserved sequences within a Gdf6 enhancer. In contrast, the other duplicon has retained the intact Uqcrb gene and (in mouse) a copy of the Gdf6 enhancer that has acquired novel mutations. The duplicons have separately maintained distinct functions of the ancestral sequence, consistent with a "subfunction partitioning" evolutionary model. These findings also provide an example of a duplication that mobilized a tissue-specific enhancer from its cognate gene, and new evidence that duplications can be associated with chromosomal rearrangements. Furthermore, these data suggest that segmental duplications could lead to evolution of novel gene expression patterns via diversification of regulatory elements. (C) 2004 Published by Elsevier Inc. C1 Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD USA. RP Mortlock, DP (reprint author), Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Dept Mol Physiol & Biophys, 519 Light Hall, Nashville, TN 37232 USA. EM mortlock@chgr.mc.vanderbilt.edu RI Mortlock, Douglas/C-9981-2010; Morlock, Doug/C-3482-2012 NR 44 TC 8 Z9 8 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 NOV PY 2004 VL 84 IS 5 BP 814 EP 823 DI 10.1016/j.ygeno.2004.07.009 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 865TD UT WOS:000224724900005 PM 15475260 ER PT J AU Hagan, JP Kozlov, SV Chiang, YS Sewell, L Stewart, CL AF Hagan, JP Kozlov, SV Chiang, YS Sewell, L Stewart, CL TI Intraspecific mating with CzechII/Ei mice rescue lethality associated with loss of function mutations of the imprinted genes, Igf2r and Cdkn1c SO GENOMICS LA English DT Article DE genomic imprinting; genetically modified animals; genetic crosses; polymorphisms; Beckwith-Wiedemann syndrome; Cdkn1c; Igf2r ID BECKWITH-WIEDEMANN-SYNDROME; MANNOSE 6-PHOSPHATE RECEPTOR; TUMOR-SUPPRESSOR GENE; FACTOR-II RECEPTOR; PERINATAL LETHALITY; MOUSE DEVELOPMENT; HAIRPIN-TAIL; TME LOCUS; P57(KIP2); GROWTH AB Maternal inheritance of targeted loss of function alleles encoding either the eye] in-dependent kinase inhibitor I C (Cdkn 1c) or the insulin-like growth factor 2 receptor (Igf2r) leads to fully penetrant perinatal lethality in C57BL/6J mice due to genomic imprinting. Here, we demonstrate that there is a marked enhancement in posmatal viability of F-1 mice carrying either the ablated Igf2r (-32%) or Cdkn1c (-83%) when the paternal genome was derived from the inbred Mus musculus muscidus CzechII/Ei strain. Genetic and molecular analyses indicated that the increased viability was not caused by relaxation of imprinted gene expression, but is the consequence of unidentified polygenic modifiers that are not imprinted. In the course of this study, restriction-site polymorphisms between 129S1 and CzechII/Ei in 21 imprinted and 14 biallelically expressed genes were identified. These polymorphisms may prove useful in determining the effects of different mutant backgrounds on genomic imprinting. Published by Elsevier Inc. C1 NCI FCRDC, Ctr Canc Res, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. RP Stewart, CL (reprint author), NCI FCRDC, Ctr Canc Res, Canc & Dev Biol Lab, NIH, POB B, Frederick, MD 21702 USA. EM stewartc@mail.ncifcrf.gov OI Hagan, John/0000-0003-0295-4898 NR 37 TC 2 Z9 2 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 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 2004 VL 84 IS 5 BP 836 EP 843 DI 10.1016/j.ygeno.2004.07.007 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 865TD UT WOS:000224724900007 PM 15475262 ER PT J AU Ramakrishnan, B Ramasamy, V Qasba, PK AF Ramakrishnan, B Ramasamy, V Qasba, PK TI Snapshots of the catalytic cycle of beta-1,4-galactosyltransferase-1 SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NCI, Struct Glycobiol Sect, LECB, CCR, Frederick, MD 21702 USA. SAIC Frederic Inc, BRP, Frederick, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 77 BP 1075 EP 1075 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400085 ER PT J AU Pozsgay, V Kubler-Kielb, J Coxon, B Ben-Menachem, G Schneerson, R AF Pozsgay, V Kubler-Kielb, J Coxon, B Ben-Menachem, G Schneerson, R TI Synthesis of major glycolipid antigens of Borrelia burgdorferi for use in conjugate vaccines against Lyme disease SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 116 BP 1087 EP 1087 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400124 ER PT J AU Kim, EJ Hanover, JA AF Kim, EJ Hanover, JA TI A novel 'cased' fluorogenic substrate for O-GlcNAcase and its variant SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 134 BP 1092 EP 1092 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400142 ER PT J AU Moon, AF Edavettal, SC Krahn, JM Munoz, EM Negishi, M Linhardt, RJ Liu, J Pedersen, LC AF Moon, AF Edavettal, SC Krahn, JM Munoz, EM Negishi, M Linhardt, RJ Liu, J Pedersen, LC TI Structural analysis of the sulfotransferase (3-OST-3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1 SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, Chapel Hill, NC 27599 USA. Rensselaer Polytech Inst, Dept Chem & Chem Biol, Troy, NY 12180 USA. NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 180 BP 1104 EP 1105 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400188 ER PT J AU Ramasamy, V Boeggeman, EE Ramakrishnan, B Ratner, DM Seeberger, PH Qasba, PK AF Ramasamy, V Boeggeman, EE Ramakrishnan, B Ratner, DM Seeberger, PH Qasba, PK TI Oligosaccharide preferences of beta 1,4-galactosyltransferase-1: Crystal structures and enzyme kinetics of the Met344His mutant of human beta 1,4-galactosyltransferase-I with the trisaccharides of N-glycan moiety SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NCI, Struct Glycobiol Sect, LECB, CCR, Frederick, MD 21702 USA. SAIC, BRP, Frederick, MD 21702 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. ETH Honggerberg, Organ Chem Lab, CH-8093 Zurich, Switzerland. NR 0 TC 1 Z9 1 U1 4 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 183 BP 1105 EP 1106 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400191 ER PT J AU Ramakrishnan, B Qasba, PK AF Ramakrishnan, B Qasba, PK TI A hypothesis on the evolutionary relationship between vertebrate and invertebrate beta-1,4-galactosyl- and N-acetylgalactosaminyl-transferases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NCI Frederick, Struct Glycobiol Sect, LECB, CCR, Frederick, MD 21702 USA. SAIC Frederick Inc, BRP, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 230 BP 1119 EP 1119 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400238 ER PT J AU Hayakawa, T Angata, T Margulies, EH Mikkelsen, T Green, ED Varki, A AF Hayakawa, T Angata, T Margulies, EH Mikkelsen, T Green, ED Varki, A TI Sialic acid binding specificity of CD33-Related Siglecs can be changed via partial gene conversion by adjacent pseudogenes SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 Univ Calif San Diego, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki, Japan. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 300 BP 1138 EP 1138 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400308 ER PT J AU Huizing, M Sparks, S Savelkoul, P Gottlieb, E Ciccone, C Sun, MS Darvish, D Naiem, S Rakocevic, G Dalakas, M Krasnewich, D Gahl, W AF Huizing, M Sparks, S Savelkoul, P Gottlieb, E Ciccone, C Sun, MS Darvish, D Naiem, S Rakocevic, G Dalakas, M Krasnewich, D Gahl, W TI Evaluation of the underlying defects causing the muscle destruction in hereditary inclusion body myopathy SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. HIBM, Res Grp, Encino, CA USA. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 394 BP 1163 EP 1164 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400402 ER PT J AU Sparks, SE Ciccone, C Lalor, M Orvisky, E Krasnewich, D Sun, MS Gahl, WA Huizing, M AF Sparks, SE Ciccone, C Lalor, M Orvisky, E Krasnewich, D Sun, MS Gahl, WA Huizing, M TI In vitro and fibroblast culture measurements of UDf-GlcNAc 2-epimerase/ManNAc kinase activity in hereditary inclusion body myopathy SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NHGRI, Sect Human Biochem Genet, MGB, NIH, Bethesda, MD 20892 USA. NIMH, NSB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 422 BP 1171 EP 1172 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400430 ER PT J AU Nguyen, DH Tangvoranuntakul, P Varki, A AF Nguyen, DH Tangvoranuntakul, P Varki, A TI Incorporation of the non-human sialic acid Neu5Gc into human leukemic cells and targeting by natural human anti-Neu5Gc SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NHGRI, Sect Human Biochem Genet, MGB, NIH, Bethesda, MD 20892 USA. NIMH, NSB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 423 BP 1172 EP 1172 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400431 ER PT J AU Dubey, H Ramakrishnan, B Boeggeman, E Qasba, PK AF Dubey, H Ramakrishnan, B Boeggeman, E Qasba, PK TI Stem sequence at the N-terminal region of B-1,4-galactosyltransferase T5 and T6 increases the folding efficiencies of their respective catalytic domains by step-wise or single step folding method SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology/Japanese-Society-for-Carbohydrate-Research CY NOV 17-20, 2004 CL Honolulu, HI SP Soc Gylcobiol, Japanese Soc Carbohydrate Res C1 NCI, Intramural Res Support Program SAIC, Lab Expt & Computat Biol, Ctr Canc Res,NIH, Frederick, MD 21702 USA. NCI, Struct Glycobiol Sect, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2004 VL 14 IS 11 MA 492 BP 1192 EP 1192 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 858QI UT WOS:000224206400500 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Living wills: Are durable powers of attorney better? SO HASTINGS CENTER REPORT LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD NOV-DEC PY 2004 VL 34 IS 6 BP 5 EP 6 DI 10.2307/3528166 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 884FU UT WOS:000226071000010 PM 15666885 ER PT J AU Miller, M AF Miller, M TI Policy analysis of the use of Hepatitis B, Hemophilus influenzae type B, Streptococcus pneumoniae-conjugate and Rotavirus vaccines in the National Immunization Schedules. Reply SO HEALTH ECONOMICS LA English DT Letter C1 NIH, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA. RP Miller, M (reprint author), NIH, Div Int Epidemiol & Populat Studies, Bldg 10, Bethesda, MD 20892 USA. EM millemar@mail.nih.gov NR 5 TC 1 Z9 1 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD NOV PY 2004 VL 13 IS 11 BP 1147 EP 1148 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 870DX UT WOS:000225035300008 ER PT J AU Simons-Morton, B Chen, RS Abroms, L Haynie, DL AF Simons-Morton, B Chen, RS Abroms, L Haynie, DL TI Latent growth curve analyses of peer and parent influences on smoking progression among early adolescents SO HEALTH PSYCHOLOGY LA English DT Article DE structural equation modeling; substance use; social influences; smoking stages ID CIGARETTE-SMOKING; SUBSTANCE USE; UNITED-STATES; DRUG-USE; INITIATION; SELECTION; PREDICTORS; FRAMEWORK; ADULTHOOD; DRINKING AB Social influences on smoking uptake were examined in latent growth curve analyses of data from 1,320 youths assessed 5 times during 6th to 9th grade. Initial smoking stage predicted increases in number of friends who smoked, indicating selection; however, initial number of friends who smoked did not predict smoking stage progression, indicating no significant effect of socialization. Associations over time among smoking stage progression, affiliation with friends who smoke, and parenting behaviors were significant, suggesting dynamic, reciprocal relationships. Parental involvement, monitoring, and expectations provided direct protective effects against smoking progression as well as indirect effects, by limiting increases in number of friends who smoke. These results are consistent with the peer selection hypothesis, confirm the powerful association over time of social influences with smoking, and provide the first evidence that parenting behavior may protect against smoking progression by limiting increases in number of friends who smoke. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Ctr New Designs Learning & Scholarship, Washington, DC 20057 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg Room 7B13,MSC 7510, Bethesda, MD 20892 USA. EM mortonb@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 43 TC 80 Z9 82 U1 3 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2004 VL 23 IS 6 BP 612 EP 621 DI 10.1037/0278-6133.23.6.612 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 868KZ UT WOS:000224913800007 PM 15546229 ER PT J AU Neumann, SA Waldstein, SR Sollers, JJ Thayer, JF Sorkin, JD AF Neumann, SA Waldstein, SR Sollers, JJ Thayer, JF Sorkin, JD TI Hostility and distraction have differential influences on cardiovascular recovery from anger recall in women SO HEALTH PSYCHOLOGY LA English DT Article DE hostility; distraction; cardiovascular reactivity; poststress recovery; impedance cardiography; heart rate variability ID WESTERN-COLLABORATIVE-GROUP; BLOOD-PRESSURE RESPONSES; HEART-RATE-VARIABILITY; MEDLEY HO SCALE; MYOCARDIAL-INFARCTION; PSYCHOLOGICAL STRESS; ARTERY DISEASE; YOUNG-ADULTS; TEST BATTERY; RISK-FACTOR AB This study investigated the relation of dispositional hostility to cardiovascular reactivity during an anger-recall task and of hostility and distraction to posttask recovery in 80 healthy women (ages 18-30). Half were randomly assigned to distraction during recovery. Hostility predicted slower systolic blood pressure and preejection period during recovery. Distraction was related to faster cardiac recovery, higher high-frequency (HF) power, lower low-frequency (LF) power and LF:HF ratios, and lower state anger and rumination during recovery. These results indicate deleterious influences of hostility on cardiovascular recovery but not during anger recall. The findings also show beneficial effects of distraction in expediting cardiovascular recovery, possibly through reducing rumination and anger. C1 Univ Maryland, Dept Psychol, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD USA. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. RP Neumann, SA (reprint author), Univ Pittsburgh, Dept Psychol, Behav Physiol Lab, 4015 O Hara St,506 OEH, Pittsburgh, PA 15260 USA. EM neumannsa@msx.upmc.edu; waldstei@umbc.edu FU NIA NIH HHS [AG15112] NR 70 TC 45 Z9 46 U1 3 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2004 VL 23 IS 6 BP 631 EP 640 DI 10.1037/0278-6133.23.6.631 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 868KZ UT WOS:000224913800009 PM 15546231 ER PT J AU Oe, S Lemmer, ER Conner, EA Factor, VM Leveen, P Larsson, J Karlsson, S Thorgeirsson, SS AF Oe, S Lemmer, ER Conner, EA Factor, VM Leveen, P Larsson, J Karlsson, S Thorgeirsson, SS TI Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice SO HEPATOLOGY LA English DT Article ID RAT HEPATOCYTES; PRIMARY CULTURE; PARTIAL-HEPATECTOMY; TRANSGENIC MICE; CRE RECOMBINASE; DNA-SYNTHESIS; FOLLISTATIN; EXPRESSION; GENE; FACTOR-BETA-1 AB Transforming growth factor beta (TGF-beta) is a potent inhibitor of hepatocyte proliferation in vitro and is suggested to be a key negative regulator of liver growth. To directly address the role of TGF-beta signaling in liver regeneration in vivo, the TGF-beta type II receptor gene (Tgfbr2) was selectively deleted in hepatocytes by crossing "floxed" Tgfbr2 conditional knockout mice with transgenic mice expressing Cre under control of the albumin promoter. Hepatocytes isolated from liver-specific Tgfbr2 knockout (R2LivKO) mice were refractory to the growth inhibitory effects of TGF-beta1. The peak of DNA synthesis after 70% partial hepatectomy occurred earlier (36 vs. 48 hours) and was 1.7-fold higher in R2LivKO mice compared with controls. Accelerated S-phase entry by proliferating R2LivKO hepatocytes coincided with the hyperphosphorylation of Rb protein and the early upregulation of cyclin D1 and cyclin E. However, by 120 hours after partial hepatectomy, hepatocyte proliferation was back to baseline in both control and R2LivKO liver. Regenerating R2LivKO liver showed evidence of increased signaling by activin A and persistent activity of the Smad pathway. Blockage of activin A signaling by the specific inhibitor follistatin resulted in increased hepatocyte proliferation at 120 hours, particularly in R2LivKO livers. In conclusion, TGF-beta regulates G(1) to S phase transition of hepatocytes, but intact signaling by TGF-beta is not required for termination of liver regeneration. Increased signaling by activin A may compensate to regulate liver regeneration when signaling through the TGF-beta pathway is abolished, and may be a principal factor in the termination of liver regeneration. C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Lund Hosp, S-22185 Lund, Sweden. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 33 TC 65 Z9 71 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2004 VL 40 IS 5 BP 1098 EP 1105 DI 10.1002/hep.20426 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870HZ UT WOS:000225049500010 PM 15389868 ER PT J AU Rahman, F Heller, T Rehermann, B AF Rahman, F Heller, T Rehermann, B TI Immune system homeostasis during acute hepatitis C: Viral escape or T-cell regulation? Reply SO HEPATOLOGY LA English DT Letter ID RIBAVIRIN C1 NIDDK, Liver Dis Sect, DDB, NIH,DHHS, Bethesda, MD USA. RP Rahman, F (reprint author), NIDDK, Liver Dis Sect, DDB, NIH,DHHS, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2004 VL 40 IS 5 BP 1229 EP 1230 DI 10.1002/hep.20478 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870HZ UT WOS:000225049500026 ER PT J AU MacArthur, RD Chen, L Peng, G Novak, RM van den Berg-Wolf, M Kozal, M Besch, L Yurik, T Schmetter, B Henley, C Dehlinger, M AF MacArthur, RD Chen, L Peng, G Novak, RM van den Berg-Wolf, M Kozal, M Besch, L Yurik, T Schmetter, B Henley, C Dehlinger, M CA CPCRA 058 Study Team TI Efficacy and safety of abacavir plus lamivudine versus didanosine plus stavudine when combined with a protease inhibitor, a nonnucleoside reverse transcriptase inhibitor, or both in HIV-1 positive antiretroviral-naive persons SO HIV CLINICAL TRIALS LA English DT Article DE antiretroviral agents; controlled clinical trials; highly active antiretroviral therapy; reverse transcriptase inhibitors ID SEQUENTIAL 3-DRUG REGIMENS; INITIAL THERAPY; INFECTION; ZIDOVUDINE; TRIAL; INDIVIDUALS; COMBINATION; NELFINAVIR; INDINAVIR; SELECTION AB Purpose: The combination of abacavir + lamivudine (ABC+3TC) versus didanosine + stavudine (ddl+d4T), each combined with other classes of antiretrovirals (ARVs) in ARV-naive patients, was compared for the combined endpoint of time to plasma HIV RNA > 50 copies/mL (at or after the 8-month visit) or death (primary endpoint) in a nested substudy of an ongoing multicenter randomized trial. Method: The substudy enrolled 182 patients; mean HIV RNA and CD4+ cell counts at baseline were 5.1 log(10) copies/mL and 212 cells/mm(3), respectively. Results: After a median follow-up of 28 months, rates of primary endpoint were 57.2 and 67.8 per 100 person-years for the ABC+3TC and ddl+d4T groups (hazard ratio [HR] = 0.81, 95% confidence interval [CI] 0.58-1.14, p = .23). Conclusion: There was a trend for treatments containing ABC+3TC to be better than treatments containing ddI+d4T with respect to HIV RNA decreases, CD4+ cell count increases, and tolerability. C1 Wayne State Univ, Div Infect Dis, Dept Med, Detroit, MI 48201 USA. Univ Minnesota, Minneapolis, MN USA. Univ Illinois, Chicago, IL USA. Temple Univ, Philadelphia, PA 19122 USA. Yale Univ, New Haven, CT USA. Tulane Univ, New Orleans, LA 70118 USA. Social & Sci Syst, Silver Spring, MD USA. So New Jersey Clin Trials, Camden, NJ USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP MacArthur, RD (reprint author), Wayne State Univ, Div Infect Dis, Dept Med, 4201 St Antoine ,UHC 7D, Detroit, MI 48201 USA. EM rmacarthur@med.wayne.edu FU PHS HHS [N01-A1-45235] NR 21 TC 10 Z9 10 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD NOV-DEC PY 2004 VL 5 IS 6 BP 361 EP 370 DI 10.1310/WEQG-QTHL-DL3X-FTXC PG 10 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 894NY UT WOS:000226800000001 PM 15682349 ER PT J AU San Jose-Robertson, L Corina, DP Ackerman, D Guillemin, A Braun, AR AF San Jose-Robertson, L Corina, DP Ackerman, D Guillemin, A Braun, AR TI Neural systems for sign language production: Mechanisms supporting lexical selection, phonological encoding, and articulation SO HUMAN BRAIN MAPPING LA English DT Article DE brain; lateralization; sign language; neuroimaging; PET ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL ORGANIZATION; FUNCTIONAL-ANATOMY; SPEECH PRODUCTION; SEMANTIC SYSTEM; PREMOTOR AREAS; HUMAN BRAIN; CORTEX; ENGLISH; FMRI AB Overt production of ASL signs was evaluated using (H2O)-O-15 PET to differentiate brain systems that support sign language production at the lexical-selection and phonological-articulatory levels. Subjects were 16 right-handed, congenitally deaf native ASL signers (10 women, six men; age 20 to 29 years). Scans were performed while subjects (1) passively viewed ASL nouns, (2) repeated nouns, (3) generated verbs in response to these nouns, (4) passively viewed videotaped segments depicting transitive actions, and (5) generated a verb to describe these actions. Conjunctions between the two verb-generation tasks revealed left-lateralized activation of perisylvian, frontal, and subcortical regions commonly observed in spoken language generation tasks and implicated in processes of semantic feature binding and lexical selection. Analysis of noun repetition minus viewing condition revealed activation of distinct systems supporting phonological encoding and articulation, including bilateral activation of sensorimotor areas and association cortices in the temporal, parietal, and occipital lobes. In addition, lexical-selection and articulatory processes were associated with activation of different corticostriatal-thalamocortical circuits: articulation with activation of the motor, and lexical-selection with activation of the prefrontal circuits, respectively. The results collectively provide insight into dissociable neural systems underlying these psycholinguistic functions. In addition, activation of regions that are typically associated with the auditory system during sign production suggests that these regions may support modality-independent linguistic processes, or may indicate cross-modal plasticity within the deaf brain. Published 2004 Wiley-Liss, Inc.(dagger) C1 Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Braun, AR (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bldg 10,Room 5N118A,10 Ctr Dr,MSC 1407, Bethesda, MD 20892 USA. EM brauna@nidcd.nih.gov FU NIDCD NIH HHS [R29 DC03099] NR 46 TC 19 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2004 VL 23 IS 3 BP 156 EP 167 DI 10.1002/hbm.20054 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 866RZ UT WOS:000224792000003 PM 15449359 ER PT J AU Bendavid, C Kleta, R Long, R Ouspenskaia, M Muenke, M Haddad, BR Gahl, WA AF Bendavid, C Kleta, R Long, R Ouspenskaia, M Muenke, M Haddad, BR Gahl, WA TI FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis SO HUMAN GENETICS LA English DT Article ID NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; PRENATAL-DIAGNOSIS; CORNEAL CRYSTALS; GENE CTNS; LYSOSOMES; MUTATIONS; TRANSPORT; CHILDREN; REMOVAL AB Cystinosis is an autosomal recessive lysosomal storage disease caused by mutations in CTNS. The most prevalent CTNS mutation, a 57-kb deletion, occurs in similar to60% of patients in the United States and northern Europe and removes exons 1-9, most of exon 10, the CTNS promoter region, and all of an adjacent gene of unknown function called CARKL. CTNS codes for the lysosomal cystine transporter, whose absence leads to intracellular cystine accumulation, widespread cellular destruction, renal Fanconi syndrome in infancy, renal glomerular failure in later childhood, and other systemic complications. Because treatment with oral cysteamine can prevent or delay these complications significantly, early and accurate diagnosis is critical. This study describes the generation of fluorescence in situ hybridization (FISH) probes for the 57-kb deletion in CTNS, enabling cytogenetics laboratories to test for this common mutation. The probes would also be able to detect a less frequent 11.7-kb deletion. A blinded study was performed using multiplex PCR analysis as the gold standard to determine the presence or absence of the 57-kb deletion. The FISH probes, evaluated on 12 lymphoblastoid cell lines from singly deleted, doubly deleted, and nondeleted patients, made the correct diagnosis in every case. This appears to be the first FISH-based diagnostic method described for any lysosomal storage disorder. It can assist in the antenatal and perinatal diagnosis of cystinosis and promote earlier salutary therapy with cysteamine. C1 NIH, Off Director, Intramural Program, Off Rare Dis, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Gahl, WA (reprint author), NIH, Off Director, Intramural Program, Off Rare Dis, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 26 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2004 VL 115 IS 6 BP 510 EP 514 DI 10.1007/s00439-004-1170-2 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 873UF UT WOS:000225305900008 PM 15365816 ER PT J AU Wang, H Parry, S Macones, G Sammel, MD Ferrand, PE Kuivaniemi, H Tromp, G Halder, I Shriver, MD Romero, R Strauss, JF AF Wang, H Parry, S Macones, G Sammel, MD Ferrand, PE Kuivaniemi, H Tromp, G Halder, I Shriver, MD Romero, R Strauss, JF TI Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM) SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN NEUTROPHIL COLLAGENASE; FLUID MATRIX METALLOPROTEINASE-8; EXTRACELLULAR-MATRIX; ADMIXTURE DYNAMICS; AFRICAN-AMERICANS; FETAL MEMBRANES; HUMAN CHORION; EXPRESSION; CELLS; ACTIVATION AB Matrix metalloproteinase 8 (MMP8), an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells. We identified three single nucleotide polymorphisms (SNPs) at -799C/T, -381A/G and +17C/G from the major transcription start site in the MMP8 gene, and determined the functional significance of these SNPs by analyzing their impact upon MMP8 promoter activity and their association with preterm premature rupture of membranes (PPROM). The minor alleles +17 (G) and -381 (G) were in complete linkage disequilibrium. A promoter fragment containing the three minor alleles had 3-fold greater activity in chorion-like trophoblast cells (BeWo, JEG-3 and HTR-8/SVneo) compared with the major allele promoter construct. Electrophoretic mobility shift assays revealed differences in BeWo nuclear protein binding to oligonucleotides representing the -381 and -799 SNPs, suggesting that the minor alleles have reduced transcription factor binding. A case-control study of African-American neonates using allele-specific primers revealed a statistically significant association between the three minor allele haplotype, which displays the highest MMP8 promoter activity in trophoblast cells, with PPROM with an odds ratio (OR) of 4.63 (P<0.0001), whereas the major allele promoter appeared to be protective (OR=0.52, P<0.0002). None of the minor alleles were individually associated with PPROM. These findings demonstrate the functional significance of SNP haplotypes in the MMP8 gene and associations with obstetrical outcomes. C1 Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NICHD, Perinatol Res Branch, Hutzel Hosp, Detroit, MI 48201 USA. Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. RP Strauss, JF (reprint author), Univ Penn, Ctr Res Reprod & Womens Hlth, 1354 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM jfs3@mail.med.upenn.edu RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NICHD NIH HHS [HD34612] NR 46 TC 79 Z9 81 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2004 VL 13 IS 21 BP 2659 EP 2669 DI 10.1093/hmg/ddh287 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 865LF UT WOS:000224703900011 PM 15367487 ER PT J AU Huang, JL Gao, PS Mathias, RA Yao, TC Chen, LC Kuo, ML Hsu, SC Plunkett, B Togias, A Barnes, KC Stellato, C Beaty, TH Huang, SK AF Huang, JL Gao, PS Mathias, RA Yao, TC Chen, LC Kuo, ML Hsu, SC Plunkett, B Togias, A Barnes, KC Stellato, C Beaty, TH Huang, SK TI Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability SO HUMAN MOLECULAR GENETICS LA English DT Article ID ATOPIC-DERMATITIS; PROMOTER; LINKAGE; POLYMORPHISMS; INFORMATION; EOSINOPHILS; POPULATION; BASOPHILS; CHILDREN; MARKER AB The gene, CRTH2, encoding a receptor for prostaglandin D-2 (PGD(2)), is located within the peak linkage region for asthma on chromosome (Chr.) 11q reported in African American families. Family-based analysis of asthma and two common SNPs [G1544C and G1651A (rs545659)] in the 3'-untranslated region of CRTH2 showed significant evidence of linkage in the presence of disequilibrium for the 1651G allele (P=0.003) of SNP rs545659. Haplotype analysis yielded additional evidence of linkage disequilibrium for the 1544G-1651G haplotype (P<0.001). Population-based case-control analyses were conducted in two independent populations, and demonstrated significant association of the 1544G-1651G haplotype with asthma in an African American population (P=0.004), and in a population of Chinese children (P<0.001). Moreover, in the Chinese children the frequency of the 1651G allele in near-fatal asthmatics was significantly higher than mild-to-moderate asthmatics (P=0.001) and normal controls (P<0.001). The 1651G allele of SNP re545659 was also associated with a higher degree of bronchial hyperresponsiveness (P<0.027). Transcriptional pulsing experiments showed that the 1544G-1651G haplotype confers a significantly higher level of reporter mRNA stability, when compared with a non-transmitted haplotype (1544C-1651A), suggesting that the CRTH2 gene on Chr. 11q is a strong candidate gene for asthma. C1 Chang Gung Childrens Hosp, Dept Pediat, Div Allergy Asthma & Rheumatol, Kewishan, Taiwan. Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21218 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Chang Gung Univ, Grad Inst Basic Sci, Dept Microbiol & Immunol, Taoyuan, Taiwan. RP Huang, SK (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM skhuang@jhmi.edu RI Kuo , Min-Liang/C-4872-2009; Hsu, Shih Chang/I-4277-2012; Huang, Shau-Ku/F-5509-2010; Stellato, Cristiana/P-3001-2015; OI Hsu, Shih Chang/0000-0002-3569-8635; Stellato, Cristiana/0000-0002-1294-8355; Hsu, Shih-Chang/0000-0003-1010-1182 FU NHLBI NIH HHS [HL-49612]; NIAID NIH HHS [AI-52468] NR 25 TC 73 Z9 78 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2004 VL 13 IS 21 BP 2691 EP 2697 DI 10.1093/hmg/ddh279 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 865LF UT WOS:000224703900014 PM 15345705 ER PT J AU Numakawa, T Yagasaki, Y Ishimoto, T Okada, T Suzuki, T Iwata, N Ozaki, N Taguchi, T Tatsumi, M Kamijima, K Straub, RE Weinberger, DR Kunugi, H Hashimoto, R AF Numakawa, T Yagasaki, Y Ishimoto, T Okada, T Suzuki, T Iwata, N Ozaki, N Taguchi, T Tatsumi, M Kamijima, K Straub, RE Weinberger, DR Kunugi, H Hashimoto, R TI Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia SO HUMAN MOLECULAR GENETICS LA English DT Article ID RAPID GLUTAMATE RELEASE; PREFRONTAL CORTEX; CORTICAL-NEURONS; RISK HAPLOTYPE; DTNBP1 GENE; 6P22.3 GENE; ASSOCIATION; RECEPTOR; PROTEIN; BRAIN AB Genetic variation in dysbindin (DTNBP1: dystrobrevin-binding protein 1) has recently been shown to be associated with schizophrenia. The dysbindin gene is located at chromosome 6p22.3, one of the most promising susceptibility loci in schizophrenia linkage studies. We attempted to replicate this association in a Japanese sample of 670 patients with schizophrenia and 588 controls. We found a nominally significant association with schizophrenia for four single nucleotide polymorphisms and stronger evidence for association in a multi-marker haplotype analysis (P=0.00028). We then explored functions of dysbindin protein in primary cortical neuronal culture. Overexpression of dysbindin induced the expression of two pre-synaptic proteins, SNAP25 and synapsin I, and increased extracellular basal glutamate levels and release of glutamate evoked by high potassium. Conversely, knockdown of endogenous dysbindin protein by small interfering RNA (siRNA) resulted in the reduction of pre-synaptic protein expression and glutamate release, suggesting that dysbindin might influence exocytotic glutamate release via upregulation of the molecules in pre-synaptic machinery. The overexpression of dysbindin increased phosphorylation of Akt protein and protected cortical neurons against neuronal death due to serum deprivation and these effects were blocked by LY294002, a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor. SiRNA-mediated silencing of dysbindin protein diminished Akt phosphorylation and facilitated neuronal death induced by serum deprivation, suggesting that dysbindin promotes neuronal viability through PI3-kinase-Akt signaling. Genetic variants associated with impairments of these functions of dysbindin could play an important role in the pathogenesis of schizophrenia. C1 Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Tokyo 1878502, Japan. Natl Inst Adv Ind Sci & Technol, Neuron RG Special Div Human Life Technol, Osaka 5638577, Japan. Fujita Hlth Univ, Sch Med, Dept Psychiat, Aichi 4701192, Japan. Nagoya Univ, Grad Sch Med, Dept Psychiat, Chuo Ku, Aichi 4668550, Japan. Showa Univ, Sch Med, Dept Psychiat, Tokyo 1428666, Japan. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Hashimoto, R (reprint author), Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, 4-1-1 Ogawahigashicho, Tokyo 1878502, Japan. EM rhashimo@ncnp.go.jp RI Hashimoto, Ryota/P-8572-2014; Ozaki, Norio/M-8908-2014; OI Hashimoto, Ryota/0000-0002-5941-4238; Ozaki, Norio/0000-0002-7360-4898; Kunugi, Hiroshi/0000-0002-7209-3790 NR 37 TC 255 Z9 270 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2004 VL 13 IS 21 BP 2699 EP 2708 DI 10.1093/hmg/ddh280 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 865LF UT WOS:000224703900015 PM 15345706 ER PT J AU van Dijk, EJ Breteler, MMB Schmidt, R Berger, K Nilsson, LG Oudkerk, M Pajak, A Sans, S de Ridder, M Dufouil, C Fuhrer, R Giampaoli, S Launer, LJ Hofman, A AF van Dijk, EJ Breteler, MMB Schmidt, R Berger, K Nilsson, LG Oudkerk, M Pajak, A Sans, S de Ridder, M Dufouil, C Fuhrer, R Giampaoli, S Launer, LJ Hofman, A CA CASCADE Consortium TI The association between blood pressure, hypertension, and cerebral white matter lesions - Cardiovascular determinants of dementia study SO HYPERTENSION LA English DT Article DE hypertension; stroke; dementia; epidemiology; ischemia; aging ID SILENT BRAIN INFARCTS; ROTTERDAM SCAN; ELDERLY-PEOPLE; MONICA PROJECT; STROKE; HEALTH; ATHEROSCLEROSIS; AUTOREGULATION; LEUKOARAIOSIS; POPULATIONS AB Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account. C1 Erasmus MC, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Karl Franzens Univ Graz, Dept Neurol, Graz, Austria. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. Univ Groningen Hosp, Dept Radiol, Groningen, Netherlands. Jagiellonian Univ, Sch Med, Inst Publ Hlth, Dept Epidemiol & Populat Studies, Krakow, Poland. Dept Hlth & Social Secur, Inst Hlth Studies, Barcelona, Spain. Hop La Pitie Salpetriere, INSERM, U360, Paris, France. McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 2T5, Canada. UCL, Dept Epidemiol & Publ Hlth, London, England. Ist Super Sanita, Lab Epidemiol & Biostat Epidemiol & Publ Hlth, I-00161 Rome, Italy. NIA, Lab Epidemiol Demog Biometry, Bethesda, MD 20892 USA. RP Breteler, MMB (reprint author), Erasmus MC, Dept Epidemiol & Biostat, POB 1738, NL-3000 DR Rotterdam, Netherlands. EM m.breteler@erasmusmc.nl RI Dufouil, Carole/J-4968-2012; van Dijk, Ewoud/J-7951-2012; Breteler, Monique /J-5058-2014 NR 26 TC 151 Z9 151 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2004 VL 44 IS 5 BP 625 EP 630 DI 10.1161/01.HYP.0000145857.98904.20 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866GI UT WOS:000224761500010 PM 15466662 ER PT J AU Franks, PW Knowler, WC Nair, S Koska, J Lee, YH Lindsay, RS Walker, BR Looker, HC Permana, PA Tataranni, PA Hanson, RL AF Franks, PW Knowler, WC Nair, S Koska, J Lee, YH Lindsay, RS Walker, BR Looker, HC Permana, PA Tataranni, PA Hanson, RL TI Interaction between an 11 beta HSD1 gene variant and birth era modifies the risk of hypertension in Pima Indians SO HYPERTENSION LA English DT Article DE genetics; epidemiology; blood pressure; nutrition; gene expression ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; HEPATIC INSULIN SENSITIVITY; ADIPOSE-TISSUE; GLUCOCORTICOID ACTION; DIABETES-MELLITUS; VISCERAL OBESITY; BLOOD-PRESSURE; ASSOCIATION; MICE; EXPRESSION AB 11beta-Hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a candidate gene for hypertension, diabetes, and obesity through altered glucocorticoid production. This study explored the association of 11betaHSD1 gene variants with diabetes, hypertension, and obesity in a longitudinal population study of American Indians (N = 918; exams = 5508). In multivariate mixed models assuming an additive effect of genotype, a 5' upstream variant (rs846910) was associated with blood pressure (diastolic blood pressure beta = 1.58 mm Hg per copy of the A allele, P = 0.0008; systolic blood pressure beta = 2.28 mm Hg per copy of the A allele, P = 0.004; mean arterial blood pressure beta = 1.83 mm Hg per copy of the A allele, P = 0.0006) and hypertension (odds ratio = 1.27 per copy of the A allele, P = 0.02). However, birth date modified these associations (test for interaction: diastolic blood pressure P = 0.16; systolic blood pressure P = 0.007; mean arterial blood pressure P = 0.01), such that the magnitude and direction of association between genotype and blood pressure changed with time. Finally, in models controlling for potential confounding by population stratification, we observed evidence of within-family effects for blood pressure (diastolic blood pressure beta = 1.77 mm Hg per copy of the A allele, P = 0.004; systolic blood pressure beta = 2.04 mm Hg per copy of the A allele, P = 0.07; mean arterial blood pressure beta = 1.85 mm Hg per copy of the A allele, P = 0.01) and for hypertension (odds ratio = 1.26 per copy of the A allele; P = 0.08). No association was observed for obesity. Associations with diabetes were similar in magnitude as reported previously but were not statistically significant. These data demonstrate association between genetic variability at 11betaHSD1 with hypertension, but these effects are modified by environmental factors. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. Univ Glasgow, Western Infirm, Gardiner Inst, Div Cardiovasc & Med Sci, Glasgow G11 6NT, Lanark, Scotland. Univ Edinburgh, Western Gen Hosp, Endocrinol Unit, Edinburgh, Midlothian, Scotland. Carl T Hayden VA Med Ctr, Phoenix, AZ USA. RP Franks, PW (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM pfranks@niddk.nih.gov RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 NR 28 TC 48 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2004 VL 44 IS 5 BP 681 EP 688 DI 10.1161/01.HYP.0000144294.28985.d5 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866GI UT WOS:000224761500019 PM 15452033 ER PT J AU Liang, JZR Higgins, WE Summers, RM Yoshida, H AF Liang, JZR Higgins, WE Summers, RM Yoshida, H TI Introduction to the special section on virtual endoscopy SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Editorial Material C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. Penn State Univ, University Pk, PA 16802 USA. NIH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. RP Liang, JZR (reprint author), SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2004 VL 23 IS 11 BP 1333 EP 1334 DI 10.1109/TMI.2004.837682 PG 2 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 868QY UT WOS:000224929300001 ER PT J AU Yao, JH Miller, M Franaszek, M Summers, RM AF Yao, JH Miller, M Franaszek, M Summers, RM TI Colonic polyp segmentation in CT colonography-based on fuzzy clustering and deformable models SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE colonic polyp segmentation; CT colonography; deformable model; fuzzy c-mean clustering ID VOLUMETRIC FEATURES AB An automatic method to segment colonic polyps in computed tomography (CT) colonography is presented in this paper. The method is based on a combination of knowledge-guided intensity adjustment, fuzzy c-mean clustering, and deformable models. The computer segmentations were compared with manual segmentations to validate the accuracy of our method. An average 76.3% volume overlap percentage among 105 polyp detections was reported in the validation, which was very good considering the small polyp size. Several experiments were performed to investigate the intraoperator and interoperator repeatability of manual colonic polyp segmentation. The investigation demonstrated that the computer-human repeatability was as good as the interoperator repeatability. The polyp segmentation was also applied in computer-aided detection (CAD) to reduce the number of false positive (FP) detections and provide volumetric features for polyp classification. Our segmentation method was able to eliminate 30% of FP detections. The volumetric features computed from the segmentation can further reduce FP detections by 50% at 80% sensitivity. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, 10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 10 TC 67 Z9 69 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2004 VL 23 IS 11 BP 1344 EP 1352 DI 10.1109/TMI.2004.826941 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 868QY UT WOS:000224929300003 PM 15554123 ER PT J AU Ashwell, JD AF Ashwell, JD TI Antigen-driven T cell expansion: Affinity rules SO IMMUNITY LA English DT Editorial Material AB TCR affinity and ligand off-rate have both been found to influence the degree of T cell activation by peptide MHC. A report in this issue of Immunity (Malherbe et al., 2004) finds that ligand off -rate does not correlate with antigen-specific peripheral T cell expansion. Moreover, the data point to the surprising notion that there exist TCR affinity thresholds and, once attained, T cells with higher affinity receptors have no competitive advantage. C1 NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 2 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 NOV PY 2004 VL 21 IS 5 BP 603 EP 604 DI 10.1016/j.immuni.2004.11.001 PG 2 WC Immunology SC Immunology GA 874QN UT WOS:000225365000001 PM 15539146 ER PT J AU Cannons, JL Yu, LJ Hill, B Mijares, LA Dombroski, D Nichols, KE Antonellis, A Koretzky, GA Gardner, K Schwartzberg, PL AF Cannons, JL Yu, LJ Hill, B Mijares, LA Dombroski, D Nichols, KE Antonellis, A Koretzky, GA Gardner, K Schwartzberg, PL TI SAP regulates T(H)2 differentiation and PKC-theta-mediated activation of NF-kappa B1 SO IMMUNITY LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; NF-KAPPA-B; CONTROLS T-CELL; KINASE-C-THETA; GENE-PRODUCT; SIGNAL-TRANSDUCTION; HUMORAL IMMUNITY; MICE DEFICIENT; ENCODING GENE; SH2 DOMAIN AB XLP is caused by mutations affecting SAP, an adaptor that recruits Fyn to SLAM family receptors. SAP-deficient mice recapitulate features of XLP, including increased T cell activation and decreased humoral responses post-infection. SAP-deficient T cells also show increased TCR-induced IFN-gamma and decreased T(H)2 cytokine production. We demonstrate that the defect in IL-4 secretion in SAP-deficient T cells is independent of increased IFN-gamma production. SAP-deficient cells respond normally to polarizing cytokines, yet show impaired TCR-mediated induction of GATA-3 and IL-4. Examination of TCR signaling revealed normal Ca2+ mobilization and ERK activation in SAP-deficient cells, but decreased PKC-theta recruitment, Bcl-10 phosphorylation, IkappaB-alpha degradation, and nuclear NF-kappaB1/p50 levels. Similar defects were observed in Fyn-deficient cells. SLAM engagement amplified PKC-theta recruitment in wt but not SAP- or Fyn-deficient cells, arguing that a SAP/Fyn-mediated pathway enhances PKC-theta/NF-kappaB1 activation and suggesting a role for this pathway in T(H)2 regulation. C1 NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Schwartzberg, PL (reprint author), NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. EM pams@mail.nih.gov NR 43 TC 163 Z9 169 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2004 VL 21 IS 5 BP 693 EP 706 DI 10.1016/j.immuni.2004.09.012 PG 14 WC Immunology SC Immunology GA 874QN UT WOS:000225365000010 PM 15539155 ER PT J AU Kay, AB Klion, AD AF Kay, AB Klion, AD TI Anti-interleukin-5 therapy for asthma and hypereosinophilic syndrome SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID MESSENGER-RNA EXPRESSION; HUMANIZED MONOCLONAL-ANTIBODY; GROWTH-FACTOR-ALPHA; EOSINOPHIL GRANULE PROTEINS; CYTOKINE GENE-EXPRESSION; IL-5 RECEPTOR-ALPHA; BASEMENT-MEMBRANE; HUMAN INTERLEUKIN-5; ATOPIC ASTHMA; AIRWAY INFLAMMATION AB Interleukin 5 (IL-5) is a key cytokine in the regulation of eosinophiha and eosinophil activation in humans. Monoclonal antibodies to anti-IL-5 have become available for use in clinical studies in humans. This article discusses the rationale for the use of anti-IL-5 therapy in asthma and hypereosinophilic syndrome and summarizes the available clinical data on the use of anti-IL-5 to treat these disorders. C1 Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Allergy & Clin Immunol, London SW3 6LY, England. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kay, AB (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Allergy & Clin Immunol, Guy Scadding Bldg,Dovehouse St, London SW3 6LY, England. EM a.b.kay@imperial.ac.uk OI Klion, Amy/0000-0002-4986-5326 NR 102 TC 23 Z9 28 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD NOV PY 2004 VL 24 IS 4 BP 645 EP + DI 10.1016/j.iac.2004.06.007 PG 23 WC Allergy; Immunology SC Allergy; Immunology GA 992XC UT WOS:000233916300008 PM 15474864 ER PT J AU Specht, S Volkmann, L Wynn, T Hoerauf, A AF Specht, S Volkmann, L Wynn, T Hoerauf, A TI Interleukin-10 (IL-10) counterregulates IL-4-dependent effector mechanisms in murine filariasis SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; VACCINE-INDUCED PROTECTION; PARASITE BRUGIA-MALAYI; LITOMOSOIDES-SIGMODONTIS; INTERFERON-GAMMA; ONCHOCERCA-VOLVULUS; HELMINTH INFECTION; CYTOKINE RESPONSES; IMMUNE-RESPONSE; BALB/C MICE AB Interleukin-10 (IL-10) was at first described as a Th2-associated cytokine, although more recent reports have shown that immunosuppression applies to both Th1 and Th2 cell responses, e.g., when produced by T regulatory cells. This concept when applied to human filariasis would argue that high parasite loads are associated with IL-10, while bona fide Th2 responses, mediated by IL-4, IL-5, and IL-13, are associated with parasite containment. To prove this relationship in causal manner, we investigated the roles of IL-4 and IL-10 in a helminth infection model in which mice genetically deficient for IL-4, IL-10, or IL-4 plus IL-10 were infected with the rodent filaria Litomosoides sigmodontis. Compared to C57BL/6 wild-type and IL-10 knockout (KO) mice, IL-4 KO mice remained susceptible, exhibiting a remarkable number of live adult worms. Interestingly however, when the IL-10 gene was knocked out simultaneously with the IL-4 gene, the susceptibility of IL-4 KO mice was reversed. Although production of IFN-gamma was increased in IL-4/IL-10 double-knockout mice, depletion of gamma interferon did not affect worm elimination, so it seems unlikely to be the major factor in mediating resistance in IL-4/IL-10 KO mice. Taken together, the results of this study add proof to the concept that has arisen for human filariasis that IL-10-dependent responses, which are associated with patency, are antagonistic to bona fide Th2 responses, which control parasite loads. The finding that knockout of IL-10 reversed a disease phenotype induced by knockout of IL-4 gives the first causal evidence of an antagonistic activity between IL-4 and IL-10 in an infection in vivo. C1 Univ Bonn, Inst Med Parasitol, D-53105 Bonn, Germany. Bernhard Nocht Inst Trop Med, Dept Helminthol, Hamburg, Germany. NIAID, Immunol Sect, Lab Parasit Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hoerauf, A (reprint author), Univ Bonn, Inst Med Parasitol, Sigmund Freud Str 25, D-53105 Bonn, Germany. EM hoerauf@parasit.meb.uni-bonn.de NR 42 TC 37 Z9 40 U1 0 U2 3 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 NOV PY 2004 VL 72 IS 11 BP 6287 EP 6293 DI 10.1128/IAI.72.11.6287-6293.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 864WS UT WOS:000224664300013 PM 15501755 ER PT J AU Fluck, C Smith, T Beck, HP Irion, A Betuela, I Alpers, MP Anders, R Saul, A Genton, B Felger, I AF Fluck, C Smith, T Beck, HP Irion, A Betuela, I Alpers, MP Anders, R Saul, A Genton, B Felger, I TI Strain-specific humoral response to a polymorphic malaria vaccine SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-2; PLASMODIUM-FALCIPARUM; ANTIBODY-RESPONSE; CROSS-REACTIVITY; RANDOMIZED TRIAL; IMMUNE-RESPONSE; CHILDREN; ANTIGEN; CHEMOPROPHYLAXIS; CHLOROQUINE AB The 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum was one of three subunits of the malaria vaccine Combination B that were tested in a phase I/IIb double-blind randomized placebo-controlled trial, which was undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because only one variant of the highly polymorphic MSP2 was used for vaccination, we examined whether the elicited response was directed against conserved or strain-specific epitopes. Postvaccination (week 12) titers of antibody against recombinantly expressed individual domains of MSP2 were measured by enzyme-linked immunosorbent assay and compared to baseline values. We found that vaccination with the 3D7 form of MSP2 induced a significant strain-specific humoral response directed against the repetitive and semiconserved family-specific part. The conserved N- and C-terminal domains were not immunogenic. Titers of antibody against the alternate FC27 family-specific domain showed a tendency to increase in vaccinated children, but there was no increase in antibodies against FC27-type 32-mer repeats. These results indicate that vaccination with one MSP2 variant mainly induced a strain-specific response, which can explain the selective effect of vaccination with combination B on the genotypes of breakthrough parasites. These findings support the inclusion of both family-specific domains (3D7 and FC27) in an improved vaccine formulation. C1 Swiss Trop Inst, CH-4002 Basel, Switzerland. Papua New Guinea Inst Med Res, Goroka, Papua N Guinea. Curtin Univ Technol, Ctr Int Hlth, Perth, WA 6001, Australia. La Trobe Univ, Dept Biochem, Bundoora, Vic, Australia. Natl Inst Hlth, Malaria Vaccine Dev Unit, Rockville, MD USA. RP Felger, I (reprint author), Swiss Trop Inst, Socinstr 57, CH-4002 Basel, Switzerland. EM ingrid.felger@unibas.ch RI Saul, Allan/I-6968-2013; Smith, Thomas/B-5569-2015; OI Saul, Allan/0000-0003-0665-4091; Smith, Thomas/0000-0002-3650-9381; Beck, Hans-Peter/0000-0001-8326-4834; Felger, Ingrid/0000-0003-1255-2606 NR 24 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2004 VL 72 IS 11 BP 6300 EP 6305 DI 10.1128/IAI.72.11.6300-6305.2004 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 864WS UT WOS:000224664300015 PM 15501757 ER PT J AU Canh, DG Lin, FY Thiem, VD Trach, DD Trong, ND Mao, ND Hunt, S Schneerson, R Robbins, JB Chu, CY Shiloach, J Bryla, DA Bonnet, MC Schulz, D Szu, SC AF Canh, DG Lin, FY Thiem, VD Trach, DD Trong, ND Mao, ND Hunt, S Schneerson, R Robbins, JB Chu, CY Shiloach, J Bryla, DA Bonnet, MC Schulz, D Szu, SC TI Effect of dosage on immunogenicity of a Vi conjugate vaccine injected twice into 2- to 5-year-old Vietnamese children SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE; TYPHOID-FEVER; SALMONELLA-TYPHI; PREVENTION; EFFICACY; INFANTS; ADULTS AB In a double-blind, randomized, and placebo-controlled previous trial, the efficacy of Vi-rEPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46 months. Vi-rEPA contained 25 mug of Vi and induced a greater-than-eightfold rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25 mug of Vi-rEPA in this age group. Two doses of WrEPA were injected 6 weeks apart. Blood samples were taken before and at 10 weeks (4 weeks after the second injection) and 1 year later. All postimmunization geometric mean (GM) levels were higher than the preimmune levels (P < 0.0001). At 10 weeks, the GM IgG anti-Vi level elicited by 25 mug (102 EU/ml) was higher than those elicited by 12.5 mug (74.7 EU/ml) and 5 mug (43 EU/ml) (P < 0.004): all of the children had greater than or equal to 3.52 EU/ml (estimated minimum protective level). One year later, the levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml, P < 0.0001) but remained significantly higher than the preimmune levels (P < 0.0001), and >96% of the children had a greater-than-eightfold rise. This study also confirmed the safety and consistent immunogenicity of the four lots of WrEPA used in this and previous trials. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Aventis Pasteur, Lyon, France. Natl Inst Hyg & Epidemiol, Diarrhea Dis Epidemiol & Field Res Stn, Hanoi, Vietnam. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Szu, SC (reprint author), NICHHD, NIH, Bldg 31,Room 2A29, Bethesda, MD 20892 USA. EM szus@mail.nih.gov OI Hunt, Steven/0000-0003-3533-0627 NR 14 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2004 VL 72 IS 11 BP 6586 EP 6588 DI 10.1128/IAI.72.11.6586-6588.2004 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 864WS UT WOS:000224664300048 PM 15501790 ER PT J AU Ferrant, JL Benjamin, CD Cutler, AH Kalled, SL Hsu, YM Garber, EA Hess, DM Shapiro, RI Kenyon, NS Harlan, DM Kirk, AD Burkly, LC Taylor, FR AF Ferrant, JL Benjamin, CD Cutler, AH Kalled, SL Hsu, YM Garber, EA Hess, DM Shapiro, RI Kenyon, NS Harlan, DM Kirk, AD Burkly, LC Taylor, FR TI The contribution of Fc effector mechanisms in the efficacy of anti-CD154 immunotherapy depends on the nature of the immune challenge SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antibody; co-stimulation; FcR; lupus; transplantation ID T-CELLS; CD40 LIGAND; COSTIMULATORY BLOCKADE; MONOCLONAL-ANTIBODIES; TRANSPLANT TOLERANCE; IN-VIVO; CD154; CARBOHYDRATE; REJECTION; LUPUS AB Blockade of the CD154-CD40 co-stimulatory pathway with anti-CD154 mAbs has shown impressive efficacy in models of autoimmunity and allotransplantation. Clinical benefit was also demonstrated in systemic lupus erythematosus (SLE) and idiopathic thrombocytopenia patients with the humanized anti-CD154 mAb, 5C8 (hu5C8). However, thromboembolic complications that occurred during the course of the hu5C8 clinical trials have proven to be a major setback to the field and safe alternative therapeutics targeting the CD154-CD40 pathway are of great interest. Recently, effector mechanisms have been shown to play a part in anti-CD154 mAb-induced transplant acceptance in murine models, while this issue remains unresolved for humoral-mediated models. Herein, aglycosyl anti-CD154 mAbs with reduced binding to FcgammaR and complement were used as a novel means to test the role of effector mechanisms in non-human primate and murine models not amenable to gene knockout technology. While aglycosyl hu5C8 mAb was relatively ineffective in rhesus renal and islet allotransplantation, it inhibited primary and secondary humoral responses to a protein immunogen in cynomolgus monkeys. Moreover, an aglycosyl, chimeric MR1 mAb (muMR1) prolonged survival and inhibited pathogenic auto-antibody production in a murine model of SLE. Thus, the mechanisms required for efficacy of anti-CD154 mAbs depend on the nature of the immune challenge. C1 Biogen Idec Inc, Cambridge, MA 02142 USA. Univ Miami, Sch Med, Diabet Res Inst, Miami, FL USA. NIDDK, Transplantat & Autoimmun Branch, NIH, Bethesda, MD USA. RP Ferrant, JL (reprint author), Biogen Idec Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA. EM janine.ferrant-orgettas@biogenidec.com RI Kirk, Allan/B-6905-2012 NR 43 TC 29 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2004 VL 16 IS 11 BP 1583 EP 1594 DI 10.1093/intimm/dxh162 PG 12 WC Immunology SC Immunology GA 862HT UT WOS:000224482300004 PM 15466914 ER PT J AU Bian, XW Chen, JH Jiang, XF Bai, JS Wang, QL Zhang, X AF Bian, XW Chen, JH Jiang, XF Bai, JS Wang, QL Zhang, X TI Angiogenesis as an immunopharmacologic target in inflammation and cancer SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE angiogenesis; chronic inflammation; cancer; metastasis ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-GROWTH; RHEUMATOID-ARTHRITIS; VASCULOGENIC MIMICRY; INHIBITORY ACTIVITY; ANTI-ANGIOGENESIS; PANCREATIC-CANCER; IN-VITRO; CELLS; METASTASIS AB Many pathological processes including wound healing, chronic inflammation and cancer require angiogenesis, i.e., the formation of new vasculature in the lesions. Accumulating evidence indicates that angiogenesis is crucial for both chronic inflammation and the growth of malignant tumors with the participation of diverse cytokines, chemokines and growth factors. It is nevertheless believed that differences exist in angiogenesis between cancer and chronic inflammatory diseases. The aim of this review is to outline the characteristics of angiogenesis in chronic inflammation and cancer. A better understanding of the angiogenic processes may facilitate the design of more effective therapies for chronic inflammation and cancer. (C) 2004 Elsevier B.V. All rights reserved. C1 Third Mil Med Univ, SW Hosp, Inst Pathol, Chongqing 400038, Peoples R China. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Bian, XW (reprint author), Third Mil Med Univ, SW Hosp, Inst Pathol, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net; zhangxia@mail.ncifcrf.gov RI Zhang, Xia/B-8152-2008; Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Zhang, Xia/0000-0002-9040-1486; Bian, Xiu-wu/0000-0003-4383-0197 NR 77 TC 36 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD NOV PY 2004 VL 4 IS 12 BP 1537 EP 1547 DI 10.1016/j.intimp.2004.07.017 PG 11 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 857QI UT WOS:000224133000011 PM 15351323 ER PT J AU Jeon, GA Lee, JS Patel, V Gutkind, JS Thorgeirsson, SS Kim, FC Chu, IS Amornphimoltham, P Park, MH AF Jeon, GA Lee, JS Patel, V Gutkind, JS Thorgeirsson, SS Kim, FC Chu, IS Amornphimoltham, P Park, MH TI Global gene expression profiles of human head and neck squamous carcinoma cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE microarrays; head and neck squamous cell carcinoma; gene expression; tumor progression; oral cancer; biomarkers; differentiation ID COMPARATIVE GENOMIC HYBRIDIZATION; LASER CAPTURE MICRODISSECTION; HUMAN ORAL KERATINOCYTES; HUMAN-PAPILLOMAVIRUS; DIFFERENTIAL EXPRESSION; PROGRESSION MODEL; CANCER STATISTICS; CDNA MICROARRAYS; GROWTH; HPV AB For genomewide monitoring and identification of biomarkers of head and neck squamous cell carcinoma (HNSCC), we have conducted a systematic characterization of gene expression profiles, using human cDNA microarrays containing 9K clones, in 25 HNSCC cell lines and I immortalized human oral keratinocyte cell line. We used normal human oral keratinocytes (NHOKs) as a reference. Our study showed that genes primarily involved in cell cycle regulation, oncogenesis, cell proliferation, differentiation, apoptosis and cell adhesion were widely altered in the 26 cell lines. Upregulated genes included known oncogenes, protein kinases, DNA-binding proteins and cell cycle regulators, while those commonly downregulated included differentiation markers, cell adhesion proteins, extracellular matrix proteins, structural proteins (keratins) and protease inhibitor proteins. Compared to NHOK, we observed a striking reduction in the expression of genes involved in terminal differentiation, suggesting that a loss in this process is an important signature of HNSCC. In addition, hierarchical clustering analysis as well as principal component analysis revealed 2 distinctive subtypes of gene expression patterns among the 26 cell lines, reflecting a degree of heterogeneity in HNSCC. By applying significance analysis of microarrays, 128 genes were selected for being distinctively expressed between the 2 groups. Genes differentially expressed in the 2 subgroups include cell proliferation-related genes, IGFBP6, EGFR and VEGFC; tumor suppression and apoptosis-related genes such as Tp53, Tp63; as well as cell cycle regulators such as CCND1 and CCND2 (cyclins D1 and D2), suggesting that the 2 subgroups might have undergone different pathways of carcinogenesis. Published 2004 Wiley-Liss, Inc. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Park, MH (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. EM parkm@mail.nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 48 TC 59 Z9 65 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2004 VL 112 IS 2 BP 249 EP 258 DI 10.1002/ijc.20399 PG 10 WC Oncology SC Oncology GA 854YJ UT WOS:000223939500011 PM 15352037 ER PT J AU Steck-Scott, S Forman, MR Sowell, A Borkowf, CB Albert, PS Slattery, M Brewer, B Caan, B Paskett, E Iber, F Kikendall, W Marshall, J Shike, M Weissfeld, J Snyder, K Schatzkin, A Lanza, E AF Steck-Scott, S Forman, MR Sowell, A Borkowf, CB Albert, PS Slattery, M Brewer, B Caan, B Paskett, E Iber, F Kikendall, W Marshall, J Shike, M Weissfeld, J Snyder, K Schatzkin, A Lanza, E CA Polyp Prevention Trial Study Grp TI Carotenoids, vitamin A and risk of adenomatous polyp recurrence in the polyp prevention trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE carotenoids; vitamin A; adenomatous polyps; epidemiology ID SERUM BETA-CAROTENE; LUNG-CANCER; COLORECTAL-CANCER; ALPHA-TOCOPHEROL; COLON-CANCER; ANTIOXIDANT VITAMINS; DIETARY INTERVENTION; SUBSEQUENT RISK; HIGH-FIBER; FOLLOW-UP AB One trial reported beta-carotene supplementation was protective of adenomatous polyp recurrence in nonsmokers. We now examine the relation of serum and dietary carotenoids and vitamin A to adenomatous polyp recurrence in a subcohort of 834 participants in a low fat, high fiber, high fruit and vegetable dietary intervention, the Polyp Prevention Trial. Multivariate odds ratio (OR) and 95% confidence intervals (Cl) of polyp recurrence were obtained using baseline or the average (first 3 years of the trial) carotenoid and vitamin A values after adjustment for covariates. Compared to the lowest quartile of baseline alpha-carotene concentrations, the OR of multiple polyp recurrence for the highest quartile was 0.55 (95% Cl = 0.30-0.99) and the OR of right-sided recurrence was 0.60 (95% Cl = 0.37-0.95). Baseline dietary intakes of alpha-carotene and vitamin A from food with/without supplements were inversely associated with any recurrence (p(for linear trend) = 0.03- alpha-carotene; p = 0.004 and p = 0.007 -intakes of vitamin A). Compared to the lowest quartile of averaged beta-carotene concentrations, the OR of multiple adenomas for the highest quartile was 0.40 (95% Cl = 0.22-0.75) with an inverse trend (p = 0.02). The risk was inversely related to averaged: alpha-carotene concentrations and right-sided polyps; alpha-carotene intake and recurrence of any, multiple and right-sided polyps; beta-carotene intake and multiple adenoma recurrence; vitamin A from food (with supplements) and each adverse endpoint. Thus, alpha-carotene and vitamin A may protect against recurrence in nonsmokers and nondrinkers or be indicative of compliance or another healthy lifestyle factor that reduces risk. (C) 2004 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Ctr Dis Control, Atlanta, GA 30333 USA. NCI, Biomet Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. WESTAT Corp, Rockville, MD 20850 USA. Kaiser Fdn, Inst Res, Oakland, CA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. USA, Walter Reed Med Ctr, Washington, DC 20310 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Pittsburgh, PA USA. Informat Management Serv Inc, Rockville, MD USA. NCI, Nutre Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA. RP Steck-Scott, S (reprint author), Univ N Carolina, Dept Nutr, CB 7461, Chapel Hill, NC 27599 USA. EM susan_scott@unc.edu RI Steck, Susan/G-5736-2013 NR 64 TC 20 Z9 20 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2004 VL 112 IS 2 BP 295 EP 305 DI 10.1002/ijc.20364 PG 11 WC Oncology SC Oncology GA 854YJ UT WOS:000223939500017 PM 15352043 ER PT J AU Feinendegen, LE Neumann, RD AF Feinendegen, LE Neumann, RD TI Dosimetry and risk from low- versus high-LET radiation of Auger events and the role of nuclide carriers SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article; Proceedings Paper CT 5th Auger Symposium CY AUG 13-15, 2003 CL Melbourne, AUSTRALIA SP LH Gray Mem Trust ID DOUBLE-STRAND BREAKS; TRIPLEX-FORMING OLIGONUCLEOTIDE; LOW-DOSE-RATE; MAMMALIAN-CELLS; MICRONUCLEUS FORMATION; I-125 DECAYS; X-RAYS; DNA; RADIOTOXICITY; DAMAGE AB Purpose: To analyse the lethality to mammalian cells of 125 I-decays in DNA, in antipyrine in the whole cell and in oligodeoxynucleotides in the nucleus outside DNA as a function of Auger event-site and number. Materials and methods: Auger events cause both low- and high-linear energy transfer energy depositions including charge neutralization at the daughter nuclide. Microdosimetry allows the expression of absorbed dose to a defined micromass and the number of such events at given sites. Published data were used to relate micromass dose and event number to the dose to reduce survival to 37% of the initial survival (D-37). Results: The D-37 of I-125-decays in DNA was 0.1 Gy in terms of absorbed dose to the cell nucleus and about 30 in terms of average decays per nucleus or whole cell. The D-37 of I-125-decays in antipyrine was 1.5 Gy for absorbed dose to the cell nucleus, about 250 in terms of average decays per nucleus and about 2 x 10(3) for average decays per whole cell. I-125-decays in oligodeoxynucleotides were much less toxic than I-125-decays in antipyrine by a factor of about 25 in terms of average absorbed dose to the cell nucleus, by a factor or about 40 in terms of average decays per cell nucleus and by a factor of six in terms of average decays per whole cell. Conclusion: The unexpected low toxicity of I-125-decays in nuclear oligodeoxynucleotides outside the DNA in comparison with I-125-decays in antipyrine in the nucleus or the whole cell demands further attention on the role of oligodeoxynucleotides in altering cellular radiation sensitivity. C1 Brookhaven Natl Lab, Upton, NY 11973 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Feinendegen, LE (reprint author), Brookhaven Natl Lab, Upton, NY 11973 USA. NR 63 TC 6 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD NOV-DEC PY 2004 VL 80 IS 11-12 SI SI BP 813 EP 822 DI 10.1080/095530004000007698 PG 10 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 890OR UT WOS:000226521200004 PM 15764388 ER PT J AU Gaidamakova, EK Neumann, RD Panyutin, IG AF Gaidamakova, EK Neumann, RD Panyutin, IG TI Antisense radiotherapy: targeting full-size mdr1 mRNA with I-125-labelled oligonucleotides SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article; Proceedings Paper CT 5th Auger Symposium CY AUG 13-15, 2003 CL Melbourne, AUSTRALIA SP LH Gray Mem Trust ID MULTIDRUG-RESISTANCE; SYNTHETIC OLIGODEOXYNUCLEOTIDE; P-GLYCOPROTEIN; I-125 DECAY; DNA; BREAKS; GENE; TRIPLEX; CELLS AB Purpose: Antisense radiotherapy is an approach based on the targeting of mRNA of specific genes by complementary oligonucleotide probes labelled with an Auger-electron-emitting radioisotope. Decay of the Auger emitter should specifically destroy the targeted mRNA while producing minimal damage to the rest of mRNA pool and the nuclear DNA. The feasibility of this approach was investigated by using full-length human multidrug-resistance gene (mdr1) mRNA as a target. Materials and methods: Antisense oligonucleotides were labelled with [I-125] I-dCTP by primer extension and annealed to target mRNA. Breaks in the target mRNA were analysed by denaturing polyacrylamide gel electriphoresis. Results: The efficiency of I-125-labelled antisense oligonucleotides in producing RNA strand breaks was tested on short synthetic RNA and DNA targets. The position and specificity of I-125-induced breaks in the full-length mRNA were then tested and compared with the cleavage of the target by RNase H. The distribution of the breaks in the longer mRNA is different from that in the short RNA targets, most likely due to a complex folding of RNA strands in the full-length mRNA. Conclusions: The authors posit that I-125-labelled antisense probes could be useful not only for targeting mRNA, but also as probes for mRNA folding in vivo. C1 Natl Inst Hlth, Dept Nucl Med, Bethesda, MD 20892 USA. Inst Mol Biol & Biophys, Novosibirsk 630117, Russia. RP Panyutin, IG (reprint author), Natl Inst Hlth, Dept Nucl Med, Bethesda, MD 20892 USA. EM igorp@helix.nih.gov NR 17 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD NOV-DEC PY 2004 VL 80 IS 11-12 SI SI BP 889 EP 893 DI 10.1080/09553000400007706 PG 5 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 890OR UT WOS:000226521200014 PM 15764398 ER PT J AU Sedelnikova, OA Panyutin, IV Neumann, RD Bonner, IM Panyutin, IG AF Sedelnikova, OA Panyutin, IV Neumann, RD Bonner, IM Panyutin, IG TI Assessment of DNA damage produced by I-125-triplex-forming oligonucleotides in cells SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article; Proceedings Paper CT 5th Auger Symposium CY AUG 13-15, 2003 CL Melbourne, AUSTRALIA SP LH Gray Mem Trust ID DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS AB Purpose: Triplex-forming oligodeoxyribonucleotides (TFOs) bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. When labeled with Auger-electron-emitting radioisotopes, TFOs are able to damage the target gene in process named antigene radiotherapy. We compared radiotoxicity and the amount of DNA damage produced within cultured cells by two I-125-labeled TFOs. one with a single target in the genome and another with multiple targets. Materials and methods: Radiotoxicity was measured by clonogenic assay while DNA damage was assessed by the number of histone gamma-H2AX foci formed at the sites of DNA double strand breaks (DSBs). Results: The TFO with multiple nuclear targets was 1.7 fold more radiotoxic and produced on average 1.9 fold more gamma-H2AX foci per cell than the TFO with a single target. Conclusion: Since the two methods gave comparable results, measuring the number of gamma-H2AX foci per decay may be a useful procedure for the assessment of cytotoxic effects and the intranuclear localization of radionuclides when they produce DSBs. C1 NIH, NMD, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. NCI, CCR, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, NMD, Ctr Clin, Dept Nucl Med, 10 Ctr Dr,Room 4D45, Bethesda, MD 20892 USA. EM igorp@helix.nih.gov NR 10 TC 19 Z9 20 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD NOV-DEC PY 2004 VL 80 IS 11-12 SI SI BP 927 EP 931 DI 10.1080/09553000400017648 PG 5 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 890OR UT WOS:000226521200020 PM 15764404 ER PT J AU Detera-Wadleigh, SD McMahon, FJ AF Detera-Wadleigh, SD McMahon, FJ TI Genetic association studies in mood disorders: issues and promise SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID BIPOLAR AFFECTIVE-DISORDER; SINGLE-NUCLEOTIDE POLYMORPHISM; GENOME SCAN METAANALYSIS; FAMILY-BASED ASSOCIATION; COMPLEX HUMAN-DISEASES; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY LOCUS; POPULATION STRATIFICATION; HIPPOCAMPAL NEUROGENESIS; SEROTONIN TRANSPORTER AB Genetic association is a powerful method for identifying genetic variants that contribute to the molecular basis of complex diseases. There is now a wealth of informative, validated and densely-spaced single nucleotide polymorphism (SNP) markers for use in association studies, and the delineation of the genome-wide haplotype architecture will greatly enhance our ability to conduct whole genome association screens, fine mapping of linkage regions, and systematic screening of functional candidate genes. Single nucleotide polymorphism-based genotyping technology has progressed dramatically to the point of high-throughput methods that can assay up to thousands of SNPs on many samples in one experiment. Genotyping cost remains a limiting factor in complex disease studies, where numerous SNPs and large sample sets are needed to maximize statistical power. Strategies designed to reduce cost include DNA pooling and analysis with tagSNPs. As larger clinical samples become available, it will be increasingly important to test for hidden stratification in case-control studies, as well as transmission distortion in family-based studies, either of which can lead to spurious association findings. As yet, there is no widely-accepted genetic association finding in mood disorders, but functional candidate genes, such as the serotonin transporter, and positional candidates, such as G72/G30 on chromosome 13q, are beginning to be identified in several studies. Relating associated variants to the phenotype represents the next critical step toward establishing the pathogenic role of gene variants in mood disorders. C1 NIMH, Genet Mood & Anxiety Disorders Unit, Mood & Anxiety Disorders Program, Intramural Res Program,NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Detera-Wadleigh, SD (reprint author), NIMH, Genet Mood & Anxiety Disorders Unit, Mood & Anxiety Disorders Program, Intramural Res Program,NIH,US Dept HHS, Bldg 35,Rm 1A205,36 Convent Dr, Bethesda, MD 20892 USA. EM sevilladetera@nih.gov RI McMahon, Francis/A-7290-2009; OI McMahon, Francis/0000-0002-9469-305X NR 88 TC 10 Z9 11 U1 1 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD NOV PY 2004 VL 16 IS 4 BP 301 EP 310 DI 10.1080/09540260400014377 PG 10 WC Psychiatry SC Psychiatry GA 882YR UT WOS:000225976800006 PM 16194763 ER PT J AU Chang, SM Kuhn, J Wen, P Greenberg, H Schiff, D Conrad, C Fink, K Robins, HI Cloughesy, T De Angelis, L Razier, J Hess, K Dancey, J Prados, MD AF Chang, SM Kuhn, J Wen, P Greenberg, H Schiff, D Conrad, C Fink, K Robins, HI Cloughesy, T De Angelis, L Razier, J Hess, K Dancey, J Prados, MD CA N Amer Brain Tumor Consortium Natl Canc Inst TI Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE chemotherapy; rapamycin; CCI-779; toxicity ID GLIOBLASTOMA-MULTIFORME; MAMMALIAN TARGET; CANCER-THERAPY; RAPAMYCIN; INHIBITOR; MTOR; PTEN; PROGNOSIS; PATHWAY AB Objectives: CCI-779 is an ester of the immunosuppressive agent sirolimus ( rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. Study design: The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Results: Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. Conclusions: The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent. C1 Univ Calif San Francisco, Neuroloncol Serv, San Francisco, CA 94143 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Virginia, Charlottesville, VA 22903 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Texas San Antonio SW, Dallas, TX USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Chang, SM (reprint author), Univ Calif San Francisco, Neuroloncol Serv, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. EM changs@neurosurg.ucsf.edu FU NCI NIH HHS [CA62399, CA62422, CA62426, CA16672, CA62455-08, U01 CA62399-09, U01 CA62421-08, U01CA62407-08]; NCRR NIH HHS [M01 RR00042, M01 RR00079, M01 RR00633, M01 RR03186] NR 25 TC 64 Z9 65 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 2004 VL 22 IS 4 BP 427 EP 435 DI 10.1023/B:DRUG.0000036685.72140.03 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 843GB UT WOS:000223065400008 PM 15292713 ER PT J AU Torrado, M Senatorov, VV Trivedi, R Fariss, RN Tomarev, SI AF Torrado, M Senatorov, VV Trivedi, R Fariss, RN Tomarev, SI TI Pdlim2, a novel PDZ-LIM domain protein, interacts with alpha-actinins and filamin A SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SEQUENCE TAG ANALYSIS; 6000 NONREDUNDANT TRANSCRIPTS; GENE-EXPRESSION PROFILE; NEIBANK PROJECT; BINDING-PROTEIN; SKELETAL-MUSCLE; SPLICE VARIANTS; CELL-MIGRATION; STRESS FIBERS; MYOSIN-VI AB PURPOSE. To characterize properties of Pdlim2, a novel PDZ and LIM domain-containing protein. METHODS. cDNA encoding Pdlim2 was identified in a cDNA library of transcripts expressed in the tissues of the rat eye irido-corneal angle. The expression pattern of the Pdlim2 gene was studied by Northern blot analysis and in situ hybridization. Proteins interacting with Pdlim2 were identified by pull-down assay and mass spectrometry. Intracellular localization of Pdlim2 was investigated by confocal microscopy. RESULTS. Rat Pdlim2 protein belongs to the ALP subfamily of proteins containing the PDZ domain in the N-terminal portion and the LIM domain in the C-terminal portion of the protein. The Pdlim2 gene was specifically expressed in the corneal epithelial cells, but not in the corneal stroma and endothelium nor in other ocular tissues. Pdlim2 was also expressed in the lung. In rat corneal and lung extracts, alpha-actinin-1, alpha-actinin-4, filamin A, and myosin heavy polypeptide 9 were co-immunoprecipitated with Pdlim2. Myosin VI was co-immunoprecipitated with Pdlim2 from corneal but not lung extracts. alpha-Actinins were the most abundant among immunoprecipitated proteins. Direct interaction of Pdlim2 with alpha-actinins and filamin was confirmed using pull-down assays and gel overlay assay with purified proteins. Pdlim2 and alpha-actinins were colocalized mainly to stress fibers after transfection into COS-7 cells. In transfected COS-7 cells, complexes of Pdlim2 and a-actinin-1 were preferentially located along the basal aspect. CONCLUSIONS. These results suggest that Pdlim2, like other ALP subfamily members, may act as an adapter that directs other proteins to the cytoskeleton. C1 NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH,DHHS, Bethesda, MD 20892 USA. NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. RP Tomarev, SI (reprint author), NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH,DHHS, Bldg 7,Room 103, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov RI Torrado, Mario/A-4889-2010 OI Torrado, Mario/0000-0001-9762-7018 NR 47 TC 42 Z9 48 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2004 VL 45 IS 11 BP 3955 EP 3963 DI 10.1167/iovs.04-0721 PG 9 WC Ophthalmology SC Ophthalmology GA 865BT UT WOS:000224678200015 PM 15505042 ER PT J AU Zhao, XJ Ramsey, KE Stephan, DA Russell, P AF Zhao, XJ Ramsey, KE Stephan, DA Russell, P TI Gene and protein expression changes in human trabecular meshwork cells treated with transforming growth factor-beta SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AQUEOUS-HUMOR OUTFLOW; OPEN-ANGLE GLAUCOMA; ANTERIOR SEGMENT; TGF-BETA-2; EYES; METALLOPROTEASE; OVEREXPRESSION; MODULATION; INTERACTS; MATRIX AB PURPOSE. To determine the genomic and proteomic expression changes in human trabecular meshwork cells when they are treated with transforming growth factor (TGF)-beta. METHODS. Human trabecular meshwork cells from five donors were cultured for 3 days with 1 ng/mL of either TGF-beta1 or -beta2. Changes in gene expression determined with gene microarrays and alterations in protein expression detected by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) were studied in these cells after the incubation. RESULTS. With both TGF-betas, there was a substantial upregulation of genes that were related to secreted proteins or extracellular matrix. This result was consistent with pathologic changes observed in disease and with experiments on perfused trabecular meshwork. Several of the gene changes suggest that other signaling pathways, such as ErbB and Writ, were altered. Changes in enzyme expression in the prostaglandin pathway indicated that the prostaglandins may have a different cellular profile in the presence of glaucoma. Two genes, osteoblast-specific factor 2 and corneal-derived transcript 6, which are highly expressed in the cells under normal conditions, were substantially upregulated with the TGF-betas. Proteomic analysis indicated that there was increased proteolysis of vimentin with both treatments. Tropomyosin la was increased in both gene and protein expression, suggesting alterations of the cytoskeleton by the disease. The TGF-beta1 treatment caused more robust changes than those induced by TGF-beta2. Three genes-aldose reductase, thioredoxin reductase 1, and glucose-6-phosphate I-dehydrogenase-were identified that were downregulated in expression. These genes had decreases in protein expression with TGF-beta1 treatment but had little change in either gene or protein expression with TGF-beta2. CONCLUSIONS. Human trabecular meshwork cells can be subjected to increased levels of TGF-beta for several years as a result of glaucoma. The results indicate that changes in extracellular matrix as well as alterations in cytoskeletal proteins occur in these cells as a result of increased TGF-beta. These results are consistent with changes observed in the trabecular meshwork in glaucoma and suggest that at least some of the histologic alterations observed in the meshwork in glaucoma may be the result of increased TGF-betas. C1 NEI, Sect Aging & Ocular Dis, NIH, Bethesda, MD 20892 USA. Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. RP Russell, P (reprint author), NEI, Sect Aging & Ocular Dis, NIH, 7 Mem Dr MSC 0703, Bethesda, MD 20892 USA. EM russellp@nei.nih.gov NR 38 TC 80 Z9 88 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 NOV PY 2004 VL 45 IS 11 BP 4023 EP 4034 DI 10.1167/iovs.04-0535 PG 12 WC Ophthalmology SC Ophthalmology GA 865BT UT WOS:000224678200025 PM 15505052 ER PT J AU Sundaram, R Lynch, MP Rawale, S Dakappagari, N Young, D Walker, CM Lemonnier, F Jacobson, S Kaumaya, PTP AF Sundaram, R Lynch, MP Rawale, S Dakappagari, N Young, D Walker, CM Lemonnier, F Jacobson, S Kaumaya, PTP TI Protective efficacy of multiepitope human leukocyte antigen-A*0201 restricted cytotoxic T-lymphocyte peptide construct against challenge with human T-cell lymphotropic virus type 1 Tax recombinant vaccinia virus SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE human T-lymphotropic virus type I cytotoxic T-lymphocyte epitopes; multivalent peptide; antigen presentation/processing; recombinant Tax vaccinia virus ID MHC CLASS-I; TROPICAL SPASTIC PARAPARESIS; HTLV-I; ENVELOPE GENE; NEUROLOGICAL DISEASE; CYNOMOLGUS MONKEYS; PRESENTED PEPTIDES; IMMUNE-RESPONSES; TARGET ANTIGEN; KAPPA-B AB Human T-cell lymphotropic virus type I (HTLV-1) is the causative agent of adult T-cell leukemia. Multiepitope T-cell vaccines are more likely to generate a broad long-lasting immune response than those composed of single epitopes. We recently reported a novel multivalent cytotoxic T-lymphocyte peptide construct derived from the Tax protein of HTLV-1 separated by arginine spacers that elicited high cellular responses against individual epitopes simultaneously in human leukocyte antigen (HLA)-A*0201 transgenic mice. We now report the effect of epitope orientation on the processing of the multiepitope construct by 20s proteasomes and the effect of the processing rates on the immogenicity of the intended epitopes. A positive correlation was found between processing rates and the immunogenicity of the intended epitopes. The construct with the highest immunogenicity for each epitope was tested for protective efficacy in a preclinical model of infection using HTLV-1 Tax recombinant vaccinia virus and HLA-A*0201 transgenic mice. Mice vaccinated with the multiepitope construct displayed a statistically significant reduction in viral replication that was dependent on CD8(+) T cells. Reduction in viral replication was also confirmed to be specific to Tax-vaccinia virus. These results demonstrate the activation of Tax specific CD8(+) T cells by vaccination and are supportive of a multivalent peptide vaccine approach against HTLV-1 infections. C1 Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. Ohio State Univ, Dept Biostat, Columbus, OH 43210 USA. Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. Inst Pasteur, Unite Immun Cellulaire Antivirale, Paris, France. NINCDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Ohio State Univ, Arthur G James Comprehens Canc Ctr, Columbus, OH 43210 USA. Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA. RP Kaumaya, PTP (reprint author), Tzagournis Med Res Facil, 420W 12th Ave,Suite 316, Columbus, OH 43210 USA. EM kaumaya.1@osu.edu FU PHS HHS [A140302] NR 55 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2004 VL 37 IS 3 BP 1329 EP 1339 DI 10.1097/00126334-200411010-00001 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 866YN UT WOS:000224809400001 PM 15483462 ER PT J AU Acosta, EP Wu, HL Hammer, SM Yu, S Kuritzkes, DR Walawander, A Eron, JJ Fichtenbaum, CJ Pettinelli, C Neath, D Ferguson, E Saah, AJ Gerber, JG AF Acosta, EP Wu, HL Hammer, SM Yu, S Kuritzkes, DR Walawander, A Eron, JJ Fichtenbaum, CJ Pettinelli, C Neath, D Ferguson, E Saah, AJ Gerber, JG CA Adult AIDS Clinical Trials TI Comparison of two indinavir/ritonavir regimens in the treatment of HIV-infected individuals SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 2nd International-AIDS-Society Conference on HIV Pathogenesis and Treatment CY JUL 13-16, 2003 CL Paris, FRANCE SP Int AIDS Soc DE antiretroviral therapy; pharmacokinetics; indinavir; ritonavir ID PROTEASE INHIBITORS; HEALTHY-VOLUNTEERS; INDINAVIR; RITONAVIR; EFFICACY; THERAPY; DISEASE AB Background: Pharmacokinetic enhancement of protease inhibitors (PIs) with low-dose ritonavir (RTV) for salvage therapy is increasingly common. The purpose of this study was to compare the pharmacokinetics, safety, and tolerability of indinavir (IDV)/RTV at 800/200 mg (arm A) and 400/400 mg (arm B) administered twice daily in HIV-infected subjects failing their first PI-based regimen. Methods: A phase I/II, randomized, open-label, 24-week study was conducted. Formal 12-hour pharmacokinetic evaluations were performed, and study visits occurred at baseline; at weeks 1, 2, and 4; and every 4 week thereafter for 24 weeks. Clinical symptoms and laboratory assessments were collected. Subjects were allowed to switch arms because of toxicity. Results: Forty-four subjects were enrolled (22 per arm). IDV predose concentration, maximum plasma concentration and area under the curve were significantly higher in arm A. Fifty-five percent and 45% of subjects in arms A and B responded (<200 copies/mL at week 24; P = 0.76), respectively. CD4 cell responses were similar. All subjects had IDV-sensitive virus at baseline and at virologic failure. Tolerability was comparable, but all grade 3 or higher triglyceride increases occurred in arm B and more subjects in arm B switched because of toxicity (5 vs. 1 triglyceride increases). Conclusions: This is the largest formal pharmacokinetic evaluation of 2 dosage combinations of IDV/RTV in HIV-infected individuals. Pharmacokinetic parameters were consistent with previous results in patients but lower than in seronegative controls. Both regimens exhibited similar tolerability and response rates. High toxicity with a low response suggests that the optimum IDV/RTV combination would include an RTV dose <400 mg and an IDV dose <800 mg in this population. C1 Univ Alabama, Div Clin Pharmacol, Sch Med, Birmingham, AL 35294 USA. Harvard Univ, Sch Publ Hlth, Chestnut Hill, MA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Frontier Sci & Technol, Amherst, NY USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Merck & Co Inc, W Point, PA USA. Univ Colorado, Hlth Sci Ctr, Div Clin Pharmacol, Denver, CO USA. RP Acosta, EP (reprint author), Univ Alabama, Div Clin Pharmacol, Sch Med, 1530 3rd Ave S,VH 116, Birmingham, AL 35294 USA. EM EAcosta@uab.edu FU NCRR NIH HHS [RR00043, RR00046, RR00051, RR00052, RR00056, RR00083, RR00096, RR00645]; NIAID NIH HHS [AI25868, AI25897, AI25903, AI27661, AI27673, AI32770, AI38858, AI46370, AI46383, AI46386, AI50410, U01 AI38858, UO1 AI32775] NR 18 TC 44 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2004 VL 37 IS 3 BP 1358 EP 1366 DI 10.1097/00126334-200411010-00004 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 866YN UT WOS:000224809400004 PM 15483465 ER PT J AU Thorpe, LE Frederick, M Pitt, J Cheng I Watts, DH Buschur, S Green, K Zorrilla, C Landesman, SH Hershow, RC AF Thorpe, LE Frederick, M Pitt, J Cheng, I Watts, DH Buschur, S Green, K Zorrilla, C Landesman, SH Hershow, RC TI Effect of hard-drug use on CD4 cell percentage, HIV RNA level, and progression to AIDS-defining class C events among HIV-infected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; disease progression; drug use; CD4 lymphocyte count; HIV RNA level ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL-MEN; CIGARETTE-SMOKING; PERIPHERAL-BLOOD; DISEASE PROGRESSION; BACTERIAL PNEUMONIA; DOCUMENTED DATES; UNITED-STATES; YOUNG-ADULTS; COCAINE USE AB (I)n vitro and animal studies suggest that cocaine and heroin increase HIV replication and suppress immune function, whereas epidemiologic studies are inconclusive regarding their effect on HIV infection progression. The authors prospectively examined the association between illicit-drug use and 4 outcome measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of HIV infection, and death) in a national cohort of HIV-infected women. Women enrolled between 1989 and 1995 were followed for 5 years and repeatedly interviewed about illicit ("hard")-drug use. Up to 3 periodic urine screens validated self-reported use. Outcomes were compared between hard-drug users (women using cocaine, heroin, methadone, or injecting drugs) and nonusers, adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard-drug use during pregnancy. In multivariate analyses, hard-drug use was not associated with change in CD4 cell percentage (P = 0.84), HIV RNA level (P = 0.48), or all-cause mortality (relative hazard = 1.10; 95% confidence interval, 0.61-1.98). Hard-drug users did, however, exhibit a higher risk of developing class C diagnoses (relative hazard = 1.65; 95% confidence interval, 1.00-2.72), especially herpes, pulmonary tuberculosis, and recurrent pneumonia. Hard-drug-using women may have a higher risk for nonfatal opportunistic infections. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Off Commun, Div Adult Community Hlth, Atlanta, GA 30333 USA. New York City Dept Hlth & Mental Hyg, New York, NY USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. NICHHD, Bethesda, MD 20892 USA. Univ Massachusetts, Worcester, MA 01605 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Puerto Rico, San Juan, PR 00936 USA. SUNY Brooklyn, Brooklyn, NY USA. Univ Illinois, Chicago, IL USA. RP Thorpe, LE (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Off Commun, Div Adult Community Hlth, M-S K-40, Atlanta, GA 30333 USA. EM lthorpe@health.nyc.gov FU NCRR NIH HHS [RR00645, RR00188]; NIAID NIH HHS [N01 AI 85339, 1 U01 AI 50274-01, U01 AI34858, U01 AI 34841]; NICHD NIH HHS [U01 HD 41983, HD-3-6-6117]; NIDA NIH HHS [9U01 DA 15054, U01 DA 15053] NR 61 TC 30 Z9 30 U1 1 U2 4 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 NOV 1 PY 2004 VL 37 IS 3 BP 1423 EP 1430 DI 10.1097/01.qai.0000127354.78706.5d PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 866YN UT WOS:000224809400011 PM 15483472 ER PT J AU Rosenberg, A Yates, JM AF Rosenberg, A Yates, JM TI Cryotherapy for treatment of anogenital warts SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE cryotherapy; HPV; genital warts; HIV positive ID EXTERNAL GENITAL WARTS; HUMAN-PAPILLOMAVIRUS INFECTION AB Human papillomavirus is a group of viruses that produce anogenital warts for which there is no cure. Untreated anogenital warts can spread and form large clusters that are bothersome, painful, and embarrassing to the patient as well as being a significant health risk. One of the infectious disease clinics of the authors' hospital sees an average of 200 HIV-positive individuals per month. Approximately 10% of these patients have anogenital warts. The attending physicians asked the clinical nursing staff if they would be willing to be trained to remove these warts using cryotherapy techniques, if patient efforts at other remedies failed. This request provoked a decision-making challenge for the staff. This article will describe the decision-making process and conclude with the procedure that was created as a result of the decision making. C1 NIH, Ctr Clin, Infect Dis Clin, Bethesda, MD 20892 USA. NIH, Ctr Clin, Ambulat Serv, Bethesda, MD 20892 USA. RP Rosenberg, A (reprint author), NIH, Ctr Clin, Infect Dis Clin, Bethesda, MD 20892 USA. NR 21 TC 1 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD NOV-DEC PY 2004 VL 15 IS 6 BP 72 EP 77 DI 10.1177/1055329004271721 PG 6 WC Nursing SC Nursing GA 872WN UT WOS:000225240000006 PM 15538018 ER PT J AU Deai, T Fukuda, M Tomoda, Y Higaki, S Hayashi, K Shimomura, Y AF Deai, T Fukuda, M Tomoda, Y Higaki, S Hayashi, K Shimomura, Y TI Excimer laser photokeratectomy reactivates latent herpes simplex virus SO JAPANESE JOURNAL OF OPHTHALMOLOGY LA English DT Article DE excimer laser; herpes simplex virus; real-time polymerase chain reaction assay; viral shedding ID KERATECTOMY; RECURRENCE AB Background: It has been reported that excimer laser irradiation might elicit herpes simplex virus (HSV) genome activation. We describe a clinical case in which HSV DNA sequences were detected quantitatively after phototherapeutic keratectomy (PTK). Case: A 90-year-old woman underwent excimer laser photokeratectomy for bilateral band-shaped keratopathy. Tear film was collected from both eyes using a Schirmer's strip before and 3 and 7 days after phototherapeutic keratectomy. Observations: HSV-DNA was quantified by a real-time polymerase chain reaction assay. HSV-DNA was detected only on the third day postoperatively in both eyes. The amount of viral DNA was 2.0 x 10(5) (OD) and 1.3 x 10(5) (OS) copies/sample, respectively. Conclusions: Excimer laser photokeratectomy stimulated viral shedding in the tear film. Ophthalmologists should be aware that laser irradiation can reactivate latent HSV. (C) Japanese Ophthalmological Society 2004. C1 Kinki Univ, Sch Med, Dept Ophthalmol, Osaka 5898511, Japan. NEI, Bethesda, MD 20892 USA. RP Deai, T (reprint author), Kinki Univ, Sch Med, Dept Ophthalmol, 377-2 Ohno Higashi, Osaka 5898511, Japan. EM deai@ganka.med.kindai.ac.jp NR 5 TC 10 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0021-5155 J9 JPN J OPHTHALMOL JI Jpn. J. Ophthalmol. PD NOV-DEC PY 2004 VL 48 IS 6 BP 570 EP 572 DI 10.1007/s10384-004-0112-9 PG 3 WC Ophthalmology SC Ophthalmology GA 877SV UT WOS:000225591400010 PM 15592782 ER PT J AU Elvevag, B Brown, GDA McCormack, T Vousden, JI Goldberg, TE AF Elvevag, B Brown, GDA McCormack, T Vousden, JI Goldberg, TE TI Identification, of tone duration, line length, and letter position: An experimental approach to timing and working memory deficits in schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID SHORT-TERM-MEMORY; ABSOLUTE IDENTIFICATION; TIME-ESTIMATION; SERIAL ORDER; NETWORK MODEL; DISCRIMINATION; INFORMATION; IMPAIRMENT; DISORDER; RECALL AB Patients with schizophrenia display numerous cognitive deficits, including problems in working memory, time estimation, and absolute identification of stimuli. Research in these fields has traditionally been conducted independently. We examined these cognitive processes using tasks that are structurally similar and that yield rich error data. Relative to healthy control participants (n = 20), patients with schizophrenia (n = 20) were impaired on a duration identification task and a probed-recall memory task but not on a line-length identification task. These findings do not support the notion of a global impairment in absolute identification in schizophrenia. However, the authors suggest that some aspect of temporal information processing is indeed disturbed in schizophrenia. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Warwick, Dept Psychol, Coventry CV4 7AL, W Midlands, England. Queens Univ Belfast, Dept Psychol, Belfast, Antrim, North Ireland. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Rm 4S235,MSC 1379, Bethesda, MD 20892 USA. EM elvevaab@intra.nimh.nih.gov RI McCormack, Teresa/C-3068-2013; Vousden, Janet/D-3620-2009; Brown, Gordon/C-9066-2009; OI Vousden, Janet/0000-0001-7237-1490 NR 56 TC 40 Z9 42 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2004 VL 113 IS 4 BP 509 EP 521 DI 10.1037/0021-843X.113.4.509 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 866JO UT WOS:000224770000003 PM 15535784 ER PT J AU Stahl, SM Vasquez, L AF Stahl, SM Vasquez, L TI Approaches to improving recruitment and retention of minority elders participating in research: Examples from selected research groups including the National Institute on Aging's Resource Centers for Minority Aging Research SO JOURNAL OF AGING AND HEALTH LA English DT Article DE National Institute on Aging Resource Centers for Minority Aging; research; recruitment; diverse populations ID AFRICAN-AMERICANS; CLINICAL-RESEARCH; ISSUES; COMMUNITY; TRIALS AB This introductory overview addresses the importance of recruiting and retaining racial and ethnic minority elders in biopsychosocial research. It highlights developments by scholars, many associated with the National Institute on Aging's Resource Centers for Minority Aging Research, to develop and reinforce a research infrastructure intended to minimize the minority/nonminority differential in health and its social sequelae for older people. C1 NIA, Individual Behav Proc Branch, NIH, Bethesda, MD 20892 USA. RP Stahl, SM (reprint author), NIA, Individual Behav Proc Branch, NIH, 7201 Wisconsin Ave,533, Bethesda, MD 20892 USA. EM Sidney_Stahl@nih.gov NR 20 TC 31 Z9 31 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD NOV PY 2004 VL 16 IS 5 SU S BP 9S EP 17S DI 10.1177/0898264304268146 PG 9 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 861NX UT WOS:000224424800002 PM 15448284 ER PT J AU Lyster, PM Guo, J Clune, T Larson, JW AF Lyster, PM Guo, J Clune, T Larson, JW TI The computational complexity and parallel scalability of atmospheric data assimilation algorithms SO JOURNAL OF ATMOSPHERIC AND OCEANIC TECHNOLOGY LA English DT Article ID ANALYSIS SYSTEM; KALMAN FILTER; ECMWF IMPLEMENTATION; FORMULATION; REANALYSIS; 3D-VAR AB This paper quantifies the computational complexity and parallel scalability of two algorithms for four-dimensional data assimilation (4DDA) at NASA's Global Modeling and Assimilation Office (GMAO). The first, the Goddard Earth Observing System Data Assimilation System (GEOS DAS), uses an atmospheric general circulation model (GCM) and an observation-space-based analysis system, the Physical-Space Statistical Analysis System (PSAS). GEOS DAS is very similar to global meteorological weather forecasting data assimilation systems but is used at NASA for climate research. The second, the Kalman filter, uses a more consistent algorithm to determine the forecast error covariance matrix than does GEOS DAS. For atmospheric assimilation, the gridded dynamical fields typically have more than 106 variables; therefore, the full error covariance matrix may be in excess of a teraword. For the Kalman filter this problem will require petaflop s(-1) computing to achieve effective throughput for scientific research. C1 NASA, Goddard Space Flight Ctr, Atmospheres Lab, Global Modeling & Assimilat Off, Greenbelt, MD 20771 USA. Univ Maryland, Dept Meteorol, College Pk, MD 20742 USA. Univ Maryland, Earth Syst Sci Interdisciplinary Ctr, College Pk, MD 20742 USA. Sci Applicat Int Corp, Gen Sci Operat, Beltsville, MD USA. Argonne Natl Lab, Div Math & Comp Sci, Argonne, IL 60439 USA. RP Lyster, PM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM lysterpe@nigms.nih.gov NR 40 TC 2 Z9 2 U1 1 U2 4 PU AMER METEOROLOGICAL SOC PI BOSTON PA 45 BEACON ST, BOSTON, MA 02108-3693 USA SN 0739-0572 J9 J ATMOS OCEAN TECH JI J. Atmos. Ocean. Technol. PD NOV PY 2004 VL 21 IS 11 BP 1689 EP 1700 DI 10.1175/JTECH1636.1 PG 12 WC Engineering, Ocean; Meteorology & Atmospheric Sciences SC Engineering; Meteorology & Atmospheric Sciences GA 870ZW UT WOS:000225099300005 ER PT J AU Yarmolinsky, MB AF Yarmolinsky, MB TI Bacteriophage P1 in retrospect and in prospect SO JOURNAL OF BACTERIOLOGY LA English DT Editorial Material ID ESCHERICHIA-COLI; LAMBDA C1 NCI, Lab Biochem, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, MB (reprint author), NCI, Lab Biochem, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM myarmo@helix.nih.gov NR 14 TC 11 Z9 11 U1 0 U2 1 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 NOV PY 2004 VL 186 IS 21 BP 7025 EP 7028 DI 10.1128/JB.186.21.7025-7028.2004 PG 4 WC Microbiology SC Microbiology GA 863QA UT WOS:000224575500001 PM 15489415 ER PT J AU Lobocka, MB Rose, DJ Plunkett, G Rusin, M Samojedny, A Lehnherr, H Yarmolinsky, MB Blattner, FR AF Lobocka, MB Rose, DJ Plunkett, G Rusin, M Samojedny, A Lehnherr, H Yarmolinsky, MB Blattner, FR TI Genome of bacteriophage P1 SO JOURNAL OF BACTERIOLOGY LA English DT Review ID SITE-SPECIFIC RECOMBINATION; P1 PLASMID-PARTITION; DNA-POLYMERASE-III; RESTRICTION-MODIFICATION GENES; INTEGRATION HOST FACTOR; SINGLE-STRANDED-DNA; PROGRAMMED TRANSLATIONAL FRAMESHIFT; STRINGENT STARVATION PROTEIN; ESCHERICHIA-COLI CHROMOSOME; ACID MODIFICATION ENZYME AB PI is a bacteriophage of Escherichia coli and other enteric bacteria. It lysogenizes its hosts as a circular, low-copy-number plasmid. We have determined the complete nucleotide sequences of two strains of a P1 thermoinducible mutant, P1 c1-100. The P1 genome (93,601 bp) contains at least 117 genes, of which almost two-thirds had not been sequenced previously and 49 have no homologs in other organisms. Protein-coding genes occupy 92% of the genome and are organized in 45 operons, of which four are decisive for the choice between lysis and lysogeny. Four others ensure plasmid maintenance. The majority of the remaining 37 operons are involved in lytic development. Seventeen operons are transcribed from sigma(70) promoters directly controlled by the master phage repressor C1. Late operons are transcribed from promoters recognized by the E. coli RNA polymerase holoenzyme in the presence of the Lpa protein, the product of a C1-controlled P1 gene. Three species of P1-encoded tRNAs provide differential controls of translation, and a P1-encoded DNA methyltransferase with putative bifunctionality influences transcription, replication, and DNA packaging. The genome is particularly rich in Chi recombinogenic sites. The base content and distribution in P1 DNA indicate that replication of P1 from its plasmid origin had more impact on the base compositional asymmetries of the P1 genome than replication from the lytic origin or replication. C1 Polish Acad Sci, Inst Biochem & Biophys, Dept Micrbial Biochem, PL-02106 Warsaw, Poland. M Sklodowska Curie Mem Inst, Ctr Oncol, Dept Tumor Biol, Gliwice, Poland. Univ Wisconsin, Genet Lab, Madison, WI USA. Ernst Moritz Arndt Univ Greifswald, Inst Microbiol, Dept Genet & Biochem, Greifswald, Germany. NCI, Lab Biochem, NIH, Bethesda, MD USA. RP Polish Acad Sci, Inst Biochem & Biophys, Dept Micrbial Biochem, Ul Pawinskiego 5A, PL-02106 Warsaw, Poland. EM lobocka@ibb.waw.pl RI Plunkett III, Guy/B-8058-2009; OI Plunkett III, Guy/0000-0003-1422-469X; Lobocka, Malgorzata/0000-0003-0679-5193 NR 354 TC 89 Z9 111 U1 3 U2 22 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2004 VL 186 IS 21 BP 7032 EP 7068 DI 10.1128/JB.186.21.7032-7068.2004 PG 37 WC Microbiology SC Microbiology GA 863QA UT WOS:000224575500003 PM 15489417 ER PT J AU Coleman, SA Fischer, ER Howe, D Mead, DJ Heinzen, RA AF Coleman, SA Fischer, ER Howe, D Mead, DJ Heinzen, RA TI Temporal analysis of Coxiella burnetii morphological differentiation SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; LEGIONELLA-PNEUMOPHILA; CHLAMYDIA-TRACHOMATIS; DEVELOPMENTAL CYCLE; STATIONARY-PHASE; GENE-EXPRESSION; DOT/ICM SYSTEM; Q-FEVER; CELLS; SECRETION AB Coxiella burnetii undergoes a poorly defined developmental cycle that generates morphologically distinct small-cell variants (SCV) and large-cell variants (LCV). We developed a model to study C. burnetii morphogenesis that uses Vero cells synchronously infected with homogeneous SCV (Nine Mile strain in phase II) harvested from aged infected cell cultures. A time course transmission electron microscopic analysis over 8 days of intracellular growth was evaluated in conjunction with one-step growth curves to correlate morphological differentiations with growth cycle phase. Lag phase occurred during the first 2 days postinfection (p.i.) and was primarily composed of SCV-to-LCV morphogenesis. LCV forms predominated over the next 4 days, during which exponential growth was observed. Calculated generation times during exponential phase were 10.2 h (by quantitative PCR assay) and 11.7 h (by replating fluorescent focus-forming unit assay). Stationary phase began at approximately 6 days p.i. and coincided with the reappearance of SCV, which increased in number at 8 days p.i. Quantitative reverse transcriptase-PCR demonstrated maximal expression of scvA, which encodes an SCV-specific protein, at 8 days p.i., while immunogold transmission electron microscopy revealed degradation of ScvA throughout lag and exponential phases, with increased expression observed at the onset of stationary phase. Collectively, these results indicate that the overall growth cycle of C burnetii is characteristic of a closed bacterial system and that the replicative form of the organism is the LCV. The experimental model described in this report will allow a global transcriptome and proteome analysis of C. burnetii developmental forms. C1 NIAID, Rocky Mt Labs, Coxiella Pathogenesis Unit,NIH, Host Parasite Interact Sect,Lab Intracellular Par, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Coxiella Pathogenesis Unit,NIH, Host Parasite Interact Sect,Lab Intracellular Par, 903S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov NR 44 TC 131 Z9 136 U1 2 U2 18 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 NOV PY 2004 VL 186 IS 21 BP 7344 EP 7352 DI 10.1128/JB.186.21.7344-7352.2004 PG 9 WC Microbiology SC Microbiology GA 863QA UT WOS:000224575500032 PM 15489446 ER PT J AU Ettema, TJG Makarova, KS Jellema, GL Gierman, HJ Koonin, EV Huynen, MA de Vos, WA van der Oost, J AF Ettema, TJG Makarova, KS Jellema, GL Gierman, HJ Koonin, EV Huynen, MA de Vos, WA van der Oost, J TI Identification and functional verification of archaeal-type phosphoenolpyruvate carboxylase, a missing link in archaeal central carbohydrate metabolism SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; PYRUVATE-CARBOXYLASE; PROTEIN SEQUENCES; DATABASE; HYPERTHERMOPHILE; BINDING; PREDICTION; GENERATION; PATHWAYS AB Despite the fact that phosphoenolpyruvate carboxylase (PEPC) activity has been measured and in some cases even purified from some Archaea, the gene responsible for this activity has not been elucidated. Using sensitive sequence comparison methods, we detected a highly conserved, uncharacterized archaeal gene family that is distantly related to the catalytic core of the canonical PEPC. To verify the predicted function of this archaeal gene family, we cloned a representative from the hyperthermophilic acidophille Sulfolobus solfataricus and functionally produced the corresponding enzyme as a fusion with the Escherichia coli maltose-binding protein. The purified fusion protein indeed displayed highly thermostable PEPC activity. The structural and biochemical properties of the characterized archaeal-type PEPC (atPEPC) from S. solfataricus are in good agreement with previously reported biochemical analyses of other archaeal PEPC enzymes. The newly identified atPEPC, with its distinct properties, constitutes yet another example of the versatility of the enzymes of the central carbon metabolic pathways in the archaeal domain. C1 Univ Wageningen & Res Ctr, Lab Microbiol Agrotechnol & Food Sci, Wageningen, Netherlands. Nijmegen Ctr Mol Life Sci, Ctr Mol & Biomol Informat, Nijmegen, Netherlands. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Ettema, TJG (reprint author), Univ Wageningen & Res Ctr, Microbiol Lab, Hesselink Suchtelenweg 4, NL-6703 CT Wageningen, Netherlands. EM thijs.ettema@wur.nl RI Gierman, Hinco/B-2727-2008; Huynen, Martijn/A-1530-2014 NR 35 TC 23 Z9 26 U1 0 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 NOV PY 2004 VL 186 IS 22 BP 7754 EP 7762 DI 10.1128/JB.186.22.7754-7762.2004 PG 9 WC Microbiology SC Microbiology GA 869HH UT WOS:000224973500034 PM 15516590 ER PT J AU Boisbouvier, J Bryce, DL O'Neil-Cabello, E Nikonowicz, EP Bax, A AF Boisbouvier, J Bryce, DL O'Neil-Cabello, E Nikonowicz, EP Bax, A TI Resolution-optimized NMR measurement of D-1(CH), D-1(CH) and D-2(CH) residual dipolar couplings in nucleic acid bases SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE carbon-13; cross-validation; DNA; heteronuclear NMR; residual dipolar coupling; RNA; resolution enhancement; TROSY ID IMPROVED SENSITIVITY; POLYACRYLAMIDE GELS; WEAK ALIGNMENT; DNA DODECAMER; STEM-LOOP; RNA; SPECTROSCOPY; PROTEINS; PHASE; MACROMOLECULES AB New methods are described for accurate measurement of multiple residual dipolar couplings in nucleic acid bases. The methods use TROSY-type pulse sequences for optimizing resolution and sensitivity, and rely on the E.COSY principle to measure the relatively small two-bond D-2(CH) couplings at high precision. Measurements are demonstrated for a 24-nt stem-loop RNA sequence, uniformly enriched in C-13, and aligned in Pf1. The recently described pseudo-3D method is used to provide homonuclear H-1-H-1 decoupling, which minimizes cross-correlation effects and optimizes resolution. Up to seven H-1-C-13 and C-13-C-13 couplings are measured for pyrimidines (U and C), including D-1(C5H5), D-1(C6H6), D-2(C5H6), D-2(C6H5), D-1(C5C4), D-1(C5C6), and D-2(C4H5). For adenine, four base couplings (D-1(C2H2), D-1(C8H8), D-1(C4C5), and D-1(C5C6)) are readily measured whereas for guanine only three couplings are accessible at high relative accuracy (D-1(C8H8), D-1(C4C5), and D-1(C5C6)). Only three dipolar couplings are linearly independent in planar structures such as nucleic acid bases, permitting cross validation of the data and evaluation of their accuracies. For the vast majority of dipolar couplings, the error is found to be less than +/-3% of their possible range, indicating that the measurement accuracy is not limiting when using these couplings as restraints in structure calculations. Reported isotropic values of the one- and two-bond J couplings cluster very tightly for each type of nucleotide. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA. RP Bax, A (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Bryce, David/A-3534-2008 OI Bryce, David/0000-0001-9989-796X NR 56 TC 26 Z9 26 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 2004 VL 30 IS 3 BP 287 EP 301 DI 10.1007/s10858-005-1846-5 PG 15 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 889AS UT WOS:000226416500007 PM 15756460 ER PT J AU Hausler, KD Horwood, NJ Chuman, Y Fisher, JL Ellis, J Martin, TJ Rubin, JS Gillespie, MT AF Hausler, KD Horwood, NJ Chuman, Y Fisher, JL Ellis, J Martin, TJ Rubin, JS Gillespie, MT TI Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoclast; RANKL; secreted frizzled-related protein; Wnt ID COLONY-STIMULATING FACTOR; DIFFERENTIATION FACTOR; SPEMANN ORGANIZER; BONE-DENSITY; CELL-LINES; RECEPTOR; LIGAND; OSTEOPROTEGERIN; MOUSE; CHONDROGENESIS AB We determined that sFRP-1 mRNA was differentially expressed by osteoblast/stromal cell lines and that sFRP-1 neutralizing antibodies and siRNA complementary to sFRP-1 coding sequence enhanced, while recombinant sFRP-1 inhibited, osteoclast formation. In studying the mechanism of action for sFRP-1, we found that sFRP-1 could bind recombinant RANKL. These results suggest potential cross-talk between Wnt and RANKL pathways. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Gillespie, MT (reprint author), St Vincents Inst Med Res, Bone Joint & Canc Unit, 41 Victoria Parade, Fitzroy, Vic 3065, Australia. EM mgillespie@sui.edu.au RI Horwood, Nicole/B-4351-2009 NR 50 TC 86 Z9 92 U1 3 U2 5 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2004 VL 19 IS 11 BP 1873 EP 1881 DI 10.1359/JBMR.040807 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865IT UT WOS:000224696600016 PM 15476588 ER PT J AU Wang, JH Alvarez, R Roderiquez, G Guan, E Norcross, MA AF Wang, JH Alvarez, R Roderiquez, G Guan, E Norcross, MA TI Constitutive association of cell surface CCR5 and CXCR4 in the presence of CD4 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chemokine receptor; chemokine; HIV-1; viral entry ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRINCIPAL HIV-1 CORECEPTOR; PROTEIN-COUPLED RECEPTOR; T-CELLS; CHEMOKINE RECEPTORS; EXPRESSION; INFECTION; ENTRY; MACROPHAGES; HETERODIMERIZATION AB Chemokine receptors CCR5 and CXCR4 are the major coreceptors of HIV-1 infection and also play fundamental roles in leukocyte trafficking, metastasis, angiogenesis, and embyogenesis. Here, we show that transfection of CCR5 into CXCR4 and CD4 expressing 3T3 cells enhances the cell surface level of CXCR4. In CCR5 high expressing cells, cell surface level of CXCR4 was incompletely modulated in the presence of the CXCR4 ligand CXCL12/SDF-1alpha. CCR5 was resistant to ligand-dependent modulation with the CCR5 ligand CCL5/RANTES. Confocal laser microscopy revealed that CCR5 was colocalized with CXCR4 on the cell surface. In CD4 expressing CCR5 and CXCR4 double positive NIH 3T3 cells, immunoprecipitation followed by Western blot analysis revealed that CCR5 was associated with CXCR4 and CD4. CXCR4 and CCR5 were not co-immunoprecipitated in cells expressing CCR5 and CXCR4 but without CD4 expression. Compared to NIH 3T3CD4 cells expressing CXCR4, the entry of an HIV-1 X4 isolate (HCF) into NIH 3T3CD4 expressing both CXCR4 and CCR5 was reduced. Our data indicate that chemokine receptors interact with each other, which may modulate chemokine-chemokine receptor interactions and HIV-1 coreceptor functions. Published 2004 Wiley-Liss, Inc(dagger). C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Lab Immunol,Off Biotechnol Prod, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Lab Immunol,Off Biotechnol Prod, NIH Bldg 29B,Room 4E12,HFM-541,8800 Rockville Pik, Bethesda, MD 20892 USA. EM wangj@cber.fda.gov NR 39 TC 29 Z9 29 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2004 VL 93 IS 4 BP 753 EP 760 DI 10.1002/jcb.20161 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868SL UT WOS:000224933200013 PM 15660419 ER PT J AU Cerrito, MG Galbaugh, T Wang, WH Chopp, T Salomon, D Cutler, ML AF Cerrito, MG Galbaugh, T Wang, WH Chopp, T Salomon, D Cutler, ML TI Dominant negative Ras enhances lactogenic hormone-induced differentiation by blocking activation of the Raf-Mek-Erk signal transduction pathway SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS; HUMAN BREAST-CANCER; BETA-CASEIN GENE; FACTOR RECEPTOR; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; MAP KINASE; LOBULOALVEOLAR DEVELOPMENT; NUCLEAR TRANSLOCATION AB Epidermal growth factor (EGF) and Ras mitogenic signal transduction pathways are frequently activated in breast carcinoma and inhibit mammary differentiation and apoptosis. HCl I mouse mammary epithelial cells, which differentiate and synthesize beta-casein following growth to confluency and stimulation with lactogenic hormones, were used to study EGF-dependent signaling during differentiation. Blocking Mek-Erk or phosphotidylinositol-3-kinase (PI-3 kinase) signaling with specific chemical inhibitors enhanced beta-casein promotor-driven luciferase activity. Because EGF stimulation of HC11 cells resulted in the activation of Ras, the effect of activated Ras (RasV12) or dominant negative (DNRasN17) on lactogen induced differentiation was examined. HC11 cell lines expressing RasV12 or DNRasN17 under the control of a tetracycline (tet)-responsive promotor were constructed. Activated RasV12 expression resulted in reduced tyrosine phosphorylation of Stat5 and a delay in beta-casein expression in response to prolactin. However, the expression of tet-regulated DNRasN17 and adenovirus-en coded DNRasN17 enhanced Stat5 tyrosine phosphorylation, Stat5 DNA binding, and P-casein transcription. The expression of DNRasN17 blocked the activation of the Mek-Erk pathway by EGF but did not prevent the phosphorylation of AKT, a measure of activation of the PI-3-kinase pathway. Moreover, the expression of DNRasN17 prevented the block to lactogenic differentiation induced by EGF. Stimulation of HC11 I cells with prolactin resulted in the association of the SHP2 phosphatase with Stat5, and this association was prevented by DNRasN17 expression. These results demonstrate that in HC11 cells DNRas inhibits the Mek-Erk pathway and enhances lactogenic hormone-induced differentiation. This occurs, in part, by inhibiting the association of the SHP2 phosphatase with Stat5. Published 2004 Wiley-Liss, Inc(dagger) C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, US Mil Canc Inst, Bethesda, MD 20814 USA. NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Cutler, ML (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, B3122,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mcutler@usuhs.mil FU NCI NIH HHS [R01 CA090908, R01CA90908] NR 57 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2004 VL 201 IS 2 BP 244 EP 258 DI 10.1002/jcp.20077 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 859JZ UT WOS:000224260700008 PM 15334659 ER PT J AU Strizzi, L Bianco, C Normanno, N Seno, M Wechselberger, C Wallace-Jones, B Khan, NI Hirota, M Sun, YP Sanicola, M Salomon, DS AF Strizzi, L Bianco, C Normanno, N Seno, M Wechselberger, C Wallace-Jones, B Khan, NI Hirota, M Sun, YP Sanicola, M Salomon, DS TI Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-cripto-1 transgenic mice SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID E-CADHERIN EXPRESSION; BREAST-CANCER CELLS; CARCINOMA-CELLS; N-CADHERIN; BETA-CATENIN; INTERMEDIATE-FILAMENTS; EXTRACELLULAR-MATRIX; VIMENTIN EXPRESSION; SIGNAL-TRANSDUCTION; ADHESION AB Epithelial-mesenchymal transition (EMT) facilitates migration and invasion of epithelial tumor cells. Cripto-1 (CR-1), a member of the epidermal growth factor-CFC protein family increases migration of cells in vitro. Here the expression of molecular markers and signaling molecules characteristic of EMT were assessed in mammary gland hyperplasias and tumors from mice expressing the human CR-1 transgene by the MMTV promoter (MMTV-CR-1) and in mouse mammary epithelial cell line HC-11 overexpressing CR-1 (HC-11/CR-1). Western blot analysis showed decreased expression of E-cadherin in MMTV-CR-1 tumors and in HC-11/CR-1 cells. The expression of N-cadherin, vimentin, cyclin-D1, and of the zinc-finger transcription factor, snail, was increased in MMTV-CR-1 tumors. Increased snail mRNA was also found in HC-11/CR-1 cells. Expression of phosphorylated (N-c-Src, P-focal adhesion kinase (FAK), P-Akt, P-glycogen synthease kinase 30 (GSK-3beta), dephosphorylated (DP)-beta-catenin, and various integrins such as, alpha 3, alpha v, beta 1, beta 3, and beta 4 was also increased in MMTV-CR-1 tumors. Immunohistochemistry showed positive staining for vimentin, N-cadherin, cyclin-D1, smooth muscle actin, fibronectin, snail, and beta-catenin in MMTV-CR-1 tumor sections. HC-11/CR-1 cells treated with the c-Src inhibitor PP2 reduced the expression of P-c-Src and of P-FAK, P-Akt, P-GSK-3beta, DP-beta-catenin all known to be activated by c-Src. Migration of HC-1I/CR-1 cells was also reduced by PP2 treatment. These results suggest that CR-1 may play a significant role in promoting the increased expression of markers and signaling molecules associated with EMT. (C) 2004 Wiley-Liss, Inc. C1 NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. INT Fdn Pascale, Dept Expt Oncol, Naples, Italy. Okayama Univ, Dept Biosci & Biotechnol, Okayama 7008530, Japan. Upper Austrian Res GmbH Zentrum, Linz, Austria. Biogen Inc, Cambridge, MA 02142 USA. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, 10 Ctr Dr,Bldg 10,Room 5B39, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov RI SENO, Masaharu /B-2092-2011; OI SENO, Masaharu /0000-0001-8547-6259; Normanno, Nicola/0000-0002-7158-2605 NR 57 TC 97 Z9 105 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2004 VL 201 IS 2 BP 266 EP 276 DI 10.1002/jcp.20062 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 859JZ UT WOS:000224260700010 PM 15334661 ER PT J AU Sausville, EA AF Sausville, EA TI Target selection issues in drug discovery and development SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 1st ISC International Conference on Cancer Therapeutics - Molecular Targets, Pharmacology and Clinical Applications CY FEB 19-21, 2004 CL Florence, ITALY SP Int Soc Chemotherapy DE oncogene; drug target; cancer treatment ID COLORECTAL-CANCER; STEPS AB Targets for cancer treatments have been proposed which address oncogenes mutated in tumors (pathogenic targets). Yet additional opportunities may come from molecules expressed in the tissue of origin (ontogenic); allow drug handling (pharmacological) or address the tumor microenvironment. The key is to define an assay that defines a therapeutic index which can be achieved in modulated target function. C1 NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Sausville, EA (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM esausville@umm.edu NR 8 TC 1 Z9 1 U1 0 U2 3 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD NOV PY 2004 VL 16 SU 4 BP 16 EP 18 PG 3 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 983MK UT WOS:000233236200004 PM 15688602 ER PT J AU Sausville, EA AF Sausville, EA TI Geldanamycin analogs SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 1st ISC International Conference on Cancer Therapeutics - Molecular Targets, Pharmacology and Clinical Applications CY FEB 19-21, 2004 CL Florence, ITALY SP Int Soc Chemotherapy DE Hsp90; ansamycin; cancer treatment ID ANSAMYCINS; INHIBITION; COMPLEX; HSP90; BINDS AB Benzoquinoid ansamycins can downregulate molecules which are chaperoned by heat shock protein (Hsp90), including numerous tyrosine kinases, steroid receptors, and cell cycle regulatory kinases. 17allylaminol7demethoxygeldanamycin (17AAG) has entered the clinic, but 17dimethyl-aminoethylaminogeldanamycin (17DMA) has emerged as an analog with potential preferential pharmaceutical features. C1 NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Sausville, EA (reprint author), Univ Maryland, Greenbaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM esausville@umm.edu NR 12 TC 7 Z9 7 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD NOV PY 2004 VL 16 SU 4 BP 68 EP 69 PG 2 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 983MK UT WOS:000233236200017 PM 15688614 ER PT J AU Muggia, FM Fojo, T AF Muggia, FM Fojo, T TI Platinums: Extending their therapeutic spectrum SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 1st ISC International Conference on Cancer Therapeutics - Molecular Targets, Pharmacology and Clinical Applications CY FEB 19-21, 2004 CL Florence, ITALY SP Int Soc Chemotherapy DE cisplatin; carboplatin; oxaliplatin; platinums AB Three decades since the introduction of cisplatin into clinical cancer treatment, this drug and its second generation analogues, carboplatin and oxaliplatin, form an integral part of recent evolving achievements in the treatment of solid tumors. For example, landmark studies have established a role for cisplatin after resection in lung cancer, and improved survival from platinum-based chemoradiation in cancer of the uterine cervix and combination chemotherapy in mesothelioma, small cell lung, ovarian, and endometrial cancers. Colon cancer survival has improved with the addition of oxaliplatin to its treatment. Here we summarize how insights into the mechanism of action of platinum compounds and studies of their structure-activity relationships may identify platinums with unusual selectivity towards tumors such as melanoma, renal cell, and breast cancer and other cancers not usually treated with existing platinums. Both new drug development and mechanistic studies with established drugs should lead to the next generation of clinical studies with platinum compounds, and their integration with emerging 'targeted therapies'. C1 NYU, Sch Med, New York, NY 10016 USA. NCI, Bethesda, MD 20204 USA. RP Muggia, FM (reprint author), NYU, Sch Med, New York, NY 10016 USA. EM franco.muggia@med.nyu.edu OI Muggia, Franco/0000-0003-0703-9146 NR 10 TC 42 Z9 44 U1 3 U2 7 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD NOV PY 2004 VL 16 SU 4 BP 77 EP 82 PG 6 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 983MK UT WOS:000233236200020 PM 15688617 ER PT J AU Bornstein, MH Leach, DB Haynes, OM AF Bornstein, MH Leach, DB Haynes, OM TI Vocabulary competence in first- and secondborn siblings of the same chronological age SO JOURNAL OF CHILD LANGUAGE LA English DT Article ID BIRTH-ORDER; COGNITIVE-DEVELOPMENT; LANGUAGE-DEVELOPMENT; FAMILY-SIZE; CHILDREN; INTELLIGENCE; PARENTS; ABILITY; GENDER; SEX AB We explored vocabulary competence in 35 firstborn and secondborn sibling pairs when each child reached 1;8 using multiple measures of maternal report, child speech, and experimenter assessment. Measures from each of the three sources were interrelated. Firstborns' vocabulary competence exceeded secondborns' only in maternal reports, not in child speech or in experimenter assessments. Firstborn girls outperformed boys on all vocabulary competence measures, and secondborn girls outperformed boys on most measures. Vocabulary competence was independent of the gender composition and, generally, of the acre difference in sibling pairs. Vocabulary competence in firstborns and secondborns was only weakly related. C1 NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bomstein@nih.gov RI Putnick, Diane/B-1707-2009; OI Putnick, Diane/0000-0002-6323-749X NR 41 TC 18 Z9 19 U1 3 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0305-0009 J9 J CHILD LANG JI J. Child Lang. PD NOV PY 2004 VL 31 IS 4 BP 855 EP 873 DI 10.1017/S03050009040o65i8 PG 19 WC Psychology, Developmental; Linguistics; Psychology, Experimental SC Psychology; Linguistics GA 888TM UT WOS:000226397100007 PM 15658749 ER PT J AU Asgharian, B Turner, ML Gibril, F Entsuah, LK Serrano, J Jensen, RT AF Asgharian, B Turner, ML Gibril, F Entsuah, LK Serrano, J Jensen, RT TI Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: Prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; FACIAL ANGIOFIBROMAS; LONG-TERM; MANAGEMENT; GENE; HYPERPARATHYROIDISM; INVOLVEMENT; CARCINOIDS; DIAGNOSIS; FEATURES AB Multiple endocrine neoplasm type 1 (MEN1) is associated with parathyroid, pancreatic, and pituitary tumors. Although most patients present with hyperparathyroidism, the diagnosis can be difficult, because a significant proportion present with other endocrinopathies or may lack a family history, and other MEN1 manifestations may be mild. Recently, multiple cutaneous lesions ( angiofibromas and collagenomas) were reported to be frequent in MEN1 patients, and it was proposed that their discovery suggested the diagnosis of MEN1. The purpose of this study was to prospectively assess the frequency and sensitivity/specificity of various cutaneous criteria for MEN1 in 110 consecutive patients with gastrinomas with or without MEN1. All patients had hormonal and functional studies to determine MEN1 status (48 with MEN1, 62 without MEN1), dermatological evaluation, and tumor imaging studies. Angiofibromas and collagenomas were more frequent in MEN1 patients (64% vs. 8% and 62% vs. 5%; P < 0.00001) and were multiple in 77-81% of the MEN1 patients. Lipomas occurred in 17%. The presence of these skin lesions did not correlate with age, disease duration, or other MEN1 features. Angiofibromas or collagenomas (single or multiple) had 50-65% sensitivity for MEN1 and 92-100% specificity. The combination criterion of multiple angiofibromas (more than three) and any collagenomas had the highest sensitivity (75%) and specificity (95%). This criterion has greater sensitivity than pituitary or adrenal disease and is comparable to hyperparathyroidism in some studies of patients with MEN1 with gastrinoma. This criterion should have sufficient sensitivity/specificity to be clinically useful. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 51 TC 42 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2004 VL 89 IS 11 BP 5328 EP 5336 DI 10.1210/jc.2004-0218 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 868XL UT WOS:000224946300008 PM 15531478 ER PT J AU Ayala, AR Pushkas, J Higley, JD Ronsaville, D Gold, PW Chrousos, GP Pacak, K Calis, KA Gerald, M Lindell, S Rice, KC Cizza, G AF Ayala, AR Pushkas, J Higley, JD Ronsaville, D Gold, PW Chrousos, GP Pacak, K Calis, KA Gerald, M Lindell, S Rice, KC Cizza, G TI Behavioral, adrenal, and sympathetic responses to long-term administration of an oral corticotropin-releasing hormone receptor antagonist in a primate stress paradigm SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENOCORTICAL SYSTEM; RHESUS-MONKEYS; MICE DEFICIENT; NORADRENERGIC NEURONS; ANXIETY DISORDERS; LOCUS-COERULEUS; CRH1 RECEPTOR; ANTALARMIN; DEPRESSION; BRAIN AB CRH is a main regulator of the stress response. This neuropeptide and its specific receptors, CRHR-1 and CRHR-2, are disseminated throughout the central nervous system. There is a significant interspecies difference in the distribution of CRHR within the central nervous system. CRH-R1 antagonists may attenuate stress-related behavior in rats without compromising adrenal function, but few studies have addressed the same question in higher mammals. Antalarmin (AA) is a specific CRHR-1 antagonist suitable for oral administration. Social separation is a potent stressor for rhesus monkeys. Therefore, we sought to investigate the hormonal responses to chronic administration of AA using a primate stress model. Eight preadolescent (4-6 kg) male rhesus monkeys received AA (20 mg/kg.d) or placebo (PBO) orally. All animals were on a regular day/light cycle and were fed with standard monkey chow daily. The study (114 d) was comprised of the following consecutive phases: adaptation, baseline, separation ( stress), recovery, and cross-over. During social separation, solid panels separated the individuals. Cerebrospinal fluid (CSF) and femoral venous blood samples were obtained once a week on the fourth day of separation under ketamine anesthesia. Serum samples were also obtained 1 and 2 h after separation. CSF samples were assayed for CRH, AA, norepinephrine ( NE) and epinephrine (EPI). Plasma was assayed for ACTH, cortisol, NE, and EPI. AA was detected in the plasma of each monkey while they were taking the active drug and in none of the animals on PBO. Among the behaviors assessed, environmental exploration, a behavior inhibited by stress, was increased during AA administration. However, AA at this dose did not affect other anxiety-related behavioral end points, including self-directed behavior, vocalization, or locomotion. We also observed that: 1) ACTH decreased between adaptation and baseline, indicating that the animals had adjusted to the novel environment; 2) ACTH and cortisol increased significantly after social separation, indicating that social separation was an adequate model for acute stress; 3) NE and EPI increased significantly during acute stress in the AA and PBO groups (P < 0.005, NE; P < 0.001, EPI); 4) after chronic stress, by d 4 of separation, ACTH levels were no longer significantly different from baseline, and NE and EPI remained slightly elevated when compared with baseline (P < 0.05, NE; P < 0.01, EPI); and 5) all the animals remained healthy and gained the expected weight during the study. In summary, oral chronic administration of a specific CRH-R1 antagonist to rhesus monkeys does not blunt the sympathoadrenal response to stress while increasing environmental exploration, a behavior that is normally suppressed during stressful events. Taken together, these findings suggest that CRHR-1 antagonists may be a valid treatment for stress-related disorders. C1 NICHHD, Pediat Endocrinol Branch, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Primate Unit,Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ayala, AR (reprint author), Bldg 10,Room 9D-42,10 Ctr Dr, Bethesda, MD 20892 USA. EM ayalaa@nih.gov NR 45 TC 24 Z9 25 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2004 VL 89 IS 11 BP 5729 EP 5737 DI 10.1210/jc.2003-032170 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 868XL UT WOS:000224946300070 PM 15531536 ER PT J AU Nakayama, T Yao, L Tosato, G AF Nakayama, T Yao, L Tosato, G TI Mast cell-derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW ANGIOGENESIS; HUMAN MULTIPLE-MYELOMA; TIE2 RECEPTOR; BALB/C MICE; CANCER; EXPRESSION; BIOLOGY; CARCINOGENESIS; PROLIFERATION AB Multiple myeloma in humans is frequently associated with mast cell infiltration and neovascularization, which correlate directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that primary murine mast cells express angiopoietin-1 (Ang-1) and low levels of VEGF-A but not Ang-2 and that 2 established murine plasmacytoma cell lines express high levels of VEGF-A but little or no Ang-1 or Ang-2. An in vivo angiogenesis assay using extracellular matrix components shows that mast cells and plasmacytoma cells, together, promote marked neovascularization composed of dilated vessels, which is prevented by neutralization of VEGF-A and Ang-1 but is only partially reduced by neutralization of either VEGF-A or Ang-1. Mast cells within extracellular matrix components express Ang-1, and recombinant Ang-1 together with plasmacytoma cells promotes extracellular matrix neovascularization similar to that induced by mast cells. A transplantation assay shows that primary mast cells accelerate tumor growth by established plasmacytoma cell lines and that neutralization of Ang-1 alone or with VEGF-A reduces significantly the growth of plasmacytomas containing mast cells. These results demonstrate that mast cell-derived Ang-1 promotes the growth of plasmacytomas by stimulating neovascularization and provide further evidence supporting a causal relationship between inflammation and tumor growth. C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bldg 10,Room 12C205,10 Ctr Dr 1907, Bethesda, MD 20892 USA. EM Tosatog@mail.nih.gov NR 61 TC 81 Z9 86 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 NOV PY 2004 VL 114 IS 9 BP 1317 EP 1325 DI 10.1172/JCI200422089 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 867WC UT WOS:000224872400021 PM 15520864 ER PT J AU O'Donnell, K Sutton, DA Rinaldi, MG Magnon, KC Cox, PA Revankar, SG Sanche, S Geiser, DM Juba, JH van Burik, JAH Padhye, A Anaissie, EJ Francesconi, A Walsh, TJ Robinson, JS AF O'Donnell, K Sutton, DA Rinaldi, MG Magnon, KC Cox, PA Revankar, SG Sanche, S Geiser, DM Juba, JH van Burik, JAH Padhye, A Anaissie, EJ Francesconi, A Walsh, TJ Robinson, JS TI Genetic diversity of human pathogenic members of the Fusarium oxysporum complex inferred from multilocus DNA sequence data and amplified fragment length polymorphism analyses: Evidence for the recent dispersion of a geographically widespread clonal lineage and nosocomial origin SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SPECIES COMPLEX; EPIDEMIOLOGY; GENEALOGIES; DISEASE; FUNGUS; IDENTIFICATION; RECOMBINATION; REPRODUCTION; GRAMINEARUM; RECOGNITION AB Fusarium oxysporum is a phylogenetically diverse monophyletic complex of filamentous ascomycetous fungi that are responsible for localized and disseminated life-threatening opportunistic infections in immunocompetent and severely neutropenic patients, respectively. Although members of this complex were isolated from patients during a pseudoepidemic in San Antonio, Tex., and from patients and the water system in a Houston, Tex., hospital during the 1990s, little is known about their genetic relatedness and population structure. This study was conducted to investigate the global genetic diversity and population biology of a comprehensive set of clinically important members of the F. oxysporum complex, focusing on the 33 isolates from patients at the San Antonio hospital and on strains isolated in the United States from the water systems of geographically distant hospitals in Texas, Maryland, and Washington, which were suspected as reservoirs of nosocomial fusariosis. In all, 18 environmental isolates and 88 isolates from patients spanning four continents were genotyped. The major finding of this study, based on concordant results from phylogenetic analyses of multilocus DNA sequence data and amplified fragment length polymorphisms, is that a recently dispersed, geographically widespread clonal lineage is responsible for over 70% of all clinical isolates investigated, including all of those associated with the pseudoepidemic in San Antonio. Moreover, strains of the clonal lineage recovered from patients were conclusively shown to genetically match those isolated from the hospital water systems of three U.S. hospitals, providing support for the hypothesis that hospitals may serve as a reservoir for nosocomial fusarial infections. C1 USDA ARS, Microbial Genom Res Unit, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Baptist Hosp, San Antonio, TX USA. Penn State Univ, Dept Plant Pathol, University Pk, PA 16802 USA. Univ Minnesota, Div Infect Dis, Minneapolis, MN USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP O'Donnell, K (reprint author), USDA ARS, Microbial Genom Res Unit, Natl Ctr Agr Utilizat Res, 1815 N Univ St, Peoria, IL 61604 USA. EM kodonnell@mail.ncaur.usda.gov RI Ducey, Thomas/A-6493-2011; Young, Jo-Anne/G-2617-2013; Geiser, David/J-9950-2013 OI Young, Jo-Anne/0000-0003-4182-341X; NR 38 TC 111 Z9 112 U1 1 U2 11 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 NOV PY 2004 VL 42 IS 11 BP 5109 EP 5120 DI 10.1128/JCM.42.11.5109-5120.2004 PG 12 WC Microbiology SC Microbiology GA 871QV UT WOS:000225149300030 PM 15528703 ER PT J AU Conville, PS Brown, JM Steigerwalt, AG Lee, JW Anderson, VL Fishbain, JT Holland, SM Witebsky, FG AF Conville, PS Brown, JM Steigerwalt, AG Lee, JW Anderson, VL Fishbain, JT Holland, SM Witebsky, FG TI Nocardia kruczakiae sp nov., a pathogen in immunocompromised patients and a member of the "N. nova complex" SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION-ENDONUCLEASE ANALYSIS; RIBOSOMAL-RNA GENE; DNA AMPLIFICATION; ASTEROIDES; VETERANA; IDENTIFICATION; SUSCEPTIBILITY; STRAINS; TAXA AB Molecular methodologies have become useful techniques for the identification of pathogenic Nocardia species and for the recognition of novel species that are capable of causing human disease. Two isolates recovered from immunocompromised patients were characterized as Nocardia nova by biochemical and susceptibility testing results. The restriction fragment length polymorphism (RFLP) patterns obtained by restriction endonuclease analysis (REA) of an amplified portion of the heat shock protein gene were identical to those obtained with the type strain of N. nova. REA of an amplified portion of the 16S rRNA gene showed RFLP patterns that were unlike those obtained for the type strain of N. nova but that were similar to those obtained for the type strains of N africana and N. veterana. Subsequent sequencing of a portion of the 16S rRNA gene produced identical results for the two patient isolates. Sequence analysis of 1,352-bp portions of the 16S rRNA gene indicated that these isolates were 99.8% similar to the recently described species N. veterana but were only 99.3, 98.1, and 98.1% similar to the type strains of N. afficana, N. nova, and N. vaccinii, respectively. DNA-DNA hybridization studies confirmed that the two patient isolates belonged to the same species but were not closely related to N. africana, N. nova, N. vaccinii, or N. veterana. The patient isolates have been designated N. kruczakiae sp. nov. Because N. africana, N. veterana, and the new species are not readily differentiated from N. nova by phenotypic methods alone, the designation "N. nova complex" can be used to designate isolates such as these that phenotypically resemble N. nova but that have not been definitively characterized by 16S rRNA gene sequencing or DNA-DNA hybridization. C1 US Dept HHS, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Microbiol Serv, Dept Lab Med, Bethesda, MD USA. CDCP, Meningitis & Special Pathogens Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis,US Dept HHS, Atlanta, GA USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Conville, PS (reprint author), US Dept HHS, NIH, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM pconville@nih.gov NR 18 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2004 VL 42 IS 11 BP 5139 EP 5145 DI 10.1128/JCM.42.11.5139-5145 PG 7 WC Microbiology SC Microbiology GA 871QV UT WOS:000225149300034 PM 15528707 ER PT J AU Fine, HA AF Fine, HA TI Toward a glioblastoma vaccine: Promise and potential pitfalls SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. NR 5 TC 7 Z9 7 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 NOV 1 PY 2004 VL 22 IS 21 BP 4240 EP 4243 DI 10.1200/JCO.2004.06.927 PG 4 WC Oncology SC Oncology GA 867LU UT WOS:000224844900002 PM 15452184 ER PT J AU Taghian, A Jeong, JH Mamounas, E Anderson, S Bryant, J Deutsch, M Wolmark, N AF Taghian, A Jeong, JH Mamounas, E Anderson, S Bryant, J Deutsch, M Wolmark, N TI Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: Results from five national surgical adjuvant breast and bowel project randomized clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 04-08, 2001 CL SAN FRANCISCO, CA SP Amer Soc Therapeut Radiol & Oncol ID PREMENOPAUSAL WOMEN; RADIATION-THERAPY; DOXORUBICIN-CYCLOPHOSPHAMIDE; POSTOPERATIVE RADIOTHERAPY; PREOPERATIVE CHEMOTHERAPY; RISK; IRRADIATION; FLUOROURACIL; METHOTREXATE; PNEUMONITIS AB Purpose To assess patterns of locoregional failure (LRF) in lymph node-positive (LN+) breast cancer patients treated with mastectomy and adjuvant chemotherapy ( tamoxifen) and without postmastectomy radiotherapy (PMRT) in five National Surgical Adjuvant Breast and Bowel Project trials. Patients and Methods \We examined 5,758 patients enrolled onto the B-15, B-16, B-18, B-22, and B-25 trials. Median follow-up time was 11.1 years. Distribution of pathologic tumor size was less than or equal to2 cm, 2.1 to 5 cm, and more than 5 cm in 30%, 52%, and 11% of patients, respectively. Distribution of the number of LN+ was one to three, four to nine, and greater than or equal to10 in 51 %, 32%, and 16% of patients, respectively. Ninety percent of patients received doxorubicin-based chemotherapy. Results The overall 10-year cumulative incidences of isolated LRF, LRF with or without distant failure (DR and DF alone as first event were 12.2%, 19.8%, and 43.3%, respectively. Cumulative incidences for LRF as first event with or without DF for patients with one to three, four to nine, and greater than or equal to: 10 LN+ were 13.0%, 24.4%, and 31.9%, respectively (P < .0001). For patients with a tumor size of greater than or equal to2 cm, 2.1 to 5.0 cm, and more than 5.0 cm, these incidences were 14.9%, 21.3%, and 24.6%, respectively (P < .0001). Multivariate analysis showed age, tumor size, premenopausal status, number of LN+, and number of dissected LN as significant predictors for LRF as first event. Conclusion In patients with large tumors and four or more LN+, LRF as first event remains a significant problem. Although PMRT is currently recommended for patients with four or more LN+, it may also have value in selected patients with one to three LN+. However, in the absence of a randomized trial examining the worth of radiotherapy in this group of patients, the value of PMRT remains unknown. (C) 2004 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Med Presbyterian, Dept Radiat Oncol, Pittsburgh, PA USA. Boston Med Ctr, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Aultman Canc Ctr, Canton, OH USA. RP Taghian, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [U10CA-69974, U10CA-12027, U10CA-69651-10] NR 30 TC 206 Z9 221 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 NOV 1 PY 2004 VL 22 IS 21 BP 4247 EP 4254 DI 10.1200/JCO.2004.01.042 PG 8 WC Oncology SC Oncology GA 867LU UT WOS:000224844900004 PM 15452182 ER PT J AU Puduvalli, VK Yung, WKA Hess, KR Kuhn, JG Groves, MD Levin, VA Zwiebel, J Chang, SM Cloughesy, TF Junck, L Wen, P Lieberman, F Conrad, CA Gilbert, MR Meyers, CA Liu, V Mehta, MP Nicholas, MK Prados, M AF Puduvalli, VK Yung, WKA Hess, KR Kuhn, JG Groves, MD Levin, VA Zwiebel, J Chang, SM Cloughesy, TF Junck, L Wen, P Lieberman, F Conrad, CA Gilbert, MR Meyers, CA Liu, V Mehta, MP Nicholas, MK Prados, M TI Phase II study of Fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American brain tumor consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER PATIENTS; N-(4-HYDROXYPHENYL) RETINAMIDE; CHEMOPREVENTION TRIAL; CLINICAL-TRIALS; RETINOIC ACID; CELL-LINES; APOPTOSIS; PHARMACOKINETICS; INDUCTION; PLASMA AB Purpose Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase 11 trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas. Patients and Methods Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days I to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m(2) bid. Results Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m(2) bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade I or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma Cm ex for fenretinide was 832 +/- 360 ng/mL at the 600 mg/m(2) bid dosage and 1,213 +/- 261 ng/mL at the 900 mg/m(2) bid dosage. Conclusion Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinde dosage, as suggested in this trial. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Wisconsin, Madison, WI 53706 USA. RP Puduvalli, VK (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 431, Houston, TX 77030 USA. EM vpuduval@mdanderson.org RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA62426, CA16672, CA62399, CA62412, CA62422, CA62455, P30 CA016672, R21 CA097767, R21 CA097767-02, U01 CA062399, U01 CA062405, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062422, U01 CA062426, U01CA62399, U01CA62405, U01CA62407-08, U01CA62421]; NCRR NIH HHS [M01 RR000042, M01 RR000056, M01 RR000079, M01 RR000633, M01 RR000865, M01 RR003186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR03186, M01-RR0865] NR 30 TC 47 Z9 48 U1 1 U2 2 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 NOV 1 PY 2004 VL 22 IS 21 BP 4282 EP 4289 DI 10.1200/JCO.2004.09.006 PG 8 WC Oncology SC Oncology GA 867LU UT WOS:000224844900008 PM 15514370 ER PT J AU Holguin, A Paxinos, E Hertogs, K Womac, C Soriano, V AF Holguin, A Paxinos, E Hertogs, K Womac, C Soriano, V TI Impact of frequent natural polymorphisms at the protease gene on the in vitro susceptibility to protease inhibitors in HIV-1 non-B subtypes SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV-1; non-B subtypes; drug resistance; protease inhibitors; natural polymorphisms ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE MUTATIONS; C REVERSE-TRANSCRIPTASE; NAIVE PATIENTS; TYPE-1 PROTEASE; UNITED-KINGDOM; CLADE-C; SPAIN; AIDS AB Background: Naturally-occurring polymorphisms at the human immunodeficiency virus type 1 (HIV- 1) protease which have been associated to resistance to protease inhibitors (PIs) in clade B viruses are frequently found in non-B subtypes, with unknown clinical significance, Objective: To assess the susceptibility of non-B viruses to different PIs. Study design: Plasma samples from 58 drug-naive individuals infected with HIV-1 non-B subtypes (2A, 22C, 2D, 1F, 29G and 2J) defined by phylogenetic analyses of the protease gene were tested using a phenotypic assay (PhenoSense, ViroLogic, South San Francisco, CA, USA). Twenty of them were further analyzed with another assay (Antivirogra(TM), Virco, Mechelen, Belgium). All 58 non-B viruses harbored amino acid substitutions associated with reduced PI susceptibility in clade B (positions 10, 20 36, 63 70, 77 and 82). Results: Using PhenoSense-HIV(TM) assay, all but two individuals harbored viruses completely susceptible to all six PIs tested (indinavir (IDV), ritonavir (RTV), saquinavir (SQV), nelfinavir (NFV), amprenavir (APV), lopinavir (LPV)). The two viruses with reduced susceptibility belonged to clade G. The first virus, which had K20I, M36I and V82I, showed 2.9-fold decreased susceptibility to APV. while the second virus showed 3.9-fold decreased susceptibility to both NFV and RTV, with amino acid substitutions K20I, M36I, L63P an V82I. Of note, several other viruses displayed the same constellation of mutations but without showing any reduced susceptibility, suggesting that these polymorphisms per se do not affect PI susceptibility. Conclusion: PI susceptibility in HIV-1 non-B viruses seems to be preserved despite the presence of polymorphic changes which have been associated to PI resistance in clade B viruses. (C) 2004 Elsevier B.V. All rights reserved. C1 Hosp Carlos III, Infect Dis Serv, Madrid, Spain. ViroLogic, San Francisco, CA USA. Virco, Mechelen, Belgium. NIH, Bethesda, MD 20892 USA. RP Soriano, V (reprint author), Calle Nueva Zelanda 54,4B, Madrid 28035, Spain. EM vsoriano@dragonet.es NR 56 TC 50 Z9 53 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 NOV PY 2004 VL 31 IS 3 BP 215 EP 220 DI 10.1016/j.jcv.2004.03.015 PG 6 WC Virology SC Virology GA 870BD UT WOS:000225028100008 PM 15465415 ER PT J AU Singec, I Knoth, R Ditter, M Volk, B Frotscher, M AF Singec, I Knoth, R Ditter, M Volk, B Frotscher, M TI Neurogranin is expressed by principal cells but not Interneurons in the rodent and monkey neocortex and hippocampus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE neocortex; hippocampus; interneuron; neurogranin; protein kinase C; calmodulin; calcium signaling ID PROTEIN-KINASE-C; LONG-TERM POTENTIATION; GLUTAMATE-RECEPTOR CHANNELS; SITE-DIRECTED MUTAGENESIS; NITRIC-OXIDE MODIFICATION; RAT-BRAIN NEUROGRANIN; SYNAPTIC PLASTICITY; DIVERSITY SERIES; RC3 NEUROGRANIN; SUBSTRATE RC3 AB As a substrate of protein kinase C(PKC), neurogranin (NG) is involved in the regulation of calcium signaling and activity-dependent plasticity. Recently, we have shown that, in the rodent cerebellum, NG is exclusively expressed by gamma-aminobutyric acidergic Golgi cells, whereas, in the monkey cerebellum, brush cells were the only neuronal population expressing NG (Singec et al. [2003] J. Comp. Neurol. 459:278-289). In the present study, we analyzed the neocortical and hippocampal expression patterns of NG in adult mouse (C57B1/6), rat (Wistar), and monkey (Cercopithecus aetiops). By using immunocytochemistry and nonradioactive in situ hybridization, we demonstrate strong NG expression by principal cells in different neocortical layers and in the hippocampus by granule cells of the dentate gyrus and pyramidal neurons of CA1-CA3. In contrast, double-labeling experiments in rodents revealed that neocortical and hippocampal interneurons expressing glutamate decarboxylase 67 (GAD67) were consistently devoid of NG. In addition, by using antibodies against parvalbumin, calbindin, and calretinin, we could demonstrate the absence of NG in interneurons of monkey frontal cortex and hippocampus. Together these findings corroborate the idea of different calcium signaling pathways in excitatory and inhibitory cells that may contribute to different modes of synaptic plasticity in these neurons. (C) 2004 Wiley-Liss, Inc. C1 Univ Freiburg, Inst Anat & Cell Biol, D-79104 Freiburg, Germany. Univ Freiburg, Dept Neuropathol, Neuroctr, D-79106 Freiburg, Germany. RP Singec, I (reprint author), NINDS, Mol Biol Lab, Natl Inst Hlth, Bldg 35,Room 3A215, Bethesda, MD 20892 USA. EM singeci@ninds.nih.gov NR 62 TC 29 Z9 29 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 1 PY 2004 VL 479 IS 1 BP 30 EP 42 DI 10.1002/cnc.20302 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 859HY UT WOS:000224255200003 PM 15389613 ER PT J AU Lu, Z Xu, Z Buchser, WJ AF Lu, Z Xu, Z Buchser, WJ TI Coding of acoustic particle motion by utricular fibers in the sleeper goby, Dormitator latifrons SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE auditory; directional hearing; ear; fish; otolithic organ ID OPSANUS-TAU; RESPONSE PROPERTIES; SACCULAR AFFERENTS; TELEOST FISH; HAIR-CELLS; FREQUENCY; TOADFISH; GOLDFISH; DIRECTIONALITY; SENSITIVITY AB It is unknown whether the fish utricle contributes to directional hearing. Here, we report response properties of single utricular fibers in a teleostfish (Dormitator latifrons) to linear accelerations at various stimulus frequencies and axes. Characteristic frequencies ranged from less than or equal to 50 - 400 Hz ( median = 80 Hz), and best frequencies shifted from 50 to 250 Hz with stimulus level. Best sensitivity of utricular fibers was distributed from -70 to -40 dB re: 1 g ( mean= - 52 dB), which is about 30 dB less sensitive than saccular fibers. Q(50%) fell between 0.16 and 11.50 ( mean= 2.04) at 15 dB above threshold. We observed temporal response patterns of entrained phase-locking, double phase-locking, phase-locked bursting, and non-phase-locked bursting. Most utricular fibers were directionally selective with various directional response profiles, and directional selectivity was stimulus-level dependent. Horizontal best-response axes were distributed in a 152degrees range while mid-sagittal best-response axes were clustered around the fish longitudinal axis, which is consistent with the horizontal orientation of the utricle and morphological polarizations of utricular hair cells. Therefore, results of this study indicate that the utricle in this vertebrate plays an auditory role in azimuth and that utricular fibers extend the response dynamic range of this species in directional hearing. C1 Univ Miami, Dept Biol, Coral Gables, FL 33146 USA. Univ Miami, Neurosci Program, Miami, FL 33101 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Lu, Z (reprint author), Univ Miami, Dept Biol, 1301 Mem Dr,Room 4, Coral Gables, FL 33146 USA. EM zlu@miami.edu OI Buchser, William/0000-0002-6675-6359 FU NIDCD NIH HHS [R01 DC03275, R29 DC03275] NR 34 TC 23 Z9 25 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD NOV PY 2004 VL 190 IS 11 BP 923 EP 938 DI 10.1007/s00359-004-0550-3 PG 16 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 872VT UT WOS:000225237900007 PM 15316732 ER PT J AU McDonald, MD Wood, CM Grosell, M Walsh, PJ AF McDonald, MD Wood, CM Grosell, M Walsh, PJ TI Glucocorticoid receptors are involved in the regulation of pulsatile urea excretion in toadfish SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE cortisol; RU486; spironolactone; toadfish; Opsanus beta; tUT; urea ID MINERALOCORTICOID-LIKE RECEPTOR; TROUT ONCORHYNCHUS-MYKISS; OPSANUS-BETA; GULF TOADFISH; RAINBOW-TROUT; PROLACTIN-RELEASE; IN-VITRO; OREOCHROMIS-MOSSAMBICUS; NITROGEN-METABOLISM; COLLECTING DUCT AB The objectives of this study were to characterize the pattern of pulsatile urea excretion in the gulf toadfish in the wake of exogenous cortisol loading and to determine the receptors involved in the regulation of this mechanism. Toadfish were fitted with indwelling arterial catheters and were infused with isosmotic NaCl for 48 h after which fish were treated with cortisol alone, cortisol+peanut oil, cortisol+RU486 (a glucocorticoid receptor antagonist) or cortisol+spironolactone (a mineralocorticoid receptor antagonist). Upon cortisol loading, fish treated with cortisol alone, cortisol+oil or cortisol+spironolactone experienced a two- to threefold reduction in pulsatile urea excretion. This reduction was due to a decrease in urea pulse size with no effect on pulse frequency compared to values measured during the control NaCl infusion period. In addition, these fish showed an increase in plasma urea concentrations upon treatment. These apparent effects of cortisol treatment were abolished in fish treated with cortisol+RU486. In contrast, these fish showed an increase in pulsatile urea excretion mediated by a twofold increase in pulse size with no change in frequency. Likewise, fish treated with cortisol+RU486 showed a significant decrease in plasma urea concentrations over the course of the experiment. The findings of this study indicate that high levels of cortisol reduce pulsatile urea excretion by decreasing pulse size. In addition, it appears that glucocorticoid receptors and not mineralocorticoid receptors are involved in the regulation of the toadfish pulsatile urea excretion mechanism. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. RP McDonald, MD (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. EM dmcdonald@rsmas.miami.edu FU NIEHS NIH HHS [ES 05705] NR 58 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1578 J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD NOV PY 2004 VL 174 IS 8 BP 649 EP 658 DI 10.1007/s00360-004-0456-y PG 10 WC Physiology; Zoology SC Physiology; Zoology GA 873UO UT WOS:000225306800009 PM 15517282 ER PT J AU Levy, LM Henkin, RI AF Levy, LM Henkin, RI TI Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE gamma-aminobutyric acid; magnetics; magnetic resonance imaging; spectroscopy; magnetic resonance spectroscopy; brain; hallucinations; taste; smell; phantosmia; phantageusia; sensory perception; sensory hallucinations; cognition; cognitive neurology ID FUNCTIONAL MRI; N-ACETYLASPARTATE; NMR-SPECTROSCOPY; MOTOR CORTEX; RAT-BRAIN; IN-VIVO; STIMULATION; PLASTICITY; TASTE; DEAFFERENTATION AB Background: Olfactory and gustatory hallucinations (phantosmias and phantageusias, respectively) are sensory distortions that commonly follow losses of olfactory and gustatory acuity (hyposmia and hypogeusia, respectively). The biochemical basis of these hallucinations is unclear. Functional magnetic resonance imaging has been used previously to demonstrate widespread and robust central nervous system (CNS) activation to memories of these sensory distortions in patients with these symptoms. In this study, possible CNS mechanisms responsible for these distortions were evaluated using magnetic resonance spectroscopy, because this technique has been used to measure various CNS metabolites in patients with neurologic disorders. Methods: Forty-seven subjects were studied: 28 normal volunteers (13 men and 15 women) and 19 patients (8 men and 11 women) with persistent oral global phantageusia and/or birhinal phantosmia studied before any treatment. Four patients (1 man and 3 women) were studied before and after pharmacologic treatment that reduced the severity of their sensory distortions. All subjects were studied in a Signa 1.5-T magnetic resonance scanner with a quadrature head coil using a modified standard 2-dimensional J-point resolved excitation in the steady state (PRESS) sequence by which gamma-aminobutyric acid (GABA), glutamic acid, choline, N-acetylaspartate, and creatine (Cre) were measured in various CNS regions. Results were expressed using Cre as a denominator to determine ratios for each measurement. Differences were defined between normal subjects and patients before treatment and in patients before and after successful pharmacologic treatment. Results: Before treatment, GABA levels in several CNS regions were lower in patients than in normal volunteers and were the only biochemical changes found; significantly lowered GABA levels were found in the cingulate, right and left insula, and left amygdala. No differences between patients and normal volunteers were found in any of the metabolites in the posterior occipital region. After treatment that inhibited sensory distortions, CNS GABA levels increased in the cingulate, insula, and amygdala but significantly only in the left insula and in the right and left amygdala. After this successful treatment, no change in any biochemical parameter was found in the posterior occipital region. Conclusions: These results indicate that decreased brain GABA levels can serve as biochemical markers of phantageusia and/or phantosmia in patients with these distortions and are the first biochemical changes in the CNS that reflect these sensory changes. After successful treatment of these distortions, CNS GABA levels increased to levels at or near normal, consistent with functional remission of these symptoms. These results substantiate a role for CNS GABA in the generation and inhibition of these sensory hallucinations. Although the underlying biochemical mechanism(s) for the generation of these decreased GABA levels are complex, because similar types of sensory hallucinations occur as auras or prodromata of epileptic seizure and migraine activity, these results suggest that there may be common biochemical changes among these disorders. C1 Taste & Smell Clin, Washington, DC 20016 USA. NINDS, Neuroimaging Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. RP Levy, LM (reprint author), Taste & Smell Clin, 5125 MacArthur Blvd NW, Washington, DC 20016 USA. EM doc@tasteandsmell.com NR 41 TC 14 Z9 14 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2004 VL 28 IS 6 BP 721 EP 727 DI 10.1097/00004728-200411000-00001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 870XS UT WOS:000225092800001 PM 15538143 ER PT J AU Phelan, JA Mulligan, R Nelson, E Brunelle, J Alves, MEAF Navazesh, M Greenspan, D AF Phelan, JA Mulligan, R Nelson, E Brunelle, J Alves, MEAF Navazesh, M Greenspan, D TI Dental caries in HIV-seropositive women SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental caries; HIV; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; SALIVARY-GLAND HYPOFUNCTION; INTERAGENCY HIV; SMOKING; RISK; PREVALENCE; XEROSTOMIA; INFECTION; DISEASE; LESIONS AB Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS ( coronal caries) and DFSrc ( root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries. C1 NYU, Coll Dent, Dept Oral Pathol, New York, NY 10010 USA. Univ So Calif, Sch Dent, Los Angeles, CA 90089 USA. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Univ Illinois, Coll Dent, Chicago, IL USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Phelan, JA (reprint author), NYU, Coll Dent, Dept Oral Pathol, Mail Code 9436,345 E 24th St, New York, NY 10010 USA. EM joan.phelan@nyu.edu FU NCRR NIH HHS [M01-RR00071, M01-RR00083]; NIAID NIH HHS [U01-AI-42590, U01-AI-34994, U01-AI-35004, U01-AI-34989, U01-AI-31834, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632] NR 18 TC 20 Z9 22 U1 0 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2004 VL 83 IS 11 BP 869 EP 873 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 894MQ UT WOS:000226796300009 PM 15505238 ER PT J AU Murakami, T Cardones, AR Hwang, ST AF Murakami, T Cardones, AR Hwang, ST TI Chemokine receptors and melanoma metastasis SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Review ID LYMPH-NODE METASTASIS; ENDOTHELIAL-CELLS; ENHANCES ADHESION; IMMUNE-RESPONSE; CANCER-CELLS; HIV-1 ENTRY; TUMOR-CELLS; T-CELLS; EXPRESSION; CXCR4 AB Cancer metastasis is the end result of a complex series of biologic events that leads to the formation of clinically significant secondary tumors at distant sites. The sites of distant metastasis are not random since certain tumors show a tendency to develop metastases in specific organs. Human melanoma, for example, demonstrates frequent metastasis to brain, lungs, lymph nodes, and skin. Herein, we review the evidence that suggests that a limited number of chemokine receptors may play critical roles in determining organ-selective metastasis in melanoma by regulating diverse processes such as chemoattraction, adhesion, and survival. In particular, we describe roles for CC chemokine receptor 7 (CCR7) in lymph node metastasis, CXC chemokine receptor 4 (CXCR4) in pulmonary metastasis, and CCR10 in skin metastasis, using a mouse model of melanoma. Preliminary evidence in this preclinical model suggests that inhibiting the function of these receptors may decrease the ability of cancer cells to disseminate to other sites and/or block their ability to survive and form tumors. Therefore, manipulation of the chemokine network could have therapeutic potential in human malignancies. (C) 2004 Published by Elsevier Ireland Ltd. on behalf of Japanese Society for Investigative Dermatology. C1 NCI, Dermatol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Jichi Med Sch, Ctr Mol Med, Div Organ Replacement Res, Minami Kawachi, Tochigi 3290498, Japan. RP Hwang, ST (reprint author), NCI, Dermatol Branch, Canc Res Ctr, Bldg 10-Rm12N246,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov NR 49 TC 109 Z9 114 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD NOV PY 2004 VL 36 IS 2 BP 71 EP 78 DI 10.1016/j.jdermsci.2004.03.002 PG 8 WC Dermatology SC Dermatology GA 871SQ UT WOS:000225154100001 PM 15519136 ER PT J AU Danforth, DN AF Danforth, DN TI All trans-retinoic acid acts synergistically with hydroxytamoxifen and transforming-growth factor beta to stimulate apoptosis in MCF-7 breast cancer cells SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CYCLE PROGRESSION; BCL-2 EXPRESSION; FACTOR-ALPHA; LINE MCF-7; TAMOXIFEN; INHIBITION; PROLIFERATION; TUMORIGENICITY; ANTIESTROGENS AB The anti-estrogen 4-hydroxytamoxifen (TAM) and vitamin A-related compounds, the retinoids, in combination act synergistically to inhibit growth of breast cancer cells in vitro and in vivo. To clarify the mechanism of this synergism, the effect of TAM and all trans-retinoic acid (AT) on proliferation of MCF-7 breast cancer cells was studied in vitro. TAM and AT acted synergistically to cause a time-dependent and dose-dependent inhibition of MCF-7 cell growth. In a temporally related manner, TAM+AT acted synergistically to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis. TAM and AT each blocked cell cycle progression throuhout 7 days of treatment but without any synergistic or additive effect on this process, indicating a selective synergism for apoptosis. The negative growth factor-transforming growth factor beta (TGFbeta) is secreted by these cells and was studied as a potential mediator of the synergistic effects of TAM+AT on apoptosis. TAM+AT acted synergistically to induce a fivefold increase in TGFbeta1 secretion over 72 h. TGFbeta1 alone had no apoptotic effects on these cells; however, TGFbeta1 in combination with AT acted synergistically to inhibit growth, to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis of these cells in a manner comparable with that noted for TAM+AT. The synergism of both TAM+AT and TGFbeta1 +AT for apoptosis was suppressed by estradiol. Co-incubation of TAM+AT with anti-TGFbeta antibody did not block downregulation of Bcl-2 protein expression or stimulation of apoptosis. The synergistic effects of TAM+AT on apoptosis therefore occur independently of TGFbeta, although TGFbeta may interact with AT in a novel manner to provide another important anti-proliferative mechanism for breast cancer cells. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP NCI, Surg Branch, NIH, Bldg 10 Rm 2B42, Bethesda, MD 20892 USA. EM David_Danforth@nih.gov NR 38 TC 16 Z9 16 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2004 VL 183 IS 2 BP 395 EP 404 DI 10.1677/joe.1.05497 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 875PQ UT WOS:000225433700015 PM 15531727 ER PT J AU Sen, R AF Sen, R TI NF-kappa B and the immunoglobulin kappa gene enhancer SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID TRANSCRIPTIONAL ACTIVATION; ALLELIC EXCLUSION; CELL DEVELOPMENT; REARRANGEMENT; LOCUS; E2A; PHOSPHORYLATION; DEMETHYLATION; LYMPHOCYTES; INDUCTION AB Enhancers regulate lineage choice and the developmental timing of antigen receptor gene rearrangements. The transcription factor NF-kappaB has been implicated as a key component of the recombination and transcription activation potential of the immunoglobulin kappa chain gene intronic enhancer. Here, I discuss the implications of the new observation that an NF-kappaB binding site-mutated enhancer in the correct biological context does not appear to affect kappa gene expression. C1 NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Sen, R (reprint author), NIA, Cellular & Mol Biol Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rs465z@nih.gov NR 24 TC 10 Z9 10 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 2004 VL 200 IS 9 BP 1099 EP 1102 DI 10.1084/jem.200441255 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 869CS UT WOS:000224961600002 PM 15520242 ER PT J AU Reina-San-Martin, B Chen, HT Nussenzweig, A Nussenzweig, MC AF Reina-San-Martin, B Chen, HT Nussenzweig, A Nussenzweig, MC TI ATM is required for efficient recombination between immunoglobulin switch regions SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE class switch recombination; somatic hypermutation; activation-induced cytidine deaminase; ATM; DNA repair ID STRAND BREAK REPAIR; HISTONE H2AX PHOSPHORYLATION; CYTIDINE DEAMINASE AID; DNA DAMAGE-RESPONSE; S-MU REGION; SOMATIC HYPERMUTATION; ATAXIA-TELANGIECTASIA; B-CELLS; DEFICIENT MICE; CIRCULAR DNA AB Ataxia telangiectasia mutated (ATM) kinase is critical for initiating the signaling pathways that lead to cell cycle checkpoints and DNA double strand break repair. In the absence of ATM, humans and puce show a primary immunodeficiency that includes low serum antibody titers, but the role of ATM in antigen-driven immunoglobulin gene diversification has not been defined. Here, we show that although ATM is dispensable for somatic hypermutation, it is required for efficient class switch recombination (CSR). The defect in CSR is not due to alterations in switch region transcription, accessibility, DNA damage checkpoint protein recruitment, or short-range intra-switch region recombination. Only long-range inter-switch recombination is defective, indicating an unexpected role for ATM in switch region synapsis during CSR. C1 Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Howard Hughes Med Inst, 1230 York Ave, New York, NY 10021 USA. EM nussen@mail.rockefeller.edu RI Reina-San-Martin, Bernardo/I-9484-2016 OI Reina-San-Martin, Bernardo/0000-0003-2083-6166 NR 83 TC 126 Z9 128 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 2004 VL 200 IS 9 BP 1103 EP 1110 DI 10.1084/jem.20041162 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 869CS UT WOS:000224961600003 PM 15520243 ER PT J AU Lumsden, JM McCarty, T Petiniot, LK Shen, R Barlow, C Wynn, TA Morse, HC Gearhart, PJ Wynshaw-Boris, A Max, EE Hodes, RJ AF Lumsden, JM McCarty, T Petiniot, LK Shen, R Barlow, C Wynn, TA Morse, HC Gearhart, PJ Wynshaw-Boris, A Max, EE Hodes, RJ TI Immunoglobulin class switch recombination is impaired in Atm-deficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE ataxia telangiectasia; Ig class switching; B lymphocytes; DNA damage; DNA repair ID DOUBLE-STRAND BREAKS; DNA-DAMAGE-RESPONSE; TELANGIECTASIA MUTATED ATM; CYTIDINE DEAMINASE AID; ATAXIA-TELANGIECTASIA; DEPENDENT PHOSPHORYLATION; B-CELLS; SOMATIC HYPERMUTATION; REGION RECOMBINATION; T-CELLS AB Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-deficient mice. In response to T cell-dependent antigen (Ag), Atm(-/-) mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and less total IgE than Atm(+/+) controls. To determine whether Atm(-/-) B cells have an intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses of purified B cells. Atm(-/-) cells secreted substantially less IgA, IgG1, IgG2a, IgG3, and IgE than wild-type (WT) controls in response to stimulation with lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines. Molecular analysis of in vitro responses indicated that WT and Atm(-/-) B cells produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm(-/-) B cells produced markedly reduced productive IgG1 and IgE transcripts. The reduction in isotype switching by Atm(-/-) B cells occurs at the level of genomic DNA recombination as measured by digestion-circularization PCR. Analysis of sequences at CSR sites indicated that there is greater microhomology at the mu-gamma1 switch junctions in ATM B cells than in wild-type B cells, suggesting that ATM function affects the need or preference for sequence homology in the CSR process. These findings suggest a role of ATM in DNA DSB recognition and/or repair during CSR. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NIH, Natl Ctr Human Genome Res, Genet Dis Res Branch, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Lumsden, JM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM lumsdenj@mail.nih.gov RI Wynn, Thomas/C-2797-2011; OI Morse, Herbert/0000-0002-9331-3705 NR 65 TC 92 Z9 94 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 2004 VL 200 IS 9 BP 1111 EP 1121 DI 10.1084/jem.20041074 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 869CS UT WOS:000224961600004 PM 15504820 ER PT J AU Walsh, PJ Wei, Z Wood, CM Loong, AM Hiong, KC Lee, SML Wong, WP Chew, SF Ip, YK AF Walsh, PJ Wei, Z Wood, CM Loong, AM Hiong, KC Lee, SML Wong, WP Chew, SF Ip, YK TI Nitrogen metabolism and excretion in Allenbatrachus grunniens (L): effects of variable salinity, confinement, high pH and ammonia loading SO JOURNAL OF FISH BIOLOGY LA English DT Article DE Allenbatrachus grunniens; ammoniotely; Batrachoididae; carbamoyl phosphate synthetase; ornithine-urea cycle; ureotely ID TOADFISH OPSANUS-BETA; PULSATILE UREA EXCRETION; UREOGENIC GULF TOADFISH; AMINO-ACID CATABOLISM; BATRACHOIDID FISHES; PORICHTHYS-NOTATUS; SUBTROPICAL BAY; EVOLUTION; PATTERNS; EXPOSURE AB The nitrogen metabolism and excretion patterns of the grunting toadfish Allenbatrachus grunniens and the effects of salinity on these processes were examined. Individuals of A. grunniens were subjected to several experimental treatments, including variable salinity (2 to 30), high pH (8.5 compared to 7.0 for controls), high environmental ammonia (10 mM) and confinement to small water volumes, and measurements were made of activities of selected enzymes of nitrogen metabolism, ammonia and urea excretion rates, and tissue and plasma contents of ammonia, urea and amino acids. Activities of key ornithine-urea cycle enzymes were rather low (e.g. liver carbamoyl phosphate synthetase III activity was 0.001 mumols min(-1) g(-1)), and A. grunniens consistently demonstrated a low capacity for urea excretion despite significant elevations of plasma and tissue ammonia contents by the high pH and high ammonia treatments. This species could thus be categorized as ammoniotelic. Total free amino acid contents in plasma and tissues were increased by the high pH and high ammonia treatments, but no patterns were discerned in individual amino acids that would indicate any preferential accumulation (e.g. alanine and glutamine) as has been noted previously in several semi-terrestrial fish species. Thus, it appeared that A. grunniens was not unusual in its patterns of nitrogen metabolism and excretion in comparison to other 'typical' teleosts. Furthermore, manipulation of salinity had no major effects on nitrogen excretion in either this species or in comparative studies with the ureotelic gulf toadfish Opsallus beta. The results are discussed in the context of the broader pattern of nitrogen metabolism and excretion in the Batrachoididae. (C) 2004 The Fisheries Society of the British Isles. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Natl Univ Singapore, Dept Sci Biol, Singapore 117543, Singapore. McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. Nanyang Technol Univ, Natl Inst Educ, Singapore 637616, Singapore. RP Walsh, PJ (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM pwalsh@rsmas.miami.edu RI Ip, Yuen Kwong/H-8041-2012; Chew, Shit Fun/I-2248-2012 NR 35 TC 10 Z9 10 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-1112 J9 J FISH BIOL JI J. Fish Biol. PD NOV PY 2004 VL 65 IS 5 BP 1392 EP 1411 DI 10.1111/j.1095-8649.2004.00538.x PG 20 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 873LW UT WOS:000225282800014 ER PT J AU Calvisi, DF Ladu, S Hironaka, K Factor, VM Thorgeirsson, SS AF Calvisi, DF Ladu, S Hironaka, K Factor, VM Thorgeirsson, SS TI Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer SO JOURNAL OF HEPATOLOGY LA English DT Article DE vitamin E; HCC; iNOS; NADPH oxidase; transgenic mouse models ID GROWTH-FACTOR-ALPHA; NITRIC-OXIDE; DNA-DAMAGE; OXIDATIVE STRESS; ACCELERATED HEPATOCARCINOGENESIS; HEPATOCELLULAR-CARCINOMA; SYNTHASE EXPRESSION; MEDIATED INHIBITION; HEME OXYGENASE; KNOCKOUT MICE AB Background/Aims: Co-expression of c-Myc and TGF-alpha in the mouse liver accelerates hepatocarcinogenesis and enhances DNA damage due to chronic oxidative stress. Dietary supplementation with vitamin E (VE) inhibits hepatocarcinogenesis and reduces chromosomal alterations in the same mice. Here we investigated the sources of reactive oxygen species (ROS) production in c-Myc/TGF-alpha transgenic mice. Methods: Inducible nitric oxide synthase (iNOS) and NADPH oxidase levels were determined in c-Myc, TGF-alpha and c-Myc/TGF-alpha mice by RT-PCR, western blot analysis and immunohistochemistry. Results: iNOS and nitrotyrosines levels were higher in the three transgenic lines when compared with wild-type mice. Preneoplastic and neoplastic lesions from c-Myc, TGF-alpha and c-Myc/TGF-alpha transgenic mice displayed upregulation of NADPH oxidase subunits p47-, 67-phox, Racl, HSP 70, and HO-1. Importantly, dietary supplementation with vitamin E abolished iNOS expression, lowered nitrotyrosines, p47-, p67-phox, and Racl levels, and suppressed HSP 70 and HO-1 proteins in c-Myc/TGF-alpha livers. Conclusions: The results suggest that iNOS and NADPH oxidase are involved in ROS generation during c-Myc/TGF-alpha hepatocarcinogenesis and are inhibited by VE treatment. The data provide additional evidence for the potential use of VE in treatment of chronic liver diseases and HCC prevention. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4146A1,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 51 TC 41 Z9 43 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2004 VL 41 IS 5 BP 815 EP 822 DI 10.1016/j.jhep.2004.07.030 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 873VM UT WOS:000225309200016 PM 15519655 ER PT J AU Levine, SJ AF Levine, SJ TI Mechanisms of soluble cytokine receptor generation SO JOURNAL OF IMMUNOLOGY LA English DT Review ID NECROSIS-FACTOR-ALPHA; STIMULATING FACTOR-RECEPTOR; HUMAN INTERLEUKIN-6 RECEPTOR; CONVERTING ENZYME ADAM17; MEMBRANE-BOUND FORMS; II IL-1 RECEPTOR; T-CELL; ACCESSORY PROTEIN; BINDING-PROTEIN; MOLECULAR-CLONING AB Soluble cytokine receptors regulate inflammatory and immune events by functioning as agonists or antagonists of cytokine signaling. As such, they act within complex receptor systems that include signaling receptors, nonsignaling decoy receptors, receptor-associated proteins, and soluble receptor antagonists. Soluble cytokine receptors can be generated by several mechanisms, which include proteolytic cleavage of receptor ectodomains, alternative splicing of mRNA transcripts, transcription of distinct genes that encode soluble cytokine-binding proteins, release of full-length receptors within the context of exosome-like vesicles, and cleavage of GPI-anchored receptors. Furthermore, the important role of soluble cytokine receptors in regulating host defense mechanisms is evidenced by viruses that encode soluble homologues of mammalian receptors and thereby evade innate host immune responses via the sequestration of essential cytokines. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov NR 113 TC 101 Z9 106 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5343 EP 5348 PG 6 WC Immunology SC Immunology GA 864XH UT WOS:000224665900003 PM 15494479 ER PT J AU Ozaki, K Spolski, R Ettinger, R Kim, HP Wang, G Qi, CF Hwu, P Shaffer, DJ Akilesh, S Roopenian, DC Morse, HC Lipsky, PE Leonard, WJ AF Ozaki, K Spolski, R Ettinger, R Kim, HP Wang, G Qi, CF Hwu, P Shaffer, DJ Akilesh, S Roopenian, DC Morse, HC Lipsky, PE Leonard, WJ TI Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of blimp-1 and bcl-61 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; CUTTING EDGE; RECEPTOR; INTERLEUKIN-21; MATURATION; CHAIN; MECHANISMS; APOPTOSIS; EXPANSION; SURVIVAL AB IL-21 is a type I cytokine whose receptor is expressed on T, B, and NK cells. Within the B cell lineage, IL-21 regulates IgG1 production and cooperates with IL-4 for the production of multiple Ab classes in vivo. Using IL-21-transgenic mice and hydrodynamics-based gene delivery of IL-21 plasmid DNA into wild-type mice as well as in vitro studies, we demonstrate that although IL-21 induces death of resting B cells, it promotes differentiation of B cells into postswitch and plasma cells. Thus, IL-21 differentially influences B cell fate depending on the signaling context, explaining how IL-21 can be proapoptotic for B cells in vitro yet critical for Ag-specific Ig production in vivo. Moreover, we demonstrate that IL-21 unexpectedly induces expression of both Blimp-1 and Bcl-6, indicating mechanisms as to how IL-21 can serve as a complex regulator of B cell maturation and terminal differentiation. Finally, BXSB-Yaa mice, which develop a systemic lupus erythematosus-like disease, have greatly elevated IL-21, suggesting a role for IL-21 in the development of autoimmune disease. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU NIDDK NIH HHS [DK56597] NR 33 TC 391 Z9 412 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5361 EP 5371 PG 11 WC Immunology SC Immunology GA 864XH UT WOS:000224665900006 PM 15494482 ER PT J AU De Rosa, SC Lu, FX Yu, J Perfetto, SP Falloon, J Moser, S Evans, TG Koup, R Miller, CJ Roederer, M AF De Rosa, SC Lu, FX Yu, J Perfetto, SP Falloon, J Moser, S Evans, TG Koup, R Miller, CJ Roederer, M TI Vaccination in humans generates broad T cell cytokine responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CROSS-PRESENTATION; DENDRITIC CELLS; FLOW-CYTOMETRY; LYMPHOCYTES; QUANTIFICATION; DIVERSITY; ANTIGENS; BLOOD AB In recent years, the quantification of T cell responses to pathogens or immunogens has become a common tool in the evaluation of disease pathogenesis or vaccine immunogenicity. Such measurements are usually limited to enumerating IFN-gamma-producing cells after ex vivo stimulation with Ag, but little is known about the phenotype or complete functional repertoire of the Ag-specific cells. We used 12-color flow cytometry to characterize Ag-specific T cells elicited by vaccines or natural infection to determine lineage and differentiation status as well as the capacity to produce four cytokines (IFN-gamma, TNF-alpha, IL-2, and IL-4) and a chemokine (MIP1beta). As expected, responding cells had a typical memory phenotype; however, the cytokine profiles associated with the responses were highly complex. The pattern of cytokine coexpression in response to specific Ags was a skewed subset of the complete repertoire (revealed by polyclonal stimulation). We found significant differences in the patterns of cytokines elicited by vaccination (where IFN-gamma was by far a subdominant response) vs natural infection; in addition, there was fairly significant intersubject variation. Our findings illustrate the limitation of the evaluation of immune responses using single functional measurements (such as IFN-gamma); in fact, it is likely that sensitive evaluation of Ag-specific T cells will require the coordinate measurement of several cytokines. The presence and variability of these, complex response profiles introduce the possibility that selective functional expression patterns may provide correlates for vaccine efficacy or disease progression. C1 NIAID, Vaccine Res Ctr, Immunotechnol Sect, NIH, Bethesda, MD 20892 USA. Calif Natl Primate Res Ctr, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Div Infect Dis, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Internal Med, Davis, CA 95616 USA. RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, Immunotechnol Sect, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM roederer@nih.gov RI Roederer, Mario/G-1887-2011 FU NCRR NIH HHS [RR14555]; NIA NIH HHS [P51AG00169]; PHS HHS [R0133169, U5429125] NR 13 TC 135 Z9 135 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5372 EP 5380 PG 9 WC Immunology SC Immunology GA 864XH UT WOS:000224665900007 PM 15494483 ER PT J AU Singh, UP Singh, S Ravichandran, P Taub, DD Lillard, JW AF Singh, UP Singh, S Ravichandran, P Taub, DD Lillard, JW TI Viral macrophage-inflammatory protein-II: A viral chemokine that differently affects adaptive mucosal immunity compared with its mammalian counterparts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; RECEPTOR HOMOLOG; CELL ACTIVATION; T-CELLS; B-CELLS; VMIP-II; COUPLED RECEPTOR; ENCODES HOMOLOGS; DNA-SEQUENCES AB Chemokines play a profound role in leukocyte trafficking and the development of adaptive immune responses. Perhaps due to their importance in host defense, viruses have adopted many of the hallmarks displayed by chemokines. In particular, viral MIP-II (vMIP-II) is a human chemokine homologue that is encoded by human herpes virus 8. vMIP-II is angiogenic, selectively chemotactic for Th2 lymphocytes, and a homologue of human I-309 and mouse TCA-3, which also differentially attracts Th2 cells. To better understand the effect of viral chemokines on mucosal immunity, we compared the affects of vMIP-II, I-309, and TCA-3 on cellular and humoral immune responses after nasal immunization with OVA. These CCR8 ligands significantly enhanced Ag-specific serum and mucosal Abs through increasing Th2 cytokine secretion by CD4(+) T cells. These alterations in adaptive humoral and cellular responses were preceded (12 h after immunization) by an increase in CD4(+) T and B cells in nasal tracts with decreases of these leukocyte populations in the lung. Interestingly, vMIP-II increased neutrophil infiltration in the lung and Ag-specific IL-10-secreting CD4(+) T cells after immunization. Although I-309 increased the number of CD28-, CD40L-, and CD30-positive, Ag-stimulated naive CD4(+) T cells, vMIP-II and TCA-3 decreased the number of CD28-, CD40L-, and CD30-positive, resting naive CD4(+) T cells. Taken together, these studies suggest that CCR8 ligands direct host Th2 responses, and vMIP-II up-regulates IL-10 responses and limits costimulatory molecule expression to mitigate host immunity. C1 Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. NIA, Immunol Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Lillard, JW (reprint author), Morehouse Sch Med, Dept Microbiol Biochem & Immunol, 720 Westview Dr, Atlanta, GA 30310 USA. EM Lillard@msm.edu FU NCRR NIH HHS [RR03034]; NIDDK NIH HHS [DK58967]; NIGMS NIH HHS [GM08248] NR 66 TC 6 Z9 9 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 NOV 1 PY 2004 VL 173 IS 9 BP 5509 EP 5516 PG 8 WC Immunology SC Immunology GA 864XH UT WOS:000224665900023 PM 15494499 ER PT J AU Mizukoshi, E Sidney, J Livingston, B Ghany, M Hoofnagle, JH Sette, A Rehermann, B AF Mizukoshi, E Sidney, J Livingston, B Ghany, M Hoofnagle, JH Sette, A Rehermann, B TI Cellular immune responses to the hepatitis B virus polymerase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID E-ANTIGEN SEROCONVERSION; T-LYMPHOCYTE RESPONSES; ACUTE VIRAL-HEPATITIS; LAMIVUDINE TREATMENT; SURFACE-ANTIGEN; HBV INFECTION; IN-VIVO; HLA-DR; CELLS; EPITOPES AB CD4(+) T cells play an important role in hepatitis B virus (HBV) infection by secretion of Th1 cytokines that down-regulate HBV replication, and by promoting CD8(+) T cell and B cell responses. We have identified and characterized 10 CD4(+) T cell epitopes within polymerase and used them to analyze the immunological effects of long-term antiviral therapy as compared with spontaneous recovery from HBV infection. Candidate epitopes were tested for binding to 14 HLA-DR molecules and in IFN-gamma ELISPOT and cytotoxicity assays using peripheral blood lymphocytes from 66 HBV-infected patients and 16 uninfected controls. All 10 epitopes bound with high affinity to the most prevalent HLA-DR Ags, were conserved among HBV genomes, and induced IFN-gamma responses from HBV-specific CD4(+) T cells. Several epitopes contained nested MHC class I motifs and stimulated HBV-specific IFN-gamma production and cytotoxicity of CD8(+) T cells. HBV polymerase-specific responses were more frequent during acute, self-limited hepatitis and after recovery (12 of 18; 67%) than during chronic hepatitis (16 of 48 (33%); p = 0.02). Antiviral therapy of chronic patients restored HBV polymerase and core-specific T cell responses during the first year of treatment, but thereafter, responses decreased and, after 3 years, were no more frequent than in untreated patients. Decreased T cell responsiveness during prolonged therapy was associated with increased prevalence of lamivudine-resistant HBV mutants and increased HBV titers. The data provide a rationale for the combination of antiviral and immunostimulatory therapy. These newly described HBV polymerase epitopes could be a valuable component of a therapeutic vaccine for a large and ethnically diverse patient population. C1 NIDDKD, Liver Dis Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Epimmune Inc, San Diego, CA 92121 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. RP Rehermann, B (reprint author), NIDDKD, Liver Dis Sect, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov FU NIAID NIH HHS [N01-AI-95362] NR 52 TC 51 Z9 59 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5863 EP 5871 PG 9 WC Immunology SC Immunology GA 864XH UT WOS:000224665900064 PM 15494540 ER PT J AU Khong, HT Yang, JC Topalian, SL Sherry, RM Mavroukakis, SA White, DE Rosenberg, SA AF Khong, HT Yang, JC Topalian, SL Sherry, RM Mavroukakis, SA White, DE Rosenberg, SA TI Immunization of HLA-A*0201 and/or HLA-DP beta 1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cancer vaccine; tumor antigens; NY-ESO-1; HLA-A2; HLA-DP ID CYTOTOXIC T-LYMPHOCYTES; IMMUNE-RESPONSE; PEPTIDE VACCINE; CELL AB HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8(+) T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1: 165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NYESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class IT-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NYESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization. C1 NCI, Surg Branch, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Canc Res Ctr, Natl Inst Hlth, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 16 TC 47 Z9 50 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP 472 EP 477 DI 10.1097/00002371-200411000-00007 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800007 PM 15534491 ER PT J AU Robinson, MR Chan, CC Yang, JC Rubin, BI Gracia, GJ Sen, HN Csaky, KG Rosenberg, SA AF Robinson, MR Chan, CC Yang, JC Rubin, BI Gracia, GJ Sen, HN Csaky, KG Rosenberg, SA TI Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma - A new cause of uveitis SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; immunotherapy; uveitis; autoimmunity; CTLA-4 antibody AB Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) is an important costimultory receptor expressed on activated T cells. CTLA-4 blockade using a monoclonal antibody (mAb) in conjunction with tumor vaccines has improved tumor responses in animal models and enhanced numerous models of T cell-associated autoimmune diseases. Two patients with stage IV metastatic melanoma vaccinated with the gp 100 melanocyte/melanoma differentiation antigen either before or during anti-CTLA-4 mAb therapy developed uveitis, This is the first report of autoimmune disease involving the eye in patients treated with anti-CTLA-4 mAb. This suggests that CTLA-4 is an important regulatory molecule for maintenance of tolerance to melanosomal antigens and prevention of uveitis. C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Robinson, MR (reprint author), NEI, NIH, 10-10S229,10 Ctr Dr MSC 1863, Bethesda, MD 20892 USA. EM robinsonm@nei.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 5 TC 87 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP 478 EP 479 DI 10.1097/00002371-200411000-00008 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800008 PM 15534492 ER PT J AU Gaittinoni, L Klebanoff, CA Palmer, DC Wrzesinski, C Kerstann, K Yu, ZY Finkelstein, SE Surman, DR Restifo, NP AF Gaittinoni, L Klebanoff, CA Palmer, DC Wrzesinski, C Kerstann, K Yu, ZY Finkelstein, SE Surman, DR Restifo, NP TI Acquisition of terminal effector functions in vitro impairs in vivo anti-tumor efficacy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S2 EP S2 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800013 ER PT J AU Hixon, J Stauffer, J Lincoln, E Back, T Jonak, Z Wigginton, J AF Hixon, J Stauffer, J Lincoln, E Back, T Jonak, Z Wigginton, J TI IL-18 induces complete regression of orthotopic primary and metastatic murine neuroblastoma tumors and potentiates antitumor immune reactivity in combination with IL-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 CCR, Pediat Oncol Branch, NCI, Frederick, MD USA. SAID Frederick, IRSP, Frederick, MD USA. Glaxo Smithkline Pharmaceut, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S17 EP S18 DI 10.1097/00002371-200411000-00066 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800067 ER PT J AU Khan, T Hixon, J Stauffer, J Lincoln, E Back, T Sayers, T Wigginton, J AF Khan, T Hixon, J Stauffer, J Lincoln, E Back, T Sayers, T Wigginton, J TI Proteasome inhibition to maximize the apoptotic potential of cytokine therapy for murine neuroblastoma tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 NCI, CCR, Pediat Oncol Branch, Frederick, MD 21701 USA. SAIC Frederick, IRSP, Frederick, MD 21701 USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S57 EP S57 DI 10.1097/00002371-200411000-00203 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800204 ER PT J AU Salcedo, R Hahn, C Stauffer, J Lincoln, E Hixon, J Shafer-Weaver, K Malyguine, A Kastelein, R Wigginton, J AF Salcedo, R Hahn, C Stauffer, J Lincoln, E Hixon, J Shafer-Weaver, K Malyguine, A Kastelein, R Wigginton, J TI Interleukin-27 enhances tumor cell MHC class I expression and specific T cell reactivity and mediates CD8+T-Cell dependent regression of primary and/or metastatic murine neuroblastoma tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 CCR, Pediat Oncol Branch, NCI, Frederick, MD USA. SAIC Frederick, IRSP, Frederick, MD USA. SAIC Frederick, LCMI, Frederick, MD USA. DNAX Res Inst Molec & Cellular Biol Inc, Dept Immunol, Palo Alto, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S17 EP S17 DI 10.1097/00002371-200411000-00065 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800066 ER PT J AU Shevach, E AF Shevach, E TI Regulatory T cells: Friend or foe SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S48 EP S48 DI 10.1097/00002371-200411000-00173 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800174 ER PT J AU Stroncek, D Basil, C Marincola, F Nagorsen, D Deola, S Smith, K Wang, E Panelli, M AF Stroncek, D Basil, C Marincola, F Nagorsen, D Deola, S Smith, K Wang, E Panelli, M TI Response of polarized-macrophages to interferon stimulation SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 NIH, Immunogenet Sect, Dept Transfus Med, CC, Bethesda, MD USA. Univ Berlin, Dept Hematol Oncol & Transfus Med, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S16 EP S17 DI 10.1097/00002371-200411000-00063 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800064 ER PT J AU Sun, K Welniak, LA Wiltrout, R Blazar, BR Murphy, WJ AF Sun, K Welniak, LA Wiltrout, R Blazar, BR Murphy, WJ TI Low total body irradiation (TBI) augments the synergistic anti-tumor effects of anti-CD40 and IL2 immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA. Nevada Canc Inst, Div Basic Res, Las Vegas, NV USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. Univ Minnesota, Ctr Canc, Div Bone Marrow Transplantat, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S19 EP S19 DI 10.1097/00002371-200411000-00070 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800071 ER PT J AU Hisada, M Stuver, SO Okayama, A Li, HC Sawada, T Hanchard, B Mueller, NE AF Hisada, M Stuver, SO Okayama, A Li, HC Sawada, T Hanchard, B Mueller, NE TI Persistent paradox of natural history of human T lymphotropic virus type I: Parallel analyses of Japanese and Jamaican carriers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 11th International Conference on Human Retrovirology: HTLV and Related Viruses CY JUN 09-12, 2003 CL San Francisco, CA ID MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; HTLV-I; INFECTED CELLS; CD8(+) CELLS; LEUKEMIA; LOAD; VIVO AB Human T lymphotropic virus type I (HTLV-I) is endemic in southern Japan and the Caribbean, but the incidence of HTLV-I-associated diseases varies across geographic areas. We compared markers of disease pathogenesis among 51 age- and sex-matched HTLV-I carrier pairs from Japan and Jamaica. The mean antibody titer (P = .03) and detection of anti-Tax antibody (P = .002) were higher in Jamaican subjects than in Japanese subjects, but provirus load was similar between the 2 groups (P = .26). The correlation between antibody titer and provirus load was more prominent among Jamaican subjects than among Japanese subjects (). These findings underscore the differences in host immune response to HTLV-I infection in 2 populations. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Miyazaki Med Coll, Dept Internal Med 2, Miyazaki 88916, Japan. Eisai Tsukuba Res Labs, Ibaraki, Japan. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8008, Rockville, MD 20852 USA. EM hisadam@exchange.nih.gov FU NCI NIH HHS [2R01-CA38450, N01-CP-40548] NR 14 TC 35 Z9 36 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 NOV 1 PY 2004 VL 190 IS 9 BP 1605 EP 1609 DI 10.1086/424598 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 859YA UT WOS:000224303100011 PM 15478065 ER PT J AU Jezowska-Bojczuk, M Kaczmarek, P Bal, W Kasprzak, KS AF Jezowska-Bojczuk, M Kaczmarek, P Bal, W Kasprzak, KS TI Coordination mode and oxidation susceptibility of nickel(II) complexes with 2 '-deoxyguanosine 5 '-monophosphate and L-histidine SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE dGMP; 8-Oxo-dGMP; Ni(II); binary complexes; ternary complexes; reactive oxygen species ID METAL-BINDING SEQUENCE; AQUEOUS-SOLUTION; GUANOSINE 5'-MONOPHOSPHATE; HISTONE H2A; X-RAY; ADENOSINE 5'-MONOPHOSPHATE; MACROCHELATE FORMATION; CRYSTAL-STRUCTURES; HYDROGEN-PEROXIDE; DNA-SYNTHESIS AB The formation of binary and ternary complexes of Ni(II) with two biologically relevant molecules, 2'-deoxyguanosine 5'-monophosphate (dGMP) and L-histidine (histidine or His) was characterized by potentiometry and UV-visible spectroscopy. For dGMP, the mononuclear complexes with stoichiometries NiH2L+, NiHL and NiL- were found. In the mixed system the ternary complexes NiH(2)LA, NiHLA(-) and NiLA(2-) were detected. In binary systems, the Ni(II) ion coordinates to dGMP through the N-7 atom of its purine ring and indirectly through a water molecule bonded to the phosphate group, while in ternary complexes Ni(II) is bonded to all three histidine donors and directly to the phosphate group of dGMP. Both binary and ternary complexes are susceptible to oxidation by H2O2, with the increased formation of 8-oxo-dGMP in the ternary system. The toxicological relevance of these findings stems from possible disturbance by the major biological Ni(II)-His complex of the nucleotide pools homeostasis through the formation of ternary species and oxidation promotion, as well as from 8-oxo-dGMP capacity to inhibit enzymatic elimination of pro-mutagenic oxidized nucleotides from such pools. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Jezowska-Bojczuk, M (reprint author), Univ Wroclaw, Fac Chem, F Joliot Curie 14, PL-50383 Wroclaw, Poland. EM mjb@wchuwr.chem.uni.wroc.pl NR 61 TC 19 Z9 19 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD NOV PY 2004 VL 98 IS 11 BP 1770 EP 1777 DI 10.1016/j.jinorgbio.2004.08.002 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 865QN UT WOS:000224717700012 PM 15522404 ER PT J AU Sauer, B Vogler, R Zimmermann, K Fujii, M Anzano, MB Schafer-Korting, M Roberts, AB Kleuser, B AF Sauer, B Vogler, R Zimmermann, K Fujii, M Anzano, MB Schafer-Korting, M Roberts, AB Kleuser, B TI Lysophosphatidic acid interacts with transforming growth factor-beta signaling to mediate keratinocyte growth arrest and chemotaxis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE lipid mediators; migration; proliferation; smad3 protein ID PROTEIN-COUPLED RECEPTORS; BREAST-CANCER CELLS; FACTOR-BINDING PROTEIN-3; TGF-BETA; SPHINGOSINE 1-PHOSPHATE; BIOACTIVE LYSOPHOSPHOLIPIDS; EXTRACELLULAR-MATRIX; FACTOR-ALPHA; MODULATION; DIFFERENTIATION AB Lysophosphatidic acid (LPA, 1-acyl-glycerol-3-phosphate) plays an important role in diverse biological responses including cell proliferation, differentiation, survival, migration, and tumor cell invasion. The most prominent source of LPA is platelets from which it is released after thrombin activation and is assumed to be an essential function of this lysophospholipid in cutaneous wound closure. Therefore, we examined the role of LPA on biological responses of keratinocytes. Although LPA potently enhances keratinocyte migration, it strongly induces growth arrest of proliferating epidermal cells. Thus, LPA possesses analogous actions to transforming growth factor-beta (TGF-beta), which is also released from degranulating platelets at wounded sites. In contrast to LPA, the intracellular signaling events of TGF-beta have been clearly identified and indicate that Smad3 is involved in chemotaxis and cell growth arrest of keratinocytes induced by this cytokine. Here we show that LPA, although it does not alter TGF-beta release is capable to activate Smad3 and results in a heteromerization with Smad4 and binding of the complex to its specific DNA-promoter elements. LPA completely fails to induce chemotaxis in Smad3-deficient cells, whereas growth inhibition is at least in part reduced. These findings indicate an essential role of Smad3 in diverse biological properties of LPA-stimulated keratinocytes. C1 Free Univ Berlin, Inst Pharm Pharmacol & Toxicol, D-14195 Berlin, Germany. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Kleuser, B (reprint author), Free Univ Berlin, Inst Pharm Pharmacol & Toxicol, Konigin Luise Str 2&4, D-14195 Berlin, Germany. EM kleuser@zedat.fu-berlin.de NR 51 TC 19 Z9 20 U1 0 U2 0 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 NOV PY 2004 VL 123 IS 5 BP 840 EP 849 DI 10.1111/j.0022-202X.2004.23458.x PG 10 WC Dermatology SC Dermatology GA 860MF UT WOS:000224347000007 PM 15482469 ER PT J AU Repertinger, SK Campagnaro, E Fuhrman, J El-Abaseri, T Yuspa, SH Hansen, LA AF Repertinger, SK Campagnaro, E Fuhrman, J El-Abaseri, T Yuspa, SH Hansen, LA TI EGFR enhances early healing after cutaneous incisional wounding SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE EGFR; keratinocytes; proliferation; wound healing ID GROWTH-FACTOR RECEPTOR; TARGETED DISRUPTION; MAST-CELLS; ANGIOGENESIS; MICE; INHIBITION; EXPRESSION; CYTOKINES; LIGANDS; RAS AB The epidermal growth factor receptor (EGFR) has been implicated in the regulation of wound healing. In order to directly evaluate the role of endogenous EGFR in cutaneous incisional wound healing, we examined EGFR null- and wild-type skin after injury. By 5 d after wounding, re-epithelialization was complete in all EGFR wild-type wounds, but in only 40% of EGFR null wounds. Delayed wound closure in EGFR null skin was accompanied by an increase in edema, longer lasting and more prominent eschar, and increased distance between apposing wound edges. EGFR altered neutrophil and mast cell infiltration, and enhanced angiogenesis. EGFR enhanced epithelial proliferation during the first 3 d following injury, although proliferation was greater in EGFR null wounds at 5 d. Although migration was decreased in EGFR null keratinocytes cultured with standard medium or in medium supplemented with transforming growth factor-alpha when compared with controls, the addition of the wound-associated motogen keratinocyte growth factor eliminated the differences between genotypes. Epithelial migration into the wound was decreased in EGFR null skin, suggesting that both EGFR-dependent and -independent mechanisms regulate migration during wound healing. These data demonstrate that EGFR regulates multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. C1 Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Hansen, LA (reprint author), Creighton Univ, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USA. EM lhansen@creighton.edu FU NCRR NIH HHS [P20 RR018788]; NIEHS NIH HHS [ES00365-01, K22 ES000365] NR 25 TC 75 Z9 82 U1 0 U2 2 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 NOV PY 2004 VL 123 IS 5 BP 982 EP 989 DI 10.1111/j.0022-202X.2004.23478.x PG 8 WC Dermatology SC Dermatology GA 860MF UT WOS:000224347000026 PM 15482488 ER PT J AU Terunuma, A Shaya, MB Udey, MC Vogel, JC AF Terunuma, A Shaya, MB Udey, MC Vogel, JC TI An in vivo competitive repopulation assay system to evaluate human keratinocyte stem cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID MULTIDRUG-RESISTANCE GENE; TRANSGENE EXPRESSION; VITRO; SELECTION; EPIDERMIS; MODEL C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N260,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. EM jonvogel@mail.nih.gov NR 11 TC 5 Z9 5 U1 0 U2 0 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 NOV PY 2004 VL 123 IS 5 BP 993 EP 995 DI 10.1111/j.0022-202X.2004.23456.x PG 3 WC Dermatology SC Dermatology GA 860MF UT WOS:000224347000028 PM 15482490 ER PT J AU Zhang, Y Horti, AG AF Zhang, Y Horti, AG TI Synthesis of 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-[F-18]fluoropyridin-4-yl)pyr idine ([F-18]NIDA 522131), a novel potential radioligand for studying extrathalamic nicotinic acetylcholine receptors by PET SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE nicotinic acetylcholine receptors; nucleophilic halogen-exchange; positron emission tomography; F-18 ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN; BINDING AB 6-Chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-[F-18]fluoropyridin-4-yl)pyridine ([F-18]NIDA 522131), a potential radioligand for studying extrathalamic nicotinic acetylcholine receptors by positron-emission tomography, was synthesized via no-carrier-added nucleophilic [F-18]fluorination of 6-chloro-3-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl) methoxy)-5-(2-iodopyridin-4-yl)vinyl)pyridine, followed by acidic deprotection. The overall radiochemical yield of the radiosynthesis was 4-8% (non-decay-corrected), the specific radioactivity was in the range of 167-335 GBq/mumol (4500-9000 mCi/mumol) and the radiochemical purity was greater than 99%. Preparation of [F-18]NIDA522131 via corresponding bromo-derivative 2 is also described. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Natl Inst Drug Abuse, NIH, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Horti, AG (reprint author), Natl Inst Drug Abuse, NIH, Neuroimaging Res Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ahorti@intra.nida.nih.gov NR 13 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 2004 VL 47 IS 13 BP 947 EP 952 DI 10.1002/jlcr.883 PG 6 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 878PA UT WOS:000225657600005 ER PT J AU Kiesewetter, DO Eckelman, WC AF Kiesewetter, DO Eckelman, WC TI Utility of azetidinium methanesulfonates for radiosynthesis of 3-[F-18]fluoropropyl amines SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE fluorine-18; aliphatic fluorination; sigma receptor; radiopharmaceutical ID RECEPTOR RADIOLIGAND; F-18; DERIVATIVES; ANTAGONISTS AB 3-Methanesulfonyloxypropyl tertiary amines were observed to cyclize to form azetidinium methanesulfonate moieties. Heat-induced cyclization of 3-methanesulfonyloxypropyl amines was utilized for preparation of azetidinium methanesulfonates. The azetidinium methanesulfonates were found to incorporate radioactive [F-18]fluoride (decay-corrected yields >60%) efficiently, resulting in an efficient synthesis of 3-[F-18]fluoropropyl tertiary amines. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NIH, Positron Emission Tomog, Ctr Clin, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIH, Positron Emission Tomog, Ctr Clin, 10-1C401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. EM dk7k@nih.gov NR 14 TC 6 Z9 6 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 2004 VL 47 IS 13 BP 953 EP 969 DI 10.1002/jlcr.884 PG 17 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 878PA UT WOS:000225657600006 ER PT J AU Taylor, ML Sehgal, D Raffeld, M Obiakor, H Akin, C Mage, RG Metcalfe, DD AF Taylor, ML Sehgal, D Raffeld, M Obiakor, H Akin, C Mage, RG Metcalfe, DD TI Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID RECEPTOR TYROSINE KINASE; PROTOONCOGENE C-KIT; SYSTEMIC MASTOCYTOSIS; URTICARIA PIGMENTOSA; CATALYTIC DOMAIN; BONE-MARROW; EXPRESSION; LEUKEMIA; DISEASE; IDENTIFICATION AB Mastocytosis is characterized by focal heterotypic clusters of mast cells and lymphocytes in the bone marrow and by a somatically acquired activating Kit mutation, D816V. The relationship of the occurrence of this mutation to the heterotypic clusters of mast cells and lymphocytes in bone marrow is unknown. We hypothesized that these two unique features of mastocytosis were related. To explore this hypothesis, laser capture microdissected mast cells, B cells, and T cells, from both lesional and non-lesional areas of bone marrow biopsy tissues from patients with mastocytosis, were examined for the D816V mutation in their DNA, using HinfI restriction digestion of nested PCR products amplified from extracts of dissected cells. The D816V mutation was detected in mast cells, B cells, and T cells from lesional but not nonlesional areas of bone marrow tissues. B cells obtained from lesional areas of tissue were also assessed for clonality and were found to at least represent an oligoclonal population. Thus, mast cells and lymphocytes within focal aggregates in the bone marrow of those with mastocytosis are more frequently positive for the codon 816 activating mutation. Further, the B cell population is oligoclonal, suggesting that clonal proliferation is unlikely to be the basis of clustering. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,Room 11C 205,MSC 1881, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov NR 23 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 BP 335 EP 342 DI 10.1016/S1525-1578(10)60529-6 PG 8 WC Pathology SC Pathology GA 885XG UT WOS:000226190000008 PM 15507672 ER PT J AU Perlmutter, MA Best, CJM Gillespie, JW Gathright, Y Gonzalez, S Velasco, A Linehan, WM Emmert-Buck, MR Chuaqui, RF AF Perlmutter, MA Best, CJM Gillespie, JW Gathright, Y Gonzalez, S Velasco, A Linehan, WM Emmert-Buck, MR Chuaqui, RF TI Comparison of snap freezing versus ethanol fixation for gene expression profiling of tissue specimens SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID LASER CAPTURE MICRODISSECTION; PARAFFIN-EMBEDDED TISSUES; HUMAN PROSTATE-CANCER; MICROARRAY ANALYSIS; AMPLIFICATION; GRADE; RNA AB Frozen tissue specimens are the gold standard for molecular analysis. However, snap freezing presents several challenges regarding collection and storage of tissue, and preservation of histological detail. We evaluate an alternative preservation method, ethanol fixation followed by paraffin embedding, by analyzing expression profiles of microdissected cells on Affymetrix oligonucleotide arrays of three matched benign prostatic hyperplasia (BPH) and tumor samples processed with each preservation method. Frozen samples generated an average present call of 26% of the probe sets, compared to 4.5% in ethanol-paraffin samples. Eighty-eight percent of the probe sets called present in the ethanol-paraffin samples were also present in the frozen specimens. Comparing ethanol-paraffin BPH to tumor, 52 probe sets showed a twofold differential expression or higher in at least two cases, 23 of which were also differentially expressed in at least one frozen case. Despite a significant drop in the number of transcripts detectable, the data suggests that the obtainable information in ethanol-fixed samples may be useful for molecular profiling where frozen tissue is not available. However, ethanol fixation and paraffin embedding of tissue specimens is not optimal for high-throughput mRNA expression analysis. Improved methods for transcript profiling of archival samples, and/or tissue processing are still required. C1 NCI, Pathogenet Unit, NIH, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD USA. Catholic Univ, Dept Pathol, Santiago, Chile. Catholic Univ, Dept Urol, Santiago, Chile. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Chuaqui, RF (reprint author), NCI, Pathogenet Unit, Ctr Adv Technol, Room 109D,8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM chuaquir@mail.nih.gov NR 20 TC 45 Z9 48 U1 1 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 BP 371 EP 377 DI 10.1016/S1525-1578(10)60534-X PG 7 WC Pathology SC Pathology GA 885XG UT WOS:000226190000013 PM 15507677 ER PT J AU Ogino, S Wilson, RB Gold, B Grody, WW AF Ogino, S Wilson, RB Gold, B Grody, WW TI Genetic risk assessment for cystic fibrosis in neonatal screening by immunoreactive trypsinogen and CFTR tests SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 10-13, 2004 CL Los Angeles, CA SP Assoc Mole Pathol C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Human Genet Sect, Frederick, MD 21701 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 MA G2 BP 408 EP 408 PG 1 WC Pathology SC Pathology GA 885XG UT WOS:000226190000020 ER PT J AU Dyer, KD Rosenberg, HF Zhang, JZ AF Dyer, KD Rosenberg, HF Zhang, JZ TI Isolation, characterization, and evolutionary divergence of mouse RNase 6: Evidence for unusual evolution in rodents SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE ribonuclease; RNase A superfamily; RNase k6; RNase 6; host defense ID EOSINOPHIL-DERIVED NEUROTOXIN; PRIMATE RIBONUCLEASE GENES; TISSUE-SPECIFIC EXPRESSION; CATIONIC PROTEIN; A SUPERFAMILY; MOLECULAR EVOLUTION; ADAPTIVE EVOLUTION; ANTIVIRAL ACTIVITY; RAPID EVOLUTION; HOST-DEFENSE AB The evolution of the ribonuclease A (RNase A) vertebrate-specific enzyme family is interesting in that specific gene lineages appear to be responding to unique selective pressures in wildly diverse manners to generate proteins that are capable of reducing the infectivity of viruses, killing systemic pathogens, and inducing the growth of blood vessels all while maintaining the signature motifs of a ribonuclease. In this paper, we present the DNA sequence and gene structure of Mus musculus RNase 6 and examine the expression pattern and enzymatic activity of the recombinant protein. M. musculus RNase 6 has a limited expression pattern compared to human RNase 6 and is an efficient ribonuclease, with a catalytic efficiency 17-fold higher than that of human protein. Evolutionary analysis reveals that RNase 6 was subject to unusual evolutionary forces (d(N)/d(S) = 1.2) in an ancestral rodent lineage before the separation of Mus and Rattus. However, more recent evolution of rodent RNase 6 has been relatively conserved, with an average d(N)/d(S) of 0.66. These data suggest that the ancestral rodent RNase 6 was subject to accelerated evolution, resulting in the conserved modern gene, which most likely plays an important role in mouse physiology. C1 NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. RP Dyer, KD (reprint author), NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM kdyer@niaid.nih.gov FU NIGMS NIH HHS [GM67030] NR 40 TC 8 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD NOV PY 2004 VL 59 IS 5 BP 657 EP 665 DI 10.1007/s00239-004-2657-0 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 867JN UT WOS:000224839000008 PM 15693621 ER PT J AU Brown, L Chefer, S Pavlova, O Vaupel, DB Koren, AO Kimes, AS Horti, AG Mukhin, AG AF Brown, L Chefer, S Pavlova, O Vaupel, DB Koren, AO Kimes, AS Horti, AG Mukhin, AG TI Evaluation of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-(S)-pyrrolidinylmethoxy) pyridine and its analogues as PET radioligands for imaging nicotinic acetylcholine receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE nicotinic acetylcholine receptor; positron emission tomography; receptor binding ID EMISSION-TOMOGRAPHY LIGAND; IN-VIVO; BINDING-SITES; GRAPHICAL ANALYSIS; C-11 RACLOPRIDE; NERVOUS-SYSTEM; MONKEY BRAIN; MOUSE-BRAIN; LOCALIZATION; EPIBATIDINE AB A novel series of compounds derived from the high-affinity nicotinic acetylcholine receptor (nAChR) ligand, 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-((1-methyl-2-(S)-pyrrolidinyl)methoxy)pyridine (Me-p-PVC), originally developed by Abbott Laboratories, was characterized in vitro in nAChR binding assays at 37degreesC to show K-i values in the range of 9-611 pm. Several compounds of this series were radiolabeled with C-11 and evaluated in vivo in mice and monkeys as potential candidates for PET imaging of nAChRs. [C-11]Me-p-PVC (K-i =56 pm at 37degreesC; logD = 1.6) was identified as a radioligand suitable for the in vivo imaging of the alpha4beta2* nAChR subtype. Compared with 2-[F-18]FA, a PET radioligand that has been successfully used in humans and is characterized by a slow kinetic of brain distribution, [C-11]Me-p-PVC is more lipophilic. As a result, [C-11]Me-p-PVC accumulated in the brain more rapidly than 2-[F-18]FA. Pharmacological evaluation of Me-p-PVC in mice demonstrated that the toxicity of this compound was comparable with or lower than that of 2-FA. Taken together, these results suggest that [C-11]Me-p-PVC is a promising PET radioligand for studying nAChR occupancy by endogenous and exogenous ligands in the brain in vivo. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Horti, AG (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ahorti@intra.nida.nih.gov NR 65 TC 11 Z9 12 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 NOV PY 2004 VL 91 IS 3 BP 600 EP 612 DI 10.1111/j.1471-4159.2004.02762.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 862XN UT WOS:000224524900009 PM 15485491 ER PT J AU Quarta, D Borycz, J Solinas, M Patkar, K Hockemeyer, J Ciruela, F Lluis, C Franco, R Woods, AS Goldberg, SR Ferre, S AF Quarta, D Borycz, J Solinas, M Patkar, K Hockemeyer, J Ciruela, F Lluis, C Franco, R Woods, AS Goldberg, SR Ferre, S TI Adenosine receptor-mediated modulation of dopamine release in the nucleus accumbens depends on glutamate neurotransmission and N-methyl-D-aspartate receptor stimulation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adenosine; caffeine; dopamine; glutamate; microdialysis; NMDA receptor; nucleus accumbens ID RAT STRIATUM; A(1) RECEPTOR; A(2A) RECEPTOR; IDENTIFIED NEURONS; BASAL GANGLIA; EXTRACELLULAR CONCENTRATIONS; AMPA/KAINATE RECEPTORS; PRESYNAPTIC INHIBITION; IONOTROPIC GLUTAMATE; ENDOGENOUS GLUTAMATE AB Adenosine, by acting on adenosine A(1) and A(2A) receptors, exerts opposite modulatory roles on striatal extracellular levels of glutamate and dopamine, with activation of A(1) inhibiting and activation of A(2A) receptors stimulating glutamate and dopamine release. Adenosine-mediated modulation of striatal dopaminergic neurotransmission could be secondary to changes in glutamate neurotransmission, in view of evidence for a preferential colocalization of A(1) and A(2A) receptors in glutamatergic nerve terminals. By using in vivo microdialysis techniques, local perfusion of NMDA (3, 10 mum), the selective A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3, 10 mum), the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 300, 1000 mum), or the non-selective A(1)-A(2A) receptor antagonist in vitro caffeine (300, 1000 mum) elicited significant increases in extracellular levels of dopamine in the shell of the nucleus accumbens (NAc). Significant glutamate release was also observed with local perfusion of CGS 21680, CPT and caffeine, but not NMDA. Co-perfusion with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV; 100 mum) counteracted dopamine release induced by NMDA, CGS 21680, CPT and caffeine. Co-perfusion with the selective A(2A) receptor antagonist MSX-3 (1 mum) counteracted dopamine and glutamate release induced by CGS 21680, CPT and caffeine and did not modify dopamine release induced by NMDA. These results indicate that modulation of dopamine release in the shell of the NAc by A(1) and A(2A) receptors is mostly secondary to their opposite modulatory role on glutamatergic neurotransmission and depends on stimulation of NMDA receptors. Furthermore, these results underscore the role of A(1) vs. A(2A) receptor antagonism in the central effects of caffeine. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch,Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. Univ Bonn, Inst Pharmaceut, D-5300 Bonn, Germany. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. NIDA, Chem & Drug Metab Sect, Behav Neurosci Branch,Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Ferre, S (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch,Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Solinas, Marcello/M-3500-2016 OI Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Solinas, Marcello/0000-0002-0664-5964 NR 58 TC 66 Z9 67 U1 1 U2 2 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 NOV PY 2004 VL 91 IS 4 BP 873 EP 880 DI 10.1111/j.1471-4159.2004.02761.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 867TI UT WOS:000224864800012 PM 15525341 ER PT J AU Lee, H Villacreses, NE Rapoport, SI Rosenberger, TA AF Lee, H Villacreses, NE Rapoport, SI Rosenberger, TA TI In vivo imaging detects a transient increase in brain arachidonic acid metabolism: a potential marker of neuroinflammation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE arachidonic acid; cytokines; imaging; lipopolysaccaride; neuroinflammation; phospholipase A2 ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PHOSPHOLIPASE A(2) EXPRESSION; PEROXISOMAL BETA-OXIDATION; ALZHEIMERS-DISEASE BRAIN; RAT CULTURED ASTROCYTES; NECROSIS-FACTOR-ALPHA; FATTY-ACIDS; SIGNAL-TRANSDUCTION; DOWN-REGULATION; TNF-ALPHA AB In a rat model of neuroinflammation produced by an intracerebral ventricular infusion of bacterial lipopolysaccaride (LPS), we measured the coefficients of incorporation (k*) of arachidonic acid (AA, 20 : 4n-6) from plasma into each of 80 brain regions, using quantitative autoradiography and intravenously injected [1-C-14]AA. Compared with control rats infused with artificial cerebrospinal fluid (aCSF), k* was increased significantly in 25 brain areas, many of them close to the CSF compartments, following 6-days of LPS infusion. The increases, ranging from 31 to 76%, occurred in frontal, motor, somatosensory, and olfactory cortex, thalamus, hypothalamus, and septal nuclei, and basal ganglia. Following 28 days of LPS infusion, k* was increased significantly in only two brain regions. Direct analyses of microwaved brain showed that 93 +/- 3 (SD) and 94 +/- 4% of brain radioactivity was in the organic extract as radiolabeled AA in the 6-day control and LPS-infused animals, respectively, compared with 91 +/- 3 and 87 +/- 6% in the 28-day control and LPS-infused animals. These results confirm that brain AA metabolism is disturbed after 6 days of LPS exposure, show this increase is transient, and that these changes can be detected and localized using in vivo imaging with radiolabeled AA. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, 501 N Columbia Rd,Room 3742 A, Grand Forks, ND 58203 USA. EM trosenberger@medicine.nodak.edu NR 83 TC 31 Z9 33 U1 0 U2 4 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2004 VL 91 IS 4 BP 936 EP 945 DI 10.1111/j.1471-4159.2004.02786.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 867TI UT WOS:000224864800018 PM 15525347 ER PT J AU Humphries, A Weller, J Klein, D Baler, R Carter, DA AF Humphries, A Weller, J Klein, D Baler, R Carter, DA TI NGFI-B (Nurr77/Nr4a1) orphan nuclear receptor in rat pinealocytes: circadian expression involves an adrenergic-cyclic AMP mechanism SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AP-1; orphan nuclear receptor ID NERVE GROWTH-FACTOR; PROTEIN-KINASE-A; SEROTONIN N-ACETYLTRANSFERASE; PITUITARY-ADRENAL AXIS; STEROID-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; NOREPINEPHRINE STIMULATION; NEUROENDOCRINE REGULATION; MEMBRANE DEPOLARIZATION AB NGFI-B (Nur77/Nr4a1) is a member of a nuclear steroid receptor subgroup that includes the related factors Nurr1 (Nr4a2) and NOR-1 (Nr4a3). These proteins do not have recognized ligands and in fact function independently as orphan receptors with transcriptional regulatory activity. In the present study, expression of the NGFI-B gene in the rat pineal gland was found to exhibit a robust circadian rhythm, with elevated levels of NGFI-B mRNA occurring at night. The rhythm of NGFI-B mRNA is translated into a circadian rhythm of NGFI-B protein, which accumulates in the nucleus of pinealocytes. In addition, there is a parallel marked nocturnal increase in pineal DNA binding activity to a NGFI-B response element (NBRE, AAAGGTCA). Pharmacological studies indicate that NGFI-B mRNA and protein levels are elevated via activation of adrenergic receptors. NGFI-B protein levels are also elevated by dibutyryl cyclic AMP, as in other systems. In the pineal gland, regulation of NGFI-B expression also involves the AP-1 protein Fra-2, based on studies with a transgenic Fra-2 knockdown rat, in which pineal NGFI-B expression increases. This set of observations extends the number of pineal genes that are known to be regulated by Fra-2, and also provides the first indication that a member of the NGFI-B group of nuclear receptors is involved in controlling gene expression in the pineal gland. C1 Univ Wales Coll Cardiff, Sch Biosci, Cardiff CF10 3US, S Glam, Wales. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Carter, DA (reprint author), Univ Wales Coll Cardiff, Sch Biosci, POB 911,Museum Ave, Cardiff CF10 3US, S Glam, Wales. EM smbdac@cardiff.ac.uk RI Carter, David/A-4479-2010 OI Carter, David/0000-0002-8419-3975 FU Medical Research Council [G9724886] NR 54 TC 31 Z9 32 U1 0 U2 2 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 NOV PY 2004 VL 91 IS 4 BP 946 EP 955 DI 10.1111/j.1471-4159.2004.02777.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 867TI UT WOS:000224864800019 PM 15525348 ER PT J AU Janabi, N Jensen, PN Major, EO AF Janabi, N Jensen, PN Major, EO TI Differential effects of interferon-gamma on the expression of cyclooxygenase-2 in high-grade human gliomas versus primary astrocytes SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE glioma; primary human astrocytes; interferon-gamma; cyclooxygenase-2 ID NITRIC-OXIDE SYNTHASE; GLIOBLASTOMA CELL-CYCLE; NECROSIS-FACTOR-ALPHA; MALIGNANT GLIOMA; IFN-GAMMA; ADENOMATOUS POLYPOSIS; ANTIGEN EXPRESSION; GENE-TRANSFER; COLON-CANCER; IN-VITRO AB We compared effects of interferon-gamma (IFNgamma) on cyclooxygenase-2 (COX-2) expression in malignant human glioma cell lines and cultured primary human astrocytes. While IFNgamma inhibited interleukin-1beta (IL1beta)-induced expression of COX-2 in the glioma cells, it enhanced expression in primary astrocytes. This differential effect correlated with the observed modulation of NFkappaB and AP-1 DNA binding activity; reduced in the glioma cells, increased in primary astrocytes. Furthermore, IFNgamma had a significantly greater anti-proliferative effect on the glioma cells than COX inhibitors. This inhibitory effect of IFNgamma on expression of COX-2 in human glioma cells may have relevance for immunotherapies directed against high-grade gliomas. Published by Elsevier B.V. C1 Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. EM nazila@free.fr; majorg@ninds.nih.gov NR 45 TC 3 Z9 4 U1 1 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 NOV PY 2004 VL 156 IS 1-2 BP 113 EP 122 DI 10.1016/j.jneuroim.2004.07.012 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 864YR UT WOS:000224669800013 PM 15465602 ER PT J AU Postman, WA AF Postman, WA TI Processing of complex sentences in a case of aphasia in Indonesian: thematic vs. linear strategies SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE aphasia; Indonesian; language comprehension; linguistic theory; syntactic deficits ID THETA-ROLE ASSIGNMENT; AGRAMMATIC COMPREHENSION; STRUCTURAL PROMINENCE; ERGATIVITY; ROLES; TRACE AB The comprehension of HS, an Indonesian-speaking man with non-fluent aphasia, was investigated using an act-out task. HS was tested on VP-conjoined and center-embedded constructions in Indonesian that contained either two active verbs or two passive verbs, an active verb in the first clause and a passive verb in the second clause, or vice versa. Another type of center-embedded construction contained an object-preposed verb in the embedded clause and either an active or passive verb in the matrix clause. HS enacted the first clause accurately on all sentence types, yet he consistently predicated the second verb of the NP with the role of agent in the first clause. This strategy resulted in appropriate enactments of sentences with an active verb in the first clause, but it led to ungrammatical interpretations of sentences whose first clause contained a passive or object-preposed verb, since in these constructions the subject of the second verb is the NP with the role of theme in the first clause. HS's response pattern supports a new computational model, the Thematic Prominence Model, which posits that in thematically oriented, free word order languages like Indonesian, the thematic prominence of arguments is more important for predication than their linear positions. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDCD, NIH, Bethesda, MD 20892 USA. RP Postman, WA (reprint author), NIDCD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM postmanw@nidcd.nih.gov NR 40 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD NOV PY 2004 VL 17 IS 6 BP 455 EP 489 DI 10.1016/j.jneuroling.2004.09.001 PG 35 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 873KD UT WOS:000225277700004 ER PT J AU Shibasaki, H Hitomi, T Mezaki, T Kihara, T Tomimoto, H Ikeda, A Shimohama, S Ito, M Oka, N AF Shibasaki, H Hitomi, T Mezaki, T Kihara, T Tomimoto, H Ikeda, A Shimohama, S Ito, M Oka, N TI A new form of congenital proprioceptive sensory neuropathy associated with arthrogryposis multiplex SO JOURNAL OF NEUROLOGY LA English DT Article DE congenital sensory ganglionopathy; sensory ataxia; arthrogryposis multiplex congenita; selective proprioceptive loss; developmental abnormality ID SOMATOSENSORY-EVOKED-POTENTIALS; HYPOMYELINATION NEUROPATHY; PERIPHERAL NEUROPATHY; NERVE; DEGENERATION; STIMULATION; CONDUCTION; AFFERENT AB We report two siblings who presented with non-progressive marked sensory ataxia associated with arthrogryposis multiplex congenita (AMC). Deep tendon reflexes and H reflex were completely absent, but F waves were preserved. The sensory nerve conduction studies indicated the presence of relatively mild sensory polyneuropathy. The conventional somatosensory evoked potentials (SEPs) showed mildly prolonged latency for both the peripheral and cortical responses, suggesting a slowed conduction through the peripheral as well as central pathway. However, the 'proprioceptive SEPs' were absent, in conformity with complete loss of joint sense. Sural nerve biopsy revealed only mild thinning of myelin in the younger sister but was entirely normal in her brother. Taken together with the characteristic electrophysiological findings, the symptoms were considered to be due to predominant involvement of a selective population of somatosensory ganglions. The present cases showed no progression of the neurological deficit what-so-ever since birth, which strongly suggests a developmental anomaly or aplasia of a limited population of peripheral sensory neurons. C1 NINDS, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto, Japan. Shiga Med Ctr Children, Moryama, Japan. S Kyoto Natl Hosp, Dept Neurol, Kyoto, Japan. RP Shibasaki, H (reprint author), NINDS, NIH, Bldg 10,Rm 5C432A, Bethesda, MD 20892 USA. EM shib@kuhp.kyoto-u.ac.jp OI Ikeda, Akio/0000-0002-0790-2598 NR 17 TC 3 Z9 3 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD NOV PY 2004 VL 251 IS 11 BP 1340 EP 1344 DI 10.1007/s00415-004-0539-4 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 877XX UT WOS:000225610400006 PM 15592729 ER PT J AU Hanson, M Honour, M Singleton, A Crawley, A Singleton, A Hardy, J Gwinn-Hardy, K AF Hanson, M Honour, M Singleton, A Crawley, A Singleton, A Hardy, J Gwinn-Hardy, K TI Analysis of familial and sporadic restless legs syndrome in age of onset, gender, and severity features SO JOURNAL OF NEUROLOGY LA English DT Article DE RLS; age onset; familial; sporadic; severity; severity ID POPULATION; PREVALENCE AB Restless Legs Syndrome is characterized by the irresistible, often indescribable unpleasant urge to move the limbs while resting. It has an estimated prevalence of similar to29.3 % in US private practice. Restless Legs Syndrome often has a familial component; whether the familial and non-familial forms differ in terms of clinical features has previously been investigated, with the only significant factor emerging as younger age at onset in familial cases. Our study further explores a possible underlying difference between familial and sporadic forms of RLS by comparing familial RLS with sporadic RLS in terms of demographic and clinical features including subject gender, age of onset, and severity measures based an the IRLSSG severity scale. Both gender and family history are significant predictors of onset age in an overall model and also significant when analyzed independently. Participants who reported more severe RLS symptoms were significantly younger in age and progressed more rapidly. Two variables from the IRLSSG severity scale were significantly associated with age of onset when tested independently: discomfort and the urge to move the limb for relief. Our analysis supports the prevailing hypothesis that RLS is divided into earlier onset disease with a clear genetic component and later onset disease wich unclear etiology, and that one or more endophenotypes might exist within the disorder which could further characterize these subjects for future genetic studies. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. RP Gwinn-Hardy, K (reprint author), NINDS, Neurogenet Branch, NIH, 6001 Execut Blvd 2142, Bethesda, MD 20892 USA. EM gwinnk@ninds.nih.gov; gwinnk@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; OI Gwinn, Katrina/0000-0002-8277-651X NR 15 TC 25 Z9 25 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD NOV PY 2004 VL 251 IS 11 BP 1398 EP 1401 DI 10.1007/s00415-004-0552-7 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 877XX UT WOS:000225610400014 PM 15592737 ER PT J AU Ambalavanar, R Tanaka, Y Selbie, WS Ludlow, CL AF Ambalavanar, R Tanaka, Y Selbie, WS Ludlow, CL TI Neuronal activation in the medulla oblongata during selective elicitation of the laryngeal adductor response SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID GLOTTIC CLOSURE REFLEX; ELECTRICALLY-INDUCED VOCALIZATION; RESPIRATORY-TRACT STIMULI; BRAIN-STEM PROJECTIONS; FINAL COMMON PATHWAY; AREA POSTREMA; NERVE-STIMULATION; SOLITARY TRACT; AFFERENT STIMULATION; VAGUS NERVE AB Swallow and cough are complex motor patterns elicited by rapid and intense electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN). The laryngeal adductor response (LAR) includes only a laryngeal response, is elicited by single stimuli to the ISLN, and is thought to represent the brain stem pathway involved in laryngospasm. To identify which regions in the medulla are activated during elicitation of the LAR alone, single electrical stimuli were presented once every 2 s to the ISLN. Two groups of five cats each were studied; an experimental group with unilateral ISLN stimulation at 0.5 Hz and a surgical control group. Three additional cats were studied to evaluate whether other oral, pharyngeal, or respiratory muscles were activated during ISLN stimulation eliciting LAR. We quantified less than or equal to22 sections for each of 14 structures in the medulla to determine if regions had increased Fos-like immunoreactive neurons in the experimental group. Significant increases (P<0.0033) occurred with unilateral ISLN stimulation in the interstitial subnucleus, the ventrolateral subnucleus, the commissural subnucleus of the nucleus tractus solitarius, the lateral tegmental field of the reticular formation, the area postrema, and the nucleus ambiguus. Neither the dorsal motor nucleus of the vagus, usually active for swallow, nor the nucleus retroambiguus, retrofacial nucleus, and the lateral reticular nucleus, usually active for cough, were active with elicitation of the laryngeal adductor response alone. The results demonstrate that the laryngeal adductor pathway is contained within the broader pathways for cough and swallow in the medulla. C1 NINDS, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), 10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-08]; NINDS NIH HHS [Z01 NS002980, Z01 NS-002980-4] NR 113 TC 23 Z9 24 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2004 VL 92 IS 5 BP 2920 EP 2932 DI 10.1152/jn.00064.2004 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 862FE UT WOS:000224475000029 PM 15212423 ER PT J AU Jung, CS Iuliano, BA Harvey-White, J Espey, MG Oldfield, EH Pluta, RM AF Jung, CS Iuliano, BA Harvey-White, J Espey, MG Oldfield, EH Pluta, RM TI Association between cerebrospinal fluid levels of asymmetric dimethyl-L-arginine, an endogenous inhibitor of endothelial nitric oxide synthase, and cerebral vasospasm in a primate model of subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE subarachnoid hemorrhage; nitric oxide; nitric oxide synthase; asymmetric dimethyl-L-arginine; vasospasm; Macaca fascicularis ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CANINE BASILAR ARTERY; HUMAN PLASMA; BLOOD-FLOW; DYSFUNCTION; DIMETHYLAMINOHYDROLASE; MONKEYS; CELLS; METHYLTRANSFERASE; LOCALIZATION AB Object. Decreased availability of nitric oxide (NO) has been proposed to evoke delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). Asymmetric dimethyl-L-arginine (ADMA) inhibits endothelial NO synthase (eNOS) and, therefore, may be responsible for decreased NO availability in cases of cerebral vasospasm. The goal of this study was to determine whether ADMA levels are associated with cerebral vasospasm in a primate model of SAH. Methods. Twenty-two cynomolgus monkeys (six control animals and 16 with SAH) were used in this study. The levels of ADMA, L-arginine, L-Citrulline, nitrites, and nitrates in cerebrospinal fluid (CSF) and serum were determined on Days 0, 7, 14, and 21 following onset of SAH. Cerebral arteriography was performed to assess the degree of vasospasm. Western blot analyses of the right and left middle cerebral arteries (MCAs) were performed to assess the expression of eNOS, type I protein-arginine methyl transferase (PRMT1) and dimethylarginine dimethylaminohydrolase (DDAH2), Cerebrospinal fluid levels of ADMA remained unchanged in the control group (six animals) and in animals with SAH that did not have vasospasm (five animals; p = 0.17), but the levels increased in animals with vasospasm (11 animals) on Day 7 post-SAH (p < 0.01) and decreased on Days 14 through 21 (p < 0.05). Cerebrospinal fluid levels of ADMA correlated directly with the degree of vasospasm (correlation coefficient = 0.7, p = 0.0001; 95% confidence interval: 0.43-0.83). Levels of nitrite and nitrate as well as those Of L-Citrulline in CSF were decreased in animals with vasospasm. Furthermore, DDAH2 expression was attenuated in the right spastic MCA on Day 7 post-SAH, whereas eNOS and PRMT1 expression remained unchanged. Conclusions. Changes in the CSF levels of ADMA are associated with the development and resolution of vasospasm found on arteriograms after SAH. The results indicate that endogenous inhibition of eNOS by ADMA may be involved in the development of delayed cerebral vasospasm. Inhibition of ADMA production may provide a new therapeutic approach for cerebral vasospasm after SAH. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. NCI, Radiat Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Neurol Surg, Rochester, MN USA. Univ Frankfurt, Dept Neurosurg, Frankfurt, Germany. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM rysiek@ninds.nih.gov NR 42 TC 48 Z9 52 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 NOV PY 2004 VL 101 IS 5 BP 836 EP 842 DI 10.3171/jns.2004.101.5.0836 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 873UL UT WOS:000225306500017 PM 15543672 ER PT J AU Volkow, ND AF Volkow, ND TI Imaging the addicted brain: From molecules to behavior SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 NIDA, NIH, Lexington, KY 40583 USA. RP Volkow, ND (reprint author), NIDA, NIH, Lexington, KY 40583 USA. NR 0 TC 17 Z9 17 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2004 VL 45 IS 11 BP 13N EP + PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 870VE UT WOS:000225086000001 PM 15584131 ER PT J AU Miles, EW Metzler, DE AF Miles, EW Metzler, DE TI Esmond Emerson Snell (1914-2003) SO JOURNAL OF NUTRITION LA English DT Biographical-Item C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Iowa State Univ, Dept Biochem & Biophys, Ames, IA 50011 USA. RP Miles, EW (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM EdithM@intra.niddk.nih.gov NR 1 TC 2 Z9 2 U1 1 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 NOV PY 2004 VL 134 IS 11 BP 2907 EP 2910 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870HB UT WOS:000225047100003 PM 15514250 ER PT J AU Seifried, HE Sorkin, BC Costello, RB AF Seifried, HE Sorkin, BC Costello, RB TI Free radicals: The pros and cons of antioxidants - Summary Report of the National Institutes of Health Symposium, held June 26-27, 2003 in Bethesda, MD SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Conference on Free Radicals - The Pros and Cons of Antioxidants CY JUN 26-27, 2003 CL Bethesda, MD SP NCI, Div Canc Prevent, NCI, Div Canc Treatment & Diagnosis, Natl Ctr Complementary & Alternat Med, NIH, Off Dietary Supplements, Amer Soc Nutrit Sci, Amer Inst Canc Res C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Seifried, HE (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 23 TC 1 Z9 1 U1 0 U2 5 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2004 VL 134 IS 11 BP 3141S EP + PG 22 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870HB UT WOS:000225047100043 ER PT J AU Mitchel, JB Yamada, K Devasahayam, N Cook, JA Subramanian, S Krishna, MC AF Mitchel, JB Yamada, K Devasahayam, N Cook, JA Subramanian, S Krishna, MC TI Novel functional imaging for tissue oxygen concentration and redox status SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT Conference on Free Radicals - The Pros and Cons of Antioxidants CY JUN 26-27, 2003 CL Bethesda, MD SP NCI, Div Canc Prevent, NCI, Div Canc Treatment & Diagnosis, Natl Ctr Complementary & Alternat Med, NIH, Off Dietary Supplements, Amer Soc Nutrit Sci, Amer Inst Canc Res DE functional imaging; hypoxia; redox imaging; electron paramagnetic resonance imaging ID TUMOR C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. EM jbm@helix.nih.gov RI Yamada, Ken-ichi/E-6318-2012 NR 6 TC 3 Z9 3 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 NOV PY 2004 VL 134 IS 11 BP 3210S EP 3210S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870HB UT WOS:000225047100065 PM 15514310 ER PT J AU Gius, D AF Gius, D TI Redox-sensitive signaling factors and antioxidants: How tumor cells respond to ionizing radiation SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT Conference on Free Radicals - The Pros and Cons of Antioxidants CY JUN 26-27, 2003 CL Bethesda, MD SP NCI, Div Canc Prevent, NCI, Div Canc Treatment & Diagnosis, Natl Ctr Complementary & Alternat Med, NIH, Off Dietary Supplements, Amer Soc Nutrit Sci, Amer Inst Canc Res DE ionizing radiation; stress response; redox; thioredoxin reductase; thioredoxin; AP-1 ID DNA-BINDING ACTIVITY; AP-1 C1 NCI, Mol Radiat Oncol Sect, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Mol Radiat Oncol Sect, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov NR 5 TC 8 Z9 8 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 NOV PY 2004 VL 134 IS 11 BP 3213S EP 3214S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870HB UT WOS:000225047100067 PM 15514312 ER PT J AU Dogulu, CF Tsilou, E Rubin, B FitzGibbon, EJ Kaiser-Kupper, MI Rennert, OM Gahl, WA AF Dogulu, CF Tsilou, E Rubin, B FitzGibbon, EJ Kaiser-Kupper, MI Rennert, OM Gahl, WA TI Idiopathic intracranial hypertension in cystinosis SO JOURNAL OF PEDIATRICS LA English DT Article ID RENAL-TRANSPLANT RECIPIENTS; NERVOUS-SYSTEM INVOLVEMENT; NEPHROPATHIC CYSTINOSIS; PSEUDOTUMOR CEREBRI; CYSTEAMINE THERAPY; LONG-TERM; CHILDREN; HYPERHOMOCYSTEINEMIA; INSUFFICIENCY; COMPLICATIONS AB Objectives To report a high frequency of idiopathic intracranial hypertension (IIH) in patients with cystinosis and to speculate on the relationship between these two disorders. Study design Retrospective case series and review of the literature regarding risk factors for the development of IIH in cystinosis. Results Eight patients with cystinosis had documented papilledema, normal neuroimaging of the brain, cerebrospinal fluid (CSF) opening pressure greater than 200 mm of H2O, and normal CSF composition. No common medication, condition, or disease except cystinosis was found in these persons. Six of the patients had received prednisone, growth hormone, cyclosporine, oral contraceptives, vitamin D, or levothyroxine at the time of onset of IIH. Five patients had previous renal transplants. Conclusion No single risk factor for the development of IIH linked IIH to cystinosis in our patients. However, thrombosis susceptibility as a result of renal disease or impaired CSF reabsorption in the arachnoid villi as a result of cystine deposition might lead to the development of IIH in cystinosis. C1 NICHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Clin Genet Sect, Ophthalm Genet & Visual Funct Branch, Acu Sect,Lab Sensorimotor Res,NIH, Bethesda, MD 20892 USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Dogulu, CF (reprint author), NICHD, Lab Clin Genom, NIH, 49 Convent Dr,Room 2C08,MSC 4429, Bethesda, MD 20892 USA. EM doguluc@mail.nih.gov NR 48 TC 18 Z9 19 U1 1 U2 1 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 NOV PY 2004 VL 145 IS 5 BP 673 EP 678 DI 10.1016/j.jpeds.2004.06.080 PG 6 WC Pediatrics SC Pediatrics GA 870VM UT WOS:000225086800026 PM 15520772 ER PT J AU Pacher, P Vaslin, A Benko, R Mabley, JG Liaudet, L Hasko, G Marton, A Batkai, S Kollai, M Szabo, C AF Pacher, P Vaslin, A Benko, R Mabley, JG Liaudet, L Hasko, G Marton, A Batkai, S Kollai, M Szabo, C TI A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DIABETIC ENDOTHELIAL DYSFUNCTION; OXIDATIVE STRESS; PHARMACOLOGICAL INHIBITION; PEROXYNITRITE FORMATION; HEART-FAILURE; NITRIC-OXIDE; RAT-HEART; ACTIVATION; SYNTHETASE; INJURY AB Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension, and aging. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging. C1 NIAAA, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. Inotek Pharmaceut Corp, Beverly, MA USA. Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, Budapest, Hungary. Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1085 Budapest, Hungary. Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1085 Budapest, Hungary. Univ Lausanne Hosp, Crit Care Div, Dept Internal Med, Lausanne, Switzerland. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, NIH, Lab Physiol Studies, Pk Bldg,Rm 445,12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Mabley, Jon/D-2296-2010; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z99 AA999999]; NIA NIH HHS [1R03 AG 21206-01] NR 40 TC 56 Z9 58 U1 0 U2 7 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 NOV PY 2004 VL 311 IS 2 BP 485 EP 491 DI 10.1124/jpet.104.069658 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 861ZE UT WOS:000224456400007 PM 15213249 ER PT J AU Mager, DE Abernethy, DR Egan, JM Elahi, D AF Mager, DE Abernethy, DR Egan, JM Elahi, D TI Exendin-4 pharmacodynamics: Insights from the hyperglycemic clamp technique SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; BETA-CELL SENSITIVITY; MINIMAL-MODEL; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; GLP-1 RECEPTOR; NIDDM SUBJECTS; KINETICS; ANTAGONIST; AGONIST AB The purpose of this study is to ascertain the pharmacodynamic properties of exendin-4, a glucose-dependent insulinotropic agent, from plasma glucose and insulin concentration-time profiles following a 60-min intravenous infusion in healthy and type 2 diabetic subjects. Plasma glucose and insulin concentrations were obtained from a previous clinical study, whereby a hyperglycemic clamp was established and maintained in healthy ( n = 7) and type 2 diabetic ( n = 7) volunteers ( plasma glucose raised 5.4 mM above fasting level). Exendin-4 was infused (0.15 pmol/ kg/min) during the 2nd hour of a 5-h clamp. A physiological pharmacodynamic model was developed and fitted to individual glucose and insulin responses simultaneously. Because drug concentrations were unavailable, hypothetical pharmacokinetic driving functions were approximated during the modeling process and used to enhance a proportionality constant relating elevated glucose and the rate of second-phase insulin release. Exendin-4 infusions produced substantial insulin release in both subject populations that required higher glucose infusion rates to maintain stable hyperglycemia. Observed plasma glucose-insulin profiles were well characterized by the final pharmacodynamic model. Apparent exendin-4 elimination rate constants for healthy and diabetic subjects were similar (0.0386 +/- 0.0192 and 0.0460 +/- 0.0145 min(-1)). Capacity and sensitivity parameters of drug effect were 2-fold lower in diabetic subjects, but mean differences were not statistically significant. Simulations confirm that diabetic subjects exhibit a reduced capacity to enhance second-phase insulin release in response to exendin-4 compared with healthy subjects. Type 2 diabetic subjects demonstrate a significant response to exendin-4, but to a lesser extent than nondiabetic subjects, despite comparable measures of apparent drug exposure and efficacy. C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Massachusetts, Sch Med, Dept Surg & Med, Worcester, MA USA. RP Mager, DE (reprint author), NIA, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM magerdo@grc.nia.nih.gov FU PHS HHS [NIA 00599] NR 29 TC 16 Z9 18 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 NOV PY 2004 VL 311 IS 2 BP 830 EP 835 DI 10.1124/jpet.104.069765 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 861ZE UT WOS:000224456400048 PM 15199095 ER PT J AU Markovic, M Fowler, BO Tung, MS AF Markovic, M Fowler, BO Tung, MS TI Preparation and comprehensive characterization of a calcium hydroxyapatite reference material SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE chemical analysis; crystal size; crystallinity; hydroxyapatite; infrared; morphology; preparation; Raman; solubility; surface area; thermal analysis; unit-cell parameters; x-ray diffraction ID LASER-RAMAN-SPECTROSCOPY; BARIUM HYDROXYAPATITES; OCTACALCIUM PHOSPHATE; VIBRATIONAL-SPECTRA; APATITES; STRONTIUM; ADSORPTION; ENAMEL AB Numerous biological and chemical studies involve the use of calcium hydroxyapatite (HA), Ca-10(PO4)(6)(OH)(2). In this study detailed physicochemical characterization of HA, prepared from an aqueous solution, was carried out employing different methods and techniques: chemical and thermal analyses, x-ray diffraction, infrared and Raman spectroscopies, scanning and transmission microscopies, and Brunauer, Emmett, and Teller (BET) surface-area method. The contents of calcium (Ca2+), phosphate (PO43-), hydroxide (OH-), hydrogenphosphate (HPO42-), water (H2O), carbonate (CO32-), and trace constituents, the Ca/P molar ratio, crystal size and morphology, surface area, unit-cell parameters, crystallinity, and solubility of this HA were determined. This highly pure, homogeneous, and highly crystalline HA is certified as a National Institute of Standards and Technology (NIST) standard reference material, SRM 2910. C1 Natl Inst Stand & Technol, Amer Dent Assoc Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, Natl Inst Dent & Craniofacial Res,Mat Sci & Engn, NIH,Dent & Med Mat Grp,Polymers Div, Skeletal Dis Branch Res Associate Program, Gaithersburg, MD 20899 USA. RP Markovic, M (reprint author), Natl Inst Stand & Technol, Amer Dent Assoc Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. FU NIDCR NIH HHS [R01 DE011789] NR 38 TC 185 Z9 189 U1 9 U2 60 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 1044-677X J9 J RES NATL INST STAN JI J. Res. Natl. Inst. Stand. Technol. PD NOV-DEC PY 2004 VL 109 IS 6 BP 553 EP 568 DI 10.6028/jres.109.042 PG 16 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 897WO UT WOS:000227036900004 PM 27366634 ER PT J AU Begier, EM Langford, CA Sneller, MC Wise, RP Ball, R AF Begier, EM Langford, CA Sneller, MC Wise, RP Ball, R CA VAERS Working Grp TI Polyarteritis nodosa reports to the Vaccine Adverse Event Reporting System (VAERS): Implications for assessment of suspected vaccine-provoked vasculitis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE vasculitis; polyarteritis nodosa; vaccination hepatitis B vaccine ID HEPATITIS-B-VIRUS; RHEUMATIC DISORDERS; HBV INFECTION; PATHOGENESIS; IMMUNIZATION AB Objective. To examine polyarteritis nodosa (PAN) reports to the Vaccine Adverse Event Reporting System (VAERS) as the initial stage in investigating the hypothesis that vaccination can very rarely cause PAN. Methods. We reviewed PAN reports submitted from 1990 through 2001 using a causal inference framework to evaluate the consistency of the reports' clinical details with this hypothesis. We also reviewed published literature relating to the hypothesized association's biological plausibility. Results. VAERS received 25 PAN reports. Ten met our case definition for definite or possible PAN and had no alternative etiology for PAN identified. Nine of these 10 followed hepatitis B vaccine with a modal peak (4 definite cases) in time to symptom onset 2 weeks after vaccination. However, all potential triggering infections were not excluded, and identification of vaccine antigens in clinical specimens was not attempted. Also, 14 of 25 reports were European, with 11 from France. All 9 French reports with a known diagnosis date began during 1994-97, when autoimmune and rheumatologic events following hepatitis B vaccine were a focus of public concern in France. Conclusion. While we identified some supportive evidence, overall, current adverse event reports do not support a causal link between vaccination and PAN. Appropriate prospective evaluation of future post-vaccination PAN cases could add to current knowledge with rigorous confirmation of diagnosis, appropriate testing for possible triggering infections including polymerase chain reaction testing for latent hepatitis B infection, and an attempt to link the vaccine antigen to pathology such as by immunohistochemical staining or immune complex identification. C1 US FDA, CBER, OBE, VSB, Rockville, MD 20852 USA. NIAID, Immunol Dis Sect, Immunoregulat Lab, NIH, Bethesda, MD USA. RP Ball, R (reprint author), US FDA, CBER, OBE, VSB, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM ballr@cber.fda.gov NR 32 TC 15 Z9 15 U1 2 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2004 VL 31 IS 11 BP 2181 EP 2188 PG 8 WC Rheumatology SC Rheumatology GA 868GB UT WOS:000224901000016 PM 15517631 ER PT J AU McVary, KT Foley, J Kusek, JW Roehrborn, C AF McVary, K. T. Foley, J. Kusek, J. W. Roehrborn, C. TI The Long Term Effects of Doxazosin, Finasteride and the Combination on Sexual Function in Men Participating in the MTOPS Study SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [McVary, K. T.] Northwestern Univ, Evanston, IL 60208 USA. [Foley, J.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. [Kusek, J. W.] NIDDK, Bethesda, MD 20892 USA. [Roehrborn, C.] Southwestern Univ, MTOPS Res Grp, Cebu, Philippines. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD NOV PY 2004 VL 1 SU 1 BP 72 EP 72 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V13HG UT WOS:000207657300161 ER PT J AU Hoagwood, KE Jensen, PS Arnold, LE Roper, M Severe, J Odbert, C Molina, BSG AF Hoagwood, KE Jensen, PS Arnold, LE Roper, M Severe, J Odbert, C Molina, BSG CA MTA Cooperative Grp TI Reliability of the services for children and adolescents-parent interview SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE mental health services; instruments; services research ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MENTAL-HEALTH-CARE; MULTIMODAL-TREATMENT; OUTCOMES; PERFORMANCE; PREVALENCE; COMMUNITY; QUALITY; SECTORS; DESIGN AB Objective: To describe the psychometric properties and test the reliability of a new instrument designed to measure mental health services use within pediatric clinical samples, the Services for Children and Adolescents-Parent Interview (SCAPI), which was developed by the National Institute of Mental Health Multimodal Treatment Study of Children With Attention Deficit Hyperactivity Disorder (MTA). Method: Similarities and differences with other measures of services use are described. Ten types of services are measured by the SCAPI. Formal test-retest reliability testing was carried out in 104 subjects with a mean time between tests of 18 days. Results: Test-retest kappa values ranged from 0.49 to 1.00, with an overall kappa value for all services of 0.97. Seven of the 10 service types had kappa values of 0.75 or higher, indicating excellent reliability. In addition, matched responses on specific questions about reasons for seeking services, starting and ending dates, number and length of visits, and type of provider seen were more than 75% for most service categories, consistently so for reporting of medications and school services. Conclusions: The SCAPI is a reliable instrument for assessing mental health and related services use and may be an especially valuable adjunct in studies involving clinical samples, especially clinical trials. C1 Columbia Univ, New York, NY 10032 USA. Columbia Univ, Ctr Advancement Childrens Mental Hlth, New York, NY USA. Ohio State Univ, Columbus, OH 43210 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Hoagwood, KE (reprint author), Columbia Univ, 1051 Riverside Dr 78, New York, NY 10032 USA. EM hoagwood@childpsych.columbia.edu OI Jensen, Peter/0000-0003-2387-0650 NR 33 TC 29 Z9 29 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2004 VL 43 IS 11 BP 1345 EP 1354 DI 10.1097/01.chi.0000139558.54948.1f PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 864JX UT WOS:000224630900011 ER PT J AU Gordon, SM Dionne, RA AF Gordon, SM Dionne, RA TI The integration of clinical research into dental therapeutics - The role of the astute clinician SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DISK IMPLANTS; DENTISTRY; PAIN AB Background. Although productive, traditional research approaches may not always address clinically relevant outcomes or translate into changes that can be made in practice. Conversely, clinical observations often result in therapeutic innovations but require verification of safety before widespread use. Overview. As a strategy for greater integration of research findings and clinical practice, the authors suggest approaches for clinicans to document clinical observations through best case series as a basis for more controlled clinical trials. The aim is to engage clinicans in the process of therapeutic innovation through clinical research. Conclusions and Practice Implications. This approach represents a necessary first step for practitioners to formulate hypotheses for further testing to identify clinically relevant outcome measures and to contribute to the evidence base for clinical practices in dentistry. C1 Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofac Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Gordon, SM (reprint author), Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. EM rdionne@dir.nidcr.nih.gov NR 28 TC 3 Z9 3 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2004 VL 135 IS 11 BP 1537 EP 1542 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 873JZ UT WOS:000225277200014 PM 15622657 ER PT J AU Chaves, PHM Xue, QL Guralnik, JM Ferrucci, L Volpato, S Fried, LP AF Chaves, PHM Xue, QL Guralnik, JM Ferrucci, L Volpato, S Fried, LP TI What constitutes normal hemoglobin concentration in community-dwelling disabled older women? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 130th Annual Meeting of the American-Public-Health-Association CY NOV 09-13, 2002 CL PHILADELPHIA, PA SP Amer Public Hlth Assoc DE anemia; hemoglobin; erythropoietin; frail elderly; mortality ID CARDIOVASCULAR-DISEASE; ANEMIA; ERYTHROPOIETIN; REGRESSION; HEALTH; AGE; MORTALITY; MODEL AB Objectives: To examine the associations between hemoglobin (Hb) concentration and (1) 5-year all-cause mortality and (2) serum erythropoietin (EPO), as the basis for the identification of data-driven thresholds, and to assess the clinical relevance of mildly low Hb. Design: Prospective study. Setting: Population based. Participants: Community-dwelling women aged 65 and older with moderate-to-severe disability-Women's Health and Aging Study I, Baltimore, Maryland, 1992-2000. Methods: Proportional hazards regression was used to model the relationship between baseline Hb (available for 686 subjects) and time to death. A generalized linear model was used to assess the cross-sectional association between Hb and EPO in 641 subjects. Results: A curvilinear slope of steady mortality decrease up to the Hb threshold of 13.9 g/dL was observed. Hb of 11 g/dL was independently associated with greater mortality than the World Health Organization (WHO) low-normal cutoff of Hb of 12 g/dL (hazard ratio (HR)=1.2, 95% confidence interval (CI)=1.1-1.4), whereas Hb of 14 g/dL was linked to 24% lower mortality (HR=0.76, 95% CI=0.63-0.92), after comprehensive adjustment for major health status and disease-burden indicators. A curvilinear, statistically significant slope of steady EPO decrease with increasing Hb up to the threshold of 14.3 g/dL was consistently observed. Conclusion: The meaningfully lower mortality risk with higher Hb levels provides empirical evidence against the notion that Hb currently perceived as mildly low is clinically benign. Furthermore, the mortality risk gradient observed even within the WHO normal Hb range suggests that Hb levels higher than what is currently recommended might offer clinical advantage. The relationship between Hb and EPO provided supporting physiological evidence for this hypothesis. C1 Johns Hopkins Univ, Johns Hopkins Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Estado Rio De Janeiro, UNATI Ctr Studies Aging & Care Elderly, Rio De Janeiro, Brazil. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Clin Invest Lab, Gerontol Res Ctr, Bethesda, MD 20892 USA. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. RP Chaves, PHM (reprint author), Johns Hopkins Univ, Johns Hopkins Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. EM pchaves@jhsph.edu RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01 AG 12112, R37 AG 19905] NR 30 TC 88 Z9 89 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 NOV PY 2004 VL 52 IS 11 BP 1811 EP 1816 DI 10.1111/j.1532-5415.2004.52502.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100003 PM 15507056 ER PT J AU McDermott, MM Guralnik, JM Greenland, P Green, D Liu, K Ridker, PM Chan, CL Criqui, MH Ferrucci, L Taylor, LM Pearce, WH Schneider, JR Oskin, SI AF McDermott, MM Guralnik, JM Greenland, P Green, D Liu, K Ridker, PM Chan, CL Criqui, MH Ferrucci, L Taylor, LM Pearce, WH Schneider, JR Oskin, SI TI Inflammatory and thrombotic blood markers and walking-related disability in men and women with and without peripheral arterial disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE inflammation; D-dimer; peripheral arterial disease; physical functioning; c-reactive protein; ankle brachial index ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; MUSCLE PROTEIN BREAKDOWN; ANKLE-BRACHIAL INDEX; C-REACTIVE PROTEIN; D-DIMER; SUBSEQUENT DISABILITY; DISABLEMENT PROCESS; ASSOCIATION; SERUM AB Objectives: To determine whether higher circulating levels of thrombotic and inflammatory markers are associated with greater disability. Design: Cross-sectional. Setting: Academic medical center. Participants: A total of 346 men and women with peripheral arterial disease (PAD) and 203 without PAD. Measurements: Disability measures were the Walking Impairment Questionnaire (WIQ) distance, speed, and stair-climbing scores and the 36-item Short-Form (SF-36) physical functioning score. The SF-36 and WIQ are scored on a 0 to 100 scale (100=best). Results: In persons with PAD, higher D-dimer levels were associated with lower WIQ speed scores (P<.001), lower stair-climbing scores (P<.04), and poorer SF-36 physical functioning scores (P<.01), adjusting for known and potential confounders. In participants without PAD, higher D-dimer levels were associated with lower WIQ distance scores (P<.03), lower speed scores (P<.05), and poorer SF-36 physical functioning scores (P<.02). Higher high-sensitivity C-reactive protein (hsCRP) levels were associated with lower WIQ distance (P<.02) and speed scores (P<.001) in persons without PAD. Most of these associations were attenuated after additional adjustment for objectively measured functional limitations. Conclusion: Higher circulating D-dimer and hsCRP levels are associated with greater disability in walking and physical functioning in individuals with and without PAD. Physiological changes that result in walking disability may mediate these associations. C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Northwestern Univ, Evanston Hosp, Dept Surg, Evanston, IL 60201 USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 18-200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU NCRR NIH HHS [RR 00048]; NHLBI NIH HHS [R01 HL 58099, R01 HL 64739] NR 36 TC 24 Z9 24 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 NOV PY 2004 VL 52 IS 11 BP 1888 EP 1894 DI 10.1111/j.1532-5415.2004.52514.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100014 PM 15507067 ER PT J AU Colbert, LH Rosen, CJ Goodpaster, BH Newman, AB Kritchevsky, SB Satterfield, S Kanaya, AM Taaffe, DR Harris, TB AF Colbert, LH Rosen, CJ Goodpaster, BH Newman, AB Kritchevsky, SB Satterfield, S Kanaya, AM Taaffe, DR Harris, TB TI Insulin-like growth factor-1 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID BODY-COMPOSITION; HORMONE; WOMEN; MEN C1 Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. St Joseph Hosp, Maine Ctr Osteoporosis Res & Educ, Bangor, ME USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Wake Forest Univ, J Paul Sticht Ctr Aging, Winston Salem, NC 27109 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Queensland, Sch Human Movement Studies, Brisbane, Qld, Australia. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Colbert, LH (reprint author), Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 NR 7 TC 7 Z9 7 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 NOV PY 2004 VL 52 IS 11 BP 1962 EP 1963 DI 10.1111/j.1532-5415.2004.52529_1.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 863WM UT WOS:000224594100029 PM 15507082 ER PT J AU Mitchell, JA Fun, J McGray, AT AF Mitchell, JA Fun, J McGray, AT TI Design of genetics home reference: A new NLM consumer health resource SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INFORMATION; INTERNET; GENECLINICS AB The authors have developed the Genetics Home Reference, a consumer resource that addresses the health implications of the Human Genome Project. The research results made possible by the Human Genome Project are being made available increasingly in scientific databases on the Internet, but, because of the often highly technical nature of these databases, they are not readily accessible to the lay public. The authors' goal is to provide a bridge between the clinical questions of the public and the richness of the data emanating from the Human Genome Project. The Genetics Home Reference currently focuses on single gene or polygenic conditions that are also topics on MEDLINEplus, the National Library of Medicine's primary consumer health site. As knowledge of genetics expands, the interrelationships between genes and diseases will continue to unfold, and the site will reflect these developments. C1 Univ Missouri, Dept Hlth Management & Informat, Columbia, MO 65211 USA. Natl Lib Med, Bethesda, MD USA. RP Mitchell, JA (reprint author), Univ Missouri, Dept Hlth Management & Informat, 324 Clark Hall, Columbia, MO 65211 USA. EM mitchelljo@health.missouri.edu NR 31 TC 14 Z9 15 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2004 VL 11 IS 6 BP 439 EP 447 DI 10.1197/jamia.M1549 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 873UB UT WOS:000225305500001 PM 15298997 ER PT J AU Chang, BL Bakken, S Brown, SS Houston, TK Kreps, GL Kukafka, R Safran, C Stavri, PZ AF Chang, BL Bakken, S Brown, SS Houston, TK Kreps, GL Kukafka, R Safran, C Stavri, PZ TI Bridging the digital divide: Reaching vulnerable populations SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID HEALTH-CARE; INFORMATION; LITERACY; SUPPORT AB The AMIA 2003 Spring Congress entitled "Bridging the Digital Divide: Informatics and Vulnerable Populations" convened 178 experts including medical informaticians, health care professionals, government leaders, policy makers, researchers, health care industry leaders, consumer advocates, and others specializing in health care provision to underserved populations. The primary objective of this working congress was to develop a framework for a national agenda in information and communication technology to enhance the health and health care of underserved populations. Discussions during four tracks addressed issues and trends in information and communication technologies for underserved populations, strategies learned from successful programs, evaluation methodologies for measuring the impact of informatics, and dissemination of information for replication of successful programs. Each track addressed current status, ideal state, barriers, strategies, and recommendations. Recommendations of the breakout sessions were summarized under the overarching themes of Policy Funding, Research, and Education and Training. The general recommendations emphasized four key themes: revision in payment and reimbursement policies, integration of health care standards, partnerships as the key to success, and broad dissemination of findings including specific feedback to target populations and other key stakeholders. C1 Columbia Univ, Sch Nursing, New York, NY 10032 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Alabama, Birmingham, AL USA. NCI, NIH, Bethesda, MD 20892 USA. Clin Support Technol, Newton, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Bakken, S (reprint author), Columbia Univ, Sch Nursing, Mailbox 6, New York, NY 10032 USA. EM suzanne.bakken@dbmi.columbia.edu RI Houston, Thomas/F-2469-2013 NR 22 TC 91 Z9 91 U1 5 U2 47 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2004 VL 11 IS 6 BP 448 EP 457 DI 10.1197/jamia.M1535 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 873UB UT WOS:000225305500002 PM 15299002 ER PT J AU Sneiderman, CA Ackerman, MJ AF Sneiderman, CA Ackerman, MJ TI Cellular radio telecommunication for health care: Benefits and risks SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID MOBILE PHONE; ELECTROMAGNETIC-INTERFERENCE; RADIOFREQUENCY RADIATION; DEVICES; SYSTEM; ASTHMA; IMPACT AB Cellular radio telecommunication has increased exponentially with many applications to health care reported. The authors attempt to summarize published applications with demonstrated effect on health care, review briefly the rapid evolution of hardware and software standards, explain current limitations and future potential of data quality and security, and discuss issues of safety. C1 Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD USA. RP Sneiderman, CA (reprint author), 8600 Rockville Pike, Bethesda, MD 20894 USA. EM charlie@nlm.nih.gov NR 32 TC 5 Z9 5 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2004 VL 11 IS 6 BP 479 EP 481 DI 10.1197/jamia.M1532 PG 3 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 873UB UT WOS:000225305500005 PM 15298996 ER PT J AU Cutalo, JM Deterding, LJ Tomer, KB AF Cutalo, JM Deterding, LJ Tomer, KB TI Characterization of glycopeptides from HIV-I-SF2 gp120 by liquid chromatography mass spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; N-LINKED GLYCANS; MANNOSE-BINDING LECTIN; ENVELOPE GLYCOPROTEIN; CORECEPTOR USAGE; SIALIC-ACID; HIV TYPE-1; GP 120; COMPLEX; OLIGOSACCHARIDES AB Previously, we have characterized the HIV-I-SF2 gp120 glycopeptides using matrix-assisted laser desorption/ ionization mass spectrometry (MALDI/MS) and nanospray electrospray ionization (ESI). Although we characterized 25 of 26 consensus glycosylation sites, we could not obtain any information about the extent of sialylation of the complex glycans. Sialylation is known to alter the biological activity of some glycoproteins, e.g., infectivity of some human and nonhuman primate lentiviruses is reduced when the envelope glycoproteins are extensively sialylated, and thus, characterization of the extent of sialylation of complex glycoproteins is of biological interest. Since neither MALDI/MS nor nanospray ESI provided much information about sialylation, probably because of suppression effects inherent in these techniques, we utilized online nanocapillary high performance liquid chromatography (nHPLC) with ESI/MS to characterize the sites and extent of sialylation on gp120. Eight of the known 26 consensus glycosylation sites of HIV-I-SF2 gp120 were determined to be sialylated. Two of these sites were previously uncharacterized complex glycans. Thirteen high mannose sites were also determined. The heterogeneity of four of these sites had not been previously characterized. In addition, a peptide containing two consensus glycosylation sites, which had previously been determined to contain complex glycans, was also determined to be high mannose aswell. (J Am Soc Mass Spectrom 2004,15,1545-1555) (C) 2004 American Society for Mass Spectrometry. C1 NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,MD-F0-03, Res Triangle Pk, NC 27709 USA. EM tomer@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU NIEHS NIH HHS [Z01 ES050150-10] NR 25 TC 46 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 2004 VL 15 IS 11 BP 1545 EP 1555 DI 10.1016/j.jasms.2004.07.008 PG 11 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 868PM UT WOS:000224925500003 PM 15519221 ER PT J AU Kuhara, T Markey, SP AF Kuhara, T Markey, SP TI In memoriam - Isamu Matsumoto SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Biographical-Item C1 Kanazawa Med Univ, Kanazawa, Ishikawa, Japan. NIH, Bethesda, MD 20892 USA. RP Kuhara, T (reprint author), Kanazawa Med Univ, Kanazawa, Ishikawa, Japan. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 2004 VL 15 IS 11 BP 1689 EP 1690 DI 10.1016/j.jasms.2004.08.008 PG 2 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 868PM UT WOS:000224925500019 ER PT J AU Kim, GH Lee, JW Oh, YK Chang, HR Joo, KW Na, KY Earm, JH Knepper, MA Han, JS AF Kim, GH Lee, JW Oh, YK Chang, HR Joo, KW Na, KY Earm, JH Knepper, MA Han, JS TI Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID INDUCED DOWN-REGULATION; THICK ASCENDING LIMB; RAT-KIDNEY MEDULLA; BRATTLEBORO RATS; WATER CHANNEL; MESSENGER-RNA; INDUCED NDI; EXPRESSION; ALDOSTERONE; CHLOROTHIAZIDE AB Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na+ concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na+ transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and a-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of gamma-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na+ transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI. C1 Seoul Natl Univ, Dept Internal Med, Clin Res Inst, Seoul Natl Univ Hosp, Seoul, South Korea. Hanyang Univ, Coll Med, Dept Internal Med, Seoul 133791, South Korea. Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea. Eulji Med Coll, Dept Internal Med, Seoul, South Korea. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Han, JS (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 28 Yongun Dong, Seoul 110744, South Korea. EM jshan@snu.ac.kr RI Oh, Yun Kyu/J-5542-2012; Na, Ki Young/J-5456-2012; Han, Jin-Suk/J-5711-2012; Joo, Kwon Wook/J-5675-2012; OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 45 TC 55 Z9 57 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2004 VL 15 IS 11 BP 2836 EP 2843 DI 10.1097/01.ASN.0000143476.93376.04 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 865EB UT WOS:000224684200008 PM 15504936 ER PT J AU Ryschkewitsch, C Jensen, P Hou, J Fahle, G Fischer, S Major, EO AF Ryschkewitsch, C Jensen, P Hou, J Fahle, G Fischer, S Major, EO TI Comparison of PCR-southern hybridization and quantitative real-time PCR for the detection of JC and BK viral nucleotide sequences in urine and cerebrospinal fluid SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE JCV; BKV; quantitation; real-time PCR; standardization ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VIRUS-DNA; SIMIAN-VIRUS-40; BRAIN; ASSOCIATION; NEPHRITIS; KIDNEY AB The presence of the human polyomaviruses JCV and BKV in immunocompromised patients can lead to lethal diseases and conditions including progressive multifocal leukoencephalopathy (PML), interstitial nephritis, hemorrhagic cystitis, and kidney allograft rejection. Typically, detection of JCV and BKV in clinical samples has employed standard PCR amplification for viral nucleotide sequences, with subsequent confirmation for viral genome specificity of PCR products by southern blot hybridization. Here, we directly tested a validated PCR-southem protocol with a TaqMan real-time PCR protocol (Applied Biosystems) to assay clinical samples of urine and cerebrospinal fluid. We found equal specificity and sensitivity with both methods. However, real-time allowed for absolute viral-genome quantitation without the use of radionucleotides and was performed more rapidly, in as little as 24 h. Such advantages are important to consider in the effort to establish international standardization of controls for the detection of JCV and BKV, which would aid in screening confidence and the reliable assessment of anti-viral therapies. Published by Elsevier B.V. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. NIH, Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 36 Convent Dr, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov NR 14 TC 77 Z9 77 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2004 VL 121 IS 2 BP 217 EP 221 DI 10.1016/j.jviromet.2004.06.021 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 860TI UT WOS:000224365700011 PM 15381359 ER PT J AU He, H Messer, RJ Sakaguchi, S Yang, GJ Robertson, SJ Hasenkrug, KJ AF He, H Messer, RJ Sakaguchi, S Yang, GJ Robertson, SJ Hasenkrug, KJ TI Reduction of retrovirus-induced immunosuppression by in vivo modulation of T cells during acute infection SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; INDUCED TNF RECEPTOR; IMMUNOLOGICAL SELF-TOLERANCE; HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-RESPONSES; AUTOIMMUNE ENCEPHALOMYELITIS; FUNCTIONAL IMPAIRMENT; EFFECTOR FUNCTION; LEISHMANIA-MAJOR; FRIEND-VIRUS AB Chronic infection with Friend retrovirus is associated with suppressed antitumor immune responses. In the present study we investigated whether modulation of T-cell responses during acute infection would restore antitumor immunity in persistently infected mice. T-cell modulation was done by treatments with DTA-1 anti-glucocorticoid-induced tumor necrosis factor receptor monoclonal antibodies. The DTA-1 monoclonal antibody is nondepleting and delivers costimulatory signals that both enhance the activation of effector T cells and inhibit suppression by regulatory T cells. DTA-1 therapy produced faster Th1 immune responses, significant reductions in both acute virus loads and pathology and, most importantly, long-term improvement of CD8(+) T-cell-mediated antitumor responses. C1 NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. Kyoto Univ, Inst Frontier Med Sci, Dept Expt Pathol, Kyoto, Japan. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov RI Sakaguchi, Shimon/C-9535-2009 NR 52 TC 38 Z9 41 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 NOV PY 2004 VL 78 IS 21 BP 11641 EP 11647 DI 10.1128/JVI.78.21.11641-11647.2004 PG 7 WC Virology SC Virology GA 863DM UT WOS:000224540900018 PM 15479805 ER PT J AU Peloponese, JM Iha, H Yedavalli, VRK Miyazato, A Li, Y Haller, K Benkirane, M Jeang, KT AF Peloponese, JM Iha, H Yedavalli, VRK Miyazato, A Li, Y Haller, K Benkirane, M Jeang, KT TI Ubiquitination of human T-Cell leukemia virus type 1 tax modulates its activity SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; PRIMARY HUMAN-LYMPHOCYTES; HTLV-I TAX; TRANSCRIPTIONAL ACTIVITY; PROTEIN TRANSFORMS; DNA-DAMAGE; ACTIVATION; ONCOPROTEIN; EXPRESSION; PROTEASOME AB Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein. Tax is a transcriptional activator which modulates expression of the viral long terminal repeat and transcription of many cellular genes. Because Tax is a critical HTLV-1 factor which mediates viral transformation of T cells during the genesis of adult T-cell leukemia, it is important to understand the processes which can activate or inactivate Tax function. Here, we report that ubiquitination of Tax is a posttranscriptional mechanism which regulates Tax function. We show that ubiquitination does not target Tax for degradation by the proteasome. Rather, ubiquitin addition modifies Tax in a proteasome-independent manner from an active to a less-active transcriptional form. C1 NIAID, Lab Mol Microbiol, Mol Virol Sect, NIH, Bethesda, MD USA. Inst Genet Humaine, Lab Virol Mol, CNRS, UPR 1142, Montpellier, France. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; OI Iha, Hidekatsu/0000-0002-0999-5636 NR 67 TC 60 Z9 62 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 NOV PY 2004 VL 78 IS 21 BP 11686 EP 11695 DI 10.1128/JVI.78.21.11686-11695.2004 PG 10 WC Virology SC Virology GA 863DM UT WOS:000224540900023 PM 15479810 ER PT J AU Cohen, JI Cox, E Pesnicak, L Srinivas, S Krogmann, T AF Cohen, JI Cox, E Pesnicak, L Srinivas, S Krogmann, T TI The varicella-zoster virus open reading frame 63 latency-associated protein is critical for establishment of latency SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; GENE-EXPRESSION; DELETION MUTANT; HERPES; TRANSCRIPT; REPLICATION; INFECTION; VACCINE; TYPE-1; RAT AB Varicella-zoster virus (VZV) expresses at least six viral transcripts during latency. One of these transcripts, derived from open reading frame 63 (ORF63), is one of the most abundant viral RNAs expressed during latency. The VZV ORF63 protein has been detected in human and experimentally infected rodent ganglia by several laboratories. We have deleted >90% of both copies of the ORF63 gene from the VZV genome. Animals inoculated with the ORF63 mutant virus had lower mean copy numbers of latent VZV genomes in the dorsal root ganglia 5 to 6 weeks after infection than animals inoculated with parental or rescued virus, and the frequency of latently infected animals was significantly lower in animals infected with the ORF63 mutant virus than in animals inoculated with parental or rescued virus. In contrast, the frequency of animals latently infected with viral mutants in other genes that are equally or more impaired for replication in vitro, compared with the ORF63 mutant, is similar to that of animals latently infected with parental VZV. Examination of dorsal root ganglia 3 days after infection showed high levels of VZV DNA in animals infected with either ORF63 mutant or parental virus; however, by days 6 and 10 after infection, the level of viral DNA in animals infected with the ORF63 mutant was significantly lower than that in animals infected with parental virus. Thus, ORF63 is not required for VZV to enter ganglia but is the first VZV gene shown to be critical for establishment of latency. Since the present vaccine can reactivate and cause shingles, a VZV vaccine based on the ORF63 mutant virus might be safer. C1 NIH, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Dis, Med Virol Sect, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov NR 35 TC 41 Z9 46 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 NOV PY 2004 VL 78 IS 21 BP 11833 EP 11840 DI 10.1128/JVI.78.21.11833-11840.2004 PG 8 WC Virology SC Virology GA 863DM UT WOS:000224540900038 PM 15479825 ER PT J AU Luo, K Liu, BD Xiao, ZX Yu, YK Yu, XH Gorelick, R Yu, XF AF Luo, K Liu, BD Xiao, ZX Yu, YK Yu, XH Gorelick, R Yu, XF TI Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging SO JOURNAL OF VIROLOGY LA English DT Article ID B MESSENGER-RNA; NUCLEIC-ACID-CHAPERONE; ASSEMBLY INTERMEDIATE COMPLEXES; VIRION INFECTIVITY FACTOR; STRAND TRANSFER-REACTIONS; IN-VIVO REPLICATION; VIRAL-DNA SYNTHESIS; AP-1 BINDING-SITE; HIV-1 VIF PROTEIN; SOR GENE-PRODUCT AB APOBEC3G exerts its antiviral activity by targeting to retroviral particles and inducing viral DNA hyper-mutations in the absence of Vif. However, the mechanism by which APOBEC3G is packaged into virions remains unclear. We now report that viral genomic RNA enhances but is not essential for human APOBEC3G packaging into human immunodeficiency virus type 1 (HIV-1) virions. Packaging of APOBEC3G was also detected in HIV-1 Gag virus-like particles (VLP) that lacked all the viral genomic RNA packaging signals. Human APOBEC3G could be packaged efficiently into a divergent subtype HIV-1, as well as simian immunodeficiency virus, strain mac, and murine leukemia virus Gag VLP. Cosedimentation of human APOBEC3G and intracellular Gag complexes was detected by equilibrium density and velocity sucrose gradient analysis. Interaction between human APOBEC3G and HIV-1 Gag was also detected by coimmunoprecipitation experiments. This interaction did not require p6, p1, or the C-terminal region of NCp7. However, the N-terminal region, especially the first 11 amino acids, of HIV-1 NCp7 was critical for HIV-1 Gag and APOBEC3G interaction and virion packaging. The linker region flanked by the two active sites of human APOBEC3G was also important for efficient packaging into HIV-1 Gag VLP. Association of human APOBEC3G with RNA-containing intracellular complexes was observed. These results suggest that the N-terminal region of HIV-1 NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization, plays an important role in APOBEC3G binding and virion packaging. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NCI, Frederick, MD 21701 USA. Zhejiang Univ, Zhejiang, Peoples R China. Jilin Univ, Jilin, Peoples R China. RP Yu, XF (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM xfyu@jhsph.edu NR 96 TC 148 Z9 154 U1 0 U2 6 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 NOV PY 2004 VL 78 IS 21 BP 11841 EP 11852 DI 10.1128/JVI.78.21.11841-11852.2004 PG 12 WC Virology SC Virology GA 863DM UT WOS:000224540900039 PM 15479826 ER PT J AU Ganesh, L Leung, K Lore, K Levin, R Panet, A Schwartz, O Koup, RA Nabel, GJ AF Ganesh, L Leung, K Lore, K Levin, R Panet, A Schwartz, O Koup, RA Nabel, GJ TI Infection of specific dendritic cells by CCR5-tropic human immunodeficiency virus type 1 promotes cell-mediated transmission of virus resistant to broadly neutralizing antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; DC-SIGN; T-CELLS; HIV-1 INFECTION; TRANS-INFECTION; ENVELOPE GLYCOPROTEINS; EBOLA-VIRUS; BLOOD; BINDING; RECEPTORS AB The tropism of human immunodeficiency virus type I for chemokine receptors plays an important role in the transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs, which are not susceptible to infection but instead internalize virus into a protected intracellular compartment and enhance the infection of T cells. Here, we define a mechanism to explain preferential transmission of CCR5-tropic viruses based on their interaction with mDCs and sensitivity to neutralizing antibodies. Infected immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus infection of T cells even in the continuous presence of neutralizing antibodies. Infectious synapses also formed normally in the presence of such antibodies. Infection of immature mDCs by CCR5-tropic virus can therefore establish a pool of infected cells that can efficiently transfer virus at the same time that they protect virus from antibody neutralization. This property of DCs may enhance infection, contribute to immune evasion, and could provide a selective advantage for CCR5-tropic virus transmission. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Biol Imaging Facil, NIH, Bethesda, MD 20892 USA. Israel Inst Biol Res, Dept Infect Dis, IL-70450 Ness Ziona, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Virol, IL-91010 Jerusalem, Israel. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Rm 4502,MSC-3005,Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 51 TC 83 Z9 86 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 NOV PY 2004 VL 78 IS 21 BP 11980 EP 11987 DI 10.1128/JVI.78.21.11980-11987.2004 PG 8 WC Virology SC Virology GA 863DM UT WOS:000224540900051 PM 15479838 ER PT J AU Tamiya, S Mardy, S Kavlick, MF Yoshimura, K Mistuya, H AF Tamiya, S Mardy, S Kavlick, MF Yoshimura, K Mistuya, H TI Amino acid insertions near gag cleavage sites restore the otherwise compromised replication of human immunodeficiency virus type 1 variants resistant to protease inhibitors SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 REVERSE-TRANSCRIPTASE; CROSS-RESISTANCE; COMBINATION THERAPY; DRUG-RESISTANCE; IN-VIVO; MUTATIONS; FITNESS; GENE; MUTANTS AB A variety of amino acid substitutions in the protease and Gag proteins have been reported to contribute to the development of human immunodeficiency virus type 1 (HIV-1) resistance to protease inhibitors. In the present study, full-length molecular infectious HIV-1 clones were generated by using HIV-1 variants isolated from heavily drug-experienced and therapy-failed AIDS patients. Of six full-length infectious clones generated, four were found to have unique insertions (TGNS, SQVN, AQQA, SRPE, APP, and/or PTAPPA) near the p17/p24 and p1/p6 Gag cleavage sites, in addition to the known resistance-related multiple amino acid substitutions within the protease. The addition of such Gag inserts mostly compromised the replication of wild-type HIV-1, whereas the primary multidrug-resistant HIV infectious clones containing inserts replicated significantly better than those modified to lack the inserts. Western blot analyses revealed that the processing of Gag proteins by wild-type protease was impaired by the presence of the inserts, whereas that by mutant protease was substantially improved. The present study represents the first report clearly demonstrating that the inserts seen in the proximity of the Gag cleavage sites in highly multi-PI resistant HIV-1 variants restore the otherwise compromised enzymatic activity of mutant protease, enabling the multi-PI-resistant HIV-1 variants to remain replication competent. C1 NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Kumamoto Univ, Sch Med, Div Clin Retrovirol & Infect Dis, Ctr AIDS Res, Kumamoto 860, Japan. Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 860, Japan. Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 860, Japan. RP Mistuya, H (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bldg 10,Rm 5A11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hmitsuya@helix.nih.gov RI Kumamoto University, CAIDS/G-8446-2013 NR 43 TC 28 Z9 29 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 NOV PY 2004 VL 78 IS 21 BP 12030 EP 12040 DI 10.1128/JVI.78.21.12030-12040.2004 PG 11 WC Virology SC Virology GA 863DM UT WOS:000224540900055 PM 15479842 ER PT J AU Gaddis, NC Sheehy, AM Ahmad, KM Swanson, CM Bishop, KN Beer, BE Marx, PA Gao, F Bibollet-Ruche, F Hahn, BH Malim, MH AF Gaddis, NC Sheehy, AM Ahmad, KM Swanson, CM Bishop, KN Beer, BE Marx, PA Gao, F Bibollet-Ruche, F Hahn, BH Malim, MH TI Further investigation of simian immunodeficiency virus vif function in human cells SO JOURNAL OF VIROLOGY LA English DT Article ID MONKEYS CERCOPITHECUS-LHOESTI; CROSS-SPECIES TRANSMISSION; HIV-1 VIF; ANTIVIRAL ACTIVITY; AFRICAN MANDRILL; ENZYME APOBEC3G; SOR GENE; IN-VIVO; TYPE-1; PROTEIN AB Primate lentivirus Vif proteins function by suppressing the antiviral activity of the cell-encoded apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) proteins APOBEC3G and APOBEC3F. It has been hypothesized that species-specific susceptibilities of APOBEC proteins to Vif proteins may help govern the transmission of primate lentiviruses to new host species. Consistent with this view and with previous results, we report that the Vif proteins of several diverse simian immunodeficiency viruses (SIVs) that are not known to infect humans are not effective inhibitors of human APOBEC3G or APOBEC3F when assessed in transient-transfection experiments. Unexpectedly, this lack of SIV Vif function did not prevent the replication of two vif-deficient SIVs (SIVtan and SlVmnd1; isolated from tantalus monkeys and mandrills, respectively) in a human T-cell line, HUT78, that expresses both APOBEC 3G and APOBEC3F, a finding which demonstrates that some SIVs are partially resistant to the antiretroviral effects of these enzymes irrespective of Vif function. Additional virus replication studies also revealed that the Vif protein of SIVtan is, in fact, active in human T cells, as it substantially enhanced the replication of its cognate virus and human immunodeficiency virus type 1. In sum, we now consider it improbable that species-specific restrictions to SIV Vif function can explain the lack of human infection with certain SIVs. Instead, our data reveal that the species-specific modulation of Vif function is more complex than previously envisioned and that additional (as-yet-unidentified) viral or host factors may be involved in regulating this dynamic interaction between host and pathogen. C1 Univ London Kings Coll, Guys Kings & St Thomas Sch Med, Dept Infect Dis, London SE1 9RT, England. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. NIAID, Mol Microbiol Lab, NIH, Rockville, MD USA. Tulane Univ, Hlth Sci Ctr, Natl Primate Res Ctr, Covington, LA USA. Duke Univ, Dept Med, Durham, NC USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Malim, MH (reprint author), Univ London Kings Coll, Guys Kings & St Thomas Sch Med, Dept Infect Dis, GKT Guys Hosp, 2nd Floor,New Guys House, London SE1 9RT, England. EM michael.malim@kcl.ac.uk OI Gaddis, Nathan/0000-0001-5205-7138; Malim, Michael/0000-0002-7699-2064; Swanson, Chad/0000-0002-6650-3634 FU NIAID NIH HHS [R01 AI050529, AI07325, AI10460, AI44596, AI46246, AI50529, F32 AI010460, R01 AI044596, R37 AI050529, T32 AI007325] NR 49 TC 60 Z9 61 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 NOV PY 2004 VL 78 IS 21 BP 12041 EP 12046 DI 10.1128/JVI.78.21.12041-12046.2004 PG 6 WC Virology SC Virology GA 863DM UT WOS:000224540900056 PM 15479843 ER PT J AU Yong, TJ Wu, TY Kozak, CA AF Yong, TJ Wu, TY Kozak, CA TI Novel host range and cytopathic variant of ecotropic friend murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; CELL TROPISM; RECEPTOR; RETROVIRUSES; GLYCOPROTEIN; INFECTION; PVC-211; PROTEIN; GENE; DNA AB A variant ecotropic Friend murine leukemia virus, F-S MLV, is capable of inducing the formation of large multinucleated syncytia in Mus dunni cells. This cytopathicity resembles that of Sp1574 MLV, a novel variant recently isolated from the spleen of a Mus spicilegus mouse neonatally inoculated with Moloney MLV. F-S MLV is an N-tropic Friend MLV that also has the unusual ability to infect hamster cells, which are normally resistant to mouse ecotropic MLVs. Syncytium induction by both F-S MLV and Sp1574 is accompanied by the accumulation of large amounts of unintegrated viral DNA, a hallmark of pathogenic retroviruses, but not previously reported for mouse ecotropic gammaretroviruses. Sequencing and site-specific mutagenesis determined that the syncytium-inducing phenotype of F-S MLV can be attributed to a single amino acid substitution (S84A) in the VRA region of the viral env gene. This site corresponds to that of the single substitution previously shown to be responsible for the cytopathicity of Spl574, S82F. The S84A substitution in F-S MLV also contributes to the ability of this virus to infect hamster cells, but Sp1574 MLV is unable to infect hamster cells. Because this serine residue is one of the critical amino acids that form the CAT-1 receptor binding site, and because M. dunni and hamster cells have variant CAT-1 receptors, these results suggest that syncytium formation as well as altered host range may be a consequence of altered interaction between virus and receptor. C1 NIAID, LMM, NIH, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, LMM, NIH, Bldg 4,Room 329,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM ckozak@niaid.nih.gov NR 29 TC 0 Z9 0 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 NOV PY 2004 VL 78 IS 22 BP 12189 EP 12197 DI 10.1128/JVI.78.22.12189-12197.2004 PG 9 WC Virology SC Virology GA 866NY UT WOS:000224781400010 ER PT J AU Muriaux, D Costes, S Nagashima, K Mirro, J Cho, E Lockett, S Rein, A AF Muriaux, D Costes, S Nagashima, K Mirro, J Cho, E Lockett, S Rein, A TI Role of murine leukemia virus nucleocapsid protein in virus assembly SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA-VIRUS; ACID-CHAPERONE ACTIVITY; TYPE-1 GAG POLYPROTEIN; PRIMER-BINDING-SITE; IN-VITRO; BASIC RESIDUES; GENOMIC RNA; VIRAL-RNA; VIRION PRODUCTION; HIV-1 AB The retroviral nucleocapsid protein (NC) originates by cleavage of the Gag polyprotein. It is highly basic and contains one or two zinc fingers. Mutations in either the basic residues or the zinc fingers can affect several events of the virus life cycle. They frequently prevent the specific packaging of the viral RNA, affect reverse transcription, and impair virion assembly. In this work, we explore the role of NC in murine leukemia virus (MLV) particle assembly and release. A panel of NC mutants, including mutants of the zinc finger and of a basic region, as well as truncations of the NC domain of Gag, were studied. Several of these mutations dramatically reduce the release of virus particles. A mutant completely lacking the NC domain is apparently incapable of assembling into particles, although its Gag protein is still targeted to the plasma membrane. By electron microscopy on thin sections of virus-producing cells, we observed that some NC mutants exhibit various stages of budding defects at the plasma membrane and have aberrant particle morphology; electron micrographs of cells expressing some of these mutants are strikingly similar to those of cells expressing "late-domain" mutants. However, the defects of NC mutants. with respect to virus release and infectivity could be complemented by an MLV lacking the p12 domain. Therefore, the functions of NC in virus budding and infectivity are completely distinct from viral late-domain function. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. NCI, Image Anal Lab, Ft Detrick, MD USA. NCI, SAIC Frederick, Ft Detrick, MD USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, POB B, Ft Detrick, MD 21702 USA. EM rein@ncifcrf.gov RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 47 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2004 VL 78 IS 22 BP 12378 EP 12385 DI 10.1128/JVI.78.22.12378-12385.2004 PG 8 WC Virology SC Virology GA 866NY UT WOS:000224781400029 PM 15507624 ER PT J AU McCurdy, LH Rutigliano, JA Johnson, TR Chen, M Graham, BS AF McCurdy, LH Rutigliano, JA Johnson, TR Chen, M Graham, BS TI Modified vaccinia virus Ankara immunization protects against lethal challenge with recombinant vaccinia virus expressing murine interleukin-4 SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; BROAD SPECIES-SPECIFICITY; SMALLPOX VACCINATION; IN-VIVO; IMMUNODEFICIENT MICE; STRAIN MVA; INFECTION; CELLS; COMPLICATIONS; QUANTITATION AB Recent events have raised concern over the use of pathogens, including variola virus, as biological weapons. Vaccination with Dryvax is associated with serious side effects and is contraindicated for many people, and the development of a safer effective smallpox vaccine is necessary. We evaluated an attenuated vaccinia virus, modified vaccinia virus Ankara (MVA), by use of a murine model to determine its efficacy against an intradermal (i.d.) or intranasal (i.n.) challenge with vaccinia virus (vSC8) or a recombinant vaccinia virus expressing murine interleukin-4 that exhibits enhanced virulence (vSC8-mIL4). After an i.d. challenge, 15 of 16 mice who were inoculated with phosphate-buffered saline developed lesions, one dose of intramuscularly administered MVA was partially protective (3 of 16 mice developed lesions), and the administration of two or three doses of MVA was completely protective (0 of 16 mice developed lesions). In unimmunized mice, an i.n. challenge with vSC8 caused a significant but self-limited illness, while vSC8-mIL4 resulted in lethal infections. Immunization with one or two doses of MVA prevented illness and reduced virus titers in mice who were challenged with either vSC8 or vSC8-mIL4. MVA induced a dose-related neutralizing antibody and vaccinia virus-specific CD8(+)-T-cell response. Mice immunized with MVA were fully protected from a low-dose vSC8-mIL4 challenge despite a depletion of CD4(+) cells, CD8(+) cells, or both T-cell subsets or an antibody deficiency. CD4(+)- or CD8(+)-T-cell depletion reduced the protection against a high-dose vSC8-mIL4 challenge, and the depletion of both T-cell subsets was associated with severe illness and higher vaccinia virus titers. Thus, MVA induces broad Immoral and cellular immune responses that can independently protect against a molecularly modified lethal poxvirus challenge in mice. These data support the continued development of MVA as an alternative candidate vaccine for smallpox. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3017,Bldg 40,Room 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 45 TC 22 Z9 23 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 NOV PY 2004 VL 78 IS 22 BP 12471 EP 12479 DI 10.1128/JVI.78.22.12471-12479.2004 PG 9 WC Virology SC Virology GA 866NY UT WOS:000224781400039 PM 15507634 ER PT J AU Baumann, JG Unutmaz, D Miller, MD Breun, SKJ Grill, SM Mirro, J Littman, DR Rein, A KewalRamani, VN AF Baumann, JG Unutmaz, D Miller, MD Breun, SKJ Grill, SM Mirro, J Littman, DR Rein, A KewalRamani, VN TI Murine T cells potently restrict human immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID HOST-RANGE RESTRICTIONS; MOUSE LEUKEMIA VIRUS; PRE-B-CELL; HIV-1 INFECTION; RETROVIRUS RESTRICTION; FV-1 RESTRICTION; VIF PROTEIN; EARLY STEPS; TYPE-1; REPLICATION AB Development of a mouse model for human immunodeficiency virus type 1 (HIV-1) infection has advanced through the progressive identification of host cell factors required for HIV-1 replication. Murine cells lack HIV-1 receptor molecules, do not support efficient viral gene expression, and lack factors necessary for the assembly and release of virions. Many of these blocks have been described using mouse fibroblast cell lines. Here we identify a postentry block to HIV-1 infection in mouse T-cell lines that has not been detected in mouse fibroblasts. While murine fibroblastic lines are comparable to human T-cell lines in permissivity to HIV-1 transduction, infection of marine T cells is 100-fold less efficient. Virus entry occurs efficiently in marine T cells. However, reduced efficiency of the completion of reverse transcription and nuclear transfer of the viral preintegration complex are observed. Although this block has similarities to the restriction of murine retroviruses by Fv1, there is no correlation of HIV-1 susceptibility with cellular Fv1 genotypes. In addition, the block to HIV-1 infection in marine T-cell lines cannot be saturated by a high virus dose. Further studies of this newly identified block may lend insight into the early events of retroviral replication and reveal new targets for antiretroviral interventions. C1 NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. Merck Res Labs, Dept Biol Chem, West Point, PA USA. NYU, Sch Med, Howard Hughes Med Inst, New York, NY USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA. RP KewalRamani, VN (reprint author), NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Bldg 535,Rm 123, Frederick, MD 21702 USA. EM vineet@ncifcrf.gov FU NIAID NIH HHS [R01 AI049131, R01 AI033856, AI 33856, AI 49131, AI 36606] NR 81 TC 34 Z9 35 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 NOV PY 2004 VL 78 IS 22 BP 12537 EP 12547 DI 10.1128/JVI.78.22.12537-12547.2004 PG 11 WC Virology SC Virology GA 866NY UT WOS:000224781400046 PM 15507641 ER PT J AU Huang, Y Yang, ZY Kong, WP Nabel, GJ AF Huang, Y Yang, ZY Kong, WP Nabel, GJ TI Generation of synthetic severe acute respiratory syndrome coronavirus pseudoparticles: Implications for assembly and vaccine production SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; INFECTIOUS-BRONCHITIS-VIRUS; MOUSE HEPATITIS-VIRUS; SARS CORONAVIRUS; M-PROTEIN; GENETIC IMMUNIZATION; MEMBRANE-PROTEIN; GENOME SEQUENCE; MAMMALIAN-CELLS; PLASMID DNA AB The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) contains four structural genes, two replicase-transcriptase open reading frames, and more than five potential genes of unknown function. Despite this relative simplicity, the molecular regulation of SARS-CoV replication and assembly is not understood. Here, we report that two viral genes, encoding the SARS-CoV membrane (M) and nucleocapsid (N) proteins, are necessary and sufficient for formation of virus-like particles. Expression vectors encoding these two proteins were synthesized by using preferred human codons. When M and N expression plasmids were cotransfected into human 293 renal epithelial cells, pseudoparticles formed readily. The addition of a third gene, encoding the spike (S) glycoprotein, facilitated budding of particles that contained a corona-like halo resembling SARS-CoV when examined by transmission electron microscopy, with a buoyant density characteristic of coronaviruses. Specific biochemical interactions of these proteins were also shown in vitro. The S, M, and N proteins of the SARS-CoV are, therefore, necessary and sufficient for pseudovirus assembly. These findings advance the understanding of the morphogenesis of SARS-CoV and enable the generation of safe, conformational mimetics of the SARS virus that may facilitate the development of vaccines and antiviral drugs. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20982 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20982 USA. EM gnabel@nih.gov NR 35 TC 73 Z9 75 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2004 VL 78 IS 22 BP 12557 EP 12565 DI 10.1128/JVI.78.22.12557-12565.2004 PG 9 WC Virology SC Virology GA 866NY UT WOS:000224781400048 PM 15507643 ER PT J AU Matrosovich, MN Matrosovich, TY Gray, T Roberts, NA Klenk, HD AF Matrosovich, MN Matrosovich, TY Gray, T Roberts, NA Klenk, HD TI Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium SO JOURNAL OF VIROLOGY LA English DT Article AB Influenza virus neuraminidase (NA) plays an essential role in release and spread of progeny virions, following the intracellular viral replication cycle. To test whether NA could also facilitate virus entry into cell, we infected cultures of human airway epithelium with human and avian influenza viruses in the presence of the NA inhibitor oseltamivir carboxylate. Twenty- to 500-fold less cells became infected in drug-treated versus nontreated cultures (P < 0.0001) 7 h after virus application, indicating that the drug suppressed the initiation of infection. These data demonstrate that viral NA plays a role early in infection, and they provide further rationale for the prophylactic use of NA inhibitors. C1 Univ Marburg, Inst Virol, D-35037 Marburg, Germany. MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow, Russia. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. RP Matrosovich, MN (reprint author), Univ Marburg, Inst Virol, Robert Koch Str 17, D-35037 Marburg, Germany. EM Mikhail.Matrosovich@med.uni-marburg.de NR 11 TC 278 Z9 298 U1 3 U2 33 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 NOV PY 2004 VL 78 IS 22 BP 12665 EP 12667 DI 10.1128/JVI.78.22.12665-12667.2004 PG 3 WC Virology SC Virology GA 866NY UT WOS:000224781400058 PM 15507653 ER PT J AU Trus, BL Chen, NQ Newcomb, WW Homa, FL Brown, JC Steven, AC AF Trus, BL Chen, NQ Newcomb, WW Homa, FL Brown, JC Steven, AC TI Structure and polymorphism of the UL6 portal protein of herpes simplex virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID CRYOELECTRON MICROSCOPY; HIGH-RESOLUTION; TAIL CONNECTOR; DNA; MACROMOLECULES; MATURATION AB By electron microscopy and image analysis, we find that baculovirus-expressed UL6 is polymorphic, consisting of rings of 11-, 12-, 13-, and 14-fold symmetry. The 12-mer is likely to be the oligomer incorporated into procapsids: at a resolution of 16 A, it has an axial channel, peripheral flanges, and fits snugly into a vacant vertex site. Its architecture resembles those of bacteriophage portal/connector proteins. C1 NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. Ctr Informat Technol, Imaging Sci Lab, Div Computat Biosci, Bethesda, MD 20892 USA. Univ Virginia, Dept Microbiol, Hlth Syst, Charlottesville, VA USA. Univ Virginia, Ctr Canc, Hlth Syst, Charlottesville, VA USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bldg 50,Room 1517,MSC 8025,50 South Dr, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov FU NIAID NIH HHS [R01 AI060836]; PHS HHS [NIH 41644] NR 21 TC 105 Z9 106 U1 0 U2 11 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 NOV PY 2004 VL 78 IS 22 BP 12668 EP 12671 DI 10.1128/JVI.78.22.12668-12671.2004 PG 4 WC Virology SC Virology GA 866NY UT WOS:000224781400059 PM 15507654 ER PT J AU Rucker, E Grivel, JC Munch, J Kirchhoff, F Margolis, L AF Rucker, E Grivel, JC Munch, J Kirchhoff, F Margolis, L TI Vpr and vpu are important for efficient human immunodeficiency virus type 1 replication and CD4(+) T-cell depletion in human lymphoid tissue ex vivo SO JOURNAL OF VIROLOGY LA English DT Article ID ACCESSORY PROTEIN; HIV-1 VPR; NEF GENE; VIRAL REPLICATION; DOWN-MODULATION; ENZYME APOBEC3G; NUCLEAR IMPORT; IN-VITRO; ACTIVATION; INFECTION AB The relevance of the accessory vpr, vpu, and nef genes for human immunodeficiency virus type 1 (HIV-1) replication in human lymphoid tissue (HLT), the major site of viral replication in vivo, is largely unknown. Here, we show that an individual deletion of nef, vpr, or vpu significantly decreases HIV-1 replication and prevents CD4(+) T-cell depletion in ex vivo HLT. However, only combined defects in all three accessory genes entirely disrupt the replicative capacity of HIV-1. Our results demonstrate that nef, vpr, and vpu are all essential for efficient viral spread in HLT, suggesting an important role in AIDS pathogenesis. C1 NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. Univ Ulm, Dept Virol, D-7900 Ulm, Germany. RP Kirchhoff, F (reprint author), NICHHD, Lab Mol & Cellular Biophys, Bldg 10,Room 9D58, Bethesda, MD 20892 USA. EM frank.kirchhoff@medizin.uni-ulm.de; margolis@helix.nih.gov NR 54 TC 25 Z9 27 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 NOV PY 2004 VL 78 IS 22 BP 12689 EP 12693 DI 10.1128/JVI.78.22.12689-12693.2004 PG 5 WC Virology SC Virology GA 866NY UT WOS:000224781400063 PM 15507658 ER PT J AU Davey, A Halverson, CF Zonderman, AB Costa, PT AF Davey, A Halverson, CF Zonderman, AB Costa, PT TI Change in depressive symptoms in the Baltimore longitudinal study of aging SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article; Proceedings Paper CT 52nd Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 19-23, 1999 CL SAN FRANCISCO, CA SP Gerontol Soc Amer ID ADULT LIFE-SPAN; NEGATIVE AFFECT; AGE; SCALE; MODEL; PERSONALITY; COMMUNITY; OLD; NEUROTICISM; HAPPINESS AB Depressive symptoms have been represented in the research and clinical literature in terms of both an episodic phenomenon and as enduring individual differences. We investigated depressive symptoms longitudinally in a sample of older adults. Participants were 737 individuals (M(Age) = 73 years initially, 39% women) in the Baltimore Longitudinal Study of Aging who provided biennial Center for Epidemiological Studies-Depression data on up to five occasions over an 8-year period. We found both trait and state-residual variability, with symptoms increasing longitudinally on all subscales and accounting for an approximately I-point increase per decade. Trait-like variability accounted for at least two thirds of the reliable variance. Interindividual differences were consistent over time, but occasion-specific variability diminished across occasions. C1 Madlyn & Leonard Abramson Ctr Jewish Life, Polisher Res Inst, N Wales, PA 19454 USA. Univ Georgia, Dept Child & Family Dev, Athens, GA 30602 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Davey, A (reprint author), Madlyn & Leonard Abramson Ctr Jewish Life, Polisher Res Inst, 1425 Horsham Rd, N Wales, PA 19454 USA. EM adavey@abramsoncenter.org NR 58 TC 22 Z9 24 U1 3 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2004 VL 59 IS 6 BP P270 EP P277 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 877JK UT WOS:000225564500002 PM 15576854 ER PT J AU Fox, CS Larson, MG Keyes, MJ Levy, D Clouse, ME Culleton, B O'Donnell, CJ AF Fox, CS Larson, MG Keyes, MJ Levy, D Clouse, ME Culleton, B O'Donnell, CJ TI Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: The Framingham Heart Study SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FL SP Amer Heart Assoc DE coronary calcification; kidney disease; risk factor ID STAGE RENAL-DISEASE; BEAM COMPUTED-TOMOGRAPHY; GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; YOUNG-ADULTS; RISK-FACTOR; PREDICTION; COMMUNITY; OUTCOMES; FAILURE AB Background. Among patients with end-stage renal disease (ESRD), the risk of cardiovascular disease is 10 to 20 times higher than the general population. Adults with ESRD have increased coronary-artery calcification (CAC) detected by electron-beam computed tomography (EBCT). Because the risk of coronary heart disease is increased even at moderate declines in kidney function, we sought to test whether high CAC scores are seen among those with mild reductions in kidney function. Methods. Men and women free of symptomatic cardiovascular disease underwent EBCT. Coronary calcium was quantified using the method described by Agatston. Renal function was estimated by glomerular filtration rate (GFR). Spearman correlation coefficients were used to test the association between GFR and CAC. Results. Three hundred nineteen subjects (162 men/157 women), mean age 60, were included. Mean GFR was 86+/-23 mL/min/ 1.73 m(2) (range 31-169; 10% with GFR <60 mL/min/1.73 m(2)). The median CAC scores by quartile of GFR were 85.9, 48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28 (P<.0001). This remained significant after adjustment for age and sex (-0.11, P<0.05), and additionally after adjustment for body mass index (-0.11, P<0.05), hypertension (-0.11, P<0.05), or total cholesterol (-0.12, P=0.04). A similar correlation was noted after multivariable adjustment (-0.10, P<0.08). Conclusion. Mild declines in kidney function are associated with subclinical coronary artery calcification in a sample of subjects free of clinically apparent cardiovascular disease. This might help explain the increased risk of cardiovascular disease among individuals with renal dysfunction. Larger ongoing studies are needed to better quantify this finding. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Brigham & Womens Hosp, Dept Endocrinol Diabetes & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Beth Israel Deaconess Hosp, Dept Radiol, Boston, MA USA. Univ Calgary, Foothills Hosp, Calgary, AB, Canada. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), MPH, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov NR 32 TC 51 Z9 53 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2004 VL 66 IS 5 BP 2017 EP 2021 DI 10.1111/j.1523-1755.2004.00973.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 862CS UT WOS:000224467900031 PM 15496174 ER PT J AU Chen, L Evans, T Anand, S Boufford, JI Brown, H Chowdhury, M Cueto, M Dare, L Dussault, G Elzinga, G Fee, E Habte, D Hanvoravongchai, P Jacobs, M Kurowski, C Michael, S Pablos-Mendez, A Sewankambo, N Solimano, G Stilwell, B de Waal, A Wibulpolprasert, S AF Chen, L Evans, T Anand, S Boufford, JI Brown, H Chowdhury, M Cueto, M Dare, L Dussault, G Elzinga, G Fee, E Habte, D Hanvoravongchai, P Jacobs, M Kurowski, C Michael, S Pablos-Mendez, A Sewankambo, N Solimano, G Stilwell, B de Waal, A Wibulpolprasert, S TI Human resources for health: overcoming the crisis SO LANCET LA English DT Article AB in this analysis of the global workforce, the joint Learning Initiative-a consortium of more than 100 health leaders-proposes that mobilisation and strengthening of human resources for health, neglected yet critical, is central to combating health crises in some of the world's poorest countries and for building sustainable health systems in all countries. Nearly all countries are challenged by worker shortage, skill mix imbalance, maldistribution, negative work environment, and weak knowledge base. Especially in the poorest countries, the workforce is under assault by HIV/AIDS, out-migration, and inadequate investment. Effective country strategies should be backed by international reinforcement. Ultimately, the crisis in human resources is a shared problem requiring shared responsibility for cooperative action. Alliances for action are recommended to strengthen the performance of all existing actors while expanding space and energy for fresh actors. C1 Harvard Univ, Global Equity Initiat, Cambridge, MA 02138 USA. WHO, CH-1211 Geneva 27, Switzerland. Univ Oxford, Dept Econ, Oxford OX1 3QU, England. NYU, Robert F Wagner Grad Sch Publ Serv, New York, NY 10012 USA. Bangladesh Rural Advancement Comm, Dhaka 1212, Bangladesh. Univ Peruana Cayetano Heredia, Lima 18, Peru. African Council Sustainable Hlth Dev, Ibadan, Nigeria. World Bank Inst, Washington, DC 20433 USA. Natl Inst Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. NIH, Natl Lib Med, Bethesda, MD 20894 USA. World Bank, Washington, DC 20433 USA. Univ Cape Town, ZA-7925 Cape Town, South Africa. Makerere Univ, Fac Med, Kampala, Uganda. Univ Chile, Santiago, Chile. Minist Publ Hlth, Nonthaburi 11000, Thailand. RP Hanvoravongchai, P (reprint author), Harvard Univ, Global Equity Initiat, Cambridge, MA 02138 USA. EM phanvora@hsph.harvard.edu RI Dussault, Gilles/I-8495-2012; Hanvoravongchai, Piya/A-1569-2012; OI Hanvoravongchai, Piya/0000-0003-4256-1271; Sewankambo, Nelson/0000-0001-9362-053X; Dussault, Gilles/0000-0002-5976-3454 NR 16 TC 501 Z9 508 U1 7 U2 58 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV-DEC PY 2004 VL 364 IS 9449 BP 1984 EP 1990 DI 10.1016/S0140-6736(04)17482-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 874BX UT WOS:000225327000037 PM 15567015 ER PT J AU Barrett, AJ AF Barrett, AJ TI Myelodysplastic syndrome - an example of misguided immune surveillance? SO LEUKEMIA RESEARCH LA English DT Editorial Material ID APLASTIC-ANEMIA; BONE-MARROW; MDS C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 9 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD NOV PY 2004 VL 28 IS 11 BP 1123 EP 1124 DI 10.1016/j.leukres.2004.06.001 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 858WH UT WOS:000224222400002 PM 15380334 ER PT J AU Assaf, Y Freidlin, RZ Rohde, GK Basser, PJ AF Assaf, Y Freidlin, RZ Rohde, GK Basser, PJ TI New modeling and experimental framework to characterize hindered and restricted water diffusion in brain white matter SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; white matter; DTI; q-space ID CENTRAL-NERVOUS-SYSTEM; SPIN-ECHO; TENSOR MRI; WEIGHTED MRI; NMR; COMPARTMENTATION; SPECTROSCOPY; ORIENTATION; ATTENUATION; ANISOTROPY AB To characterize anisotropic water diffusion in brain white matter, a theoretical framework is proposed that combines hindered and restricted models of water diffusion (CHARMED) and an experimental methodology that embodies features of diffusion tensor and q-space MRI. This model contains a hindered extra-axonal compartment, whose diffusion properties are characterized by an effective diffusion tensor, an an intra-axonal compartment, whose diffusion properties are characterized by a restricted model of diffusion within cylinders. The hindered model primarily explains the Gaussian signal attenuation observed at low b values; the restricted non-Gaussian model does so at high b. Both high and low b data obtained along different directions are required to estimate various microstructural parameters of the composite model, such as the nerve fiber orientation(s), the T-2-weighted extra- and intra-axonal volume fractions, and principal diffusivities. The proposed model provides a description of restricted diffusion in 3D given by a 3D probability distribution (average propagator), which is obtained by 3D Fourier transformation of the estimated signal attenuation profile. The new model is tested using synthetic phantoms and validated on excised spinal cord tissue. This framework shows promise in determining the orientations of two or more fiber compartments more precisely and accurately than with diffusion tensor imaging. Published 2004 Wiley-Liss, Inc(dagger). C1 Tel Aviv Sourasky Med Ctr, Dept Radiol, Wohl Inst Adv Imaging, Funct Brain Imaging Unit, IL-64239 Tel Aviv, Israel. Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. NIH, Telemed & Appl Imaging Sect, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Assaf, Y (reprint author), Tel Aviv Sourasky Med Ctr, Dept Radiol, Wohl Inst Adv Imaging, Funct Brain Imaging Unit, IL-64239 Tel Aviv, Israel. EM asafyan@zahav.net.il RI Basser, Peter/H-5477-2011 NR 41 TC 238 Z9 240 U1 1 U2 25 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 NOV PY 2004 VL 52 IS 5 BP 965 EP 978 DI 10.1002/mrm.20274 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 868YI UT WOS:000224948700002 PM 15508168 ER PT J AU Jones, DK Basser, PJ AF Jones, DK Basser, PJ TI "Squashing peanuts and smashing pumpkins": How noise distorts diffusion-weighted MR data SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion-weighted; DWI; MRI; ADC; noise; artifacts; trace; FA; DT-MRI ID MAGNETIC-RESONANCE; HUMAN BRAIN; CEREBRAL-ISCHEMIA; WHITE-MATTER; TENSOR MRI; LOW SNR; ANISOTROPY; NMR; SYSTEMS; WATER AB New diffusion-weighted imaging (DWI) methods, including high-b, q-space, and high angular resolution MRI methods, attempt to extract information about non-Gaussian diffusion in tissue that is not provided by low-b-value (b approximate to 1000 s mm(-2)) diffusion or diffusion tensor magnetic resonance imaging (DT-MRI). Additionally, DWI data with higher spatial resolution are being acquired to resolve fine anatomic structures, such as white matter fasciculi. Increasing diffusion-weighting or decreasing voxel size can reduce the signal-to-noise ratio so that some DWI signals are close to the background noise level. Here we report several new artifacts that can be explained by considering how background noise affects the peanut-shaped angular apparent diffusion coefficient (ADC) profile. These include an orientationally dependent deviation from Gaussian behavior of the ADC profile, an underestimation of indices of diffusion anisotropy, and a correlation between estimates of mean diffusivity and diffusion anisotropy. We also discuss how noise can cause increased gray/white matter DWI contrast at higher b values and an apparent elevation of diffusion anisotropy in acute ischemia. Importantly, all of these artifacts are negligible in the b-value range typically used in DT-MRI of brain (b approximate to 1000 s mm(-2)). Finally, we demonstrate a strategy for ameliorating the rectified noise artifact in data collected at higher b values. Published 2004 Wiley-Liss, Inc(dagger). C1 NICHHD, Sect Tissue Biophys & Biomemet, Lab Integrat Med & Biophys, NIH, Bethesda, MD 20892 USA. RP Jones, DK (reprint author), NICHHD, Sect Tissue Biophys & Biomemet, Lab Integrat Med & Biophys, NIH, Bldg 13,Room 3W16E,13 S Dr, Bethesda, MD 20892 USA. EM jonesde@mail.nih.gov RI Jones, Derek/D-1460-2009; Basser, Peter/H-5477-2011; OI Jones, Derek/0000-0003-4409-8049 NR 40 TC 264 Z9 267 U1 1 U2 19 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 NOV PY 2004 VL 52 IS 5 BP 979 EP 993 DI 10.1002/mrm.20283 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 868YI UT WOS:000224948700003 PM 15508154 ER PT J AU Beg, MF Helm, PA McVeigh, E Miller, MI Winslow, RL AF Beg, MF Helm, PA McVeigh, E Miller, MI Winslow, RL TI Computational cardiac anatomy using MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE computational anatomy; diffusion tensor MRI; cardiac architecture; fiber orientation; remodeling ID LEFT-VENTRICULAR WALL; DIFFUSION TENSOR; DIFFEOMORPHISMS; MORPHOMETRY; ACTIVATION; GEOMETRY; HEART; DOG AB Ventricular geometry and fiber orientation may undergo global or local remodeling in cardiac disease. However, there are as yet no mathematical and computational methods for quantifying variation of geometry and fiber orientation or the nature of their remodeling in disease. Toward this goal, a landmark and image intensity-based large deformation diffeomorphic metric mapping (LDDMM) method to transform heart geometry into common coordinates for quantification of shape and form was developed. Two automated landmark placement methods for modeling tissue deformations expected in different cardiac pathologies are presented. The transformations, computed using the combined use of landmarks and image intensities, yields high-registration accuracy of heart anatomies even in the presence of significant variation of cardiac shape and form. Once heart anatornies have been registered, properties of tissue geometry and cardiac fiber orientation in corresponding regions of different hearts may be quantified. Magn Reson Med 52: 1167-1174, 2004. Published 2004 Wiley-Liss, Inc(dagger). C1 Johns Hopkins Univ, Sch Med, Whitaker Biomed Engn Inst, Baltimore, MD 21218 USA. Whiting Sch Engn, Baltimore, MD 21218 USA. NHLBI, Cardiac Energet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Winslow, RL (reprint author), Johns Hopkins Univ, Sch Med, Whitaker Biomed Engn Inst, Rm 201B Clark Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM rwinslow@bme.jhu.edu RI Miller, Michael I./A-3213-2010 FU Intramural NIH HHS [Z01 HL004608-08]; NHLBI NIH HHS [HL52307, HL70894, P50 HL052307, R01 HL070894, R01 HL105239] NR 30 TC 33 Z9 36 U1 0 U2 7 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 NOV PY 2004 VL 52 IS 5 BP 1167 EP 1174 DI 10.1002/mrm.20255 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 868YI UT WOS:000224948700024 PM 15508155 ER PT J AU Scacheri, PC Crabtree, JS Kennedy, AL Swain, GP Ward, JM Marx, SJ Spiegel, AM Collins, FS AF Scacheri, PC Crabtree, JS Kennedy, AL Swain, GP Ward, JM Marx, SJ Spiegel, AM Collins, FS TI Homozygous loss of menin is well tolerated in liver, a tissue not affected in MEN1 SO MAMMALIAN GENOME LA English DT Article ID TUMOR-SUPPRESSOR GENE; MULTIPLE ENDOCRINE NEOPLASIA; MUTATIONS; BRCA1; MOUSE; MICE; INSULINOMAS; TYPE-1 AB Most tumor suppressor genes show a widespread pattern of expression, yet individuals with germline, heterozygous loss of function of such genes develop tumors in a restricted set of tissues. This paradox has generated a multitude of speculative hypotheses. The gene for multiple endocrine neoplasia type I (MEN1) encodes a ubiquitously expressed tumor suppressor of unknown function called menin. Humans and mice with germline, heterozygous loss-of-function mutations in the MEN1 gene almost always develop at least one endocrine tumor by late adulthood, and examination of those tumors invariably reveals loss of the wild-type allele. To investigate the paradox of tissue-specific tumor phenotype in MEN1, mice homozygous for an Men1 gene with exons 3-8 flanked by 1oxP sites were bred to transgenic mice expressing cre from the albumin promoter. This strategy allowed us to generate mice with homozygous deletion of the Men1 gene in liver, a tissue not normally predisposed to developing tumors in humans or mice with heterozygous MEN1 loss-of-function mutations. Livers that were completely null for menin expression appeared entirely normal and remained tumor free until late adulthood. These results argue against certain hypotheses previously proposed for the tissue specificity of tumor suppressor genes and provide insights to the mechanism of tissue specificity in MEN1. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD 20892 USA. RP Scacheri, PC (reprint author), NHGRI, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. EM fc23a@nih.govz NR 16 TC 36 Z9 36 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 2004 VL 15 IS 11 BP 872 EP 877 DI 10.1007/s00335-004-2395-z PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 866DS UT WOS:000224754600002 PM 15672591 ER PT J AU Johnson-Masotti, AP Laud, PW Hoffmann, RG Hayat, MJ Pinkerton, SD AF Johnson-Masotti, AP Laud, PW Hoffmann, RG Hayat, MJ Pinkerton, SD TI A Bayesian approach to net health benefits: An illustration and application to modeling HIV prevention SO MEDICAL DECISION MAKING LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 19-23, 2002 CL BALTIMORE, MD SP Soc Med Decis Making DE cost-effectiveness; Bayesian; net benefit; HIV ID COST-EFFECTIVENESS ANALYSIS; PROBABILISTIC SENSITIVITY-ANALYSIS; RISK REDUCTION INTERVENTION; BLOOD-PRESSURE CONTROL; CLINICAL-TRIAL DATA; CONFIDENCE-INTERVALS; EFFECTIVENESS RATIOS; DECISION TREES; ANTIRETROVIRAL THERAPY; ECONOMIC-EVALUATION AB Purpose. To conduct a cost-effectiveness analysis of HIV prevention when costs and effects cannot be measured directly. To quantify the total estimation of uncertainty due to sampling variability as well as inexact knowledge of HIV transmission parameters. Methods. The authors focus on estimating the incremental net health benefit (INHB) in a randomized trial of HIV prevention with intervention and control conditions. Using a Bernoulli model of HIV transmission, changes in the participants' risk behaviors are converted into the number of HIV infections averted. A sampling model is used to account for variation in the behavior measurements. Bayes's theorem and Monte Carlo methods are used to attain the stated objectives. Results. The authors obtained a positive mean INHB of 0.0008, indicating that advocacy training is just slightly favored over the control condition for men, assuming a $50,000 per quality-adjusted life year (QALY) threshold. To be confident of a positive INHB, the decision maker would need to spend more than $100,000 per QALY. C1 McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8P 1H1, Canada. Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Johnson-Masotti, AP (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, 25 Main St W,Suite 2000, Hamilton, ON L8P 1H1, Canada. EM johnmas@mcmaster.ca FU AHRQ HHS [R03 HS11364]; NIMH NIH HHS [P30-MH52776] NR 89 TC 2 Z9 2 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2004 VL 24 IS 6 BP 634 EP 653 DI 10.1177/0272989X04271040 PG 20 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 872KR UT WOS:000225206600007 PM 15534344 ER PT J AU Badano, A Gagne, RM Gallas, BD Jennings, RJ Boswell, JS Myers, KJ AF Badano, A Gagne, RM Gallas, BD Jennings, RJ Boswell, JS Myers, KJ TI Lubberts effect in columnar phosphors SO MEDICAL PHYSICS LA English DT Article DE noise transfer; phosphor blur; modulation transfer function; Monte Carlo simulation; columnar phosphor; Cesium Iodide ID DETECTIVE QUANTUM EFFICIENCY; MODULATION TRANSFER-FUNCTION; RAY FLUORESCENT SCREENS; PHOTOGRAPHIC EMULSIONS; RADIATION DETECTORS; MAMMOGRAPHY; DEVICES; SCINTILLATORS; SYSTEMS; LAYERS AB Noise transfer in granular x-ray imaging phosphor screens is not proportional to the square of the magnitude of the signal transfer when the transfer properties are considered for the entire screen thickness, unless appropriately weighted at each depth of interaction. This property, known as the Lubberts effect, has not yet been studied in columnar structured screens because of a lack of a generalized description of the depth-dependent light transport. In this paper, we investigate the signal and noise transfer characteristics of columnar phosphors used in digital mammography detectors using DETECT-II, an optical Monte Carlo light transport simulation code. We first validate our choice of optical parameters for the description of granular and columnar screens using published normalized modulation transfer (MTF) experimental data. Our calculations of MTF match empirically measured MTFs for a granular film/screen analog system, and for an indirect x-ray digital imaging system with CsI:T1 screen representative of digital mammography systems. Using the depth-dependent spread functions and collection efficiencies, we calculate the signal and noise transfer functions and the Lubberts fraction, which is the ratio of the signal transfer function to the noise transfer function, for different screen thicknesses of granular and columnar phosphors. We find that the Lubberts fraction of a 85 mum granular screen model corresponding to a Gd2O2S:Tb screen is similar to the fraction for a 100 mum columnar CsI:T1 screen. C1 US FDA, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov OI Boswell, Jonathan/0000-0003-4552-7490; Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 38 TC 39 Z9 39 U1 1 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2004 VL 31 IS 11 BP 3122 EP 3131 DI 10.1118/1.1796151 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874TI UT WOS:000225372300022 PM 15587665 ER PT J AU Gallas, BD Boswell, JS Badano, A Gagne, RM Myers, KJ AF Gallas, BD Boswell, JS Badano, A Gagne, RM Myers, KJ TI An energy- and depth-dependent model for x-ray imaging SO MEDICAL PHYSICS LA English DT Article DE x-ray spectra; x-ray interactions; point processes; phosphors; optical transport; digital detectors; signal detection; model observers; pixel fill factor; image quality ID DETECTIVE QUANTUM EFFICIENCY; DIGITAL RADIOGRAPHY; OBJECTIVE ASSESSMENT; NOISE-PROPAGATION; PIXEL SIZE; OBSERVER; SYSTEMS; SIGNAL; MAMMOGRAPHY; DETECTABILITY AB In this paper, we model an x-ray imaging system, paying special attention to the energy- and depth-dependent characteristics of the inputs and interactions: x rays are polychromatic, interaction depth and conversion to optical photons is energy-dependent, optical scattering and the collection efficiency depend on the depth of interaction. The model we construct is a random function of the point process that begins with the distribution of x rays incident on the phosphor and ends with optical photons being detected by the active area of detector pixels to form an image. We show how the point-process representation can be used to calculate the characteristic statistics of the model. We then simulate a Gd2O2S:Tb phosphor, estimate its characteristic statistics, and proceed with a signal-detection experiment to investigate the impact of the pixel fill factor on detecting spherical calcifications (the signal). The two extremes possible from this experiment are that SNR2 does not change with fill factor or changes in proportion to fill factor. In our results, the impact of fill factor is between these extremes, and depends on the diameter of the signal. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Gallas, BD (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 67 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2004 VL 31 IS 11 BP 3132 EP 3149 DI 10.1118/1.1806293 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874TI UT WOS:000225372300023 PM 15587666 ER PT J AU Iannotti, RJ Claytor, RP Horn, TS Chen, R AF Iannotti, RJ Claytor, RP Horn, TS Chen, R TI Heart rate monitoring as a measure of physical activity in children SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE assessment; methodology; energy expenditure; exercise; adolescence ID DOUBLY LABELED WATER; DAILY ENERGY-EXPENDITURE; INDIRECT CALORIMETRY; ADOLESCENTS; VALIDATION AB Purpose: Using a larger sample and broader range of activities than most previous investigations of HR monitoring, this study examined the need for individual calibration of the HR-VO2 prediction equation, the effect of including low-intensity activities when establishing the HR-VO2 equation, comparisons of different methods for calculating HR-VO2 prediction equations for maximum energy expenditure (EE) variance, and the effect of these different methods when applied to free-living HR data. Methods: Forty-three children ages 8 to 12 completed laboratory assessments of the relationship between HR and VO2. Different methods of estimating daily EE were applied to free-living HR data collected from 37 of these children. Results: There was significant individual variation in the HR-VO2 prediction equations. HR monitoring predicted VO2 during low-intensity activities, below most established cut points. Individual differences persisted during both high- and low-intensity activities. Although a HR-VO2 prediction equation generated from the group accounted for 85% of the variance in EE, significant improvements in prediction were achieved with individualized HR-VO2 prediction equations that took into account low-intensity activity levels. Conclusion: Generic equations derived from group data may be suitable for some applications. However, for investigators requiring more precision, individual HR-VO2 equations significantly improve prediction. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, Bethesda, MD 20892 USA. Miami Univ, Oxford, OH 45056 USA. Georgetown Univ, Washington, DC USA. RP Iannotti, RJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. EM iannottr@mail.nih.gov NR 21 TC 10 Z9 12 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2004 VL 36 IS 11 BP 1964 EP 1971 DI 10.1249/01.MSS.0000145445.54609.82 PG 8 WC Sport Sciences SC Sport Sciences GA 869SO UT WOS:000225004700021 PM 15514514 ER PT J AU Collins, KD AF Collins, KD TI Ions from the Hofmeister series and osmolytes: effects on proteins in solution and in the crystallization process SO METHODS LA English DT Review ID 2ND VIRIAL-COEFFICIENT; BOND VALENCE SUMS; ESCHERICHIA-COLI; ELECTROLYTE-SOLUTIONS; ANGSTROM RESOLUTION; PHYSICAL-CHEMISTRY; ALPHA-LACTALBUMIN; CRYSTAL-STRUCTURE; SALT-SOLUTIONS; BINDING-SITES AB Sephadex G-10 gel sieving chromatography, Jones-Dole viscosity B coefficients, and solution neutron and X-ray diffraction are used to show that small ions of high charge density (e.g., sulfate, phosphate, the carboxylate, sodium, and fluoride) are strongly hydrated (kosmotropes) whereas large monovalent ions of low charge density (e.g., ammonium, chloride, potassium, and the positively charged amino acid side chains) are weakly hydrated (chaotropes). The heats of solution of the crystalline alkali halides are then used to show that only oppositely charged ions of equal water affinity spontaneously form inner sphere ion pairs, and that this controls ion binding to proteins. The net charge on a protein is a major determinant of its solubility. Finally, the surface potential difference and surface tension at an air-salt solution interface are used to generate a simple model for how ions affect protein stability and solubility through indirect interactions at the protein-solution interface. A few comments about small neutral osmolytes are also included. (C) 2004 Published by Elsevier Inc. C1 Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. NCI, Macromol NMR Sect, Struct Biophys Lab, Ft Detrick, MD 21702 USA. RP Collins, KD (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, 108 N Greene St, Baltimore, MD 21201 USA. EM kcollins@umaryland.edu NR 111 TC 524 Z9 533 U1 12 U2 172 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 NOV PY 2004 VL 34 IS 3 BP 300 EP 311 DI 10.1016/j.ymeth.2004.03.021 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 868YX UT WOS:000224950300005 PM 15325648 ER PT J AU Maric, I Bryant, R Abu-Asab, M Cohen, JI Vivero, A Jaffe, ES Raffeld, M Tsokos, M Banks, PM Pittaluga, S AF Maric, I Bryant, R Abu-Asab, M Cohen, JI Vivero, A Jaffe, ES Raffeld, M Tsokos, M Banks, PM Pittaluga, S TI Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults SO MODERN PATHOLOGY LA English DT Article DE CD4-positive cells; electron microscopy; HHV-6; lymphadenitis; T lymphocytes ID HUMAN-HERPESVIRUS 6; INFECTION; VIRUS; LYMPHADENOPATHY; LYMPHOCYTES; EXPRESSION AB In contrast to other causes of herpetic lymphadenitis, the histological features associated with human herpesvirus-6 (HHV-6) infection have remained elusive since its discovery in 1986. We describe the histologic and phenotypic changes associated with acute HHV-6 lymphadenitis in two immunocompetent adults who presented with fever, fatigue, generalized lymphadenopathy, and elevated liver enzymes. Serologic tests for human immunodeficiency virus, acute Epstein-Barr virus, and cytomegalovirus infection were negative. Lymph node biopsies were consistent with viral lymphadenitis. Intranuclear and cytoplasmic inclusions were identified in CD4-positive T lymphocytes in expanded paracortical areas. Immunohistochemical staining with monoclonal antibody to the HHV-6 gp60/110 kDa envelope glycoprotein showed that the inclusions were positive for viral antigen. Electron microscopy demonstrated numerous viral particles in the cytoplasm and nucleus, characteristic of Herpesviridae family. Clustering of viral particles was observed, which has previously been reported only in infected tissue culture cells. PCR followed by sequencing of DNA extracted from the lymph nodes identified the virus as HHV-6, type B. This is the first report that documents distinctive histologic features of HHV-6 lymphadenitis and demonstrates that the cells harboring the virus in vivo are CD4-positive T lymphocytes. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Carolinas Med Ctr, Dept Pathol, Charlotte, NC 28203 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Pittaluga, S (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM stefpitt@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 27 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 2004 VL 17 IS 11 BP 1427 EP 1433 DI 10.1038/modpathol.3800179 PG 7 WC Pathology SC Pathology GA 863SE UT WOS:000224581500017 PM 15494709 ER PT J AU Muller, WG Rieder, D Kreth, G Cremer, C Trajanoski, Z McNally, JG AF Muller, WG Rieder, D Kreth, G Cremer, C Trajanoski, Z McNally, JG TI Generic features of tertiary chromatin structure as detected in natural chromosomes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHIRONOMUS-TENTANS; EXPRESSED GENES; BALBIANI RINGS; HUMAN GENOME; ORDER; TRANSCRIPTION; VISUALIZATION; MICROSCOPY; FIBER; DNA AB Knowledge of tertiary chromatin structure in mammalian interphase chromosomes is largely derived from artificial tandem arrays. In these model systems, light microscope images reveal fibers or beaded fibers after high-density targeting of transactivators to insertional domains spanning several megabases. These images of fibers have lent support to chromonema fiber models of tertiary structure. To assess the relevance of these studies to natural mammalian chromatin, we identified two different similar to400-kb regions on human chromosomes 6 and 22 and then examined light microscope images of interphase tertiary chromatin structure when the regions were transcriptionally active and inactive. When transcriptionally active, these natural chromosomal regions elongated, yielding images characterized by a series of adjacent puncta or "beads", referred to hereafter as beaded images. These elongated structures required transcription for their maintenance. Thus, despite marked differences in the density and the mode of transactivation, the natural and artificial systems showed similarities, suggesting that beaded images are generic features of transcriptionally active tertiary chromatin. We show here, however, that these images do not necessarily favor chromonema fiber models but can also be explained by a radial-loop model or even a simple nucleosome affinity, random-chain model. Thus, light microscope images of tertiary structure cannot distinguish among competing models, although they do impose key constraints: chromatin must be clustered to yield beaded images and then packaged within each cluster to enable decondensation into adjacent clusters. C1 NCI, Fluorenscence Imaging Grp, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Graz Univ Technol, Inst Genom & Bioinformat, Christian Doppler Lab Genom & Bioinformat, A-8010 Graz, Austria. Univ Heidelberg, Kirchhoff Inst Phys, D-6900 Heidelberg, Germany. RP McNally, JG (reprint author), NCI, Fluorenscence Imaging Grp, Lab Receptor Biol & Gene Express, Bldg 41,Room B516,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov NR 47 TC 41 Z9 41 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2004 VL 24 IS 21 BP 9359 EP 9370 DI 10.1128/MCB.24.21.9359-9370.2004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868WH UT WOS:000224943300010 PM 15485905 ER PT J AU Valasek, L Nielsen, KH Zhang, F Fekete, CA Hinnebusch, AG AF Valasek, L Nielsen, KH Zhang, F Fekete, CA Hinnebusch, AG TI Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; IN-VIVO; MULTIFACTOR COMPLEX; RIBOSOMAL-SUBUNIT; MEDIATE BINDING; YEAST; RECOGNITION; DOMAIN; SITES; ROLES AB The N-terminal domain (NTD) of NIP1/eIF3c interacts directly with eIF1 and eIF5 and indirectly through eIF5 with the eIF2-GTP-Met-tRNA(i)(Met) ternary complex (TC) to form the multifactor complex (MFC). We investigated the physiological importance of these interactions by mutating 16 segments spanning the NIP1-NTD. Mutations in multiple segments reduced the binding of eIF1 or eIF5 to the NIP1-NTD. Mutating a C-terminal segment of the NIP1-NTD increased utilization of UUG start codons (Sui(-) phenotype) and was lethal in cells expressing eIF5-G31R that is hyperactive in stimulating GTP hydrolysis by the TC at AUG codons. Both effects of this NIP1 mutation were suppressed by eIF1 overexpression, as was the Sui- phenotype conferred by eIF5-G31R. Mutations in two N-terminal segments of the NIP1-NTD suppressed the Sui(-) phenotypes produced by the eIF1-D83G and eIF5-G31R mutations. From these and other findings, we propose that the NIP1-NTD coordinates an interaction between eIF1 and e1F5 that inhibits GTP hydrolysis at non-AUG codons. Two NIP1-NTD mutations were found to derepress GCN4 translation in a manner suppressed by overexpressing the TC, indicating that MFC formation stimulates TC recruitment to 40S ribosomes. Thus, the NIP1-NTD is required for efficient assembly of preinitiation complexes and also regulates the selection of AUG start codons in vivo. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Microbiol, Prague, Czech Republic. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A,Rm B1-A-13, Bethesda, MD 20892 USA. EM valasekl@biomed.cas.cz; ahinnebusch@nih.gov RI Valasek, Leos/I-5743-2014 NR 30 TC 94 Z9 98 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2004 VL 24 IS 21 BP 9437 EP 9455 DI 10.1128/MCB.24.21.9437-9455.2004 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868WH UT WOS:000224943300017 PM 15485912 ER PT J AU Liu, SH Milne, GT Kuremsky, JG Fink, GR Leppla, SH AF Liu, SH Milne, GT Kuremsky, JG Fink, GR Leppla, SH TI Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CANDIDATE TUMOR-SUPPRESSOR; HAMSTER OVARY CELLS; SACCHAROMYCES-CEREVISIAE; DIPHTHERIA-TOXIN; POSTTRANSLATIONAL MODIFICATION; CHROMOSOME 17P13.3; RESISTANT MUTANTS; FACTOR-II; J-DOMAIN; GENE AB Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria and is the target of diphtheria toxin, is formed in yeast by the actions of five proteins, Dph1 to -5, and a still unidentified amidating enzyme. Dph2 and Dph5 were previously identified. Here, we report the identification of the remaining three yeast proteins (Dph1, -3, and -4) and show that all five Dph proteins have either functional (Dph1, -2, -3, and -5) or sequence (Dph4) homologs in mammals. We propose a unified nomenclature for these proteins (e.g., HsDph1 to -5 for the human proteins) and their genes based on the yeast nomenclature. We show that Dph1 and Dph2 are homologous in sequence but functionally independent. The human tumor suppressor gene OVCA1, previously identified as homologous to yeast DPH2, is shown to actually be HsDPH1. We show that HsDPH3 is the previously described human diphtheria toxin and Pseudomonas exotoxin A sensitivity required gene 1 and that DPH4 encodes a CSL zinc finger-containing Dnaj-like protein. Other features of these genes are also discussed. The physiological function of diphthamide and the basis of its ubiquity remain a mystery, but evidence is presented that Dph1 to -3 function in vivo as a protein complex in multiple cellular processes. C1 MIT, Dept Biol, Cambridge, MA 02142 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), MIT, Dept Biol, Cambridge, MA 02142 USA. EM gfink@wi.mit.edu; sleppla@niaid.nih.gov NR 32 TC 79 Z9 86 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2004 VL 24 IS 21 BP 9487 EP 9497 DI 10.1128/MCB.24.21.9487-9497.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868WH UT WOS:000224943300021 PM 15485916 ER PT J AU Kim, SS Cao, L Li, CL Xu, XL Huber, LJ Chodosh, LA Deng, CX AF Kim, SS Cao, L Li, CL Xu, XL Huber, LJ Chodosh, LA Deng, CX TI Uterus hyperplasia and increased carcinogen-induced tumorigenesis in mice carrying a targeted mutation of the Chk2 phosphorylation site in Brca1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-DAMAGE RESPONSE; ATM-DEPENDENT PHOSPHORYLATION; DOUBLE-STRAND BREAKS; CELL-CYCLE; CHECKPOINT CONTROL; IN-VIVO; CANCER SUSCEPTIBILITY; IONIZING IRRADIATION; HEREDITARY BREAST; 1100DELC MUTATION AB The tumor suppressor BRCA1 contains multiple functional domains that interact with many proteins. After DNA damage, BRCA1 is phosphoryllated by CHK2 at serine 988, followed by a change in its intracellular location. To study the functions of CHK2-dependent phosphorylation of BRCA1, we generated a mouse model carrying the mutation S971A (S971 in mouse Brca1 corresponds to S988 in human BRCA1) by gene targeting. Brca1(S971A/S971A) mice were born at the expected ratio without a developmental defect, unlike previously reported Brca1 mutant mice. However, Brca1(S971A/S971A) mice suffered a moderately increased risk of spontaneous tumor formation, with a majority of females developing uterus hyperplasia and ovarian abnormalities by 2 years of age. After treatment with DNA-damaging agents, Brca1(S971A/S971A) mice exhibited several abnormalities, including increased body weight, abnormal hair growth pattern, lymphoma, mammary tumors, and endometrial tumors. In addition, the onset of tumor formation became accelerated, and 80% of the mutant mice had developed tumors by 1 year of age. We demonstrated that the Brca1(S971A/S971A) cells displayed reduced ability to activate the G(2)/M cell cycle checkpoint upon gamma-irradiation and to stabilize p53 following N-methyl-N'-nitro-N-nitrosoguanidine treatment. These observations suggest that Chk2 phosphorylation of S971 is involved in Brca1 function in modulating the DNA damage response and repressing tumor formation. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM ChuxiaD@BDGl0.NIDDK.NIH.gov RI deng, chuxia/N-6713-2016 NR 58 TC 23 Z9 23 U1 2 U2 4 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 NOV PY 2004 VL 24 IS 21 BP 9498 EP 9507 DI 10.1128/MCB.24.21.9498-9507.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868WH UT WOS:000224943300022 PM 15485917 ER PT J AU Schwartz, EI Intine, RV Maraia, RJ AF Schwartz, EI Intine, RV Maraia, RJ TI CK2 is responsible for phosphorylation of human La protein serine-366 and can modulate rpL37 5 '-terminal oligopyrimidine mRNA metabolism SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERNAL RIBOSOME ENTRY; POLYMERASE-III TRANSCRIPTION; SITE-MEDIATED TRANSLATION; FLOW-CYTOMETRIC DETECTION; PRECURSOR TRANSFER-RNAS; SS-B AUTOANTIGEN; CASEIN KINASE-II; SACCHAROMYCES-CEREVISIAE; PHOSPHATIDYLSERINE EXPRESSION; POLIOVIRUS RNA AB La protein binds precursors to 5S rRNA, tRNAs, and other transcripts that contain 3' UUU-OH and also promotes their maturation in the nucleus. Separate from this function, human La has been shown to positively modulate the translation of mRNAs that contain complex 5' regulatory motifs that direct internal initiation of translation. Nonphosphorylated La (npLa) inhibits pre-tRNA processing, while phosphorylation of human La serine-366 (S-366) promotes pre-tRNA processing. npLa was found specifically associated with a class of mRNAs; that have unusually short 5' untranslated regions comprised of terminal oligopyrimidine (5'TOP) tracts and that encode ribosomal proteins and translation elongation factors. Although La S-366 represents a CK2 phosphorylation site, there was no evidence that CK2 phosphorylates it in vivo. We used the CK2-specific inhibitor, 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), and antisense-mediated knockdown to demonstrate that CK2 is responsible for La S-366 phosphorylation in vivo. Hypophosphorylation was not associated with significant change in total La levels or proteolytic cleavage. Quantitative reverse transcription-PCR revealed increased association of the 5'TOP-mRNA encoding ribosomal protein L37 (rpL37) with La after TBB treatment. Transfection revealed more rpL37 mRNA associated with nonphosphorylatable La A(366) than with La S-366, concomitant with La A(366)-specific shift of a fraction of L37 mRNA off polysomes. The data indicate that CK2 phosphorylates La S-366 in vivo, that this limits 5'TOP mRNA binding, and that increasing npLa leads to greater association with potentially negative effects on TOP mRNA translation. Consistent with data that indicate that phosphorylation reverses negative effects of npLa on tRNA production, the present data suggest that CK2 phosphorylation of La can affect production of the translational machinery. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), 6 Ctr Dr,Rm 3A08, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov NR 58 TC 43 Z9 44 U1 1 U2 2 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 NOV PY 2004 VL 24 IS 21 BP 9580 EP 9591 DI 10.1128/MCB.24.21.9580-9591.2004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868WH UT WOS:000224943300029 PM 15485924 ER PT J AU Liu, YF Herschkovitz, A Boura-Halfon, S Ronen, D Paz, K LeRoith, D Zick, Y AF Liu, YF Herschkovitz, A Boura-Halfon, S Ronen, D Paz, K LeRoith, D Zick, Y TI Serine phosphorylation proximal to its phosphotyrosine binding domain inhibits insulin receptor substrate 1 function and promotes insulin resistance SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SUBSTRATE-1 TYROSINE PHOSPHORYLATION; KINASE-C ISOFORMS; BETA-CELLS INS-1; RECEPTOR SUBSTRATE-1; PROTEIN-KINASE; SERINE/THREONINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; JUXTAMEMBRANE REGION; SIGNALING PATHWAYS; B ACTIVATION AB Ser/Thr phosphorylation of insulin receptor substrate (IRS) proteins negatively modulates insulin signaling. Therefore, the identification of serine sites whose phosphorylation inhibit IRS protein functions is of physiological importance. Here we mutated seven Ser sites located proximal to the phosphotyrosine binding domain of insulin receptor substrate 1 (IRS-1) (S265, S302, S325, S336, S358, S407, and S408) into Ala. When overexpressed in rat hepatoma Fao or CHO cells, the mutated IRS-1 protein in which the seven Ser sites were mutated to Ala (IRS-1(7A)), unlike wild-type IRS-1 (IRS-1(WT)), maintained its Tyr-phosphorylated active conformation after prolonged insulin treatment or when the cells were challenged with inducers of insulin resistance prior to acute insulin treatment. This was due to the ability of IRS-17A to remain complexed with the insulin receptor (IR), unlike IRS-1(WT), which underwent Ser phosphorylation, resulting in its dissociation from IR. Studies of truncated forms of IRS-1 revealed that the region between amino acids 365 to 430 is a main insulin-stimulated Ser phosphorylation domain. Indeed, IRS-1 mutated only at S408, which undergoes phosphorylation in vivo, partially maintained the properties of IRS-17A and conferred protection against selected inducers of insulin resistance. These findings suggest that S408 and additional Ser sites among the seven mutated Ser sites are targets for IRS-1 kinases that play a key negative regulatory role in IRS-1 function and insulin action. These sites presumably serve as points of convergence, where physiological feedback control mechanisms, which are triggered by insulin-stimulated IRS kinases, overlap with IRS kinases triggered by inducers of insulin resistance to terminate insulin signaling. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NIH, Diabet Branch, Bethesda, MD 20892 USA. RP Zick, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM yehiel.zick@weizmann.ac.il NR 40 TC 77 Z9 85 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2004 VL 24 IS 21 BP 9668 EP 9681 DI 10.1128/MCB.24.21.9668-9681.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868WH UT WOS:000224943300037 PM 15485932 ER PT J AU Lee, BS Grewal, SIS Klar, AJS AF Lee, BS Grewal, SIS Klar, AJS TI Biochemical interactions between proteins and mat1 cis-acting sequences required for imprinting in fission yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MATING-TYPE LOCUS; SCHIZOSACCHAROMYCES-POMBE; DNA-REPLICATION; DAUGHTER CELLS; S-POMBE; SITE; INITIATION; POLYMERASE; ASYMMETRY; GENES AB DNA recombination required for mating type (mat1) switching in Schizosaccharomyces pombe is initiated by mat1 imprinting. The imprinting event is regulated by mat1 cis-acting elements and by several trans-acting factors, including swi1 (for switch), swi3, swi7, and sap1. swi1 and swi3 were previously shown to function in dictating unidirectional mat1 DNA replication by controlling replication fork movement around the mat1 region and, second, by pausing fork progression around the imprint site. With biochemical studies, we investigated whether the trans-acting factors function indirectly or directly by binding to the mat1 cis-acting sequences. First, we report the identification and DNA sequence of the swi3 gene. swi3 is not essential for viability, and, like the other factors, it exerts a stimulatory effect on imprinting. Second, we showed that only Swi1p and Swi3p interact to form a multiprotein complex and that complex formation did not require their binding to a DNA region defined by the smt-0 mutation. Third, we found that the Swi1p-Swi3p complex physically binds to a region around the imprint site where pausing of replication occurs. Fourth, the protein complex also interacted with the mat1-proximal polar terminator of replication (RTS1). These results suggest that the stimulatory effect of swi1 and swi3 on switching and imprinting occurs through interaction of the Swi1p-Swi3p complex with the mat1 regions. C1 Natl Canc Inst Frederick, Gene Regulat & Chromosome Biol Lab, Ft Detrick, MD 21702 USA. RP Klar, AJS (reprint author), Natl Canc Inst Frederick, Gene Regulat & Chromosome Biol Lab, Ft Detrick, MD 21702 USA. EM klar@ncifcrf.gov NR 42 TC 21 Z9 23 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 NOV PY 2004 VL 24 IS 22 BP 9813 EP 9822 DI 10.1128/MCB.24.22.9813-9822.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867DV UT WOS:000224823300011 PM 15509785 ER PT J AU Park, JE Park, CJ Sakchaisri, K Karpova, T Asano, S McNally, J Sunwoo, YG Leem, SH Lee, KS AF Park, JE Park, CJ Sakchaisri, K Karpova, T Asano, S McNally, J Sunwoo, YG Leem, SH Lee, KS TI Novel functional dissection of the localization-specific roles of budding yeast polo kinase Cdc5p SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE CDC5; IN-VITRO REGULATION; CELL-CYCLE; MITOTIC EXIT; SCHIZOSACCHAROMYCES-POMBE; ANAPHASE TRANSITION; SWE1P DEGRADATION; BODY DUPLICATION; SPB DUPLICATION; PROTEIN-KINASE AB Budding yeast polo kinase Cdc5p localizes to the spindle pole body (SPB) and to the bud-neck and plays multiple roles during M-phase progression. To dissect localization-specific mitotic functions of Cdc5p, we tethered a localization-defective N-terminal kinase domain of Cdc5p (Cdc5pDeltaC) to the SPB or to the bud-neck with components specifically localizing to one of these sites and characterized these mutants in a cdc5Delta background. Characterization of a viable, SPB-localizing, CDC5DeltaC-CNM67 mutant revealed that it is defective in timely degradation of Swe1p, a negative regulator of Cdc28p. Loss of BFA1, a negative regulator of mitotic exit, rescued the lethality of a neck-localizing CDC5DeltaC-CDC12 or CDC5DeltaC-CDC3 mutant but yielded severe defects in cytokinesis. These data suggest that the SPB-associated Cdc5p activity is critical for both mitotic exit and cytokinesis, whereas the bud neck-localized Cdc5p is required for proper Swe1p regulation. Interestingly, a cdc5Delta bfa1Delta swe1Delta triple mutant is viable but grows slowly, whereas cdc5Delta cells bearing both CDC5DeltaC-CNM67 and CDC5DeltaC-CDC12 grow well with only a mild cell cycle delay. Thus, SPB- and the bud-neck-localized Cdc5p control most of the critical Cdc5p functions and downregulation of Bfa1p and Swe1p at the respective locations are two critical factors that require Cdc5p. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Dong A Univ, Dept Biol, Pusan, South Korea. Mahidol Univ, Fac Sci, Dept Pharmacol, Bangkok, Thailand. RP Lee, KS (reprint author), NCI, Lab Metab, NIH, 9000 Rockville Pike,Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kyunglee@pop.nci.nih.gov NR 53 TC 20 Z9 20 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 NOV PY 2004 VL 24 IS 22 BP 9873 EP 9886 DI 10.1128/MCB.24.22.9873-9886.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867DV UT WOS:000224823300016 PM 15509790 ER PT J AU Kim, G Lee, TH Wetzel, P Geers, C Robinson, MA Myers, TG Owens, JW Wehr, NB Eckhaus, MW Gros, G Wynshaw-Boris, A Levine, RL AF Kim, G Lee, TH Wetzel, P Geers, C Robinson, MA Myers, TG Owens, JW Wehr, NB Eckhaus, MW Gros, G Wynshaw-Boris, A Levine, RL TI Carbonic anhydrase III is not required in the mouse for normal growth, development, and life span SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RABBIT SKELETAL-MUSCLE; S-THIOLATION; PHOSPHATASE-ACTIVITY; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; RAT-LIVER; PROTEIN; EXPRESSION; PEROXYMONOCARBONATE; SULFHYDRYLS AB Carbonic anhydrase III is a cytosolic protein which is particularly abundant in skeletal muscle, adipocytes, and liver. The specific activity of this isozyme is quite low, suggesting that its physiological function is not that of hydrating carbon dioxide. To understand the cellular roles of carbonic anhydrase III, we inactivated the Car3 gene. Mice lacking carbonic anhydrase III were viable and fertile and had normal life spans. Carbonic anhydrase III has also been implicated in the response to oxidative stress. We found that mice lacking the protein had the same response to a hyperoxic challenge as did their wild-type siblings. No anatomic alterations were noted in the mice lacking carbonic anhydrase III. They had normal amounts and distribution of fat, despite the fact that carbonic anhydrase III constitutes about 30% of the soluble protein in adipocytes. We conclude that carbonic anhydrase III is dispensable for mice living under standard laboratory husbandry conditions. C1 NHLBI, Biochem Lab, Res Technol Branch, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NHGRI, Div Vet Resources, Off Res Serv, NIH, Bethesda, MD 20892 USA. NHGRI, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Hannover Med Sch, Zentrum Physiol, Hannover, Germany. RP Levine, RL (reprint author), NHLBI, Biochem Lab, Res Technol Branch, NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Gros, Gerolf/K-8421-2012; Levine, Rodney/D-9885-2011 NR 38 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2004 VL 24 IS 22 BP 9942 EP 9947 DI 10.1128/MCB.24.22.9942-9947.2004 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867DV UT WOS:000224823300022 PM 15509796 ER PT J AU Kim, YJ Sekiya, F Poulin, B Bae, YS Rhee, SG AF Kim, YJ Sekiya, F Poulin, B Bae, YS Rhee, SG TI Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma 2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BRUTONS-TYROSINE-KINASE; ANTIGEN RECEPTOR; T-CELL; SIGNAL-TRANSDUCTION; C-GAMMA; PHOSPHATIDYLINOSITOL 3-KINASE; MEDIATED ACTIVATION; PHOSPHOINOSITIDE 3-KINASE; CALCIUM SIGNALS; SH3 DOMAIN AB Phospholipase C-gamma2 (PLC-gamma2) plays an important role in B-cell signaling. Phosphorylation of various tyrosine residues of PLC-gamma2 has been implicated in regulation of its lipase activity. With the use of antibodies specific for each of the putative phosphorylation sites, we have now shown that PLC-gamma2 is phosphorylated on Y753, Y759, and Y1217 in response to engagement of the B-cell receptor in Ramos cells, as well as in murine splenic B cells. In cells stimulated maximally via this receptor, the extent of phosphorylation of Y1217 was three times that of Y753 or of Y759. Stimulation of Jurkat T cells or platelets via their immunoreceptors also elicited phosphorylation of Y753 and Y759 but not that of Y1217. A basal level of phosphorylation of Y753 was apparent in unstimulated lymphocytes. The extent of phosphorylation of Y753 and Y759, but not that of Y1217, correlated with the lipase activity of PLC-gamma2. Examination of the effects of various pharmacological inhibitors and of RNA interference in Ramos cells suggested that Btk is largely, but not completely, responsible for phosphorylation of Y753 and Y759, whereas phosphorylation of Y1217 is independent of Btk. Finally, phosphorylation of Y1217 and that of Y753 and Y759 occurred on different PLC-gamma2 molecules. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. RP Rhee, SG (reprint author), Bldg 50,Room 3523,50 South Dr,MSC 8015, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 53 TC 59 Z9 61 U1 1 U2 4 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 NOV PY 2004 VL 24 IS 22 BP 9986 EP 9999 DI 10.1128/MCB.24.22.9986-9999.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867DV UT WOS:000224823300026 PM 15509800 ER PT J AU Jordan, IK Marino-Ramirez, L Wolf, YI Koonin, EV AF Jordan, IK Marino-Ramirez, L Wolf, YI Koonin, EV TI Conservation and coevolution in the scale-free human gene coexpression network SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE gene expression; human evolution; natural selection; network; self-organization; substitution rate ID PROTEIN-PROTEIN INTERACTIONS; PHYLOGENETIC ANALYSIS; EXPRESSION PATTERNS; METABOLIC NETWORKS; SIMPLE DEPENDENCE; EVOLUTIONARY RATE; DUPLICATE GENES; MICROARRAY DATA; GENOME; NUMBER AB The role of natural selection in biology is well appreciated. Recently, however, a critical role for physical principles of network self-organization in biological systems has been revealed. Here, we employ a systems level view of genome-scale sequence and expression data to examine the interplay between these two sources of order, natural selection and physical self-organization, in the evolution of human gene regulation. The topology of a human gene coexpression network, derived from tissue-specific expression profiles, shows scale-free properties that imply evolutionary self-organization via preferential node attachment. Genes with numerous coexpressed partners (the hubs of the coexpression network) evolve more slowly on average than genes with fewer coexpressed partners, and genes that are coexpressed show similar rates of evolution. Thus, the strength of selective constraints on gene sequences is affected by the topology of the gene coexpression network. This connection is strong for the coding regions and 3' untranslated regions (UTRs), but the 5' UTRs appear to evolve under a different regime. Surprisingly, we found no connection between the rate of gene sequence divergence and the extent of gene expression profile divergence between human and mouse. This suggests that distinct modes of natural selection might govern sequence versus expression divergence, and we propose a model, based on rapid, adaptation-driven divergence and convergent evolution of gene expression patterns, for how natural selection could influence gene expression divergence. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Jordan, IK (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural NIH HHS [NIH0011392375, Z01 LM000073-12, Z99 LM999999] NR 55 TC 125 Z9 129 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 2004 VL 21 IS 11 BP 2058 EP 2070 DI 10.1093/molbev/msh222 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 864RH UT WOS:000224650100006 PM 15282333 ER PT J AU Huang, AY Castellino, F Torabi-Parizi, P Germain, RN AF Huang, AY Castellino, F Torabi-Parizi, P Germain, RN TI Impact of self and foreign antigen recognition on T cell interactions with dendritic cells as revealed by dynamic in situ two-photon imaging SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 30 BP 6A EP 6A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800031 ER PT J AU Malide, D Basta, S Bennick, JR Yewdell, JW AF Malide, D Basta, S Bennick, JR Yewdell, JW TI Real time visualization of cytotoxic T lymphocyte killing of vaccinia virus infected target cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Light Microscopy Facil, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 29 BP 6A EP 6A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800030 ER PT J AU Marini, JC Leiken, S Bergwitz, C Uveges, TE Kozloff, KM Forlino, A Kuznetsova, NV Goldstein, SA Gronowitcz, G AF Marini, JC Leiken, S Bergwitz, C Uveges, TE Kozloff, KM Forlino, A Kuznetsova, NV Goldstein, SA Gronowitcz, G TI Homozygosity for a dominant-negative type I collagen mutation attenuates the type IVOI phenotype of the heterozygous Brtl mouse: Insight into disease mechanism SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, NIH, Bethesda, MD USA. NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA. Univ Michigan, Ortho Res Labs, Ann Arbor, MI 48109 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 31 BP 7A EP 7A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800032 ER PT J AU Lazarus, BD Hanover, JA AF Lazarus, BD Hanover, JA TI Isoform specific glycosylation of tau by O-linked GlcNAc transferase: Implications for tauopathies SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, LCBB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2004 VL 15 SU S MA 91 BP 17A EP 18A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800092 ER PT J AU Love, DC Hennessey, PT Hanover, JA AF Love, DC Hennessey, PT Hanover, JA TI The role of O-linked GlcNAc transferase (OGT) in the insulin signalling pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 92 BP 18A EP 18A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800093 ER PT J AU Eppinga, RD Li, Y Lin, JL Lin, JJ AF Eppinga, RD Li, Y Lin, JL Lin, JJ TI Actin interacting proteins, tropomyosin, caldesmon, and myosin Va, influence equatorial and global cortical force during cell division SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Iowa, Iowa City, IA USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 121 BP 23A EP 23A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800122 ER PT J AU Xu, X Tsan, G Rao, K Hammer, JA AF Xu, X Tsan, G Rao, K Hammer, JA TI Melanophilin and myosin Va surf the microtubule plus end on EB1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Cell Biol Labs, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 152 BP 28A EP 28A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800153 ER PT J AU Zhang, J Chen, G Xiang, X Hammer, JA AF Zhang, J Chen, G Xiang, X Hammer, JA TI Studies on the function of myosin V in Aspergillus nidulans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 USUHS, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 154 BP 28A EP 28A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800155 ER PT J AU Carroll, S Sood, T Rothstein, EC Balaban, RS AF Carroll, S Sood, T Rothstein, EC Balaban, RS TI Mitochondria distribution within intact murine fast-twitch and slow-twitch skeletal muscle fibers: An NAD(P)H fluorescence study SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 32A EP 32A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800176 ER PT J AU Lu, S Borst, DE Horowits, R AF Lu, S Borst, DE Horowits, R TI N-RAP expression during mouse heart development SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 177 BP 32A EP 33A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800178 ER PT J AU McCroskery, S Daniels, MP AF McCroskery, S Daniels, MP TI Transmembrane agrin regulates filopodia in hippocampal neurons SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 281 BP 51A EP 51A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800282 ER PT J AU Vartanian, K Katagiri, Y Peter, P Tan, F Wang, H Geller, HM AF Vartanian, K Katagiri, Y Peter, P Tan, F Wang, H Geller, HM TI Quantitative analysis of microtubule polymerization in extracellular matrix-mediated axon guidance SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 289 BP 52A EP 52A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800290 ER PT J AU Sameni, M Dosescu, J Mai, J Yamada, KM Sloane, BF AF Sameni, M Dosescu, J Mai, J Yamada, KM Sloane, BF TI beta 1 integrin regulates proteolysis of extracellular matrix by breast carcinoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Wayne State Univ, Detroit, MI USA. Natl Inst Dent & Craniofacial Res, Dev Biol Lab, NIH, Bethesda, MD USA. RI Sloane, Bonnie/A-1050-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 341 BP 62A EP 62A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800342 ER PT J AU Leikina, E Melikov, K Delanoe, H Waring, AJ Lehrer, RI Chernomordik, LV AF Leikina, E Melikov, K Delanoe, H Waring, AJ Lehrer, RI Chernomordik, LV TI Retrocyclin-2 inhibits early stages of membrane fusion reactions mediated by envelope glycoproteins of diverse viruses SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, SOMB, LCMB, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RI Melikov, Kamran/A-6604-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 403 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800404 ER PT J AU Zaitseva, E Mittal, A Griffin, D Chernomodrik, L AF Zaitseva, E Mittal, A Griffin, D Chernomodrik, L TI Fusion pathway mediated by Sindbis virus E1 glycoprotein: Membrane intermediates and capsid-envelope interactions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, SOMB, LCMB, NIH, Bethesda, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 402 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800403 ER PT J AU Puri, N Roche, PA AF Puri, N Roche, PA TI Ternary SNARE complexes are associated with lipid rafts in RBL mast cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 416 BP 75A EP 75A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800417 ER PT J AU Hinshaw, JE Moon, K Danino, D AF Hinshaw, JE Moon, K Danino, D TI Structural analysis of dynamin suggests a mechanism in membrane constriction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. NIH, LCBB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 428 BP 77A EP 77A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800429 ER PT J AU Lee, D Zhao, X Greene, L Eisenberg, E AF Lee, D Zhao, X Greene, L Eisenberg, E TI Depletion of GAK/auxilin 2 by RNAi: Effect on clathrin distribution and receptor mediated endocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 433 BP 78A EP 78A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800434 ER PT J AU Ramos, C Melikov, KC Zaitseva, E Wilson, KL Chernomordik, LV AF Ramos, C Melikov, KC Zaitseva, E Wilson, KL Chernomordik, LV TI Characterization of early stages of nuclear envelope assembly driven by cytosolic proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Johns Hopkins Univ, Sch Med, Dept Cell Biol & Anat, Baltimore, MD 21205 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 452 BP 81A EP 82A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800453 ER PT J AU Kollmorgen, GE Mameza, MG Richter, D Kreienkamp, H AF Kollmorgen, GE Mameza, MG Richter, D Kreienkamp, H TI Phosphorylation of post synaptic shank proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Inst Cell Biol & Clin Neurobiol, Hamburg, Germany. NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 523 BP 95A EP 95A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800524 ER PT J AU Cai, Q Gerwin, C Sheng, Z AF Cai, Q Gerwin, C Sheng, Z TI Kinesin I and its associated adaptor syntabulin transport syntaxin vesicle to the neuronal processes of hippocampal neurons SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 538 BP 97A EP 97A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800539 ER PT J AU Gannot, G Tangrea, MA Gillespie, JW Erickson, HS Wallis, BS Knezevic, V Hartmann, DP Chuaqui, RF Emmert-Buck, MR AF Gannot, G Tangrea, MA Gillespie, JW Erickson, HS Wallis, BS Knezevic, V Hartmann, DP Chuaqui, RF Emmert-Buck, MR TI High-throughput antibody screening of clinical serum samples SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, CCR, LP, NIH, Gaithersburg, MD USA. Georgetown Univ, Washington, DC USA. GeneSyst 2020, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 564 BP 102A EP 102A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800565 ER PT J AU Ishikawa, T Maurizi, MR Steven, AC AF Ishikawa, T Maurizi, MR Steven, AC TI Functional architecture of the ATP-dependent Clp proteases: Discrimination of static and mobile elements by cryo-electron microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 ETH, Dept Biol, Zurich, Switzerland. NCI, LCB, NIH, Bethesda, MD 20892 USA. NIAMS, LSBR, NIH, Bethesda, MD USA. RI Ishikawa, Takashi/E-5023-2017 OI Ishikawa, Takashi/0000-0002-1976-7477 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 570 BP 103A EP 103A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800571 ER PT J AU Leapman, R Zhang, G Talbot, T Laquerriere, P Kocsis, E AF Leapman, R Zhang, G Talbot, T Laquerriere, P Kocsis, E TI Electron spectroscopic tomography: a new technique for 3D imaging of nucleic acids in cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. RI Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 NR 0 TC 0 Z9 0 U1 1 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 NOV PY 2004 VL 15 SU S MA 582 BP 105A EP 105A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800583 ER PT J AU Zhao, B Li, Y Jones, NL Kruth, IS AF Zhao, B Li, Y Jones, NL Kruth, IS TI Human monocyte-derived macrophages differentiated with M-CSF+IL-10 show spontaneous cholesterol accumulation during incubation with native LDL SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 606 BP 109A EP 109A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800607 ER PT J AU Altan-Bonnet, G Stefanova, I Germain, RN AF Altan-Bonnet, G Stefanova, I Germain, RN TI The T cells' signaling machinery sets the threshold for sensitive and fast self/non-self discrimination SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 610 BP 110A EP 110A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800611 ER PT J AU Kim, PK Mullen, RT Lippincott-Schwartz, J AF Kim, PK Mullen, RT Lippincott-Schwartz, J TI Evidence for endoplasmic reticulum origins of peroxisomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. Univ Guelph, Dept Bot, Guelph, ON N1G 2W1, Canada. NR 0 TC 1 Z9 1 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 621 BP 112A EP 112A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800622 ER PT J AU McCormick, P Martina, J Bonifacino, J AF McCormick, P Martina, J Bonifacino, J TI Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 633 BP 114A EP 114A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800634 ER PT J AU Helip-Wooley, A Dorward, H Stanescu, H Hess, R Westbroek, W Boissy, R Gahl, WA Huizing, M AF Helip-Wooley, A Dorward, H Stanescu, H Hess, R Westbroek, W Boissy, R Gahl, WA Huizing, M TI The cell biology of Hermansky-Pudlak syndrome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 636 BP 115A EP 115A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648800637 ER PT J AU Scaffidi, P Misteli, T AF Scaffidi, P Misteli, T TI Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 664 BP 120A EP 120A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801009 ER PT J AU Snapp, E Sharma, A Shaffer, K Lippincott-Schwartz, J Hegde, R AF Snapp, E Sharma, A Shaffer, K Lippincott-Schwartz, J Hegde, R TI Monitoring chaperone engagement of substrate in living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, NIH, Cell Biol & Metab Branch, Bethesda, MD USA. OI Snapp, Erik/0000-0001-9482-2272 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 670 BP 121A EP 121A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801015 ER PT J AU Ono, A Ablan, SD Lockett, SJ Nagashima, K Freed, EO AF Ono, A Ablan, SD Lockett, SJ Nagashima, K Freed, EO TI Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 gag targeting to the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21701 USA. NCI, NIH, SAIC, Res Technol Program,Image Anal Lab, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 680 BP 122A EP 123A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801025 ER PT J AU Sankar, J McCoy, MT Deng, X Ladenheim, B Cluster, A Cai, N Cadet, JL AF Sankar, J McCoy, MT Deng, X Ladenheim, B Cluster, A Cai, N Cadet, JL TI Calcineurin/NFAT-induced up-regulation of the FasL/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis in the rat striatum SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDA, NIH, IRP DHHS, Mol Neuropsychiat Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 733 BP 132A EP 133A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801078 ER PT J AU Krasnova, IN Ladenheim, B Cadet, JL AF Krasnova, IN Ladenheim, B Cadet, JL TI Amphetamine-induced neuronal apoptosis is attenuated in Bax-Null mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDA, NIH, DHHS, Mol Neuropsychiat Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 734 BP 133A EP 133A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801079 ER PT J AU Battelle, B Sellers, JR Kempler, KE Mapel, GM Fisler, H Stevens, S Yamashita, R Toth, J AF Battelle, B Sellers, JR Kempler, KE Mapel, GM Fisler, H Stevens, S Yamashita, R Toth, J TI Limulus myosin III: Identification of a major PKA and autophosphorylation site, and studies of its actin binding and kinase activities SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Florida, Whitney Lab, St Augustine, FL 32086 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Univ Florida, ICBR Prot Chem Core, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 837 BP 151A EP 151A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801182 ER PT J AU Kovacs, M Wang, F Sellers, JR AF Kovacs, M Wang, F Sellers, JR TI Unique mechanism of action of Myosin-X, a membrane motor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. RI Kovacs, Mihaly/A-6841-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 839 BP 151A EP 151A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801184 ER PT J AU Yang, Y Xu, Q Anderson, JB Sellers, JR AF Yang, Y Xu, Q Anderson, JB Sellers, JR TI Characterization of Drosophila myosin VIIb SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 846 BP 152A EP 152A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801191 ER PT J AU Zelenka, PS Ledee, DR AF Zelenka, PS Ledee, DR TI The Cdk5 activator, p39, interacts with non-muscle myosin light chain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 886 BP 160A EP 160A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801231 ER PT J AU Fletcher, PL Fletcher, MD Fainter, LK Martin, BM AF Fletcher, PL Fletcher, MD Fainter, LK Martin, BM TI Exocrine pancreatic secretion and signaling events associated with the actin/microfilament cytoskeleton SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 E Carolina Univ, Brody Sch Med, Greenville, NC USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 942 BP 169A EP 169A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801287 ER PT J AU Cutler, M Dougherty, G Chopp, T Qi, S AF Cutler, M Dougherty, G Chopp, T Qi, S TI The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Inst Deafness & Communicat Disorders, Sect Struct Cell Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 970 BP 175A EP 175A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801315 ER PT J AU Isenberg, JS Calzada, M Zhou, L Guo, N Lawler, J Roberts, D AF Isenberg, JS Calzada, M Zhou, L Guo, N Lawler, J Roberts, D TI Thrombospondin-1 is not necessary for proliferation but contributes to motility of vascular smooth muscle cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 985 BP 177A EP 177A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801330 ER PT J AU Honda, A Al-Awar, OS Hay, JC Donaldson, JG AF Honda, A Al-Awar, OS Hay, JC Donaldson, JG TI Membrin, an ER-Golgi SNARE, is an Arf1 receptor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 1 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 NOV PY 2004 VL 15 SU S MA 1050 BP 189A EP 189A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801395 ER PT J AU Liu, W Duden, R Phair, R Lippincott-Schwartz, J AF Liu, W Duden, R Phair, R Lippincott-Schwartz, J TI In vivo dynamics of ArfGAP1 and its functional interaction with Arf1 and coatomer on Golgi membranes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, CBMB, NIH, Bethesda, MD USA. Univ Cambridge, Cambridge, England. Bioinformat Serv, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1059 BP 191A EP 191A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801404 ER PT J AU Fletcher, PL Fletcher, MD Martin, BM AF Fletcher, PL Fletcher, MD Martin, BM TI Exocrine pancreatic cellular response and the biochemical characteristics of Tityus trinitatis scorpion venom toxins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 E Carolina Univ, Brody Sch Med, Greenville, NC USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1074 BP 193A EP 194A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801419 ER PT J AU Khurana, T Kimmel, AR AF Khurana, T Kimmel, AR TI A Rab21/LIM-only complex regulates phagocytosis by repressing the action of an associated CH-LIM protein SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1101 BP 198A EP 198A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801446 ER PT J AU Weigert, R Donaldson, JG AF Weigert, R Donaldson, JG TI The small GTP-ase Rab22a regulates the recycling of membrane proteins internalized independently of clathrin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1103 BP 199A EP 199A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801448 ER PT J AU Prufer, K Barsony, J AF Prufer, K Barsony, J TI Mutational analysis of putative nuclear localization sequences in nuclear receptors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Louisiana State Univ, Baton Rouge, LA 70803 USA. NIDDK, Lab Cell Biol & Biochem, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1133 BP 204A EP 204A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801478 ER PT J AU Daelemans, D Costes, SV Lockett, S Pavlakis, GN AF Daelemans, D Costes, SV Lockett, S Pavlakis, GN TI Kinetic and molecular analysis of the nuclear export factor CRM1 association with its cargo in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Rega Inst, Louvain, Belgium. SAIC Frederick, Image Anal Lab, Frederick, MD USA. NCI, Human Retrovirus Sect, Frederick, MD 21701 USA. RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1138 BP 205A EP 205A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801483 ER PT J AU Iser, WB Wolkow, CA AF Iser, WB Wolkow, CA TI Stress triggers the nuclear localization of non-neuronal acetylcholinesterase in C-elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1139 BP 205A EP 205A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801484 ER PT J AU Kametaka, S Mattera, R Bonifacino, JS AF Kametaka, S Mattera, R Bonifacino, JS TI EGF-dependent phosphorylation of GGA3 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1175 BP 212A EP 212A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801520 ER PT J AU Lefrancois, S Janvier, K Boehm, M Ooi, C Bonifacino, JS AF Lefrancois, S Janvier, K Boehm, M Ooi, C Bonifacino, JS TI An interdomain interaction regulates the recruitment of AP-3 to membranes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. Altana Pharma AG, Constance, Germany. CuraGen Corp, Branford, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1173 BP 212A EP 212A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801518 ER PT J AU Correa-Cerro, LS Wassif, C Kratz, L Kelly, R Porter, FD AF Correa-Cerro, LS Wassif, C Kratz, L Kelly, R Porter, FD TI Simvastatin therapy improves the biochemical abnormality in a hypomorphic Smith-Lemli-Opitz syndrome mouse model SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, NIH, Bethesda, MD USA. Kennedy Krieger Inst, Clin Mass Spectrometry Lab, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1179 BP 213A EP 213A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801524 ER PT J AU Hose, SL Zigler, JS Sinha, D AF Hose, SL Zigler, JS Sinha, D TI Reduced apoptosis during ocular development in the Nuc1 mutant rat SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1182 BP 213A EP 213A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801527 ER PT J AU Walker, DL Vacha, SJ Kirby, ML Lo, CW AF Walker, DL Vacha, SJ Kirby, ML Lo, CW TI An essential role for connexin43 in coronary vasculogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Agilent Technol, Palo Alto, CA USA. Duke Univ, Med Ctr, Neonatal Perinatal Res Inst, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1191 BP 215A EP 215A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801536 ER PT J AU Yu, Q Shen, Y Chatterjee, B Siegfried, B Leatherbury, L Rosenthal, J Lucas, J Wessels, A Spurney, C Wu, Y Kirby, M Svenson, K Lo, C AF Yu, Q Shen, Y Chatterjee, B Siegfried, B Leatherbury, L Rosenthal, J Lucas, J Wessels, A Spurney, C Wu, Y Kirby, M Svenson, K Lo, C TI Ultrasound phenotyping and the recovery of ENU induced mouse mutations causing congenital cardiovascular anomalies SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Dev Biol Lab, Bethesda, MD 20892 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. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1195 BP 216A EP 216A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801540 ER PT J AU Yan, J Xu, L Crawford, G Burgess, S AF Yan, J Xu, L Crawford, G Burgess, S TI The forkhead transcription factor FoxI1 remains bound to condensed mitotic chromosomes and stably remodels hetrochromatin structure SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHGRI, GTB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1340 BP 243A EP 243A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802064 ER PT J AU Quimby, B Yong-Gonzalez, V Strunnikov, A Dasso, M AF Quimby, B Yong-Gonzalez, V Strunnikov, A Dasso, M TI The PML protein has SUMO E3-like activity in yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, NIH, Lgrd, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1380 BP 250A EP 250A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802104 ER PT J AU Wei, Q AF Wei, Q TI Pitx2a binds to human papillomavirus (HPV) E6 protein and inhibits E6-mediated p53 degradation in HeLa cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1384 BP 250A EP 250A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802108 ER PT J AU Dey, A Mochizuki, K Ozato, K AF Dey, A Mochizuki, K Ozato, K TI Reduced expression of bromodomain protein Brd4 impedes Rb inactivation add S phase entry SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHHD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1404 BP 254A EP 254A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802128 ER PT J AU Ross, KE Cohen-Fix, O AF Ross, KE Cohen-Fix, O TI The FEAR pathway, but not the Mitotic Exit Network, affects nuclear positioning during anaphase in budding yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1422 BP 257A EP 257A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802146 ER PT J AU Bao, J Wei, Q Takeda, K Ma, X Liu, C Adelstein, RS AF Bao, J Wei, Q Takeda, K Ma, X Liu, C Adelstein, RS TI Ablating nonmuscle myosin II-B with cDNA encoding GFP-nonmuscle myosin heavy chain II-A partially rescues II-B knockout mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NIH, Transgen Core Fac, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1508 BP 272A EP 273A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802232 ER PT J AU Chung, M Kawamoto, S AF Chung, M Kawamoto, S TI Mouse nonmusele myosin heavy chain II-C gene has tissue-dependent alternative promoters SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1507 BP 272A EP 272A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802231 ER PT J AU Conti, M Even-Ram, S Liu, C Yamada, KM Adelstein, RS AF Conti, M Even-Ram, S Liu, C Yamada, KM Adelstein, RS TI Cell-cell adhesion defects following ablation of nonmuscle myosin heavy chain II-A in mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NIH, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. NIH, Transgen Core Fac, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1509 BP 273A EP 273A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802233 ER PT J AU Kim, K Kovacs, M Preston, YA Harvey, EV Kawamoto, S Sellers, JR Adelstein, RS AF Kim, K Kovacs, M Preston, YA Harvey, EV Kawamoto, S Sellers, JR Adelstein, RS TI Functional characterization of nonmusele heavy meromyosin II-B mutants and II-C alternatively spliced isoforms SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 1510 BP 273A EP 273A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802234 ER PT J AU Ma, X Kawamoto, S Liu, C Adelstein, RS AF Ma, X Kawamoto, S Liu, C Adelstein, RS TI A point mutation in nonmusele myosin heavy chain II-B disrupts cortical basement membrane in mouse brains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NIH, Transgen Core Fac, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1511 BP 273A EP 273A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802235 ER PT J AU Shu, S Liu, X Korn, ED AF Shu, S Liu, X Korn, ED TI Similarities and differences between dictyostelium myosin II-null cells and blebbistatin-inhibited wild-type cells reveal new roles for Dictyostelium myosin II SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1515 BP 274A EP 274A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802239 ER PT J AU Savelkoul, PJ Gottlieb, EM Ciccone, C Sun, M Rakocevic, G Sparks, S Dalakas, MC Krasnewich, D Gahl, WA Huizing, M AF Savelkoul, PJ Gottlieb, EM Ciccone, C Sun, M Rakocevic, G Sparks, S Dalakas, MC Krasnewich, D Gahl, WA Huizing, M TI Hypoglycosylation of alpha-Dystroglyean, due to UDP-GIcNAc 2-epimerase/ManNAc kinase mutations, causes the muscle destruction of Hereditary Inclusion Body Myopathy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHGRI, NIH, MGB, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1530 BP 276A EP 277A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802254 ER PT J AU Ferreira, PA Cai, Y Bowmick, R Aslanukov, A Raz, D Raz, D Bush, R Sieving, P Lu, X AF Ferreira, PA Cai, Y Bowmick, R Aslanukov, A Raz, D Raz, D Bush, R Sieving, P Lu, X TI Integration of RanBP2-mediated molecular processes: Implications in the transport and function of mitochondria components, and cellular function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Columbia Univ, New York, NY USA. NIDCD, NIH, Bethesda, MD USA. NEI, NIH, Bethesda, MD 20892 USA. RI Ferreira, Paulo/A-3893-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1547 BP 279A EP 280A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802271 ER PT J AU Gerald, NJ Reed, S Dwyer, DM AF Gerald, NJ Reed, S Dwyer, DM TI The K39 kinesin tail domain is required for localization in Leishmania donovani cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Corixa Corp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1549 BP 280A EP 280A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802273 ER PT J AU Comer, FI Lippincott, CK Masbad, JJ Parent, CA AF Comer, FI Lippincott, CK Masbad, JJ Parent, CA TI The PH domain containing protein, CRAC, regulates both adenylyl cyclase activation and chemotaxis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1578 BP 285A EP 285A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802302 ER PT J AU Galbraith, CG Yamada, KM Galbraith, J AF Galbraith, CG Yamada, KM Galbraith, J TI Migrating cells use lateral actin movement to position primed integrins at their leading edge SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDCR, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1587 BP 287A EP 287A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802311 ER PT J AU Wei, C Francis, R Xu, X Lo, C AF Wei, C Francis, R Xu, X Lo, C TI Coorinate regulation of connexin43 and N-cadherin cell surface trafficking and the modulation of cell motility SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1591 BP 287A EP 287A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802315 ER PT J AU Akaki, M Ribeiro, JM Dvorak, JA AF Akaki, M Ribeiro, JM Dvorak, JA TI Chernotaxis between Plasmodium berghei sporozoites and salivary glands of Anopheles stephensi mosquitoes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1597 BP 288A EP 288A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802321 ER PT J AU Francis, RJ Lo, CW AF Francis, RJ Lo, CW TI Primoridal germ cell migration in the connexin43 knockout mouse embryo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1595 BP 288A EP 288A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802319 ER PT J AU Holmes, G Romanova, LY Chay, K Mushinski, J AF Holmes, G Romanova, LY Chay, K Mushinski, J TI Phosphorylation of paxillin affects B-lymphocytic polarization and migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Genet Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1594 BP 288A EP 288A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802318 ER PT J AU Nguyen-Blackwood, RD Bretscher, AP AF Nguyen-Blackwood, RD Bretscher, AP TI Localization of merlin, ezrin and EBP50 in MRC-5 and JEG-3 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, NIH, Rockville, MD USA. Cornell Univ, Ithaca, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1608 BP 290A EP 290A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802332 ER PT J AU Dhume, A Horowits, R AF Dhume, A Horowits, R TI N-RAP knockdown disrupts myofibrils in striated muscle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1610 BP 291A EP 291A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802334 ER PT J AU Kuznetsova, SA Day, AJ Mosher, DF Roberts, DD AF Kuznetsova, SA Day, AJ Mosher, DF Roberts, DD TI Thrombospondin-1 specifically interacts with the link domain of TSG-6. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. Univ Wisconsin, Dept Med, Madison, WI USA. RI Roberts, David/A-9699-2008; Day, Anthony/O-1658-2015 OI Roberts, David/0000-0002-2481-2981; Day, Anthony/0000-0002-1415-3134 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1663 BP 300A EP 300A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802387 ER PT J AU Ashok, A Barnes, AM Marini, JC AF Ashok, A Barnes, AM Marini, JC TI Chaperone-procollagen interactions in osteogenesis imperfecta C-propeptide mutations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Bone & Extacellular Matrix Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1673 BP 302A EP 302A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802397 ER PT J AU Hikita, ST Vistica, BP Gery, I Clegg, DO AF Hikita, ST Vistica, BP Gery, I Clegg, DO TI Investigation of the pro-inflammatory function of osteopontin in retinal autoimmune disease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1675 BP 302A EP 303A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802399 ER PT J AU Xu, X Linask, K Francis, R Chatterjee, B Borg, T Lo, C AF Xu, X Linask, K Francis, R Chatterjee, B Borg, T Lo, C TI Connexin43 modulating of integrin cell signaling in neural crest cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, LDB, NIH, Bethesda, MD USA. Univ S Carolina, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1717 BP 310A EP 311A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802441 ER PT J AU Chen, KG Szakacs, G Annereau, J Rouzaud, F Liang, X Valencia, JC Nagineni, CN Hooks, JJ Hearing, VJ Gottesman, MM AF Chen, KG Szakacs, G Annereau, J Rouzaud, F Liang, X Valencia, JC Nagineni, CN Hooks, JJ Hearing, VJ Gottesman, MM TI Principal expression of two mRNA isoforms (ABCB5 alpha and ABCB5 beta) of the ATP-binding cassette transporter ABCB5 in melanoma cells and in melanocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RI Szakacs, Gergely/A-2580-2009; Chen, Kevin/D-6769-2011 OI Szakacs, Gergely/0000-0002-9311-7827; Chen, Kevin/0000-0003-2983-6330 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1719 BP 311A EP 311A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802443 ER PT J AU Zhang, F Yim, Y Eisenberg, E Greene, L AF Zhang, F Yim, Y Eisenberg, E Greene, L TI Interaction of GGA1 with clathrin in vitro SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Cell Biol Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1748 BP 316A EP 316A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802472 ER PT J AU Hayakawa, E Tokumasu, F Takeuchi, T Dvorak, JA AF Hayakawa, E Tokumasu, F Takeuchi, T Dvorak, JA TI Lipoarabinomannan, a Mycobacterium tuberculosis-derived lipid modulates raft-like membrane domain structure SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. Presto, Japan Sci & Technol Agcy, Kawaguchi, Japan. Keio Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1759 BP 318A EP 318A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802483 ER PT J AU Li, Y Prinz, W AF Li, Y Prinz, W TI ABC-transporters mediate nonvesicular, raft-modulated sterol movement from the plasma membrane to the ER SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV PY 2004 VL 15 SU S MA 1758 BP 318A EP 318A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802482 ER PT J AU Hayashi, T Takebayashi,M Su, TP AF Hayashi, T Takebayashi,M Su, TP TI Roles of endoplasmic reticulum (ER) lipid microdomains in cellular differentiation regulated by Sigma-1 receptors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Natl Kure Med Ctr, Hiroshima, Japan. NIDA, Cellular Pathobiol Unit, NIH, Baltimore, MD USA. RI Hayashi, Teruo/A-9690-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 1769 BP 320A EP 320A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802493 ER PT J AU Koo, T Brown, F Al-Awar, O Donaldson, J AF Koo, T Brown, F Al-Awar, O Donaldson, J TI ArRi regulates Rac1-induced ruffling by interacting with human Delta kalirin7 in HeLa SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1792 BP 324A EP 324A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802516 ER PT J AU Chi, Y Jeang, K AF Chi, Y Jeang, K TI Human SUN1 protein plays a critical role in maintaining normal nuclear integrity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1804 BP 326A EP 326A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802528 ER PT J AU Mochizuki, K Tamura, T Dey, A Ozato, K AF Mochizuki, K Tamura, T Dey, A Ozato, K TI Small interfering (si)-RNA for bromodomain proteins reveal a critical role for Brd4 in G1/S transition in NIH-3T3 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1820 BP 329A EP 329A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802544 ER PT J AU Nishiyama, A Dey, A Ozato, K AF Nishiyama, A Dey, A Ozato, K TI Bromodomain protein Brd4 is essential for the recovery from antimicrotubule drug induced mitotic arrest SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Lmgr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1822 BP 329A EP 329A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802546 ER PT J AU Toyama, R Rebbert, M Dey, A Ozato, K Dawid, B AF Toyama, R Rebbert, M Dey, A Ozato, K Dawid, B TI The BRD4 protein associates with transcriptionally inactive chromosomes during early embryogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1827 BP 330A EP 330A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802551 ER PT J AU Hibbert, CS Pederson, T Rein, A AF Hibbert, CS Pederson, T Rein, A TI Signal recognition particle RNA comprises a significant fraction of the RNA in retrovirus particles and interacts with the genomic RNA in murine leukemia virus particles. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1839 BP 332A EP 332A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802563 ER PT J AU Pendrak, ML Roberts, DD AF Pendrak, ML Roberts, DD TI Processing of the 20S rRNA precursor in Candida albicans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1840 BP 332A EP 333A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802564 ER PT J AU Gattegno, T Shemer, G Mittal, A Suissa, M Valansi, C Kolotuev, I Nguyen, KC Hall, DH Chernomordik, LV Podbilewicz, B AF Gattegno, T Shemer, G Mittal, A Suissa, M Valansi, C Kolotuev, I Nguyen, KC Hall, DH Chernomordik, LV Podbilewicz, B TI eff-1 is sufficient and essential for asymmetric cell fusion in C-elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Technion Israel Inst Technol, IL-32000 Haifa, Israel. NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. Albert Einstein Coll Med, Ctr C Elegans Anat, Dept Neurosci, Bronx, NY 10467 USA. RI Mittal, Aditya/E-3087-2010; Podbilewicz, Benjamin/N-4825-2014 OI Mittal, Aditya/0000-0002-4030-0951; NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 1857 BP 335A EP 336A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802581 ER PT J AU Song, L Sun, H Tuan, RS AF Song, L Sun, H Tuan, RS TI Elucidating the function of canonical Wnt signaling in adult stem cell differentiation using combined biological and computational approaches SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1885 BP 340A EP 341A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802609 ER PT J AU Lou, H Kim, S Zaitsev, E Snell, CR Lu, B Loh, PY AF Lou, H Kim, S Zaitsev, E Snell, CR Lu, B Loh, PY TI Sorting of BDNF in the regulated secretory pathway requires interaction with carboxypeptidase E SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Cellular Neurobiol Sect, NIH, Bethesda, MD USA. NICHD, Sect Neural Dev & Plastic, NIH, Bethesda, MD USA. RI Lu, Bai/A-4018-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 1901 BP 343A EP 343A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648802625 ER PT J AU Stewart, DH Haggerty, CM Ponciano-Jackson, D Freebern, WJ Oberoi, P Figg, WD Gardner, K Biebuyck, HA Wohlstadter, JN AF Stewart, DH Haggerty, CM Ponciano-Jackson, D Freebern, WJ Oberoi, P Figg, WD Gardner, K Biebuyck, HA Wohlstadter, JN TI Elucidation of drug responses by profiling signal transduction pathways using cytokine and biomarker panels SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Meso Scale Discovery, Gaithersburg, MD USA. NIH, Ctr Adv Technol, Bethesda, MD 20892 USA. NCI, Canc Therapeut Branch, Bethesda, MD USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 351A EP 352A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803017 ER PT J AU Hochheiser, HS Allan, C Burel, J Creager, D Eliceiri, KW Falconi, A Goldberg, IG Johnston, J Mellen, J Rueden, C Sorger, PK Swedlow, JR AF Hochheiser, HS Allan, C Burel, J Creager, D Eliceiri, KW Falconi, A Goldberg, IG Johnston, J Mellen, J Rueden, C Sorger, PK Swedlow, JR TI The open microscopy environment: Informatics, visualization and quantitative analysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Dundee, Wellcome Trust Bioctr, Dundee, Scotland. MIT, Dept Biol, Cambridge, MA 02139 USA. Univ Wisconsin, Lab Opt & Computat Instrumentat, Madison, WI USA. RI Goldberg, Ilya/H-5307-2011 OI Goldberg, Ilya/0000-0001-8514-6110 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 352A EP 352A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803019 ER PT J AU Orlov, N Macura, T Goldberg, IG AF Orlov, N Macura, T Goldberg, IG TI Automated classifiers for quantitative image analysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Goldberg, Ilya/H-5307-2011 OI Goldberg, Ilya/0000-0001-8514-6110 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 352A EP 352A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803020 ER PT J AU Kim, Y Lampert, S Philpott, C AF Kim, Y Lampert, S Philpott, C TI A receptor domain controls the intracellular sorting of the ferrichrome transporter, ARN1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 356A EP 356A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803038 ER PT J AU Meshorer, E Brown, DT Misteli, T AF Meshorer, E Brown, DT Misteli, T TI Dynamic plasticity of structural chromatin proteins in embryonic stem cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Jackson, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 361A EP 361A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803067 ER PT J AU Forsythe, ME Love, DC Hennessey, PT Ashwell, G Brodigan, TM Krause, M Hanover, JA AF Forsythe, ME Love, DC Hennessey, PT Ashwell, G Brodigan, TM Krause, M Hanover, JA TI Altered lipid and carbohydrate storage in Caenorhabditis elegans lacking O-linked-N-acetylglucosaminyltransferase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, LCBB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2025 BP 366A EP 366A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803095 ER PT J AU Peterson, AW Pendrak, ML Roberts, DD AF Peterson, AW Pendrak, ML Roberts, DD TI ATP specifically binds to and regulates HBR1, an activator of mating locus a gene expression in C-albicans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2023 BP 366A EP 366A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803093 ER PT J AU Boyarchak, Y Amaoutov, A Dasso, M AF Boyarchak, Y Amaoutov, A Dasso, M TI Bub1 is essential for the kinetochore localization of Aurora B/Survivin complex in Xenopus egg extracts SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2112 BP 382A EP 382A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803182 ER PT J AU Levy, JR Wallace, KE Sumner, CJ Tokito, M Fischbeck, KH Holzbaur, EL AF Levy, JR Wallace, KE Sumner, CJ Tokito, M Fischbeck, KH Holzbaur, EL TI The G59S dynactin mutation causes motorneuron degeneration through both loss-of-function and protein aggregation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NINDS, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2176 BP 393A EP 393A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803246 ER PT J AU Mahadeo, DC Smoot, RL Roselova, P Parent, CA AF Mahadeo, DC Smoot, RL Roselova, P Parent, CA TI Chemokine stimulation of adenylyl cyclase requires a cytosolic factor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Natl Canc Inst, Cellular & Mol Biol Lab, Bethesda, MD USA. Natl Inst Hlth, HHMI, Res Scholars Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2213 BP 400A EP 400A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803282 ER PT J AU Xu, X Meier-Schellersheim, M Jiao, X Nelson, L Jin, T AF Xu, X Meier-Schellersheim, M Jiao, X Nelson, L Jin, T TI Quantitative imaging of single live cells reveals spatiotemporal dynamics of multi-step signaling events of chemoattractant gradient sensing in Dictyostelium SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Immunogenet Lab, Rockville, MD 20852 USA. NIAID, Immunol Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2214 BP 400A EP 400A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803283 ER PT J AU Sidhu, G Li, W Laryngakas, N Balla, T Southwick, FS AF Sidhu, G Li, W Laryngakas, N Balla, T Southwick, FS TI Listeria monocytogenes needs host phosphoinositide-3-kinase for intracellular actin-based motility and filopod formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Florida, Gainesville, FL USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2242 BP 405A EP 405A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803311 ER PT J AU Jang, M Conley, M Ferland, P Cleveland-Donovan, K DeGiorgis, J Bearer, E AF Jang, M Conley, M Ferland, P Cleveland-Donovan, K DeGiorgis, J Bearer, E TI Zipcode for the synapse: Live imaging identifies a peptide sufficient to deliver large cargo within axons to the synapse SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Brown Med Sch, Providence, RI USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NIH, Bethesda, MD 20892 USA. CALTECH, Pasadena, CA 91125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2249 BP 406A EP 406A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803318 ER PT J AU Addepalli, MK Connell, KF AF Addepalli, MK Connell, KF TI Characterization of bs7, a mutation affecting centrosome duplication and microtubule organization in C. elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2272 BP 410A EP 410A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803341 ER PT J AU Lu, Y Wahl, LM AF Lu, Y Wahl, LM TI Oxidative stress augments the production of matrix-matlloproteinase-1 through the activation of NF-kappa B plus a pathway of COX-2/CREB in human primary monocytes activated by lippolysaccharide SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDCR, Immune Patheol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2293 BP 414A EP 414A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803362 ER PT J AU Washburn, N Weir, MD Prabhu, V Yamada, KM AF Washburn, N Weir, MD Prabhu, V Yamada, KM TI Fluorescence correlation spectroscopy investigation of growth factor dynamics in three-dimensional extracellular matrices SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NIST, Gaithersburg, MD 20899 USA. NIDCR, NIH, Bethesda, MD USA. RI Weir, Michael/M-7729-2013 OI Weir, Michael/0000-0002-7961-3787 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2294 BP 414A EP 414A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803363 ER PT J AU Ichikawa, N Iwabuchi, K Yanagida, M Murayama, K Suzuki, N Nomizu, M Yamada, Y Arikawa-Hirasawa, E AF Ichikawa, N Iwabuchi, K Yanagida, M Murayama, K Suzuki, N Nomizu, M Yamada, Y Arikawa-Hirasawa, E TI Laminin-1 G domain peptide AG73 promotes neurite outgrowth in PC12 cells via GM1 and syndecan-4 signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Juntendo Univ, Dept Neurol, Tokyo, Japan. Juntendo Univ, Inst Environm & Genderspecif Med, Chiba, Japan. Juntendo Univ, Div Proteom, Tokyo, Japan. Juntendo Univ, Biomol Sci BioMed Res Ctr, Tokyo, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. Tokyo Univ Pharm & Life Sci, Sch Pharmaceut Sci, Biochim Clin Lab, Tokyo, Japan. NIDCR, Cdbrb, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2308 BP 416A EP 416A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803377 ER PT J AU Ozyildirim, AM Wistow, G Gao, J Wang, J Dickinson, D Laurie, GW AF Ozyildirim, AM Wistow, G Gao, J Wang, J Dickinson, D Laurie, GW TI First lacrimal gland EST database reveals an unusual number of predicted hypothetical proteins - Many coding for putative signaling molecules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Virginia, Charlottesville, VA 22903 USA. NEI, Sect Mol Struct & Funct, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Oral Biol, Augusta, GA 30912 USA. RI Laurie, Gordon/A-5244-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2312 BP 417A EP 417A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803381 ER PT J AU Schreiner, A Jakob, V Bharti, S Oswald, C Starzinski-Powitz, A AF Schreiner, A Jakob, V Bharti, S Oswald, C Starzinski-Powitz, A TI Association of integral membrane protein shrew-1 with cadherin-catenin complexes and caveolin-1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Frankfurt, D-6000 Frankfurt, Germany. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2356 BP 425A EP 426A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803425 ER PT J AU Masilamani, M Sanni, TB Kabat, J Borrego, F Coligan, JE AF Masilamani, M Sanni, TB Kabat, J Borrego, F Coligan, JE TI CD94/NKG2A inhibitory natural killer cell synapse, membrane dynamics and intracellular trafficking SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Lab Allerg Dis, Receptor Cell Biol Sect, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2374 BP 428A EP 429A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803443 ER PT J AU Grodnitzky, JA Hsu, WH Kimber, MJ Day, TA Donaldson, JG AF Grodnitzky, JA Hsu, WH Kimber, MJ Day, TA Donaldson, JG TI Somatostatin activates Arf6-PLD signaling cascade through an EFA6A-dependent pathway in HIT-T15 beta-cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Iowa State Univ, Ames, IA USA. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2378 BP 429A EP 429A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803447 ER PT J AU Jiao, X Zhang, N Xu, X Oppenheim, JJ Jin, T AF Jiao, X Zhang, N Xu, X Oppenheim, JJ Jin, T TI Ligand-induced partitioning of human CXCR1 chemokine receptors with lipid-raft microenvironments facilitates G-protein-dependent signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Natl Inst Allergy & Infect, Immunogenet Lab, NIH, Rockville, MD USA. NCI, Mol Immunoregulat Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2383 BP 430A EP 430A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803452 ER PT J AU Hirayama, T Yahiro, K Wada, A Moss, J AF Hirayama, T Yahiro, K Wada, A Moss, J TI Essential region of receptor tyrosine phosphatase beta, RPTPbeta, for interaction with Helicobacter pylori vacuolating cytotoxin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Nagasaki Univ, Dept Bacteriol, Nagasaki, Japan. Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba, Japan. NHLBI, P CCMB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2398 BP 433A EP 433A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803467 ER PT J AU Souza, AM Jamur, MC Siraganian, RP Oliver, C AF Souza, AM Jamur, MC Siraganian, RP Oliver, C TI Characterization of RBL-2H3 mast cell variants deficient in the ganglioside recognized by mAb AA4 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 USP, Fac Med, Ribeirao Preto, SP, Brazil. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Receptors & Signal Transduct Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2407 BP 434A EP 435A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803476 ER PT J AU Rane, NS Fons, RD Yonkovich, JL Hegde, RS AF Rane, NS Fons, RD Yonkovich, JL Hegde, RS TI A preemptive quality control system at the mammalian endoplasmic reticulum SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2454 BP 443A EP 443A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803523 ER PT J AU Jeong, S Pise-Masison, CA Radonovich, MF Brady, JN AF Jeong, S Pise-Masison, CA Radonovich, MF Brady, JN TI IKK beta and phosphorylation of p65 plays a critical role for tax inhibition of p53 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Natl Canc Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S BP 447A EP 447A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803546 ER PT J AU Mabon, SA Misteli, T AF Mabon, SA Misteli, T TI Differential recruitment of pre-mRNA splicing factors to alternatively spliced transcripts in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2482 BP 448A EP 448A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803551 ER PT J AU Sueyoshi, T Moore, R Negishi, M AF Sueyoshi, T Moore, R Negishi, M TI A membrane subunit of protein phosphatase 1, PPPIR16A, signals drug-induced CAR nuclear translocation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2484 BP 448A EP 449A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803553 ER PT J AU Monje, PV Gutkind, S AF Monje, PV Gutkind, S TI Regulation of the transcriptional activity of c-Fos by ERK: A novel role for the prolyl-isomerase Pin1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Miami, Sch Med, Miami Project Cure Paralysis, Miami, FL 33152 USA. Natl Inst Dental Res, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2490 BP 449A EP 450A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803559 ER PT J AU Brown, DT Izard, T Misteli, T AF Brown, DT Izard, T Misteli, T TI Structural mapping of protein-chromatin interactions in native chromatin of living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Mississippi, Med Ctr, Dept Biochem, Jackson, MS 39216 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2502 BP 451A EP 452A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803571 ER PT J AU Rebustini, IT Hoffman, MP AF Rebustini, IT Hoffman, MP TI Blocking the FGFR signaling in the mouse submandibular gland and its effects on the patterns of branching morphogenesis and organ development SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2509 BP 453A EP 453A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803578 ER PT J AU Rebustini, IT Stewart, LS Hoffman, MP AF Rebustini, IT Stewart, LS Hoffman, MP TI FGFR signaling regulates laminin a5 and matrix metalloproteinase gene expression during morphogenesis of mouse submandibular glands in organ culture. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2510 BP 453A EP 453A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803579 ER PT J AU Bharti, S Cui, Y Hennighausen, L AF Bharti, S Cui, Y Hennighausen, L TI Studies on the role of Stat5 in cell proliferation using primary Stat5-null cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2534 BP 457A EP 457A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803603 ER PT J AU Wolf, Y Kashina, A AF Wolf, Y Kashina, A TI Posttranslational protein arginylation: In silico analysis of molecular targets SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2551 BP 457A EP 457A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803600 ER PT J AU Reid, E Biscocho, N Gundersen, GG Zaal, KJ Ralston, E AF Reid, E Biscocho, N Gundersen, GG Zaal, KJ Ralston, E TI LiCl targets are involved in remodeling the Golgi complex (GC) during myogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAMS, NIH, Bethesda, MD USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2550 BP 460A EP 460A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803619 ER PT J AU Greene, L Elibero, A Eisenberg, E AF Greene, L Elibero, A Eisenberg, E TI Partitioning of the trans-Golgi network during mitosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2562 BP 462A EP 462A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803631 ER PT J AU Joshi, MB Owings, JP Andersen, JF Dwyer, DM AF Joshi, MB Owings, JP Andersen, JF Dwyer, DM TI Characterization and conservation of a secretory invertase in various species of the human pathogen Leishmania SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NIAID, LMVR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2563 BP 462A EP 462A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803632 ER PT J AU Mayer, G Miller, LH AF Mayer, G Miller, LH TI Characterization of the Plasmodium falciparum erythrocyte-binding ligand EBL-1. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Lab Malaria & Vector Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2575 BP 464A EP 465A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803644 ER PT J AU Arie, T Fairhurst, RM Brittain, N Wellems, TE Dvorak, JA AF Arie, T Fairhurst, RM Brittain, N Wellems, TE Dvorak, JA TI Host genotype modulates the surface topography of Plasmodium falciparum-infected erythrocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Lab Malaria & Vector Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2577 BP 465A EP 465A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803646 ER PT J AU Furuya, T Mu, J Hayton, K Liu, A Duan, J Joy, DA Vaidya, AB Wellems, TE Su, X AF Furuya, T Mu, J Hayton, K Liu, A Duan, J Joy, DA Vaidya, AB Wellems, TE Su, X TI Disruption of P-falciparum pfmdv leads to sexulal development arrest and impaired male fertility SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Bethesda, MD USA. Drexel Univ, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2576 BP 465A EP 465A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803645 ER PT J AU McQueen, PG McKenzie, FE AF McQueen, PG McKenzie, FE TI Theoretical studies of dual-species Plasmodium infections: effects of competition for red blood cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIH, Mscl deb cit, Bethesda, MD USA. NIH, Fic, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2579 BP 465A EP 465A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803648 ER PT J AU Tokumasu, F Fairhurst, RM Brittain, N Wellems, TE Dvorak, JA AF Tokumasu, F Fairhurst, RM Brittain, N Wellems, TE Dvorak, JA TI Accelerated band 3 clustering in Plasmodium falciparum-infected homozygous hemoglobin C erythrocytes assayed by single-cell antocorrelation analysis using quantum dots SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2578 BP 465A EP 465A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803647 ER PT J AU Kimchi-Sarfaty, C Sherman, A Vieira, W Meyron-Holtz, E Chinnasamy, D Scavo, L Gottesman, MM AF Kimchi-Sarfaty, C Sherman, A Vieira, W Meyron-Holtz, E Chinnasamy, D Scavo, L Gottesman, MM TI SV40 in vitro packaging vectors - An effective gene delivery system in differentiating cells of mesenchymal origin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. St Lukes Hosp, Immunotherapy Program, Cell Biol Lab, Vince Lombardi Gene Therapy Lab, Milwaukee, WI USA. NIDDK, Childrens Natl Med Ctr, NIH, Bethesda, MD USA. RI Meyron-Holtz, Esther/B-5991-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2598 BP 469A EP 469A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803667 ER PT J AU Wu, Y Doe, E Liu, C Lo, C AF Wu, Y Doe, E Liu, C Lo, C TI Highthough put recovery of mouse Cx47 mutations with a gentoype base screen of embryonic stem cells using DHPLC and CeII endonuclease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NHLBI, LDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2004 VL 15 SU S MA 2601 BP 469A EP 469A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803670 ER PT J AU Wallis, BS Chuaqui, RF Gillespie, JW Pohida, TJ Bonner, RF Emmert-Buck, MR Tangrea, MA AF Wallis, BS Chuaqui, RF Gillespie, JW Pohida, TJ Bonner, RF Emmert-Buck, MR Tangrea, MA TI Expression microdissection: A novel operator-independent method for tissue dissection SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 NCI, Pathol Lab, Gaithersburg, MD USA. NIH, Computat Biosci & Engn Lab, Bethesda, MD USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2004 VL 15 SU S MA 2602 BP 470A EP 470A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803671 ER PT J AU Ozog, MA Bernier, SM Bates, DC Chatterjee, B Lo, CW Naus, CCG AF Ozog, MA Bernier, SM Bates, DC Chatterjee, B Lo, CW Naus, CCG TI The complex of ciliary neurotrophic factor-ciliary neurotrophic factor receptor alpha up-regulates connexin43 and intercellular coupling in Astrocytes via the Janus tyrosine kinase/signal transducer and activator of transcription pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GAP-JUNCTIONAL COMMUNICATION; LEUKEMIA INHIBITORY FACTOR; CENTRAL-NERVOUS-SYSTEM; CULTURED ASTROCYTES; OSTEOBLASTIC CELLS; GENE-EXPRESSION; GROWTH-FACTORS; CNTF RECEPTOR; SPREADING DEPRESSION; PROTEIN CONNEXIN-43 AB Cytokines regulate numerous cell processes, including connexin expression and gap junctional coupling. In this study, we examined the effect of ciliary neurotrophic factor (CNTF) on connexin43 (Cx43) expression and intercellular coupling in astrocytes. Murine cortical astrocytes matured in vitro were treated with CNTF (20 ng/ml), soluble ciliary neurotrophic factor receptor alpha (CNTFRalpha) (200 ng/ml), or CNTF-CNTFRalpha. Although CNTF and CNTFRalpha alone had no effect on Cx43 expression, the heterodimer CNTF-CNTFRalpha significantly increased both Cx43 mRNA and protein levels. Cx43 immunostaining correlated with increased intercellular coupling as determined by dye transfer analysis. By using the pharmacological inhibitor alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG490), the increase in Cx43 was found to be dependent on the Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Immunocytochemical analysis revealed that CNTF-CNTFRalpha treatment produced nuclear localization of phosphorylated STAT3, whereas CNTF treatment alone did not. Transient transfection of constructs containing various sequences of the Cx43 promoter tagged to a LacZ reporter into ROS 17/2.8 cells confirmed that the promoter region between -838 to -1693 was deemed necessary for CNTF-CNTFRalpha to induce heightened expression. CNTF-CNTFRalpha did not alter Cx30 mRNA levels, suggesting selectivity of CNTF-CNTFRalpha for connexin signaling. Together in the presence of soluble receptor, CNTF activates the JAK/STAT pathway leading to enhanced Cx43 expression and intercellular coupling. C1 Univ British Columbia, Dept Anat & Cell Biol, Vancouver, BC, Canada. Univ Western Ontario, Canadian Inst Hlth Res Grp Skeletal Dev & Remodel, Dept Anat & Cell Biol, Vancouver, BC V6T 1Z3, Canada. NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Naus, CCG (reprint author), Univ British Columbia, Dept Anat & Cell Biol, Vancouver, BC, Canada. EM cnaus@interchange.ubc.ca NR 89 TC 32 Z9 34 U1 0 U2 1 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 NOV PY 2004 VL 15 IS 11 BP 4761 EP 4774 DI 10.1091/mbc.E04-03-0271 PG 14 WC Cell Biology SC Cell Biology GA 864QQ UT WOS:000224648400003 PM 15342787 ER PT J AU Vecerova, J Koberna, K Malinsky, J Soutoglou, E Sullivan, T Stewart, CL Raska, I Misteli, T AF Vecerova, J Koberna, K Malinsky, J Soutoglou, E Sullivan, T Stewart, CL Raska, I Misteli, T TI Formation of nuclear splicing factor compartments is independent of lamins A/C SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MAMMALIAN-CELLS; LIVING CELLS; RNA; ENVELOPE; TRANSCRIPTION; ORGANIZATION; ARCHITECTURE; PROTEINS; PURIFICATION; DYNAMICS AB Nuclear lamins are major architectural elements of the mammalian cell nucleus, and they have been implicated in the functional organization of the nuclear interior, possibly by providing structural support for nuclear compartments. Colocalization studies have suggested a structural role for lamins in the formation and maintenance of pre-mRNA splicing factor compartments. Here, we have directly tested this hypothesis by analysis of embryonic fibroblasts from knock-out mice lacking A- and C-type lamins. We show that the morphology and cellular properties of splicing factor compartments are independent of A- and C-type lamins. Genetic loss of lamins A/C has no effect on the cellular distribution of several pre-mRNA splicing factors and does not affect the compartment morphology as examined by light and electron microscopy. The association of splicing factors with the nuclear matrix fraction persists in the absence of lamins A/C. Live cell microscopy demonstrates that the intranuclear positional stability of splicing factor compartments is maintained and that the exchange dynamics of SF2/ASF between the compartments and the nucleoplasm is not affected by loss of lamin A/C. Our results demonstrate that formation and maintenance of intranuclear splicing factor compartments is independent of lamins A/C, and they argue against an essential structural role of lamins A/C in splicing factor compartment morphology. C1 NCI, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Expt Med, Dept Cell Biol, Prague, Czech Republic. Charles Univ, Fac Med 1, Inst Cellular Biol & Pathol, Prague, Czech Republic. NCI, Lab Canc & Dev Biol, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov RI Malinsky, Jan/H-2484-2014 OI Malinsky, Jan/0000-0002-1433-0989 NR 37 TC 15 Z9 16 U1 0 U2 1 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 NOV PY 2004 VL 15 IS 11 BP 4904 EP 4910 DI 10.1091/mbc.E04-07-0645 PG 7 WC Cell Biology SC Cell Biology GA 864QQ UT WOS:000224648400015 PM 15356259 ER PT J AU Lee, YJ Jeong, SY Karbowski, M Smith, CL Youle, RJ AF Lee, YJ Jeong, SY Karbowski, M Smith, CL Youle, RJ TI Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DYNAMIN-RELATED PROTEIN; CYTOCHROME-C RELEASE; DOMINANT OPTIC ATROPHY; WD REPEAT PROTEIN; OUTER-MEMBRANE; SACCHAROMYCES-CEREVISIAE; COMPONENT FIS1P; GTPASE; BAX; MORPHOLOGY AB During apoptosis, the mitochondrial network fragments. Using short hairpin RNAs for RNA interference, we manipulated the expression levels of the proteins hFis1, Drp1, and Opa1 that are involved in mitochondrial fission and fusion in mammalian cells, and we characterized their functions in mitochondrial morphology and apoptosis. Down-regulation of hFis1 powerfully inhibits cell death to an extent significantly greater than down-regulation of Drp1 and at a stage of apoptosis distinct from that induced by Drp1 inhibition. Cells depleted of Opa1 are extremely sensitive to exogenous apoptosis induction, and some die spontaneously by a process that requires hFis1 expression. Wild-type Opa1 may function normally as an antiapoptotic protein, keeping spontaneous apoptosis in check. However, if hFis1 is downregulated, cells do not require Opa1 to prevent apoptosis, suggesting that Opa1 may be normally counteracting the proapoptotic action of hFis1. We also demonstrate in this study that mitochondrial fragmentation per se does not result in apoptosis. However, we provide further evidence that multiple components of the mitochondrial morphogenesis machinery can positively and negatively regulate apoptosis. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Light Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov NR 49 TC 562 Z9 581 U1 8 U2 32 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 NOV PY 2004 VL 15 IS 11 BP 5001 EP 5011 DI 10.1091/mbc.E04-04-0294 PG 11 WC Cell Biology SC Cell Biology GA 864QQ UT WOS:000224648400023 PM 15356267 ER PT J AU Liang, HY Salinas, RA Leal, BZ Kosakowska-Cholody, T Michejda, CJ Waters, SJ Herman, TS Woynarowski, JM Woynarowska, BA AF Liang, HY Salinas, RA Leal, BZ Kosakowska-Cholody, T Michejda, CJ Waters, SJ Herman, TS Woynarowski, JM Woynarowska, BA TI Caspase-mediated apoptosis and caspase-independent cell death induced by irofulven in prostate cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of AACR CY MAR, 2001 CL NEW ORLEANS, LA SP AACR ID PERMEABILITY TRANSITION PORE; MGI 114 HMAF; ADENINE-NUCLEOTIDE TRANSLOCASE; LUNG-CARCINOMA XENOGRAFT; CYTOCHROME-C RELEASE; ANTITUMOR HYDROXYMETHYLACYLFULVENE; MITOCHONDRIAL DYSFUNCTION; IN-VITRO; 6-HYDROXYMETHYLACYLFULVENE; TUMOR AB lrofulven (hydroxymethylacylfulvene) is a novel antitumor drug, which acts by alkylating cellular macromolecular targets. The drug is a potent inducer of apoptosis in various types of tumor cells, whereas it is nonapoptotic in normal cells. This study defined molecular responses to irofulven involving mitochondrial dysfunction and leading to death of prostate tumor LNCaP-Pro5 cells. lrofulven caused early (2-5 hours) translocation of the proapoptotic Bax from cytosol to mitochondria followed by the dissipation of mitochondrial membrane potential and cytochrome c release at 4 to 12 hours. These effects preceded caspase activation and during the first 6 hours were not affected by caspase inhibitors. Processing of caspase-9 initiated the caspase cascade at similar to6 hours and progressed over time. The activation of the caspase cascade provided a positive feedback loop that enhanced Bcl-2-independent translocation and cytochrome c release. General and specific caspase inhibitors abrogated irofulven-induced apoptotic DNA fragmentation with the following order of potency: pan-caspase greater than or equal to caspase-9 > caspase-8/6 > caspase-2 > caspase-3/7 > caspase-1/4. Abrogation of caspase-mediated DNA fragmentation failed to salvage irofulventreated cells from growth inhibition and loss of viability, demonstrating a substantial contribution of a caspase-independent cell death. Monobromobimane, an inhibitor of alternative caspase-independent apoptotic pathway that is mediated by mitochondrial permeability transition, antagonized both apoptosis, measured as phosphatidylserine externalization, and cytotoxicity of irofulven. Collectively, the results indicate that irofulven-induced signaling is integrated at the level of mitochondrial dysfunction. The induction of both caspase-dependent and caspase-independent death pathways is consistent with pleiotropic effects of irofulven, which include targeting of cellular DNA and. proteins. C1 Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX 78245 USA. Natl Canc Inst, Frederick, MD USA. MGI Pharma Inc, Bloomington, MN USA. RP Woynarowski, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, 1DD Bldg,14960 Omicron Dr, San Antonio, TX 78245 USA. EM jmw1@saci.org; bwoynar@saci.org RI Woynarowski, Jan/A-5915-2008 FU NCI NIH HHS [CA78706, CA112175] NR 54 TC 16 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2004 VL 3 IS 11 BP 1385 EP 1396 PG 12 WC Oncology SC Oncology GA 870PS UT WOS:000225070800005 PM 15542777 ER PT J AU Matsusue, K Gavrilova, O Lambert, G Brewer, HB Ward, JM Inoue, Y LeRoith, D Gonzalez, FJ AF Matsusue, K Gavrilova, O Lambert, G Brewer, HB Ward, JM Inoue, Y LeRoith, D Gonzalez, FJ TI Hepatic CCAAT/enhancer binding protein alpha mediates induction of lipogenesis and regulation of glucose homeostasis in leptin-deficient mice SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GTP GENE-TRANSCRIPTION; LEMLI-OPITZ-SYNDROME; C/EBP-ALPHA; NF-Y; FARNESYL DIPHOSPHATE; MOLECULAR-CLONING; LIPID HOMEOSTASIS; INSULIN-SECRETION; LEUCINE-ZIPPER; KNOCKOUT MICE AB CCAAT/enhancer binding protein alpha (C/EBPalpha)is a critical factor in glucose metabolism in the neonate as revealed by conventional C/EBPalpha-null mice that do not survive beyond the first day after birth because of severe hypoglycemia and a deficiency in hepatic glycogen accumulation. To elucidate the function of C/EBPalpha in leptin-deficient mouse (ob/ob) liver, a C/EBPalpha-liver null mouse on an ob/ob background (ob/ob-C/EBPalpha/Cre(+)) was produced using a floxed C/EBPalpha allele and Cre recombinase under control of the albumin promoter (AlbCre). The C/EBPalpha-deficient liver in ob/ob mice had significantly decreased triglyceride content compared with equivalent mice lacking the AlbCre transgene (ob/ob-C/EBPalpha/Cre(+)). Expression of genes involved in lipogenesis including fatty acid synthase, acetyl-coenzyme A carboxylase, stearoyl-coenzyme A desaturase 1 and ATP-citrate lyase dramatically decreased in ob/ob-C/EBPalpha/Cre(+) mouse liver. Induction of these lipogenic genes by a high-carbohydrate diet caused an exacerbation in the development of fatty liver and an increase in liver size, hepatic triglyceride, and cholesterol contents in ob/ob-C/EBPalpha/Cre(+) mice but not in ob/obC/EBPalpha/Cre(+) mice. Deficiency in hepatic C/EBPalpha expression caused an exacerbation of hyperglycemia because of decreased insulin secretion. Taken together, these results indicate that hepatic C/EBPalpha plays a critical role in the acceleration of lipogenesis in ob/ob mice and in glucose homeostasis by the indirect regulation of insulin secretion. C1 NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. NIAID, Comparat Med Branch, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Hop Hotel Dieu, INSERM, Unite 539, F-44000 Nantes, France. RP Gonzalez, FJ (reprint author), NCI, NIH, Lab Metab, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 56 TC 35 Z9 35 U1 1 U2 5 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 NOV PY 2004 VL 18 IS 11 BP 2751 EP 2764 DI 10.1210/me.2004-0213 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865VP UT WOS:000224732600012 PM 15319454 ER PT J AU Angaroni, CJ de Kremer, RD Argarana, CE Paschini-Capra, AE Giner-Ayala, AN Pezza, RJ Pan, CJ Chou, JY AF Angaroni, CJ de Kremer, RD Argarana, CE Paschini-Capra, AE Giner-Ayala, AN Pezza, RJ Pan, CJ Chou, JY TI Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE glycogen storage disease type Ia; glucose-6-phosphatase; argentine; mutational analyses AB Glycogen storage disease type la (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecular study of this gene was carried out in 11 Argentinean patients from 8 unrelated families. Four missense (p.Gln54Pro, p.Arg83Cys, p.Thr16Arg, and p.Tyr209Cys) and one deletion (c.79delC) mutations have been identified. Two novel mutations, p.Thr16Arg (c.47C>G) located within the amino-terminal domain and p.Tyr209Cys (c.626A>G) situated in the sixth transmembrane helix, were uncovered in this study. Site-directed mutagenesis and transient expression assays demonstrated that both p.Thr16Arg and p.Tyr209Cys mutations abolished enzymatic activity as well as reduced G6Pase stability. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Nacl Cordoba, CEMECO, Catedra Clin Pediat, Fac Ciencias Med,Hosp Ninos Santisima Trinidad, RA-5000 Cordoba, Argentina. Univ Nacl Cordoba, Fac Ciencias Quim, CIQUIBIC, RA-5000 Cordoba, Argentina. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Angaroni, CJ (reprint author), Univ Nacl Cordoba, CEMECO, Catedra Clin Pediat, Fac Ciencias Med,Hosp Ninos Santisima Trinidad, RA-5000 Cordoba, Argentina. EM celiangaroni@hotmail.com NR 9 TC 8 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2004 VL 83 IS 3 BP 276 EP 279 DI 10.1016/j.ymgme.2004.06.010 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 876KS UT WOS:000225496300011 PM 15542400 ER PT J AU Lingelbach, K Kirk, K Rogerson, S Langhorne, J Carucci, DJ Waters, A AF Lingelbach, K Kirk, K Rogerson, S Langhorne, J Carucci, DJ Waters, A TI Molecular approaches to malaria SO MOLECULAR MICROBIOLOGY LA English DT Article ID DRUG/METABOLITE TRANSPORTER SUPERFAMILY; FALCIPARUM-INFECTED ERYTHROCYTES; PARASITE PLASMODIUM-FALCIPARUM; MOSQUITO ANOPHELES-GAMBIAE; APICAL MEMBRANE ANTIGEN-1; CHLOROQUINE RESISTANCE; GENOME SEQUENCE; SURFACE PROTEIN; LIFE-CYCLE; VAR GENES C1 Univ Marburg, FB Biol, Marburg, Germany. Australian Natl Univ, Sch Biochem & Mol Biol, Canberra, ACT, Australia. Univ Melbourne, Melbourne, Vic, Australia. Natl Inst Med Res, MRC, London NW7 1AA, England. Fdn Natl Inst Hlth, Bethesda, MD USA. Leiden Univ, Med Ctr, Ctr Infect Dis, Dept Parasitol, Leiden, Netherlands. RP Lingelbach, K (reprint author), Univ Marburg, FB Biol, Marburg, Germany. EM lingelba@staff.uni-marburg.de RI Waters, Andy/C-9377-2009; Kirk, Kiaran/C-8299-2009; OI Waters, Andy/0000-0001-8900-2982; Kirk, Kiaran/0000-0002-5613-2622; Rogerson, Stephen/0000-0003-4287-1982 NR 57 TC 3 Z9 3 U1 0 U2 1 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 NOV PY 2004 VL 54 IS 3 BP 575 EP 587 DI 10.1111/j.1365-2958.2004.04362.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 862XA UT WOS:000224523500001 PM 15491351 ER PT J AU Lewis, DEA Adhya, S AF Lewis, DEA Adhya, S TI Axiom of determining transcription start points by RNA polymerase in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID GALACTOSE OPERON PROMOTERS; OPEN COMPLEX-FORMATION; AMP RECEPTOR PROTEIN; SENSITIVE SELECTION; SITE SELECTION; CYCLIC-AMP; GAL PROMOTERS; IN-VIVO; DNA; INITIATION AB To investigate the determining factors in the selection of the transcription start points (tsp) by RNA polymerase of Escherichia coli, we systematically deleted or substituted single base pairs (bps) at 25 putative critical positions in the two extended -10 promoters, P1 and P2, of the gal operon. These changes extend downstream from -24 to +1 of the P1 promoter. In vitro transcription assays using supercoiled DNA templates revealed a preference for a purine in the non-template strand for tsp in both promoters. The optimal tsp is the 11th bp counting downstream from the -10 position. A single bp deletion anywhere from -10 to +1 switched the tsp to the next available purine 2-3 bp downstream on the non-template strand whereas deleting a single bp at position from -24 to -11 did not affect the tsp. The nature of the 10 bp sequence of the -10 to -1 region, while affecting promoter strength, did not influence tsp. The cAMP-CRP complex, which stimulates P1 and represses P2, did not affect the tsp selection process. The rules of tsp selection by RNA polymerase containing sigma(70) in gal and pyr promoters discussed here may be applicable to others. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 33 TC 30 Z9 30 U1 0 U2 0 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 NOV PY 2004 VL 54 IS 3 BP 692 EP 701 DI 10.1111/j.1365-2958.2004.04318.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 862XA UT WOS:000224523500010 PM 15491360 ER PT J AU Blaha, B Semsey, S Ferenczi, S Csiszovszki, Z Papp, PP Orosz, L AF Blaha, B Semsey, S Ferenczi, S Csiszovszki, Z Papp, PP Orosz, L TI A proline tRNA(CGG) gene encompassing the attachment site of temperate phage 16-3 is functional and convertible to suppressor tRNA SO MOLECULAR MICROBIOLOGY LA English DT Article ID RHIZOBIUM-MELILOTI; ESCHERICHIA-COLI; PATHOGENICITY ISLANDS; RECOMBINATION; INTEGRATION; PLASMID; IDENTIFICATION; EVOLUTION; CHROMOSOME; SEQUENCES AB Several temperate bacteriophage utilize chromosomal sequences encoding putative tRNA genes for phage attachment. However, whether these sequences belong to genes which are functional as tRNA is generally not known. In this article, we demonstrate that the attachment site of temperate phage 16-3 (attB) nests within an active proline tRNA gene in Rhizobium meliloti 41. A loss-of-function mutation in this tRNA gene leads to significant delay in switching from lag to exponential growth phase. We converted the putative Rhizobium gene to an active amber suppressor gene which suppressed amber mutant alleles of genes of 16-3 phage and of Escherichia coli origin in R. meliloti 41 and in Agrobacterium tumefaciens GV2260. Upon lysogenization of R. meliloti by phage 16-3, the proline tRNA gene retained its structural and functional integrity. Aspects of the co-evolution of a temperate phage and its bacterium host is discussed. The side product of this work, i.e. construction of amber suppressor tRNA genes in Rhizobium and Agrobacterium, for the first time widens the options of genetic study. C1 Agr Biotechnol Ctr, Inst Genet, H-2100 Godollo, Hungary. Eotvos Lorand Univ, Fac Sci, Dept Genet, H-1117 Budapest, Hungary. Hungarian Acad Sci, Res Grp Mol Genet, H-1117 Budapest, Hungary. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Orosz, L (reprint author), Agr Biotechnol Ctr, Inst Genet, Szent Gyorgyi A 4, H-2100 Godollo, Hungary. EM orosz@abc.hu RI Papp, Peter/A-6907-2013; Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495 NR 50 TC 3 Z9 3 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2004 VL 54 IS 3 BP 742 EP 754 DI 10.1111/j.1365-2958.2004.04300.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 862XA UT WOS:000224523500014 PM 15491364 ER PT J AU Das, N Chattoraj, DK AF Das, N Chattoraj, DK TI Origin pairing ('handcuffing') and unpairing in the control of P1 plasmid replication SO MOLECULAR MICROBIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; COPY-NUMBER CONTROL; DNA-REPLICATION; INITIATOR PROTEIN; ESCHERICHIA-COLI; NEGATIVE CONTROL; RK2 REPLICATION; BINDING-SITES; REPA; REPRESSOR AB The P1 plasmid origin has an array of five binding sites (iterons) for the plasmid-encoded initiator protein RepA. Saturation of these sites is required for initiation. Iterons can also pair via their bound RepAs. The reaction, called handcuffing, is believed to be the key to control initiation negatively. Here we have determined some of the mechanistic details of the reaction. We show that handcuffed RepA-iteron complexes dissociate when they are diluted or challenged with cold competitor iterons, suggesting spontaneous reversibility of the handcuffing reaction. The complex formation increases with increased RepA binding, but decreases upon saturation of binding. Complex formation also decreases in the presence of molecular chaperones (DnaK and DnaJ) that convert RepA dimers to monomers. This indicates that dimers participate in handcuffing, and that chaperones are involved in reversing handcuffing. They could play a direct role by reducing dimers and an indirect role by increasing monomers that would compete out the weaker binding dimers from the origin. We propose that an increased monomer to dimer ratio is the key to reverse handcuffing. C1 NCI, Biochem Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, CCR, NIH, Bethesda, MD 20892 USA. EM chattord@mail.nih.gov NR 46 TC 32 Z9 32 U1 2 U2 3 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 NOV PY 2004 VL 54 IS 3 BP 836 EP 849 DI 10.1111/j.1365-2958.2004.04322.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 862XA UT WOS:000224523500021 PM 15491371 ER PT J AU Vanderpool, CK Gottesman, S AF Vanderpool, CK Gottesman, S TI Involvement of a novel transcriptional activator and small RNA in post-transcriptional regulation of the glucose phosphoenolpyruvate phosphotransferase system SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; MESSENGER-RNA; NONCODING RNAS; COMPARATIVE GENOMICS; RPOS TRANSLATION; MAJOR GLUCOSE; PTS OPERON; TRANSPORTER; GENES; EXPRESSION AB RyaA is a small non-coding RNA in Escherichia coli that was identified by its ability to bind tightly to the RNA chaperone Hfq. This study reports the role of RyaA in mediating the cellular response to glucose-specific phosphoenolypyruvate phosphotransferase system (PTS)-dependent phosphosugar stress. Aiba and co-workers have shown that a block in the metabolism of glucose 6-phosphate causes transient growth inhibition and post-transcriptional regulation of ptsG, encoding the glucose-specific PTS transporter. We found that RyaA synthesis was induced by a non-metabolizable glucose phosphate analogue and was necessary for relief of the toxicity of glucose phosphate stress. Expression of RyaA was sufficient to cause a rapid loss of ptsG mRNA, probably reflecting degradation of the message mediated by RyaA:ptsG pairing. The ryaA gene was renamed sgrS, for sugar transport-related sRNA. Expression of sgrS is regulated by a novel transcriptional activator, SgrR (formerly YabN), which has a putative DNA-binding domain and a solute-binding domain similar to those found in certain transport proteins. Our results suggest that under conditions of glucose phosphate accumulation, SgrR activates SgrS synthesis, causing degradation of ptsG mRNA. Decreased ptsG mRNA results in decreased production of glucose transport machinery, thus limiting further accumulation of glucose phosphate. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 47 TC 178 Z9 185 U1 2 U2 11 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 NOV PY 2004 VL 54 IS 4 BP 1076 EP 1089 DI 10.1111/j.1365-2958.2004.04348.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 867QW UT WOS:000224858300018 PM 15522088 ER PT J AU Lu, XP Huang, W Worthington, S Drabik, P Osman, R Gershengorn, MC AF Lu, XP Huang, W Worthington, S Drabik, P Osman, R Gershengorn, MC TI A model of inverse agonist action at thyrotropin-releasing hormone receptor type 1: Role of a conserved tryptophan in helix 6 SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; TRH RECEPTOR; EXTRACELLULAR LOOPS; MOLECULAR-DYNAMICS; BINDING POCKET.; REFINED MODEL; RHODOPSIN; ACTIVATION; LIGAND; IDENTIFICATION AB A binding pocket for thyrotropin-releasing hormone (TRH) within the transmembrane helices of the TRH receptor type 1 (TRH-R1) has been identified based on experimental evidence and computer simulations. To determine the binding site for a competitive inverse agonist, midazolam, three of the four residues that directly contact TRH and other residues that restrain TRH-R1 in an inactive conformation were screened by mutagenesis and binding assays. We found that two residues that directly contact TRH, Asn-110 in transmembrane helix 3 (3.37) and Arg-306 in transmembrane helix 7 (7.39), were important for midazolam binding but another, Tyr-282 in transmembrane helix 6 (6.51), was not. A highly conserved residue, Trp-279 in transmembrane helix 6 (6.48), which was reported to be critical in stabilizing TRH-R1 in an inactive state but not for TRH binding, was critical for midazolam binding. We used our previous model of the unoccupied TRH-R1 to generate a model of the TRH-R1/midazolam complex. The experimental results and the molecular model of the complex suggest that midazolam binds to TRH-R1 within a transmembrane helical pocket that partially overlaps the TRH binding pocket. This result is consistent with the competitive antagonism of midazolam binding. We suggest that the mechanism of inverse agonism effected by midazolam involves its direct interaction with Trp-279, which contributes to the stabilization of the inactive conformation of TRH-R1. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA. RP Gershengorn, MC (reprint author), NIDDK, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov NR 33 TC 15 Z9 16 U1 0 U2 0 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 NOV PY 2004 VL 66 IS 5 BP 1192 EP 1200 DI 10.1124/mol.104.000349 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 863RH UT WOS:000224578900013 PM 15306657 ER PT J AU Moayeri, M Ramezani, A Morgan, RA Hawley, TS Hawley, RG AF Moayeri, M Ramezani, A Morgan, RA Hawley, TS Hawley, RG TI Sustained phenotypic correction of hemophilia A mice following oncoretroviral-mediated expression of a bioengineered human factor VIII gene in long-term hematopoietic repopulating cells SO MOLECULAR THERAPY LA English DT Article DE hemophilia A; factor VIII gene therapy; oncoretroviral vector; hematopoietic stem cells ID SEVERE COMBINED IMMUNODEFICIENCY; TRANSDUCED BONE-MARROW; RETROVIRAL VECTORS; STEM-CELLS; IN-VIVO; LENTIVIRAL VECTORS; PROGENITOR CELLS; THERAPEUTIC LEVELS; BETA-GLOBIN; ENGRAFTMENT AB Hematopoietic stem cells (HSCs) are an attractive target cell population for hemophilia A gene therapy because of their capacity to regenerate the hematolymphoid system permanently following transplantation. Here we transplanted bone marrow (BM) cells transduced with a splicing-optimized MSCV oncoretroviral vector expressing a secretion-improved human factor VIII gene into immunocompromised hemophilic mice that had received a reduced dose conditioning regimen. An enhanced green fluorescent protein (EGFP) reporter gene linked to an encephalomyocarditis virus internal ribosome entry site was incorporated into the vector to allow preselection of transduced cells and facile evaluation of engraftment. Sustained expression of EGFP was demonstrated in the peripheral blood, and therapeutic levels of factor VIII were detected in the plasma of the majority of the recipients for the duration of the observation period (up to 22 weeks). Coordinate expression of factor VIII and EGFP (up to 19 weeks) was transferred to secondary BM transplant recipients, indicating that long-term repopulating HSCs had been successfully gene modified. Notably, the hemophilic phenotype of all treated mice was corrected, thus demonstrating the potential of HSC-directed oncoretroviral-mediated factor VIII gene transfer as a curative therapeutic strategy for hemophilia A. C1 George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Flow Cytometry Core Facil, Washington, DC 20037 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. NCI, Natl Inst Hlth, Surg Branch, Bethesda, MD 20892 USA. RP Hawley, RG (reprint author), George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Suite 419,2300 Eye St NW, Washington, DC 20037 USA. EM rghawley@gwu.edu FU NHLBI NIH HHS [HL65519, HL66305] NR 52 TC 39 Z9 42 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 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2004 VL 10 IS 5 BP 892 EP 902 DI 10.1016/j.ymthe.2004.08.006 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 879II UT WOS:000225709400013 PM 15509507 ER PT J AU Chiocca, EA Abbed, KM Tatter, S Louis, DN Hochberg, FH Barker, F Kracher, J Grossman, SA Fisher, JD Carson, K Rosenblum, M Mikkelsen, T Olson, J Markert, J Rosenfeld, S Nabors, LB Brem, S Phuphanich, S Freeman, S Kaplan, R Zwiebel, J AF Chiocca, EA Abbed, KM Tatter, S Louis, DN Hochberg, FH Barker, F Kracher, J Grossman, SA Fisher, JD Carson, K Rosenblum, M Mikkelsen, T Olson, J Markert, J Rosenfeld, S Nabors, LB Brem, S Phuphanich, S Freeman, S Kaplan, R Zwiebel, J TI A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting SO MOLECULAR THERAPY LA English DT Article DE glioma; brain tumor; clinical trial; ONYX-015; gene therapy; oncolytic virus; experimental therapy; virotherapy; adenovirus; conditionally replicating adenoviruses ID REPLICATION-SELECTIVE ADENOVIRUS; HERPES-SIMPLEX-VIRUS; BRAIN-TUMORS; NECK-CANCER; INTRAVENOUS-INFUSION; GENE-TRANSFER; HEAD; CARCINOMA; DL1520; MUTANT AB ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 107 plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and I patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu. C1 NABTT CNS Consortium, Baltimore, MD 21231 USA. Onyx Pharmaceut, Redmond, CA USA. NCI, Natl Inst Hlth, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Chiocca, EA (reprint author), NABTT CNS Consortium, 1650 Orleans St,Room G93, Baltimore, MD 21231 USA. EM jfisher@jhmi.edu NR 34 TC 199 Z9 211 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2004 VL 10 IS 5 BP 958 EP 966 DI 10.1016/j.ymthe.2004.07.021 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 879II UT WOS:000225709400019 PM 15509513 ER PT J AU Muthane, U Chickabasaviah, Y Kaneski, C Shankar, SK Narayanappa, G Christopher, R Govindappa, SS AF Muthane, U Chickabasaviah, Y Kaneski, C Shankar, SK Narayanappa, G Christopher, R Govindappa, SS TI Clinical features of adult G(M1) gangliosidosis: Report of three Indian patients and review of 40 cases SO MOVEMENT DISORDERS LA English DT Article DE Gaucher-like cells; G(M1) gangliosidosis; dystonia; facial grimacing; putamenal hyperintensities ID BETA-GALACTOSIDASE DEFICIENCY; GM1 GANGLIOSIDOSIS; RECTAL BIOPSY; GM1-GANGLIOSIDOSIS; DYSTONIA; JUVENILE; PATTERNS AB Deficiency of enzyme acid beta-galactosidase causes G(M1) gangliosidosis. Patients with adult G(M1) gangliosidosis typically present with generalized dystonia. We describe clinical, bone marrow, and radiological features of adult G(M1) gangliosidosis to help improve its recognition. We report 3 Indian patients and review of reports between 1981 and October 2002. The disease frequently is reported in the Japanese literature (75%). Patients are normal at birth and have normal early motor and mental development. Onset is within the first decade with abnormal gait, or worsening of speech is an initial symptom. Dystonia occurs in 97% of patients. Facial dystonia described as "facial grimacing" observed in similar to90% could be an important clinical clue. Dysarthria/anarthria (97%) is frequent, and eye movements are normal. Bone marrow examination may show Gaucher-like foam cells (39%). Magnetic resonance imaging (MRI) frequently (90.9%) shows bilateral symmetrical putamenal hyperintensities on T2-weighted and proton density images. Diagnosis is confirmed by demonstrating deficiency of beta-galactosidase. Adult (Type 3) Gm, Gangliosidosis commonly presents with generalized dystonia with prominent facial dystonia, severe speech disturbances, and normal eye movements. Bone marrow frequently shows Gaucher-like foam cells. MRI shows typical lesions in the putamen. Deficiency of beta-galactosidase in fibroblasts confirms the diagnosis. (C) 2004 Movement Disorder Society. C1 Natl Inst Mental Hlth & Neurosci, Dept Neurol, Bangalore 560029, Karnataka, India. Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India. NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. Natl Inst Mental Hlth & Neurosci, Dept Neuroradiol, Bangalore 560029, Karnataka, India. RP Muthane, U (reprint author), Natl Inst Mental Hlth & Neurosci, Dept Neurol, Hosur Rd, Bangalore 560029, Karnataka, India. EM umuthane@usa.net OI Kaneski, Christine/0000-0003-1453-2502 NR 20 TC 31 Z9 33 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2004 VL 19 IS 11 BP 1334 EP 1341 DI 10.1002/mds.20193 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 868WE UT WOS:000224943000012 PM 15389993 ER PT J AU Ponten, I AF Ponten, I TI Effect of structure and sequence on mutations induced by site-specific polycyclic aromatic hydrocarbon diol epoxide-DNA adducts SO MUTAGENESIS LA English DT Meeting Abstract C1 NCI Frederick, Chem Carcinogenesis Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2004 VL 19 IS 6 MA 3 BP 499 EP 500 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 873DA UT WOS:000225258300015 ER PT J AU Friesen, MD Kirk, GD Hainaut, P AF Friesen, MD Kirk, GD Hainaut, P TI Measurement of Ser-249 TP53 mutation in plasma DNA by short oligonucleotide mass analysis (SOMA): a mass spectrometric approach to mutation analysis SO MUTAGENESIS LA English DT Meeting Abstract C1 Int Agcy Res Canc, F-69372 Lyon, France. NCI, Rockville, MD USA. RI Kirk, Gregory/A-8484-2009; Friesen, Marlin/D-7328-2012; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2004 VL 19 IS 6 MA 6 BP 500 EP 500 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 873DA UT WOS:000225258300018 ER PT J AU Wainer, IW AF Wainer, IW TI Finding time for allosteric interactions SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID BINDING C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov NR 10 TC 5 Z9 5 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 NOV PY 2004 VL 22 IS 11 BP 1376 EP 1377 DI 10.1038/nbt1104-1376 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 869CL UT WOS:000224960600026 PM 15529160 ER PT J AU Simon, R AF Simon, Richard TI When is a genomic classifier ready for prime time? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 10 TC 14 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2004 VL 1 IS 1 BP 4 EP 5 DI 10.1038/ncponc0006 PG 2 WC Oncology SC Oncology GA V43JJ UT WOS:000202931100003 PM 16264774 ER PT J AU Churchill, G Airey, DC Allayee, H Angel, JM Attie, AD Beatty, J Beavis, WD Belknap, JK Bennett, B Berrettini, W Bleich, A Bogue, M Broman, KW Buck, KJ Buckler, E Burmeister, M Chesler, EJ Cheverud, JM Clapcote, S Cook, MN Cox, RD Crabbe, JC Crusio, WE Darvasi, A Deschnepper, CF Doerge, RW Farber, CR Forejt, J Gaile, D Garlow, SJ Geiger, H Gershenfeld, H Gordon, T Gu, J Gu, WK de Haan, G Hayes, NL Heller, C Himmelbauer, H Hitzemann, R Hunter, K Hsu, HC Iraqi, FA Ivandic, B Jacob, HJ Jansen, RC Jjepsen, KJ Johnson, DK Johnson, TE Kempermann, G Kendziorski, C Kotb, M Kooy, RF Llamas, B Lammert, F Lassalle, JM Lowenstein, PR Lu, L Lusiss, A Manly, KF Marcucio, R Matthews, D Medrano, JF Miller, DR Mittleman, G Mock, BA Mogil, JS Montagutelli, X Morahan, G Morris, DG Mott, R Nadeau, JH Nagase, H Nowakowski, RS O'Hara, BF Osadchuk, AV Page, GP Paigen, B Paigen, K Palmer, AA Pan, HJ Peltonen-Palotie, L Peirce, J Pomp, D Pravenec, M Prows, DR Qi, ZH Reeves, RH Roder, J Rosen, GD Schadt, EE Schalkwyk, LC Seltzer, Z Shimomura, K Shou, SM Sillanpaa, MJ Siracusa, LD Snoeck, HW Spearow, JL Svenson, K Tarantino, LM Threadgill, D Toth, LA Valdar, W de Villena, FPM Warden, C Whatley, S Williams, RW Wiltshire, T Yi, NJ Zhang, DB Zhang, M Zou, F AF Churchill, G Airey, DC Allayee, H Angel, JM Attie, AD Beatty, J Beavis, WD Belknap, JK Bennett, B Berrettini, W Bleich, A Bogue, M Broman, KW Buck, KJ Buckler, E Burmeister, M Chesler, EJ Cheverud, JM Clapcote, S Cook, MN Cox, RD Crabbe, JC Crusio, WE Darvasi, A Deschnepper, CF Doerge, RW Farber, CR Forejt, J Gaile, D Garlow, SJ Geiger, H Gershenfeld, H Gordon, T Gu, J Gu, WK de Haan, G Hayes, NL Heller, C Himmelbauer, H Hitzemann, R Hunter, K Hsu, HC Iraqi, FA Ivandic, B Jacob, HJ Jansen, RC Jjepsen, KJ Johnson, DK Johnson, TE Kempermann, G Kendziorski, C Kotb, M Kooy, RF Llamas, B Lammert, F Lassalle, JM Lowenstein, PR Lu, L Lusiss, A Manly, KF Marcucio, R Matthews, D Medrano, JF Miller, DR Mittleman, G Mock, BA Mogil, JS Montagutelli, X Morahan, G Morris, DG Mott, R Nadeau, JH Nagase, H Nowakowski, RS O'Hara, BF Osadchuk, AV Page, GP Paigen, B Paigen, K Palmer, AA Pan, HJ Peltonen-Palotie, L Peirce, J Pomp, D Pravenec, M Prows, DR Qi, ZH Reeves, RH Roder, J Rosen, GD Schadt, EE Schalkwyk, LC Seltzer, Z Shimomura, K Shou, SM Sillanpaa, MJ Siracusa, LD Snoeck, HW Spearow, JL Svenson, K Tarantino, LM Threadgill, D Toth, LA Valdar, W de Villena, FPM Warden, C Whatley, S Williams, RW Wiltshire, T Yi, NJ Zhang, DB Zhang, M Zou, F CA Complex Trait Consortium TI The Collaborative Cross, a community resource for the genetic analysis of complex traits SO NATURE GENETICS LA English DT Article ID ENVIRONMENT; STRAINS; MICE AB The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, Smithville, TX USA. Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Natl Ctr Genome Resources, Santa Fe, NM USA. Oregon Hlth Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Hannover Med Sch, Inst Lab Anim Sci & Cent Anim Facil, D-3000 Hannover, Germany. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. Vet Affairs Med Ctr, Dept Behav Neurosci, Portland, OR USA. Cornell Univ, Inst Genom Divers, Ithaca, NY USA. Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI USA. Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. QTL & Modifier Loci Grp, MRC Mammalian Genet Unit, Harwell, Oxon, England. Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA USA. Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Evolut Systemat & Ecol, IL-91905 Jerusalem, Israel. Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. ASCR, Inst Genet Mol, Videnska, Czech Republic. SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Biostat, Buffalo, NY 14260 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. Univ Cincinnati, Med Ctr, Div Expt Hematol, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45267 USA. Univ Texas SW, Dallas, TX USA. NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY USA. Univ Tennessee, Ctr Hlth Sci, Dept Orthopaed Surg Campbell Clin, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Ctr Genom & Bioinformat, Dept Pathol, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Ctr Dis Connect Tissues, Memphis, TN 38163 USA. Univ Groningen, Dept Stem Cell Biol, NL-9700 AB Groningen, Netherlands. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Stanford Univ, Stanford, CA 94305 USA. Max Planck Inst Mol Genet, Berlin, Germany. NIH, Bethesda, MD 20892 USA. Univ Alabama, Clin Immunol & Rheumatol, Birmingham, AL USA. Int Livestock Res Inst, Nairobi, Kenya. Univ Heidelberg, Dept Med 3, Heidelberg, Germany. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. Groningen Bioinformat Ctr, Inst Math & Comp Sci, Groningen, Netherlands. Mt Sinai Sch Med, Dept Orthopaed, New York, NY USA. Oak Ridge Natl Lab, Div Life Sci, Mammalian Genet Grp, Oak Ridge, TN USA. Charite Univ Med Berlin, Max Delbruck Ctr Mol Med, Dept Expt Neurol, Berlin, Germany. Univ Wisconsin, Med Sci Ctr, Dept Biostat & Med Informat, Madison, WI USA. Univ Tennessee, Ctr Hlth Sci, Dept Surg, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. Univ Aachen, Univ Hosp Aachen, Dept Med 3, Aachen, Germany. Univ Toulouse 3, Ctr Rech Cognit Anim, F-31062 Toulouse, France. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Gene Therapeut Res Inst, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept MIMG, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Orthopaed Surg, San Francisco, CA USA. NCI, CCR, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Psychol, Montreal, PQ, Canada. McGill Univ, Ctr Res Pain, Montreal, PQ, Canada. Inst Pasteur, Unite Genet Mammiferes, Paris, France. Western Australian Inst Med Res, Ctr Diabet Res, Perth, WA, Australia. Yale Univ, Sch Med Pulm & Crit Care Med, New Haven, CT USA. Wellcome Trust Ctr Human Genet, Oxford, England. Case Western Reserve Univ, Cleveland, OH 44106 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Kentucky, Lexington, KY USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. Columbia Genome Ctr, New York, NY USA. Univ Helsinki, Dept Med Genet, Natl Publ Hlth Inst, Biomedicum Helsinki,Dept Mol Med, FIN-00014 Helsinki, Finland. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Nebraska, Dept Anim Sci, Lincoln, NE USA. Acad Sci Czech Republ, Inst Physiol, Prague, Czech Republic. Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. McKusick Nathans Inst Genet Med, Baltimore, MD USA. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Rosetta Inpharmat LLC Merck & Co, Res Genet, Seattle, WA USA. Inst Psychiat, SGDP Ctr, London, England. Univ Toronto, Ctr Study Pain, Pain Genet & Phenom Res Unit, Toronto, ON, Canada. Program Neurosci, Toronto, ON, Canada. Northwestern Univ, Ctr Funct Genom, Evanston, IL USA. Shriners Hosp Crippled Children, Res Ctr, Portland, OR USA. Univ Helsinki, Rolf Nevanlinna Inst, Dept Math & Stat, FIN-00014 Helsinki, Finland. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Mt Sinai Sch Med, Dept Cell & Gene Med, New York, NY USA. Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. Novartis Res Fdn, Genom Inst, San Diego, CA USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. So Illinois Univ, Sch Med, Springfield, IL USA. KCL Inst Psychiat, Dept Neurosci, London, England. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Churchill, G (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM garyc@jax.org RI Threadgill, David/N-4425-2013; Deschepper, Christian/J-4783-2015; Crusio, Wim/A-7070-2008; Kooy, Frank/F-5276-2014; Kempermann, Gerd/F-5416-2010; Pravenec, Michal/B-1666-2012; Matthews, Douglas/F-6867-2012; Forejt, Jiri/G-7719-2012; Schalkwyk, Leonard/A-2150-2010; Burmeister, Margit/A-3157-2013; Jansen, Ritsert/C-1160-2013; Roder, John/G-6468-2013; Palmer, Abraham/L-2158-2014; de Haan, Gerald/D-2081-2015; Nowakowski, Richard/C-3217-2016 OI Williams, Robert/0000-0001-8924-4447; Threadgill, David/0000-0003-3538-1635; Deschepper, Christian/0000-0001-6234-4667; Rosen, Glenn/0000-0001-8281-5446; Nowakowski, Richard/0000-0002-5006-3670; Farber, Charles/0000-0002-6748-4711; Llamas, Bastien/0000-0002-5550-9176; Crusio, Wim/0000-0001-6638-202X; Kooy, Frank/0000-0003-2024-0485; Kempermann, Gerd/0000-0002-5304-4061; Forejt, Jiri/0000-0002-2793-3623; Schalkwyk, Leonard/0000-0001-7030-5756; Burmeister, Margit/0000-0002-1914-2434; Jansen, Ritsert/0000-0003-2977-9110; Palmer, Abraham/0000-0003-3634-0747; de Haan, Gerald/0000-0001-9706-0138; FU NIAAA NIH HHS [P60 AA010760] NR 16 TC 459 Z9 474 U1 3 U2 47 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 NOV PY 2004 VL 36 IS 11 BP 1133 EP 1137 DI 10.1038/ng1104-1133 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 867HI UT WOS:000224832800005 PM 15514660 ER PT J AU Proia, RL AF Proia, RL TI Gangliosides help stabilize the brain SO NATURE GENETICS LA English DT Editorial Material ID MICE; GM3; SENSITIVITY; EXHIBIT; NERVE AB Defects in the breakdown of gangliosides are associated with a class of disorders known as lysosomal storage diseases. Now, a defect in the synthesis of gangliosides, glycolipids that contain sialic acid and are abundant in the brain, has been shown to underlie an inherited form of epilepsy. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg 10,Room 9N-314,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 NR 15 TC 21 Z9 23 U1 1 U2 2 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 NOV PY 2004 VL 36 IS 11 BP 1147 EP 1148 DI 10.1038/ng1104-1147 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 867HI UT WOS:000224832800010 PM 15514666 ER PT J AU Noma, K Sugiyama, T Cam, H Verdel, A Zofall, M Jia, ST Moazed, D Grewal, SIS AF Noma, K Sugiyama, T Cam, H Verdel, A Zofall, M Jia, ST Moazed, D Grewal, SIS TI RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing SO NATURE GENETICS LA English DT Article ID FISSION YEAST CENTROMERES; HISTONE H3 METHYLATION; EPIGENETIC CONTROL; HETEROCHROMATIN DOMAIN; LYSINE-9 METHYLATION; DROSOPHILA; DNA; PLANTS; RECOGNITION; PATHWAYS AB RNA interference is a conserved mechanism by which double-stranded RNA is processed into short interfering RNAs (siRNAs) that can trigger both post-transcriptional and transcriptional gene silencing. In fission yeast, the RNA-induced initiation of transcriptional gene silencing (RITS) complex contains Dicer-generated siRNAs and is required for heterochromatic silencing. Here we show that BITS components, including Argonaute protein, bind to all known heterochromatic loci. At the mating-type region, BITS is recruited to the centromere-homologous repeat cenH in a Dicer-dependent manner, whereas the spreading of BITS across the entire 20-kb silenced domain, as well as its subsequent maintenance, requires heterochromatin machinery including Swi6 and occurs even in the absence of Dicer. Furthermore, our analyses suggest that RNA interference machinery operates in cis as a stable component of heterochromatic domains with BITS tethered to silenced loci by methylation of histone H3 at Lys9. This tethering promotes the processing of transcripts and generation of additional siRNAs for heterochromatin maintenance. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Grewal, SIS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov RI Verdel, Andre/M-5201-2013; OI Sugiyama, Tomoyasu/0000-0001-5704-6606 NR 35 TC 254 Z9 266 U1 0 U2 8 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 NOV PY 2004 VL 36 IS 11 BP 1174 EP 1180 DI 10.1038/ng1452 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 867HI UT WOS:000224832800020 PM 15475954 ER PT J AU Meetei, AR Levitus, M Xue, YT Medhurst, AL Zwaan, M Ling, C Rooimans, MA Bier, P Hoatlin, M Pals, G de Winter, JP Wang, WD Joenje, H AF Meetei, AR Levitus, M Xue, YT Medhurst, AL Zwaan, M Ling, C Rooimans, MA Bier, P Hoatlin, M Pals, G de Winter, JP Wang, WD Joenje, H TI X-linked inheritance of Fanconi anemia complementation group B SO NATURE GENETICS LA English DT Article ID CHROMOSOME INACTIVATION; NUCLEAR-COMPLEX; BRCA PATHWAY; GENE; MOUSE; FEMALE; COMMON; CELLS AB Fanconi anemia is an autosomal recessive syndrome characterized by diverse clinical symptoms, hypersensitivity to DNA crosslinking agents, chromosomal instability and susceptibility to cancer(1,2). Fanconi anemia has at least 11 complementation groups (A, B, C, D1, D2, E, F, G, I, J, L)(3,4); the genes mutated in 8 of these have been identified. The gene BRCA2 was suggested to underlie complementation group B, but the evidence is inconclusive(5). Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA(3,6,7). Unexpectedly, the gene encoding this protein, FANCB, is localized at Xp22.31 and subject to X-chromosome inactivation. X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B. Its presence as a single active copy and essentiality for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular machinery that maintains genomic integrity. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. VU Univ, Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands. VU Univ, Med Ctr, Dept Pediat & Hematol Oncol, NL-1007 MB Amsterdam, Netherlands. Oregon Hlth & Sci Univ, Div Mol Med & Mol Med Genet, Portland, OR 97239 USA. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,TRIAD Ctr Room 3000, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov; joenje@vumc.nl RI Pals, Gerard/A-5198-2011 NR 25 TC 177 Z9 190 U1 2 U2 10 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 NOV PY 2004 VL 36 IS 11 BP 1219 EP 1224 DI 10.1038/ng1458 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 867HI UT WOS:000224832800027 PM 15502827 ER PT J AU Collins, FS AF Collins, FS TI What we do and don't know about 'race', 'ethnicity', genetics and health at the dawn of the genome era SO NATURE GENETICS LA English DT Article AB A true understanding of disease risk requires a thorough examination of root causes. 'Race' and 'ethnicity' are poorly defined terms that serve as flawed surrogates for multiple environmental and genetic factors in disease causation, including ancestral geographic origins, socioeconomic status, education and access to health care. Research must move beyond these weak and imperfect proxy relationships to define the more proximate factors that influence health. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM fc23a@nih.gov NR 11 TC 120 Z9 121 U1 1 U2 7 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 NOV PY 2004 VL 36 IS 11 SU S BP S13 EP S15 DI 10.1034/ng1436 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 867PH UT WOS:000224854000005 PM 15507997 ER PT J AU Zhu, JF Min, B Hu-Li, J Watson, CJ Grinberg, A Wang, Q Killeen, N Urban, JF Guo, LY Paul, WE AF Zhu, JF Min, B Hu-Li, J Watson, CJ Grinberg, A Wang, Q Killeen, N Urban, JF Guo, LY Paul, WE TI Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses SO NATURE IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; CYTOKINE GENE-EXPRESSION; T-CELLS; IN-VIVO; TH2 DIFFERENTIATION; LINEAGE COMMITMENT; IL-4 PRODUCTION; ACTIVATED RAT; CUTTING EDGE; MICE AB Expression of the transcription factor GATA-3 is strongly associated with T helper type 2 (T(H)2) differentiation, but genetic evidence for its involvement in this process has been lacking. Here, we generated a conditional GATA-3-deficient mouse line. In vitro deletion of Gata3 diminished both interleukin 4 (IL-4)-dependent and IL-4-independent T(H)2 cell differentiation; without GATA-3, T(H)1 differentiation occurred in the absence of IL-12 and interferon-gamma. Gata3 deletion limited the growth of T(H)2 cells but not T(H)1 cells. Deletion of Gata3 from established T(H)2 cells abolished IL-5 and IL-13 but not IL-4 production. In vivo deletion of Gata3 using OX40-Cre eliminated T H 2 responses and allowed the development of interferon-gamma-producing cells in mice infected with Nippostrongylus brasiliensis. Thus, GATA-3 serves as a principal switch in determining T(H)1-T(H)2 responses. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. USDA, Nutrient Requirements & Funct Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jfzhu@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012; OI Urban, Joseph/0000-0002-1590-8869 NR 48 TC 336 Z9 354 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2004 VL 5 IS 11 BP 1157 EP 1165 DI 10.1038/ni1128 PG 9 WC Immunology SC Immunology GA 865HG UT WOS:000224692700013 PM 15475959 ER PT J AU Wellems, TE AF Wellems, TE TI Transporter of a malaria catastrophe SO NATURE MEDICINE LA English DT Editorial Material ID TRANSMEMBRANE PROTEIN PFCRT; PLASMODIUM-FALCIPARUM; CHLOROQUINE-RESISTANCE; MUTATIONS; EFFLUX AB Amantadine, a proton-channel blocker used to treat influenza, also inhibits growth of the malaria parasite Plasmodium falciparum. The drug is most active against parasite strains resistant to the increasingly ineffective drug chloroquine. The molecular basis of this enhanced activity is now examined, opening the door to new ways to attack chloroquine resistance. C1 NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tew@helix.nih.gov NR 13 TC 21 Z9 21 U1 0 U2 1 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 NOV PY 2004 VL 10 IS 11 BP 1169 EP 1171 DI 10.1038/nm1104-1169 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 866PR UT WOS:000224785900025 PM 15516913 ER PT J AU Beauchamp, MS Argall, BD Bodurka, J Duyn, JH Martin, A AF Beauchamp, MS Argall, BD Bodurka, J Duyn, JH Martin, A TI Unraveling multisensory integration: patchy organization within human STS multisensory cortex SO NATURE NEUROSCIENCE LA English DT Article ID SUPERIOR TEMPORAL SULCUS; OCULAR DOMINANCE; MACAQUE MONKEY; RHESUS-MONKEY; HUMAN BRAIN; PROJECTIONS; OBJECTS; SIGNAL; TRACER; SPEECH AB Although early sensory cortex is organized along dimensions encoded by receptor organs, little is known about the organization of higher areas in which different modalities are integrated. We investigated multisensory integration in human superior temporal sulcus using recent advances in parallel imaging to perform functional magnetic resonance imaging (fMRI) at very high resolution. These studies suggest a functional architecture in which information from different modalities is brought into close proximity via a patchy distribution of inputs, followed by integration in the intervening cortex. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NINDS, Sect Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Beauchamp, MS (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM mbeauchamp@nih.gov RI Duyn, Jozef/F-2483-2010; Argall, Brenna/G-2543-2011; martin, alex/B-6176-2009; OI Beauchamp, Michael/0000-0002-7599-9934 NR 15 TC 277 Z9 277 U1 4 U2 30 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 NOV PY 2004 VL 7 IS 11 BP 1190 EP 1192 DI 10.1038/nn1333 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 866CB UT WOS:000224749400010 PM 15475952 ER PT J AU Amedi, A Floel, A Knecht, S Zohary, E Cohen, LG AF Amedi, A Floel, A Knecht, S Zohary, E Cohen, LG TI Transcranial magnetic stimulation of the occipital pole interferes with verbal processing in blind subjects SO NATURE NEUROSCIENCE LA English DT Article ID INFERIOR PREFRONTAL CORTEX; VISUAL-CORTEX; ACTIVATION; MEMORY; BRAIN; ORGANIZATION; CONNECTIONS; DEPRIVATION; CORTICES; PEOPLE AB Recent neuroimaging studies in blind persons show that the occipital cortex, including the primary visual cortex (V1), is active during language-related and verbal-memory tasks. No studies, however, have identified a causal link between early visual cortex activity and successful performance on such tasks. We show here that repetitive transcranial magnetic stimulation (rTMS) of the occipital pole reduces accuracy on a verb-generation task in blind subjects, but not in sighted controls. An analysis of error types revealed that the most common error produced by rTMS was semantic; phonological errors and interference with motor execution or articulation were rare. Thus, in blind persons, a transient 'virtual lesion' of the left occipital cortex interferes with high-level verbal processing. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Dept Neurobiol, Inst Life Sci, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, IL-91904 Jerusalem, Israel. Univ Munster, D-48148 Munster, Germany. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. EM udiz@lobster.ls.huji.ac.il; cohenl@ninds.nih.gov RI Floel, Agnes/A-9426-2017; OI Knecht, Stefan/0000-0003-1056-9228 NR 35 TC 131 Z9 132 U1 2 U2 10 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 NOV PY 2004 VL 7 IS 11 BP 1266 EP 1270 DI 10.1038/nn1328 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 866CB UT WOS:000224749400020 PM 15467719 ER PT J AU Rastogi, T Hildesheim, A Sinha, R AF Rastogi, T Hildesheim, A Sinha, R TI Opportunities for cancer epidemiology in developing countries SO NATURE REVIEWS CANCER LA English DT Article ID INDOOR AIR-POLLUTION; LUNG-CANCER; GASTRIC-CANCER; DRINKING-WATER; HEPATOCELLULAR-CARCINOMA; STOMACH-CANCER; HUMAN-PAPILLOMAVIRUS; PRIMARY PREVENTION; CERVICAL-CANCER; DIETARY FACTORS AB Most cancer epidemiology studies involve people living in North America and Europe, which represent only a fraction of the global population. The wide variety of dietary, lifestyle and environmental exposures, as well as the genetic variation among people in developing countries can provide valuable new information on factors that contribute to cancer or that protect against it. What are the challenges and advantages to performing large epidemiological studies in developing nations? C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Rockville, MD 20852 USA. EM sinhar@nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 60 TC 71 Z9 74 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2004 VL 4 IS 11 BP 909 EP 917 DI 10.1038/nrc1475 PG 9 WC Oncology SC Oncology GA 867AY UT WOS:000224815700017 PM 15516963 ER PT J AU Goldrosen, MH Straus, SE AF Goldrosen, MH Straus, SE TI Complementary and alternative medicine: assessing the evidence for immunological benefits SO NATURE REVIEWS IMMUNOLOGY LA English DT Editorial Material ID ST-JOHNS-WORT; RANDOMIZED CONTROLLED-TRIAL; VITAMIN-A SUPPLEMENTATION; POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; WILFORDII HOOK-F; HUMAN LACTOBACILLUS STRAIN; FISH-OIL; IMMUNE FUNCTION; CYTOKINE PRODUCTION AB With words such as AIDS, allergy and autoimmunity embedded in the popular lexicon, we often equate health with the precision and the tenor of responses to allergens and microorganisms. This leads many people to seek their own solutions to sustain, restore or even boost their immune competence, hoping to live more comfortably and longer. Here, we consider the social and clinical contexts in which these promises of enhanced immunity are pursued through popular practices known as complementary and alternative medicine and the evidence that supports these. C1 NIH, Natl Ctr Complementary & Alternat Med, Off Director, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Off Sci Review, Bethesda, MD 20817 USA. RP Straus, SE (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Off Director, Bldg 31,Room 2B11,31 Ctr Dr, Bethesda, MD 20892 USA. EM strauss@nccam.nih.gov NR 112 TC 21 Z9 22 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2004 VL 4 IS 11 BP 912 EP 921 DI 10.1038/nri1486 PG 10 WC Immunology SC Immunology GA 867BQ UT WOS:000224817500016 PM 15516970 ER PT J AU Rein, A AF Rein, A TI Take two SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID MURINE LEUKEMIA-VIRUS; RNA DIMERIZATION; MESSENGER-RNA; GENOMIC RNA; ENCAPSIDATION; SIGNAL; IDENTIFICATION; MOLECULES; VIRIONS; REGION AB Retrovirus particles contain a dimeric form of their genomic RNA. A recent study suggests a mechanism that might underlie the selective incorporation of dimeric RNAs into assembling virus particles. C1 NCI Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Rein, A (reprint author), NCI Frederick, HIV Drug Resistance Program, POB B,1050 Boyle St,Bldg 535,Room 211, Frederick, MD 21702 USA. EM rein@ncifcrf.go NR 18 TC 9 Z9 9 U1 0 U2 0 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 NOV PY 2004 VL 11 IS 11 BP 1034 EP 1035 DI 10.1038/nsmb1104-1034 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 867MV UT WOS:000224847600006 PM 15523477 ER PT J AU Kouzine, F Liu, JH Sanford, S Chung, HJ Levens, D AF Kouzine, F Liu, JH Sanford, S Chung, HJ Levens, D TI The dynamic response of upstream DNA to transcription-generated torsional stress SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; C-MYC GENE; RNA-POLYMERASE; INDIVIDUAL NUCLEOSOMES; ESCHERICHIA-COLI; HUMAN GENOME; IN-VITRO; CHROMATIN; PROMOTERS; PROTEIN AB The torsional stress caused by counter-rotation of the transcription machinery and template generates supercoils in a closed topological domain, but has been presumed to be too short-lived to be significant in an open domain. This report shows that transcribing RNA polymerases dynamically sustain sufficient torsion to perturb DNA structure even on linear templates. Assays to capture and measure transcriptionally generated torque and to trap short-lived perturbations in DNA structure and conformation showed that the transient forces upstream of active promoters are large enough to drive the supercoil-sensitive far upstream element (FUSE) of the human c-myc into single-stranded DNA. An alternative non-B conformation of FUSE found in stably supercoiled DNA is not accessible dynamically. These results demonstrate that dynamic disturbance of DNA structure provides a real-time measure of ongoing genetic activity. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 46 TC 75 Z9 77 U1 0 U2 9 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 NOV PY 2004 VL 11 IS 11 BP 1092 EP 1100 DI 10.1038/nsmb848 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 867MV UT WOS:000224847600019 PM 15502847 ER PT J AU Krestel, HE Mihaljevic, ALA Hoffman, DA Schneider, A AF Krestel, HE Mihaljevic, ALA Hoffman, DA Schneider, A TI Neuronal co-expression of EGFP and beta-galactosidase in mice causes neuropathology and premature death SO NEUROBIOLOGY OF DISEASE LA English DT Article DE cytoplasmic GFP and beta-gal; GCSF and minocycline; neurogenic paresis; protein aggregates; ubiquitin ID GREEN FLUORESCENT PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; MAMMALIAN-CELLS; IN-VIVO; EXPRESSION; GENE; TETRACYCLINE; LOCALIZATION; MUTATIONS; PROMOTER AB Dose-dependent co-expression of enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-gal) in the cytoplasm of forebrain neurons of two independent mouse lines resulted in growth retardation, weakness, and premature lethality. In primary motor cortex and striatum, apoptosis, glial fibrillary acidic protein proliferation, and cell loss were found. In addition, we observed aggregations of EGFP and beta-gal that colocalized with ubiquitin. GFP is unlikely to be toxic per se, as a third mouse line that expressed twice as much GFP in the cytoplasm of forebrain neurons as the two affected lines was normal. Cytoplasmic aggregations of EGFP and beta-gal occurred in affected and phenotypically normal mice suggesting a storage function rather than being detrimental. We successfully prolonged survival of affected mice with granulocyte colony-stimulating factor (GCSF) and the antibiotic minocycline. These compounds could protect neurons from EGFP and beta-gal-induced dysfunction, as demise of mice started after treatment was discontinued. (C) 2004 Elsevier Inc. All rights reserved. C1 Max Planck Inst Med Res, Dept Mol Neurobiol, D-69120 Heidelberg, Germany. NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Axaron Biosci AG, D-69120 Heidelberg, Germany. RP Krestel, HE (reprint author), Max Planck Inst Med Res, Dept Mol Neurobiol, Jahnstr 29, D-69120 Heidelberg, Germany. EM krestel@mpimf-heidelberg.mpg.de RI Hoffman, Dax/E-5155-2011; OI Hoffman, Dax/0000-0001-6999-2157; Schneider, Armin/0000-0003-0296-0059 NR 30 TC 24 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2004 VL 17 IS 2 BP 310 EP 318 DI 10.1016/j.nbd.2004.05.012 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 866EV UT WOS:000224757500019 PM 15474368 ER PT J AU Murray, EA Wise, SP AF Murray, EA Wise, SP TI What, if anything, is the medial temporal lobe, and how can the amygdala be part of it if there is no such thing? SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Review DE recognition memory; discrimination learning; perirhinal cortex; hippocampus; basal ganglia; declarative memory ID AUDITORY SECONDARY REINFORCEMENT; IMPAIRED RECOGNITION MEMORY; RHINAL CORTEX ABLATIONS; MONKEYS MACACA-MULATTA; PERIRHINAL CORTEX; RHESUS-MONKEYS; VISUAL RECOGNITION; BASOLATERAL AMYGDALA; EXCITOTOXIC LESIONS; HIPPOCAMPAL-LESIONS AB yShould the medial temporal lobe (MTL) of primates-which includes allocortical structures such as the hippocampus, neocortical structures such as the parahippocampal cortex, and nuclear structures such as the basolateral amygdala-be considered a single "thing"? According to the prevailing view, here termed the reification theory, the answer is yes. According to this theory, the MTL functions as an amalgamated entity that provides the neuronal mechanisms for declarative memory; the greater the damage to the MTL or any of its components, the greater the deleterious effects on declarative memory. A countervailing view, here called the balkanization theory, holds that the various components of the MTL process and store different kinds of information. According to this theory, damage to each part of the MTL causes a unique set of behavioral deficits-some involving memory, others involving perception, and yet others involving response selection. The empirical neuropsychological evidence favors the balkanization theory, as do some new concepts in theoretical neuroanatomy. Published by Elsevier Inc. C1 NIMH, Lab Neuropsychol, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Lab Neuropsychol, Bldg 49,Room 1 B80,MSC 4415,49 Convent Dr, Bethesda, MD 20892 USA. EM eam@ln.nimh.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 110 TC 26 Z9 26 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD NOV PY 2004 VL 82 IS 3 BP 178 EP 198 DI 10.1016/j.nlm.2004.05.005 PG 21 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 863XH UT WOS:000224596300003 PM 15464403 ER PT J AU McDonald, RJ Devan, BD Hong, NS AF McDonald, RJ Devan, BD Hong, NS TI Multiple memory systems: The power of interactions SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Review DE interactions; memory; hippocampus; dorsal striaturn; amygdala; prefrontal cortex; nucleus accumbens; anxiety; depression; fear; obsessive-compulsive disorder; schizophrenia; drug addiction; drug abuse ID OBSESSIVE-COMPULSIVE DISORDER; CONDITIONED PLACE PREFERENCE; PRENATAL ETHANOL EXPOSURE; STRIATUM IMPAIR ACQUISITION; STIMULUS-RESPONSE HABIT; H-3 GLUTAMATE BINDING; DORSAL STRIATUM; WATER MAZE; HIPPOCAMPAL-FORMATION; CONTEXTUAL FEAR AB Two relatively simple theories of brain function will be used to demonstrate the explanatory power of multiple memory systems in your brain interacting cooperatively or competitively to directly or indirectly influence cognition and behaviour. The view put forth in this mini-review is that interactions between memory systems produce normal and abnormal manifestations of behaviour, and by logical extension, an understanding of these complex interactions holds the key to understanding debilitating brain and psychiatric disorders. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Lethbridge, Canadian Ctr Behav Neurosci, Dept Psychol & Neurosci, Lethbridge, AB T1K 3M4, Canada. NIA, Gerontol Res Ctr, Lab Expt Gerontol, Behav Neurosci Sect,NIH, Baltimore, MD USA. RP McDonald, RJ (reprint author), Univ Lethbridge, Canadian Ctr Behav Neurosci, Dept Psychol & Neurosci, Lethbridge, AB T1K 3M4, Canada. EM r.mcdonald@uleth.ca NR 113 TC 53 Z9 53 U1 4 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD NOV PY 2004 VL 82 IS 3 BP 333 EP 346 DI 10.1016/j.nlm.2004.05.009 PG 14 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 863XH UT WOS:000224596300014 PM 15464414 ER PT J AU Eldreth, DA Matochik, JA Cadet, JL Bolla, KI AF Eldreth, DA Matochik, JA Cadet, JL Bolla, KI TI Abnormal brain activity in prefrontal brain regions in abstinent marijuana users SO NEUROIMAGE LA English DT Article DE psychoactive substance use disorder; brain-imaging techniques; neuropathology; cognitive neuroscience ID ANTERIOR CINGULATE CORTEX; CANNABINOID RECEPTOR; INTOXICATION; PERFORMANCE; MEMORY; ACTIVATION; STUDENTS; ABUSERS AB We used PET 150 and a modified version of the Stroop task to determine if 25-day abstinent heavy marijuana (MJ) users have persistent deficits in executive cognitive functioning (ECF) and brain activity. Performance on a modified version of the Stroop task and brain activity was compared between 25-day abstinent, heavy marijuana users (n = 11), and a matched comparison group (n = 11). The 25-day abstinent marijuana users showed no deficits in performance on the modified version of the Stroop task when compared to the comparison group. Despite the lack of performance differences, the marijuana users showed hypoactivity in the left perigenual anterior cingulate cortex (ACC) and the left lateral prefrontal cortex (LPFC) and hyperactivity in the hippocampus bilaterally, when compared to the comparison group. These results suggest that marijuana users display persistent metabolic alterations in brain regions responsible for ECF. It may be that marijuana users recruit an alternative neural network as a compensatory mechanism during performance on a modified version of the Stroop task. These differences in brain activity may be a common denominator in the evolution of maladaptive behaviors such as substance abuse and other neuropsychiatric disorders. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. NIH, Neuroimaging Res Branch, DHHS, NIDA,Intramural Res Program, Baltimore, MD 21224 USA. NIH, Mol Neuropsychiat Branch, DHHS, NIDA,Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. RP Bolla, KI (reprint author), Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Neurol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM kbolla@jhmi.edu FU NCRR NIH HHS [M01 RR02719]; NIDA NIH HHS [DA 11426] NR 42 TC 139 Z9 146 U1 6 U2 17 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 NOV PY 2004 VL 23 IS 3 BP 914 EP 920 DI 10.1016/j.neuroimage.2004.07.032 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 873BP UT WOS:000225254100013 PM 15528091 ER PT J AU Han, X Pham, DL Tosun, D Rettmann, ME Xu, CY Prince, JL AF Han, X Pham, DL Tosun, D Rettmann, ME Xu, CY Prince, JL TI CRUISE: Cortical reconstruction using implicit surface evolution SO NEUROIMAGE LA English DT Article DE magnetic resonance; T1-weighted MR brain images; cerebral cortex; cortical reconstruction; human brain mapping ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; COORDINATE SYSTEM; HUMAN BRAIN; DEFORMABLE MODELS; SEGMENTATION; MRI; REGISTRATION; ALGORITHM; TOPOLOGY AB Segmentation and representation of the human cerebral cortex from magnetic resonance (MR) images play an important role in neuroscience and medicine. A successful segmentation method must be robust to various imaging artifacts and produce anatomically meaningful and consistent cortical representations. A method for the automatic reconstruction of the inner, central, and outer surfaces of the cerebral cortex from T1-weighted MR brain images is presented. The method combines a fuzzy tissue classification method, an efficient topology correction algorithm, and a topology-preserving geometric deformable surface model (TGDM). The algorithm is fast and numerically stable, and yields accurate brain surface reconstructions that are guaranteed to be topologically correct and free from self-intersections. Validation results on real MR data are presented to demonstrate the performance of the method. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. Siemens Corp Res, Imaging & Visualizat Dept, Princeton, NJ 08540 USA. RP Prince, JL (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. EM prince@jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 FU NINDS NIH HHS [R01NS37747] NR 74 TC 135 Z9 135 U1 4 U2 6 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 NOV PY 2004 VL 23 IS 3 BP 997 EP 1012 DI 10.1016/j.neuroimage.2004.06.043 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 873BP UT WOS:000225254100022 PM 15528100 ER PT J AU Birn, RM Cox, RW Bandettini, PA AF Birn, RM Cox, RW Bandettini, PA TI Experimental designs and processing strategies for fMRI studies involving overt verbal responses SO NEUROIMAGE LA English DT Article DE overt speech; motion; event-related paradigms ID EVENT-RELATED FMRI; CEREBRAL CORTICAL REPRESENTATION; INDEPENDENT COMPONENT ANALYSIS; FUNCTIONAL MRI; CORTEX; HUMANS; MOTION; POWER AB Event-related paradigms have been used increasingly in the past few years for the localization of function in tasks involving overt speech. These designs exploit the differences in the temporal characteristics between the rapid motion-induced and the slower hemodynamic signal changes. The optimization of these designs and the best way to analyze the acquired data has not yet been fully explored. The purpose of this study is to investigate various design and analysis strategies for maximizing the detection of function while minimizing task-induced motion artifacts. Both event-related and blocked paradigms can be specifically designed to meet these goals. Various event-related and blocked designs were compared both in simulation and in experiments involving overt word reading in their ability to detect function and to avoid speech-induced motion artifact. A blocked design with task and control durations of 10 s and an event-related design with a minimum stimulus duration (SD) of 5 s and an average interstimulus interval (ISI) of 10 s were found to optimally detect blood oxygenation leveldependent signal changes without significant motion artifact. Ignoring images acquired during the speech can help recover function in areas particularly affected by motion but substantially reduces the detection power in other regions. Using the stimulus timing as an additional regressor to model the motion offers little benefit in practice due to the variability of the motion-induced signal change. Published by Elsevier Inc. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Birn, RM (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr Bldg 10,Room 1D80, Bethesda, MD 20892 USA. EM rbim@nih.gov NR 29 TC 92 Z9 93 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2004 VL 23 IS 3 BP 1046 EP 1058 DI 10.1016/j.neuroimage.2004.07.039 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 873BP UT WOS:000225254100027 PM 15528105 ER PT J AU Chu, RN de Zwart, JA van Gelderen, P Fukunaga, M Kellman, P Holroyd, T Duyn, JH AF Chu, RN de Zwart, JA van Gelderen, P Fukunaga, M Kellman, P Holroyd, T Duyn, JH TI Hunting for neuronal currents: absence of rapid MRI signal changes during visual-evoked response SO NEUROIMAGE LA English DT Article DE neuronal currents; magnetoencephalography; human brain ID MAGNETIC-RESONANCE; FUNCTIONAL MRI; 1.5 T; BRAIN; CORTEX; BOLD; REPRESENTATION; STIMULATION; FIELDS; TESLA AB While recent reports have advocated the use of magnetic resonance imaging (MRI) to detect the effects of neuronal currents associated with human brain activity, only preliminary experimental data have been presented so far to demonstrate the feasibility of the method. Furthermore, it has not been adequately demonstrated that (1) MRI can separate neuronal current (NC) effects from other effects such as blood oxygen level-dependent (BOLD) contrast; (2) MRI has adequate sensitivity to detect NCs in vivo. In this work, we introduce a method that can separate slow (e.g., BOLD) processes from potential rapid (e.g., NC) processes and apply this method to investigate whether MRI allows detection of an NC response to a visual stimulus. MRI studies (n = 8) at 3.0 T using a sensitive multichannel detector showed insignificant effects related to NCs (averaged t < 0.05), in the presence of a highly significant BOLD signal Q = 6.15 +/- 0.90). In contrast, magnetoencephalography (MEG) experiments performed under similar conditions on the same subjects showed highly significant electrical activity Q = 7.90 +/- 2.28). It is concluded that, under the conditions used in this study, the sensitivity of MRI to detect evoked responses through NCs is at least an order of magnitude below that of BOLD-based functional MRI (fMRI) or MEG and too low to be practically useful. Published by Elsevier Inc. C1 NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NIMH, MEG Facil, NIH, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bldg 10,Room B1D-118,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 26 TC 52 Z9 54 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2004 VL 23 IS 3 BP 1059 EP 1067 DI 10.1016/j.neuroimage.2004.07.003 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 873BP UT WOS:000225254100028 PM 15528106 ER PT J AU Kernich, CA AF Kernich, CA TI Cognitive function in the elderly SO NEUROLOGIST LA English DT Article C1 Univ Hosp Hlth Syst, Fac Serv, Dept Med, Cleveland, OH USA. RP Kernich, CA (reprint author), Natl Inst Neurol Disorders & Stroke, POB 5801, Bethesda, MD 20824 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD NOV PY 2004 VL 10 IS 6 BP 347 EP 348 DI 10.1097/01.nrl.0000144289.39808.8f PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 871FD UT WOS:000225114300006 PM 15518601 ER PT J AU McDonald, RJ Hong, NS Devan, BD AF McDonald, RJ Hong, NS Devan, BD TI The challenges of understanding mammalian cognition and memory-based behaviours: an interactive learning and memory systems approach SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE multiple memory systems; hippocampus; amygdala; dorsal striatum; interactions; incidental learning; covert memory; spatial; context; fear; stimulus-response; habit ID CONDITIONED PLACE PREFERENCE; LONG-TERM POTENTIATION; CONFIGURAL ASSOCIATION THEORY; STIMULUS-REWARD ASSOCIATIONS; AMYGDALA CENTRAL NUCLEUS; HEAD DIRECTION CELLS; MORRIS WATER MAZE; HIPPOCAMPAL-FORMATION; RETROGRADE-AMNESIA; CONTEXTUAL FEAR AB Various research problems are presented to illustrate the utility of using the interactive multiple learning and memory systems view to better understand normal and abnormal manifestations of mammalian behaviour. Evidence for incidental learning and memory processes is presented and various implications of this work are discussed. Empirical and theoretical work directed at understanding the cognitive and non-cognitive processes associated with place learning in the water task and context conditioning during aversive events is also presented. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Lethbridge, Canadian Ctr Behav Neurosci, Dept Psychol & Neurosci, Lethbridge, AB T1K 3M4, Canada. Natl Inst Aging, Gerontol Res Ctr, Lab Expt Gerontol, Behav Neurosci Sect,NIH, Baltimore, MD USA. RP McDonald, RJ (reprint author), Univ Lethbridge, Canadian Ctr Behav Neurosci, Dept Psychol & Neurosci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM r.mcdonald@uleth.ca NR 167 TC 39 Z9 40 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD NOV PY 2004 VL 28 IS 7 BP 719 EP 745 DI 10.1016/j.neubiorev.2004.09.014 PG 27 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 876QF UT WOS:000225511500009 PM 15555681 ER PT J AU Talanov, VS Yordanov, AT Garmestani, K Milenic, DE Arora, HC Plascjak, PS Eckelman, WC Waldmann, TA Brechbiel, MW AF Talanov, VS Yordanov, AT Garmestani, K Milenic, DE Arora, HC Plascjak, PS Eckelman, WC Waldmann, TA Brechbiel, MW TI Preparation and in vivo evaluation of novel linkers for At-211 labeling of proteins SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE At-211; astatine; SAPS; radioimmunotherapy; monoclonal antibody; alpha particle ID INORGANIC ASTATINE CHEMISTRY; MONOCLONAL-ANTIBODY THERAPY; T-CELL LEUKEMIA; EMITTING RADIONUCLIDES; TISSUE DISTRIBUTION; ANTI-CD20 ANTIBODY; COMPLEX-FORMATION; BISMUTH TARGETS; N-SUCCINIMIDYL; RADIOIMMUNOTHERAPY AB The syntheses, radiolabeling, antibody conjugation and in vivo evaluation of new linkers for At-211 labeling of monoclonal antibodies are described. Syntheses of the N-succinimidyl esters and labeling with At-211 to form succinimidyl 4-methoxymethyl-3-[At-211]astatobenzoate (9) and succinimidyl 4-methylthiomethyl-3-[At-211]astatobenzoate (11) from the corresponding bromo-aryl esters is reported. Previously reported succinimidyl N-{4-[At-211]astatophenethyl}succinamate (SAPS) is employed as a standard of in vivo stability. Each agent is conjugated with Herceptin in parallel with their respective I-125 analogue, succinimidyl 4-methoxymethyl-3-[I-125]iodobenzoate (10), succinimidyl 4-methylthiomethyl-3-[ I-125]iodobetizoate (12) and succinimidyl N-{4-[I-125]iodophenethyl}succinamate (SIPS), respectively, for comparative assessment in LS-174T xenograft-bearing mice. With 9 and 11, inclusion of an electron pair donor in the ortho position does not appear to provide in vivo stability comparable to SAPS. Variables in radiolabeling chemistry of these three agents with At-211 are notable. Sequential elimination of acetic acid and oxidizing agent, N-chlorosuccininlide (NCS), from the At-211 radiolabeling protocol for forming SAPS improves yield, product purity and consistency. NCS appears to be critical for the radiolabeling of 6 with At-211. Formation of 11, however, is found to require the absence of NCS. Elimination of acetic acid is found to have no effect on radiolabeling efficiency or yield for either of these reactions. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM martinwb@mail.mh.gov NR 56 TC 13 Z9 14 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2004 VL 31 IS 8 BP 1061 EP 1071 DI 10.1016/j.nucmedbio.2004.08.005 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 888HZ UT WOS:000226366100010 PM 15607488 ER PT J AU Koviack, P AF Koviack, P TI A review of the effect of an accommodation program to support nurses with functional limitations SO NURSING ECONOMICS LA English DT Review AB The nursing shortage inspired a creative approach to fulfill staffing needs while supporting the recovery of injured or ill staff through the Medical and Reasonable Accommodation Program (MRAP). Facts supporting both the need and value of a program such as this include nurses being ranked sixth in the top ten professions at risk for back injury and employee recovery periods being shortened by return to work arrangements. Employees must request entry into the program, be evaluated for their functional restrictions, and complete an evaluation and orientation program prior to having their abilities matched with staffing needs listed in "The Accommodations Bank." Assignments range from non-clinical jobs such as data analysis and chart review to modified clinical assignments such as patient education and admission history taking. Benefits of MRAP to the organization include filling shift needs with regular staff hours instead of overtime or agency staff hours while benefits to the employee include the opportunity to remain productive instead of incurring sick or unpaid days. C1 NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. NPCS Med & Reasonable Accomodat Program, Bethesda, MD USA. RP Koviack, P (reprint author), NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. NR 7 TC 6 Z9 6 U1 0 U2 1 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD NOV-DEC PY 2004 VL 22 IS 6 BP 320 EP + PG 6 WC Nursing SC Nursing GA 046HC UT WOS:000237801200005 PM 15651590 ER PT J AU Vahratian, A Zhang, J Troendle, JF Savitz, DA Siega-Riz, AM AF Vahratian, A Zhang, J Troendle, JF Savitz, DA Siega-Riz, AM TI Maternal prepregnancy overweight and obesity and the pattern of labor progression in term nulliparous women SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LA SP Soc Maternal Fetal Med ID BODY-MASS INDEX; WEIGHT-GAIN RECOMMENDATIONS; PREGNANCY COMPLICATIONS; CESAREAN DELIVERY; HEIGHT; RISK; AGE; POPULATION; OUTCOMES AB OBJECTIVE: To examine the effect of maternal overweight and obesity on labor progression. METHODS: We analyzed data from 612 nulliparous women witha term pregnancy that participated in the Pregnancy, Infection, and Nutrition Study from 1995 to 2002. The median duration of labor by each centimeter of cervical dilation was computed for normal-weight (body mass index [BMI] 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI > 29.0 kg/m(2)) women and used as a measurement of labor progression. RESULTS: After adjusting for maternal height, labor induction, membrane rupture, oxytocin use, epidural analgesia, net maternal weight gain, and fetal size, the median duration of labor from 4 to 10 cm was significantly longer for both overweight and obese women, compared with normal-weight women (7.5, 7.9, and 6.2 hours, respectively). For overweight women, the prolongation was concentrated around 4-6 cm, whereas for obese women, their labor was significantly slower before 7 cm. CONCLUSION: Labor progression in overweight and obese women was significantly slower than that of normal-weight women before 6 cm of cervical dilation. Given that nearly one half of women of childbearing age are either overweight or obese, it is critical to consider differences in labor progression by maternal prepregnancy BMI before additional interventions are performed. (C) 2004 by The American College of Obstetricians and Gynecologists. C1 Univ N Carolina, Sch Publ Hlth, Dept Maternal & Child Hlth, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Nutr, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD USA. RP Vahratian, A (reprint author), Univ Michigan, Dept Obstet & Gynecol, L4000 Womens Hosp, 1500 E Med Ctr Dr, Ann Arbor, MI 48108 USA. EM amv@med.umich.edu RI Vahratian, Anjel/A-1182-2011 FU NCRR NIH HHS [RR00046]; NICHD NIH HHS [HD05798, HD28684, HD37584]; PHS HHS [S0807-18/20, S455-16/17] NR 27 TC 128 Z9 135 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2004 VL 104 IS 5 BP 943 EP 951 DI 10.1097/01.AOG.0000142713.53197.91 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 875JH UT WOS:000225415900010 PM 15516383 ER PT J AU Massad, LS Evans, CT Minkoff, H Watts, DH Strickler, HD Darragh, T Levine, A Anastos, K Moxley, M Passaro, DJ AF Massad, LS Evans, CT Minkoff, H Watts, DH Strickler, HD Darragh, T Levine, A Anastos, K Moxley, M Passaro, DJ TI Natural history of grade 1 cervical intraepithelial neoplasia in women with human immunodeficiency virus SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; LOOP ELECTROSURGICAL EXCISION; INTERAGENCY HIV; POSITIVE WOMEN; RISK-FACTORS; PREVALENCE; DISEASE; HPV; REGRESSION AB OBJECTIVE: We sought to estimate rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN 1) among women with human immunodeficiency virus (HIV). METHODS: In a multicenter prospective cohort study, HIV-seropositive and HIV-seronegative women were evaluated colposcopically after receiving an abnormal cytology test result between November 1994 and September 2002. Women with CIN 1 were included, except those who had undergone hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women who were included were followed cytologically twice yearly, with colposcopy repeated for atypia or worse. RESULTS: We followed 223 women with CIN 1 (202 HIV seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years; 95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person-years, 95% CI 10 16/100 person-years) versus 14 (67%) seronegative women (32/100 person-years, relative risk 0.40, 95% CI 0.25-0.66; P <.001). In multivariate analysis, regression was associated with human papillomavirus (HPV) detection (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P =.001; and for high-risk 0.34, 95% CI 0.20-0.55, P <.001 versus no HPV detected) and Hispanic ethnicity (HR 0.48, 95% CI 0.230.98; P =.04); HIV serostatus was only marginally linked to regression (HR 0.52, 95% CI 0.27-1.03; P =.06), but seropositive women were less likely to regress when analysis was limited to 146 women with HPV detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P =.006). CONCLUSION: Grade I cervical intraepithelial neoplasia infrequently progresses in women with HIV. Thus, observation appears safe absent other indications for treatment. (C) 2004 by The American College of Obstetricians and Gynecologists. C1 So Illinois Univ, Dept Obstet & Gynecol, Sch Med, Springfield, IL 62794 USA. Univ Illinois, Chicago, IL 60680 USA. SUNY, Maimonides Med Ctr, Brooklyn, NY 11219 USA. NICHHD, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Georgetown Univ, Washington, DC 20057 USA. RP Massad, LS (reprint author), So Illinois Univ, Dept Obstet & Gynecol, Sch Med, POB 19640, Springfield, IL 62794 USA. EM LSMASSAD@ameritech.net FU NCI NIH HHS [CA85178-01]; NCRR NIH HHS [M-01-RR-00083, M01-RR-00079]; NIAID NIH HHS [U01-AI-34993, U01-AI-42590, U01-AI-35004, U01-AI-31834, U01-AI-34994]; NICHD NIH HHS [U01-HD-32632] NR 30 TC 20 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2004 VL 104 IS 5 BP 1077 EP 1085 DI 10.1097/01.AOG.0000143256.63961.c0 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 875JH UT WOS:000225415900031 PM 15516404 ER PT J AU Trimble, EL Schoenfeldt, M AF Trimble, EL Schoenfeldt, M TI Clinical Trials Referral Resource SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Trimble, EL (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2004 VL 18 IS 13 BP 1642 EP 1642 PG 1 WC Oncology SC Oncology GA 052DX UT WOS:000238212700012 PM 15648296 ER PT J AU Gaston-Johansson, F Lachica, EM Fall-Dickson, JM Kennedy, MJ AF Gaston-Johansson, F Lachica, EM Fall-Dickson, JM Kennedy, MJ TI Psychological distress, fatigue, burden of care, and quality of life in primary caregivers of patients with breast cancer undergoing autologous bone marrow transplantation SO ONCOLOGY NURSING FORUM LA English DT Article ID FAMILY CAREGIVERS; CHRONIC ILLNESS; SUPPORT; INDEX; NEEDS; DEPRESSION; OUTCOMES; HEALTH; IMPACT AB Purpose/Objectives: To determine the effects of sociodemographic variables, psychological distress, fatigue, and quality of-life (QOL) on burden of care in primary caregivers of patients with breast cancer undergoing autologous bone marrow transplantation (BMT). Design: Descriptive, correlational, predictive. Setting: Urban National Cancer Institute-designated comprehensive cancer center in the eastern United States. Sample: Convenience sample of 102 primary caregivers. Methods: Participants completed the sociodemographic data form, Piper Fatigue Scale; Beck Depression Inventory, State-Trait Anxiety Inventory, QOL Index, and Measurement of Objective and Subjective Burden Scales prior to BMT during an oncology clinic visit. Main Research Variables: Depression, anxiety, fatigue, QOL, and burden of care. Findings: Mean fatigue scores were low. Primary caregivers experienced moderate state anxiety and low trait anxiety. Some experienced severe depression. The objective burden of care mean score was slightly higher than the subjective mean score. Mean QOL scores were low. All variables were significantly intercorrelated, except subjective sensory fatigue. Significant correlations were found and temporal and between age and subjective burden, and income with fatigue temporal subscale, and state and trait anxiety. Family subscale of QOL was a significant predictor of objective burden. Age and trait anxiety were significant predictors of subjective burden. Conclusions: Primary caregivers of patients With breast cancer scheduled for BMT experience fatigued anxiety, burden of care, and low QOL. These caregivers may have tried to meet their needs and the patients' needs simultaneously. Implications for Nursing: Health-care providers need to proactively assess primary caregivers of patients for fatigue, psychological distress, burden of care, and decreased QOL and provide nursing interventions tailored to individual needs. C1 Johns Hopkins Univ, Sch Nursing, Int Program, Baltimore, MD 21218 USA. NINR, Lab Symptom Management, NIH, Bethesda, MD 20892 USA. Trinity Coll Dublin, Sch Med, Dept Hematol Oncol, Dublin, Ireland. St James Hosp, Dublin 8, Ireland. RP Gaston-Johansson, F (reprint author), Johns Hopkins Univ, Sch Nursing, Int Program, Baltimore, MD 21218 USA. EM fannie@son.jhmi.edu NR 53 TC 51 Z9 52 U1 0 U2 3 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2004 VL 31 IS 6 BP 1161 EP 1169 DI 10.1188/04.ONF.1161-1169 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 875RQ UT WOS:000225439800015 PM 15547639 ER PT J AU Lim, WK Mathur, R Koh, A Yeoh, R Chee, SP AF Lim, WK Mathur, R Koh, A Yeoh, R Chee, SP TI Ocular manifestations of dengue fever SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Retina Club Meeting CY OCT 10, 2003 CL Will Eye Hosp, Philadelphia, PA HO Will Eye Hosp ID INTERNATIONAL TRAVELERS; HEMORRHAGIC-FEVER; INFECTION; VIRUS AB Purpose: To evaluate ocular manifestations associated with dengue fever. Design: Retrospective case series and literature review. Methods: Clinical records of patients with dengue fever who subsequently had ocular symptoms and signs develop were reviewed. The clinical presentation and ocular complications were evaluated. Results: Six patients, 5 females and 1 male, were seen with a sudden decrease in vision 6 to 7 days after the initial manifestations of dengue fever were identified. The diagnosis was confirmed by detection of denguespecific IgM antibodies (IgM enzyme-linked immunoassay). The presenting best-corrected visual acuity ranged from 20/30 to counting fingers, and ocular involvement was bilateral but asymmetric in 5 cases and unilateral in 1 case. Fundus findings included small, intraretinal, whitish lesions, with localized retinal and retinal pigment epithelium (RPE) disturbance, small dot hemorrhages, and vascular sheathing around the macula and the papillomacular bundle. Fluorescein angiography showed arteriolar focal knobby hyperfluorescence at the macula with mild staining of the vascular walls and leakage at the level of the RPE. All 5 cases that had indocyanine green angiography done showed early diffuse choroidal hyperfluorescence with late silhouetting of the larger choroidal vessels. Five patients received steroid therapy: 1 topical, 2 periocular, and 2 oral. Over 2 to 4 months, RPE discoloration was observed over the affected areas. After the acute episode, 3 patients showed partial recovery of vision, and in the remaining patients, the visual acuity remained stable. Conclusions: Ocular complications associated with dengue fever are rare but may result in permanent visual impairment. (C) 2004 by the American Academy of Ophthalmology. C1 Singapore Natl Eye Ctr, Singapore 168751, Singapore. Natl Univ Singapore, Singapore 117548, Singapore. NEI, NIH, Bethesda, MD 20892 USA. RP Chee, SP (reprint author), Singapore Natl Eye Ctr, 11,3rd Hosp Ave, Singapore 168751, Singapore. EM chee_soon_phaik@snec.com.sg NR 29 TC 53 Z9 57 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2004 VL 111 IS 11 BP 2057 EP 2064 DI 10.1016/j.ophtha.2004.03.038 PG 8 WC Ophthalmology SC Ophthalmology GA 866JZ UT WOS:000224771100013 PM 15522372 ER PT J AU Akpek, EK Chan, CC Shen, DF Green, WR AF Akpek, EK Chan, CC Shen, DF Green, WR TI Lack of herpes virus DNA in choroidal tissues of a patient with serpiginous choroiditis SO OPHTHALMOLOGY LA English DT Article ID INDOCYANINE GREEN ANGIOGRAPHY; SIMPLEX VIRUS; THYMIDINE KINASE; VIRAL-ANTIGEN; UVEITIS; LATENCY; IMMUNOSUPPRESSION; HERPESVIRUSES; CHOROIDOPATHY; CYCLOSPORINE AB Objective: To investigate the role of herpes viruses in the etiology of serpiginous choroiditis. Design: Interventional case report. Participant. A 59-year-old male patient with long-term history of serpiginous choroiditis. Intervention: The patient's affected eye was obtained during autopsy. Polymerase chain reaction was performed in the microdissected choroidal tissues. Results: Histopathologic examination demonstrated active inflammation with lymphocytic infiltration of the choroid. No viral DNA was amplified using pairs of herpes simplex virus (HSV) P1/P2 (for HSV-1, HSV-2, Epstein-Barr virus [EBV], cytomegalovirus [CMV] and human herpes virus [HHV]-8), and varicella-zoster virus [VZV] P1/P2 (for VZV, HHV-6, HHV-7) in the infiltrating lymphocytes or choroidal tissues. Conclusions: The current observation suggests a lack of a role for herpetic viral etiology in the etiopathogenesis of serpiginous choroiditis. (C) 2004 by the American Academy of Ophthalmology. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Akpek, EK (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Maumenee 317, Baltimore, MD 21287 USA. EM esakpek@jhmi.edu NR 31 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2004 VL 111 IS 11 BP 2071 EP 2075 DI 10.1016/j.ophtha.2004.03.034 PG 5 WC Ophthalmology SC Ophthalmology GA 866JZ UT WOS:000224771100015 PM 15522374 ER PT J AU Hebden, JC Guerrero, JJG Chernomordik, V Gandjbakhche, AH AF Hebden, JC Guerrero, JJG Chernomordik, V Gandjbakhche, AH TI Experimental evaluation of an anisotropic scattering model of a slab geometry SO OPTICS LETTERS LA English DT Article ID OPTICAL-PROPERTIES; PHOTON MIGRATION; CONTRAST FUNCTIONS; TRANSILLUMINATION; DIFFUSION; TISSUES AB A model has been developed based on random walk theory that allows the diffusion of light along a principal axis to differ from that in orthogonal directions. We present expressions that describe the time-resolved intensity measured across a slab and on the surface of a semi-infinite medium for a principal axis oriented parallel or perpendicular to the surface. The model of time-resolved transmittance is compared with experimental data acquired by use of a phantom consisting of wax fibers arranged within a solid cube of resin. It is shown that a single set of optical parameters is sufficient to model the experimental measurements acquired across all three orientations of the cube. (C) 2004 Optical Society of America. C1 UCL, Dept Med Phys & Bioengn, London WC1E 6JA, England. Univ Nacl Autonoma Mexico, Ctr Ciencias Aplicadas & Desarrollo Tecnol, Mexico City 04510, DF, Mexico. Inst Child Hlth & Human Dev, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Hebden, JC (reprint author), UCL, Dept Med Phys & Bioengn, 11-20 Capper St, London WC1E 6JA, England. EM jem@medphys.ucl.ac.uk NR 12 TC 19 Z9 19 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD NOV 1 PY 2004 VL 29 IS 21 BP 2518 EP 2520 DI 10.1364/OL.29.002518 PG 3 WC Optics SC Optics GA 863YR UT WOS:000224600000020 PM 15584280 ER PT J AU Curino, A Patel, V Nielsen, BS Iskander, AJ Ensley, JF Yoo, GH Holsinger, FC Myers, JN El-Nagaar, A Kellman, RM Shillitoe, EJ Molinolo, AA Gutkind, JS Bugge, TH AF Curino, A Patel, V Nielsen, BS Iskander, AJ Ensley, JF Yoo, GH Holsinger, FC Myers, JN El-Nagaar, A Kellman, RM Shillitoe, EJ Molinolo, AA Gutkind, JS Bugge, TH TI Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography SO ORAL ONCOLOGY LA English DT Article DE laser capture microdissection; oral cancer; plasminogen activator; plasminogen activator inhibitor; squamous cell carcinoma; urokinase; zymography ID SQUAMOUS-CELL CARCINOMA; CATHEPSIN-D; MATRIX METALLOPROTEINASE-2; PROGNOSTIC-SIGNIFICANCE; UROKINASE RECEPTOR; STROMAL CELLS; IN-VITRO; HEAD; NECK; EXPRESSION AB Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAl-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAl-1 complexes, and tPA-PAl-1 complexes in 11 tumors and adjacent nonmalignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAl-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 mug protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer. (C) 2004 Published by Elsevier Ltd. C1 NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Mol Carcinogenesis Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. Wayne State Univ, Dept Otolaryngol Head & Neck Surg, Univ Hlth Ctr 5E, Detroit, MI 48201 USA. Wayne State Univ, Dept Internal Med, Karmanos Canc Ctr, Univ Hlth Ctr 5E, Detroit, MI 48201 USA. Univ Texas, Dept Head & Neck Surg, MD Anderson Canc Ctr, Houston, TX 77030 USA. SUNY Syracuse, Coll Med, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 29 TC 15 Z9 15 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD NOV PY 2004 VL 40 IS 10 BP 1026 EP 1032 DI 10.1016/j.oraloncology.2004.05.011 PG 7 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 871QG UT WOS:000225147700009 PM 15509494 ER PT J AU Ohls, RK Ehrenkranz, RA Das, A Dusick, AM Yolton, K Romano, E Delaney-Black, V Papile, LA Simon, NP Steichen, JJ Lee, KG AF Ohls, RK Ehrenkranz, RA Das, A Dusick, AM Yolton, K Romano, E Delaney-Black, V Papile, LA Simon, NP Steichen, JJ Lee, KG CA Natl Institute Child Hlth Human Dev Neonatal Res Network TI Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron SO PEDIATRICS LA English DT Article DE erythropoietin; parenteral iron; neurodevelopment; preterm infant ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; TRANSFUSION REQUIREMENTS; PRETERM INFANTS; RAT-BRAIN; FOLLOW-UP; IN-VITRO; MULTICENTER; EXPRESSION; PREMATURITY; HEMORRHAGE AB Background. Clinical trials evaluating the use of erythropoietin (Epo) have demonstrated a limited reduction in transfusions; however, long-term developmental follow-up data are scarce. Objective. We compared anthropometric measurements, postdischarge events, need for transfusions, and developmental outcomes at 18 to 22 months' corrected age in extremely low birth weight (ELBW) infants treated with early Epo and supplemental iron therapy with that of placebo/control infants treated with supplemental iron alone. Methods. The National Institute of Child Health and Human Development Neonatal Research Network completed a randomized, controlled trial of early Epo and iron therapy in preterm infants less than or equal to1250 g. A total of 172 ELBW (less than or equal to1000-g birth weight) infants were enrolled ( 87 Epo and 85 placebo/control). Of the 72 Epo-treated and 70 placebo/control ELBW infants surviving to discharge, follow-up data ( growth, development, rehospitalization, transfusions) at 18 to 22 months' corrected age were collected on 51 of 72 Epo-treated infants (71%) and 51 of 70 placebo/controls (73%) by certified examiners masked to the treatment group. Statistical significance was determined using chi(2) analysis. Results. There were no significant differences between treatment groups in weight or length or in the percentage of infants weighing <10th percentile either at the time of discharge or at follow-up, and no difference was found in the mean head circumference between groups. A similar percentage of infants in each group was rehospitalized (38% Epo and 35% placebo/control) for similar reasons. There were no differences between groups with respect to the percentage of infants with Bayley-II Mental Developmental Index <70 (34% Epo and 36% placebo/control), blindness (0% Epo and 2% placebo/control), deafness or hearing loss requiring amplification ( 2% Epo and 2% placebo/control), moderate to severe cerebral palsy (16% Epo and 18% placebo/control) or the percentage of infants with any of the above-described neurodevelopmental impairments (42% Epo and 44% placebo/control). Conclusions. Treatment of ELBW infants with early Epo and iron does not significantly influence anthropometric measurements, need for rehospitalization, transfusions after discharge, or developmental outcome at 18 to 22 months' corrected age. C1 Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Indiana Univ, Dept Pediat, Indianapolis, IN 46204 USA. Univ Tennessee, Newborn Ctr, Memphis, TN USA. Wayne State Univ, Div Neonatol & Perinatal Med, Detroit, MI USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. Harvard Univ, Joint Program Neonatol, Boston, MA 02115 USA. NICHHD, Bethesda, MD 20892 USA. RP Ohls, RK (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA. EM rohls@unm.edu FU NCRR NIH HHS [M01 RR 00997, M01 RR 06022, M01 RR 08084, M01 RR02635, M01 RR 00750, M01 RR 02172, M01 RR 01032]; NICHD NIH HHS [U10 HD34167, U10 HD27853, U10 HD27871, U10 HD27856, U10 HD21385, U10 HD21415, U10 HD27881, U10 HD27851, U01 HD36790] NR 31 TC 62 Z9 68 U1 0 U2 1 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 NOV PY 2004 VL 114 IS 5 BP 1287 EP 1291 DI 10.1542/peds.2003-1129-L PG 5 WC Pediatrics SC Pediatrics GA 867KY UT WOS:000224842700014 PM 15520109 ER PT J AU Bornstein, MH Cote, LR AF Bornstein, MH Cote, LR TI ''Who is sitting across from me?" Immigrant mothers' knowledge of parenting and children's development SO PEDIATRICS LA English DT Article DE pediatrics; child-development knowledge; child health; child development; parenting; acculturation; immigration; parent education ID MATERNAL ATTITUDES; CARE; INFORMATION; COGNITIONS; EDUCATION; OUTCOMES; BELIEFS; INFANTS; IDEAS AB Objective. Although parents' knowledge about child development and child rearing is relevant to pediatric practice, very little is known about immigrant parents' knowledge. To fill this gap in research, this study investigated parenting knowledge in 2 groups of mothers who had immigrated to the United States. Design. Japanese and South American immigrant mothers of 2-year-olds completed a standardized survey of parenting knowledge and provided information about sociodemographic and infant health status. Their data were compared with European American mothers in the United States. Results. Immigrant mothers scored similar to70% on the evaluation of parenting knowledge, significantly lower than multigenerational US mothers. The majority of immigrant mothers did not know correct answers for 25% of the items, and their incorrect answers were mostly to questions about normative child development. Conclusions. Parents' knowledge is relevant to pediatricians' evaluations of the health and welfare of children as understood by their parents. Gaps in parenting knowledge have implications for clinical interactions with parents, child diagnosis, pediatric training, and parent education. C1 NICHHD, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge, Bethesda, MD 20892 USA. EM marc_bornstein@nih.gov NR 81 TC 21 Z9 21 U1 1 U2 6 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 NOV PY 2004 VL 114 IS 5 BP E557 EP E564 DI 10.1542/peds.2004-0713 PG 8 WC Pediatrics SC Pediatrics GA 867KY UT WOS:000224842700052 PM 15520089 ER PT J AU Chuman, Y Uren, A Cahill, J Regan, C Wolf, V Kay, BK Rubin, JS AF Chuman, Y Uren, A Cahill, J Regan, C Wolf, V Kay, BK Rubin, JS TI Identification of a peptide binding motif for secreted frizzled-related protein-1 SO PEPTIDES LA English DT Article DE sFRP-1; phage display; peptide motif; Wnt; DGR ID NECROSIS-FACTOR RECEPTOR; CELL GROWTH; OSTEOCLAST DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; COLORECTAL-CANCER; TISSUE INHIBITORS; WNT ANTAGONIST; DOMAIN; GENE; FAMILY AB Secreted Frizzled-related proteins (sFRPs) bind Wnts and modulate their activity. To identify putative sFRP-1 binding motifs, we screened an M 13 phage displayed combinatorial peptide library. A predominant motif, LN-VDGRW-L/V, was present in similar to70% of the phage that bound sFRP-1. Use of peptide/alkaline phosphatase chimeras and alanine scanning confirmed that the conserved motif was important for sFRP-1 recognition. The dissociation constant for a peptide/sFRP-1 complex was 3.9 muM. Additional analysis revealed that DGR was the core of the binding motif. Although Wnt proteins lack this sequence, other proteins possessing the DGR motif may function as novel binding partners for sFRP-1. Published by Elsevier Inc. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Rubin, JS (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM rubinj@helix.nih.gov NR 53 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2004 VL 25 IS 11 BP 1831 EP 1838 DI 10.1016/j.peptides.2004.07.010 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 868QX UT WOS:000224929200001 PM 15501513 ER PT J AU Calcagno, AM Fostel, JM Reyner, EL Sinaga, E Alston, JT Mattes, WB Siahaan, TJ Ware, JA AF Calcagno, AM Fostel, JM Reyner, EL Sinaga, E Alston, JT Mattes, WB Siahaan, TJ Ware, JA TI Effects of an E-cadherin-derived peptide on the gene expression of Caco-2 cells SO PHARMACEUTICAL RESEARCH LA English DT Article DE Caco-2 cells; E-cadherin; gene expression; HAV peptide; microarrays ID GROWTH-FACTOR-BETA; MICROVESSEL ENDOTHELIAL-CELLS; MOLECULAR-CLONING; PROTEIN; ADHESION; JUNCTION; SUPERFAMILY; MODULATION; BINDING; OVEREXPRESSION AB Purpose. The goal of this study was to determine the effects of exposure to an HAV peptide (Ac-SHAVSS-NH2) on the protein and gene expression in Caco-2 cells, a model for the intestinal mucosa. Methods. Caco-2 cells were incubated with either 100 or 500 muM of the hexapeptide then evaluated over a 48-h time period. Results. Cell detachment from the monolayer was seen only after 48 h of exposure to the peptide, with the greatest effects occurring with a peptide concentration of 500 muM. Total protein expression of E-cadherin showed a decrease of nearly 20% at the 24-h time point for each concentration examined, whereas no significant changes were detected at the other time points studied. Short term exposure to a 500 muM solution of Ac-SHAVSS-NH2 caused few changes in gene expression as determined by Affymetrix GeneChip(R) microarrays; however, longer exposure periods produced numerous changes in the treated cells. The variations in mRNA expression indicate that this HAV peptide has an effect in the E-cadherin signaling pathways. The greatest increases in mRNA expression were found in genes regulating excretion or degradation of the peptide. Conclusions. This work suggests that this HAV peptide produces effects that reach beyond modulation of adhesion. C1 Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA. Pharmacia Corp, Kalamazoo, MI 49007 USA. RP Calcagno, AM (reprint author), NCI, Bethesda, MD 20892 USA. EM calcagnoa@mail.nih.gov RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU NIBIB NIH HHS [EB 00226]; NIGMS NIH HHS [GM 08359] NR 39 TC 1 Z9 1 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD NOV PY 2004 VL 21 IS 11 BP 2085 EP 2094 DI 10.1023/B:PHAM.0000048201.00143.72 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 871MH UT WOS:000225137300017 PM 15587932 ER PT J AU Takebayashi, M Hayashi, T Su, TP AF Takebayashi, M Hayashi, T Su, TP TI A perspective on the new mechanism of antidepressants: Neuritogenesis through sigma-1 receptors SO PHARMACOPSYCHIATRY LA English DT Article ID SIGMA(1) RECEPTOR AGONIST; CENTRAL-NERVOUS-SYSTEM; GUINEA-PIG BRAIN; NEUROACTIVE STEROIDS; BINDING-SITES; RAT-BRAIN; BEHAVIORAL DESPAIR; MAJOR DEPRESSION; PROTEIN-KINASE; PC12 CELLS AB Sigma receptors were first described as one of the opiate receptor subtypes. Now it is well established that sigma receptors, existing as subtypes sigma-1 and sigma-2, are unique non-opioid receptors which are implicated in higher-ordered brain functions. Sigma-1 receptors have high to moderate affinities for (+)benzomorphans and also many psychotrophic drugs and neurosteroids. Sigma-1 receptor agonists and certain neurosteroids such as dehydroepiandrosterone sulfate (DHEA-S) have antidepressant-like effects in animal behavioral models of depression. The antidepressant-like effect induced by sigma-1 receptor agonists may involve intracellular Ca2+ mobilization such that sigma-1 receptor agonists modulate Ca2+ release from endoplasmic reticulum (ER) in a cytoskeletal protein-dependent manner. In addition, growth factor-induced neurite outgrowth is mediated through sigma-1 receptors, suggesting a role of antidepressants in neuroplasticity. Igmesine (JO1783), OPC-14523 and SA4503, have recently been developed as sigma-1 agonists and are found to have antidepressant-like activity perhaps with fewer side effects. This article reviews the new potential use of sigma-1 receptor ligands in the treatment of mood disorder. C1 DHHS, NIH, Cellular Pathobiol Unit, IRP,CNBR,NIDA, Baltimore, MD 21224 USA. Natl Hosp, Kure Med Ctr, Inst Clin Res, Kure 7370023, Japan. RP Su, TP (reprint author), DHHS, NIH, Cellular Pathobiol Unit, IRP,CNBR,NIDA, Triad Bldg,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM TSU@intra.nida.nih.gov RI Hayashi, Teruo/A-9690-2008 NR 62 TC 44 Z9 45 U1 1 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD NOV PY 2004 VL 37 SU 3 BP S208 EP S213 DI 10.1055/s-2004-832679 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 879QZ UT WOS:000225733600007 PM 15547787 ER PT J AU He, YY Chignell, CF Miller, DS Andley, UP Roberts, JE AF He, YY Chignell, CF Miller, DS Andley, UP Roberts, JE TI Phototoxicity in human lens epithelial cells promoted by St. John's Wort SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ULTRAVIOLET-RADIATION; HYPERICUM-PERFORATUM; OCULAR PHOTOTOXICITY; LIGHT; DAMAGE; CAROTENOIDS; INHIBITION; MEMBRANE; CATARACT; EXPOSURE AB St. John's Wort (SJW), an over-the-counter antidepressant, contains hypericin, which absorbs light in the UV and visible ranges and is phototoxic to skin. To determine if it also could be phototoxic to the eye, we exposed human lens epithelial cells to 0.1-10 muM hypericin and irradiated them with 4 J/cm(2) UV-A or 0.9 J/cm(2) visible light. Neither hypericin exposure alone nor light exposure alone reduced cell viability. In contrast, cells exposed to hypericin in combination with UV-A or visible light underwent necrosis and apoptosis. The ocular antioxidants lutein and N-acetyl cysteine did not prevent damage. Thus, ingested SJW is potentially phototoxic to the eye and could contribute to early cataractogenesis. Precautions should be taken to protect the eye from intense sunlight while taking SJW. C1 Fordham Univ, Dept Nat Sci, New York, NY 10023 USA. Natl Inst Environm Hlth Sci, Lab Chem & Pharmacol, Res Triangle Pk, NC USA. Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. RP Roberts, JE (reprint author), Fordham Univ, Dept Nat Sci, 113 W 60th St,Room 813, New York, NY 10023 USA. EM jroberts@fordha-m.edu NR 32 TC 11 Z9 11 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2004 VL 80 IS 3 BP 583 EP 586 DI 10.1562/0031-8655(2004)080<0583:PIHLEC>2.0.CO;2 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 890PX UT WOS:000226524400033 PM 15623347 ER PT J AU Gafner, S Lee, SK Cuendet, M Barthelemy, S Vergnes, L Labidalle, S Mehta, RG Boone, CW Pezzuto, JM AF Gafner, S Lee, SK Cuendet, M Barthelemy, S Vergnes, L Labidalle, S Mehta, RG Boone, CW Pezzuto, JM TI Biologic evaluation of curcumin and structural derivatives in cancer chemoprevention model systems SO PHYTOCHEMISTRY LA English DT Article DE curcumin; curcurnin derivatives; cancer chemoprevention; cyclooxygenase; ornithine decarboxylase; inducible nitric oxide synthase; gene expression ID NF-KAPPA-B; CYCLOOXYGENASE-2 EXPRESSION; IN-VITRO; ORNITHINE-DECARBOXYLASE; ANTIINFLAMMATORY DRUGS; EPITHELIAL-CELLS; GENE-EXPRESSION; PROSTAGLANDIN; CYTOTOXICITY; ACTIVATION AB Curcumin is a natural product widely used as a spice in food. It has been shown to inhibit cyclooxygenase (COX)-1 and -2 and to suppress lipopolysaccharide-induced COX-2 and NOS gene expression. In the present study, curcumin and 22 of its derivatives were evaluated for their chemopreventive potential. Based on COX-2 inhibition, curcumin (IC50 = 15.9 muM), 1,7-bis(3-fluoro-4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (19) (IC50 = 23.7 muM) and 2,6-bis(3-fluoro-4-hydroxybenzylidene)cyclohexanone (23) (IC50 = 5.5 muM) were found to be most potent. Tricyclic derivatives 2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone (10), 2,6-bis(4-hydroxy-3,5-dimethoxybenzylidene)cyclohexanone (13) and 2,5-bis(4-hydroxy-3,5-dimethoxybenzylidene)cyclopentanone (21) inhibited LPS-induced COX-2 and NOS gene expression in murine macrophages with potency equal to curcumin. RT-PCR experiments demonstrated suppression of COX-2 and NOS gene expression occurred at the transcriptional level. The most active compounds in the macrophage assays, 13 and 23, were also the most cytotoxic, however. Topical application of curcumin, 10, 13, 21, and 6, a methoxy derivative of curcumin, showed strong inhibition of 12-O-tetradecanoyl-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity in mouse skin. These data suggest that structural elements responsible for COX-1 and COX-2 inhibition do not correlate well with those responsible for inhibiting COX-2 and NOS gene expression, but elements capable of inhibiting COX-2 and NOS gene expression also contribute to inhibition of TPA-induced ODC activity. The most potent compounds in these assays, 10, 13 and 21, as well as curcumin, were further evaluated for inhibition of 7,12-dimethylbenz(a)anthracene (DMBA)-induced preneoplastic lesion formation in a mouse mammary organ culture model, and dose-dependent responses were observed. Most potent effects were at concentrations between 1 and 5 muM for 10, 13 and 21, and at 10 muM for curcumin. These data demonstrate the substitution pattern on the aromatic moiety is especially crucial for activity. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Illinois, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Coll Pharm, Chicago, IL 60612 USA. Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. Univ Toulouse, Fac Pharm, F-31062 Toulouse 04, France. Univ Illinois, Coll Med, Dept Surg Oncol, Chicago, IL 60612 USA. NCI, Chemoprevent Agent Dev Res Grp, DCP, Bethesda, MD 20892 USA. RP Pezzuto, JM (reprint author), Purdue Univ, Sch Pharm & Pharm Sci, Heine Pharm Bldg,575 Stadium Mall Dr, W Lafayette, IN 47907 USA. EM jpezzuto@purdue.edu FU NCI NIH HHS [P01 CA48112] NR 43 TC 89 Z9 93 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD NOV PY 2004 VL 65 IS 21 BP 2849 EP 2859 DI 10.1016/j.phytochem.2004.08.008 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 871RQ UT WOS:000225151400002 PM 15501252 ER PT J AU Romero, HM Berlett, BS Jensen, PJ Pell, EJ Tien, M AF Romero, HM Berlett, BS Jensen, PJ Pell, EJ Tien, M TI Investigations into the role of the plastidial peptide methionine sulfoxide reductase in response to oxidative stress in Arabidopsis SO PLANT PHYSIOLOGY LA English DT Article ID HEAT-SHOCK-PROTEIN; DAMAGE; CHLOROPLAST; RESIDUES; OZONE; GENE; BIOSYNTHESIS; PEROXIDASE; EXPRESSION; SUBUNITS AB Peptidyl Met residues are readily oxidized by reactive oxygen species to form Met sulfoxide. The enzyme peptide Met sulfoxide reductase (PMSR) catalyzes the reduction of Met sulfoxides back to Met. In doing so, PMSR is proposed to act as a last-chance antioxidant, repairing proteins damaged from oxidative stress. To assess the role of this enzyme in plants, we generated multiple transgenic lines with altered expression levels of the plastid form of PMSR (PMSR4). In transgenic plants, PMSR4 expression ranged from 95% to 40% (antisense) and more than 600% (overexpressing lines) of wild-type plants. Under optimal growing conditions, there is no effect of the transgene on the phenotype of the plants. When exposed to different oxidative stress conditions-methyl viologen, ozone, and high light-differences were observed in the rate of photosynthesis, the maximum quantum yield (F-v(l)/F-m ratio), and the Met sulfoxide content of the isolated chloroplast. Plants that overexpressed PMSR4 were more resistant to oxidative damage localized in the chloroplast, and plants that underexpressed PMSR4 were more susceptible. The Met sulfoxide levels in proteins of the soluble fraction of chloroplasts were increased by methyl viologen and ozone, but not by high-light treatment. Under stress conditions, the overexpression of PMSR4 lowered the sulfoxide content and underexpression resulted in an overall increase in content. C1 Penn State Univ, Intercoll Program Plant Physiol, University Pk, PA 16802 USA. Penn State Univ, Dept Biochem & Mol Biol, Dept Plant Pathol, University Pk, PA 16802 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Tien, M (reprint author), Penn State Univ, Intercoll Program Plant Physiol, University Pk, PA 16802 USA. EM mxt3@psu.edu NR 38 TC 93 Z9 101 U1 3 U2 10 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 EI 1532-2548 J9 PLANT PHYSIOL JI Plant Physiol. PD NOV PY 2004 VL 136 IS 3 BP 3784 EP 3794 DI 10.1104/pp.104.046656 PG 11 WC Plant Sciences SC Plant Sciences GA 873XU UT WOS:000225315600037 PM 15516509 ER PT J AU Kiley, PJ Storz, G AF Kiley, PJ Storz, G TI Exploiting thiol modifications SO PLOS BIOLOGY LA English DT Editorial Material ID OXYR TRANSCRIPTION FACTOR; DISULFIDE BOND FORMATION; ANTI-SIGMA FACTOR; STREPTOMYCES-COELICOLOR; ESCHERICHIA-COLI; SULFINIC ACID; REDOX; ACTIVATION; STRESS; ZINC C1 Univ Wisconsin, Sch Med, Dept Biomol Chem, Madison, WI 53706 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Kiley, PJ (reprint author), Univ Wisconsin, Sch Med, Dept Biomol Chem, Madison, WI 53706 USA. EM pjkiley@wiscmail.wisc.edu OI Storz, Gisela/0000-0001-6698-1241 NR 28 TC 48 Z9 49 U1 1 U2 9 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 NOV PY 2004 VL 2 IS 11 BP 1714 EP 1717 AR e400 DI 10.1371/journal.pbio.0020400 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 871UT UT WOS:000225160300003 PM 15547642 ER PT J AU Cookson, MR AF Cookson, MR TI Molecules that cause or prevent Parkinson's disease SO PLOS BIOLOGY LA English DT Editorial Material ID MUTANT ALPHA-SYNUCLEIN; PROTEIN; DJ-1; MUTATIONS; NEUROTOXICITY; DEGRADATION; MECHANISMS; DOPAMINE; CDCREL-1; DEATH C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM Cookson@mail.nih.gov NR 23 TC 4 Z9 4 U1 0 U2 0 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 NOV PY 2004 VL 2 IS 11 BP 1717 EP 1720 AR e401 DI 10.1371/journal.pbio.0020401 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 871UT UT WOS:000225160300004 PM 15547643 ER PT J AU Rountree, RB Schoor, M Chen, H Marks, ME Harley, V Mishina, Y Kingsley, DM AF Rountree, RB Schoor, M Chen, H Marks, ME Harley, V Mishina, Y Kingsley, DM TI BMP receptor signaling is required for postnatal maintenance of articular cartilage SO PLOS BIOLOGY LA English DT Article ID MORPHOGENETIC PROTEIN-RECEPTOR; CHONDROCYTE-SPECIFIC ENHANCER; PROGRAMMED CELL-DEATH; TGF-BETA-SUPERFAMILY; II COLLAGEN GENE; MOUSE LIMB; OSTEOGENIC PROTEIN-1; GERMLINE MUTATIONS; JUVENILE POLYPOSIS; MATRIX SYNTHESIS AB Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member) to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be investigated as a possible therapeutic strategy for maintaining the health of joint linings. C1 Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. Monash Med Ctr, Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Kingsley, DM (reprint author), Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. EM kingsley@cmgm.stanford.edu OI Harley, Vincent/0000-0002-2405-1262 FU NIAMS NIH HHS [R37 AR042236] NR 78 TC 147 Z9 154 U1 2 U2 8 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 NOV PY 2004 VL 2 IS 11 BP 1815 EP 1827 AR e355 DI 10.1371/journal.pbio.0020355 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 871UT UT WOS:000225160300013 PM 15492776 ER PT J AU Lebedev, MA Messinger, A Kralik, JD Wise, SP AF Lebedev, MA Messinger, A Kralik, JD Wise, SP TI Representation of attended versus remembered locations in prefrontal cortex SO PLOS BIOLOGY LA English DT Article ID SPATIAL WORKING-MEMORY; DELAYED-RESPONSE PERFORMANCE; DOWN ATTENTIONAL CONTROL; MONKEY CEREBRAL-CORTEX; FRONTAL EYE FIELD; NEURONAL-ACTIVITY; VISUAL RESPONSES; BEHAVIORAL ENHANCEMENT; VISUOSPATIAL ATTENTION; VISUOMOTOR ACTIVITY AB A great deal of research on the prefrontal cortex (PF), especially in nonhuman primates, has focused on the theory that it functions predominantly in the maintenance of short-term memories, and neurophysiologists have often interpreted PF's delay-period activity in the context of this theory. Neuroimaging results, however, suggest that PF's function extends beyond the maintenance of memories to include aspects of attention, such as the monitoring and selection of information. To explore alternative interpretations of PF's delay-period activity, we investigated the discharge rates of single PF neurons as monkeys attended to a stimulus marking one location while remembering a different, unmarked location. Both locations served as potential targets of a saccadic eye movement. Although the task made intensive demands on short-term memory, the largest proportion of PF neurons represented attended locations, not remembered ones. The present findings show that short-term memory functions cannot account for all, or even most, delay-period activity in the part of PF explored. Instead, PF's delay-period activity probably contributes more to the process of attentional selection. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Lebedev, MA (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Ctr Neuroengn, Durham, NC 27710 USA. EM lebedev@neuro.duke.edu RI Lebedev, Mikhail/H-5066-2016 OI Lebedev, Mikhail/0000-0003-0355-8723 NR 100 TC 114 Z9 116 U1 0 U2 5 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 NOV PY 2004 VL 2 IS 11 BP 1919 EP 1935 AR e365 DI 10.1371/journal.pbio.0020365 PG 17 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 871UT UT WOS:000225160300022 PM 15510225 ER PT J AU Smith, DL Dushoff, J McKenzie, FE AF Smith, DL Dushoff, J McKenzie, FE TI The risk of a mosquito-borne infection in a heterogeneous environment SO PLOS BIOLOGY LA English DT Article ID VECTOR BREEDING SITES; MALARIA TRANSMISSION; SOUTHERN MOZAMBIQUE; ANOPHELES-GAMBIAE; CLINICAL MALARIA; SRI-LANKA; CHILDREN; MODELS; EPIDEMIOLOGY; DISPERSAL AB A common assumption about malaria, dengue, and other mosquito-borne infections is that the two main components of the risk of human infection-the rate at which people are bitten ( human biting rate) and the proportion of mosquitoes that are infectious-are positively correlated. In fact, these two risk factors are generated by different processes and may be negatively correlated across space and time in heterogeneous environments. Uneven distribution of blood-meal hosts and larval habitat creates a spatial mosaic of demographic sources and sinks. Moreover, mosquito populations fluctuate temporally, forced by environmental variables such as rainfall, temperature, and humidity. These sources of spatial and temporal heterogeneity in the distribution of mosquito populations generate variability in the human biting rate, in the proportion of mosquitoes that are infectious, and in the risk of human infection. To understand how heterogeneity affects the epidemiology of mosquito-borne infections, we developed a set of simple models that incorporate heterogeneity in a stepwise fashion. These models predict that the human biting rate is highest shortly after the mosquito densities peak, near breeding sites where adult mosquitoes emerge, and around the edges of areas where humans are aggregated. In contrast, the proportion of mosquitoes that are infectious reflects the age structure of mosquito populations; it peaks where old mosquitoes are found, far from mosquito breeding habitat, and when mosquito population density is declining. Finally, we show that estimates for the average risk of infection that are based on the average entomological inoculation rate are strongly biased in heterogeneous environments. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Princeton Univ, Princeton, NJ 08544 USA. RP Smith, DL (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM smitdave@mail.nih.gov RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU Intramural NIH HHS [Z99 TW999999] NR 50 TC 142 Z9 144 U1 1 U2 32 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 NOV PY 2004 VL 2 IS 11 BP 1957 EP 1964 AR e368 DI 10.1371/journal.pbio.0020368 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 871UT UT WOS:000225160300025 PM 15510228 ER PT J AU Koup, RA AF Koup, RA TI Reconsidering early HIV treatment and supervised treatment interruptions SO PLOS MEDICINE LA English DT Editorial Material ID T-CELL RESPONSES; ANTIRETROVIRAL THERAPY; INFECTION; CD4(+); VIRUS; VIREMIA C1 NIAID, Human Immunol Program, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Koup, RA (reprint author), NIAID, Human Immunol Program, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov NR 12 TC 4 Z9 4 U1 0 U2 0 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 NOV PY 2004 VL 1 IS 2 BP 109 EP 110 AR e41 DI 10.1371/journal.pmed.0010041 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 902TG UT WOS:000227378800006 PM 15578109 ER PT J AU Stuge, TB Holmes, SP Saharan, S Tuettenberg, A Roederer, M Weber, JS Lee, PP AF Stuge, TB Holmes, SP Saharan, S Tuettenberg, A Roederer, M Weber, JS Lee, PP TI Diversity and recognition efficiency of T cell responses to cancer SO PLOS MEDICINE LA English DT Article ID HETEROCLITIC ANTIGEN ANALOGS; METASTATIC MELANOMA PATIENTS; FUNCTIONAL AVIDITY; IN-VIVO; DENDRITIC CELLS; TCR AVIDITY; TUMOR-IMMUNOTHERAPY; VIRUS-INFECTION; REACTIVE CTL; PEPTIDE AB Background Melanoma patients vaccinated with tumor-associated antigens frequently develop measurable peptide-specific CD8+ T cell responses; however, such responses often do not confer clinical benefit. Understanding why vaccine-elicited responses are beneficial in some patients but not in others will be important to improve targeted cancer immunotherapies. Methods and Findings We analyzed peptide-specific CD8+ T cell responses in detail, by generating and characterizing over 200 cytotoxic T lymphocyte clones derived from T cell responses to heteroclitic peptide vaccination, and compared these responses to endogenous anti-tumor T cell responses elicited naturally (a heteroclitic peptide is a modification of a native peptide sequence involving substitution of an amino acid at an anchor residue to enhance the immunogenicity of the peptide). We found that vaccine-elicited T cells are diverse in T cell receptor variable chain beta expression and exhibit a different recognition profile for heteroclitic versus native peptide. In particular, vaccine-elicited T cells respond to native peptide with predominantly low recognition efficiency-a measure of the sensitivity of a T cell to different cognate peptide concentrations for stimulation-and, as a result, are inefficient in tumor lysis. In contrast, endogenous tumor-associated-antigen-specific T cells show a predominantly high recognition efficiency for native peptide and efficiently lyse tumor targets. Conclusions These results suggest that factors that shape the peptide-specific T cell repertoire after vaccination may be different from those that affect the endogenous response. Furthermore, our findings suggest that current heteroclitic peptide vaccination protocols drive expansion of peptide-specific T cells with a diverse range of recognition efficiencies, a significant proportion of which are unable to respond to melanoma cells. Therefore, it is critical that the recognition efficiency of vaccine-elicited T cells be measured, with the goal of advancing those modalities that elicit T cells with the greatest potential of tumor reactivity. C1 Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. RP Lee, PP (reprint author), Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA. EM ppl@stanford.edu OI Stuge, Tor B/0000-0002-6933-8419; Holmes, Susan/0000-0002-2208-8168 FU NCI NIH HHS [R01 CA 090809, R01 CA090809] NR 42 TC 74 Z9 76 U1 0 U2 3 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 NOV PY 2004 VL 1 IS 2 BP 149 EP 160 AR e28 DI 10.1371/journal.pmed.0010028 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 902TG UT WOS:000227378800015 PM 15578105 ER PT J AU Reynolds, KD Bishop, DB Chou, CP Xie, B Nebeling, L Perry, CL AF Reynolds, KD Bishop, DB Chou, CP Xie, B Nebeling, L Perry, CL TI Contrasting mediating variables in two 5-a-day nutrition intervention programs SO PREVENTIVE MEDICINE LA English DT Article DE mediators; school-based; nutrition intervention; fruit and vegetable consumption ID VEGETABLE CONSUMPTION; PHYSICAL-ACTIVITY; CARDIOVASCULAR HEALTH; DIETARY ASSESSMENT; ADOLESCENT TRIAL; PSYCHOSOCIAL DETERMINANTS; NORMATIVE CONDUCT; FOCUS THEORY; POWER PLUS; SCHOOL AB Background. Researchers have advocated mediational analysis for behavioral intervention studies to link the supporting theory used in an intervention with the mediating variables and with its ultimate success or failure. Few mediational analyses have been reported for school-based nutrition studies. The conduct of mediational analyses within multi-site studies may provide advantages for the standardization of methods and for the replication and generalizability of findings. Methods. This study identified mediators of two school-based nutrition interventions for 4th graders. Three variables were tested on the four criteria necessary to establish mediation of intervention effects on changes in fruit and vegetable consumption (FVC) in 4th graders (Alabama, N = 1584; Minnesota, N = 522). FVC was measured in children using 24-h dietary recalls. Mediators were assessed using questionnaires completed by children and parents. Results. All criteria were met in Alabama for a single-item measure of knowledge of the 5-a-day daily consumption guideline. Knowledge and parent consumption satisfied one criterion in Minnesota. Knowledge accounted for 9.78% of the total intervention effect in Alabama. Conclusions. Knowledge of the 5-a-day guideline for fruit and vegetable consumption may mediate intervention effects. Future work should include tests of mediational models in multi-site studies. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Alhambra, CA 91803 USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. NCI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Reynolds, KD (reprint author), Univ So Calif, Inst Hlth Promot & Dis Prevent Res, 1000 S Fremont Ave,Unit 8, Alhambra, CA 91803 USA. EM kdreynol@usc.edu FU NCI NIH HHS [CA59776, CA59805, R01 CA059805] NR 61 TC 30 Z9 30 U1 4 U2 10 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 NOV PY 2004 VL 39 IS 5 BP 882 EP 893 DI 10.1016/j.ypmed.2004.03.022 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 866MX UT WOS:000224778700006 PM 15475020 ER PT J AU Arheart, KL Sly, DF Trapido, EJ Rodriguez, RD Ellestad, AJ AF Arheart, KL Sly, DF Trapido, EJ Rodriguez, RD Ellestad, AJ TI Assessing the reliability and validity of anti-tobacco attitudes/beliefs in the context of a campaign strategy SO PREVENTIVE MEDICINE LA English DT Article DE tobacco control; attitudes/beliefs; youth prevention; mass media ID FLORIDA TRUTH CAMPAIGN; MEDIA CAMPAIGN; SMOKING; YOUTH AB Objectives. To identify multi-item attitude/belief scales associated with the theoretical foundations of an anti-tobacco counter-marketing campaign and assess their reliability and validity. Methods. The data analyzed are from two state-wide, random, cross-sectional telephone surveys [n(S1) = 1,079, n(S2) = 1,150]. Items forming attitude/belief scales are identified using factor analysis. Reliability is assessed with Chronbach's alpha. Relationships among scales are explored using Pearson correlation. Validity is assessed by testing associations derived from the Centers for Disease Control and Prevention's (CDC) logic model for tobacco control program development and evaluation linking media exposure to attitudes/beliefs, and attitudes/beliefs to smoking-related behaviors. Adjusted odds ratios are employed for these analyses. Results. Three factors emerged: traditional attitudes/beliefs about tobacco and tobacco use, tobacco industry manipulation and anti-tobacco empowerment. Reliability coefficients are in the range of 0.70 and vary little between age groups. The factors are correlated with one-another as hypothesized. Associations between media exposure and the attitude/belief scales and between these scales and behaviors are consistent with the CDC logic model. Conclusions. Using reliable, valid multi-item scales is theoretically and methodologically more sound than employing single-item measures of attitudes/beliefs. Methodological, theoretical and practical implications are discussed. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. CDC, Off Smoking & Hlth, Atlanta, GA 30349 USA. NCI, Div Canc Control & Populat Sci, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Tobacco Res & Evaluat Coordinating Ctr, Miami, FL 33136 USA. Wisconsin Dept Hlth & Family Serv, Div Publ Hlth, Madison, WI 53701 USA. RP Arheart, KL (reprint author), Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, 1801 NW 9th Ave,D-93, Miami, FL 33136 USA. EM karheart@med.miami.edu NR 28 TC 6 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 NOV PY 2004 VL 39 IS 5 BP 909 EP 918 DI 10.1016/j.ypmed.2004.03.028 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 866MX UT WOS:000224778700009 PM 15475023 ER PT J AU Zimmerman, DM Sehnert, SS Epstein, DH Pickworth, WB Robinson, ML Moolchan, ET AF Zimmerman, DM Sehnert, SS Epstein, DH Pickworth, WB Robinson, ML Moolchan, ET TI Smoking topography and trajectory of asthmatic adolescents requesting cessation treatment SO PREVENTIVE MEDICINE LA English DT Article DE tobacco; smoking; adolescent; asthma; health; smoking; topography; smoking trajectory ID PEDIATRIC ASTHMA; RISK; NICOTINE AB Background. Teenage smokers cite health concerns as their primary motivators for tobacco smoking cessation. Smoke exposure aggravates the clinical course of asthma, yet few reports have examined the association between asthma and smoking topography and trajectory. Methods. Before their enrollment in a smoking cessation trial, we assessed the smoking topography (i.e., puff volume, maximum puff velocity, puff duration, and interpuff interval) and smoking trajectory (i.e., age of first cigarette, age of daily smoking, time to treatment request, and prior quit attempts) in 30 self-reported asthmatic and 92 nonasthmatic tobacco-dependent teenagers (mean age, 15.2 +/- 1.3 years, 28.7% Afican-American). Approximately one-half of asthmatics used prescribed medications for their asthma. Results. There was no significant difference in smoking topography or smoking trajectory variables between asthmatic and nonasthmatic adolescents, nor between medicated and nonmedicated asthma subgroups. Conclusions. Although tobacco smoking exacerbates asthmatic symptoms, these data suggest that age of smoking initiation, as well as smoking topography characteristics in asthmatic adolescents, does not differ from those of adolescents without asthma. These findings highlight the need for more effective health counseling of asthmatic youth regarding the physical and behavioral effects of smoking. Published by The Institute For Cancer Prevention and Elsevier Inc. C1 US Dept HHS, NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), US Dept HHS, NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 16 TC 7 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV PY 2004 VL 39 IS 5 BP 940 EP 942 DI 10.1016/j.ypmed.2004.03.032 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 866MX UT WOS:000224778700013 PM 15475027 ER PT J AU Boscoe, FP Miller, BA AF Boscoe, FP Miller, BA TI Population estimation error and its impact on 1991-1999 cancer rates SO PROFESSIONAL GEOGRAPHER LA English DT Article DE population estimates; error of closure; 2000 census; cancer rates ID PUBLIC-HEALTH; RACE DATA; CENSUS 2000; ETHNICITY; TRENDS; CLASSIFICATION; REPRESENTATION; SURVEILLANCE; EPIDEMIOLOGY; STATISTICS AB The error of closure in the 2000 census, or the difference between estimated and enumerated populations, poses special problems for public agencies that rely on census data. Nationally and at the state level, populations were only slightly underestimated, but underestimations were high in rapidly growing counties in the South and intermontaine West, as well as in New York City. Race-specific estimates proved far less reliable, with severe overestimates and underestimates of all racial groups in various counties nationwide. We offer explanations for the estimation error and discuss its impact on cancer rates and trends and its implications for cancer surveillance research. C1 New York State Dept Hlth, Albany, NY 12237 USA. NCI, Canc Stat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Boscoe, FP (reprint author), New York State Dept Hlth, Albany, NY 12237 USA. EM fpb01@health.state.ny.us; bm33q@nih.gov NR 57 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0033-0124 J9 PROF GEOGR JI Prof. Geogr. PD NOV PY 2004 VL 56 IS 4 BP 516 EP 529 PG 14 WC Geography SC Geography GA 863LD UT WOS:000224562300006 ER PT J AU Kataeva, IA Uversky, VN Brewer, JM Schubot, F Rose, JP Wang, BC Ljungdahl, LG AF Kataeva, IA Uversky, VN Brewer, JM Schubot, F Rose, JP Wang, BC Ljungdahl, LG TI Interactions between immunoglobulin-like and catalytic modules in Clostridium thermocellum cellulosomal cellobiohydrolase CbhA SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE fold; glycosidase; interactions; module protein; stability ID CARBONIC-ANHYDRASE-B; CIRCULAR-DICHROISM; THERMOTOGA-MARITIMA; DOMAIN INTERACTIONS; BINDING DOMAIN; CRYSTAL-STRUCTURE; FOLDING PATHWAY; XYLANASE XYNA; PROTEIN; STABILITY AB Cellobiohydrolase CbhA from Clostridium thermocellum cellulosome is a multi-modular protein composed starting from the N-terminus of a carbohydrate-binding module (CBM) of family 4, an immunoglobulin(Ig)-like module, a catalytic module of family 9 glycoside hydrolases (GH9), X1(1) and X1(2) modules, a CBM of family 3 and a dockerin module. Deletion of the Ig-like module from the Ig-GH9 construct results in complete inactivation of the GH9 module. The crystal structure of the Ig-GH9 module pair reveals the existence of an extensive module interface composed of over 40 amino acid residues of both modules and maintained through a large number of hydrophilic and hydrophobic interactions. To investigate the importance of these interactions between the two modules, we compared the secondary and tertiary structures and thermostabilities of the individual Ig-like and GH9 modules and the Ig-GH9 module pair using both circular dichroism (CD) spectroscopy and differential scanning calorimetry (DSC). Thr230, Asp262 and Asp264 of the Ig-like module are located in the module interface of the Ig-GH9 module pair and are suggested to be important in 'communication' between the modules. These residues were mutated to alanyl residues. The structure, stability and catalytic properties of the native Ig-GH9 and its D264A and T230A/D262A mutants were compared. The results indicate that despite being able to fold relatively independently, the Ig-like and GH9 modules interact and these interactions affect the final fold and stability of each module. Mutations of one or two amino acid residues lead to destabilization and change of the mechanism of thermal unfolding of the polypeptides. The enzymatic properties of native Ig-GH9, D264A and T230A/D262A mutants are similar. The results indicate that inactivation of the GH9 module occurs as a result of multiple structural disturbances finally affecting the topology of the catalytic center. C1 Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142292, Russia. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Kataeva, IA (reprint author), Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. EM kataeva@uga.edu RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 55 TC 29 Z9 29 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD NOV PY 2004 VL 17 IS 11 BP 759 EP 769 DI 10.1093/protein/gzh094 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 899GS UT WOS:000227133500001 PM 15596428 ER PT J AU Klarmann, GJ Eisenhauer, BM Yi, Z Sitaraman, K Chatterjee, DK Hecht, SM Le Grice, SFJ AF Klarmann, GJ Eisenhauer, BM Yi, Z Sitaraman, K Chatterjee, DK Hecht, SM Le Grice, SFJ TI Site- and subunit-specific incorporation of unnatural amino acids into HIV-1 reverse transcriptase SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE reverse transcriptase; HIV-1; unnatural amino acid; cell-free transcription/translation; coupled transcription/translation ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHOTO-CROSS-LINKING; GENETIC-CODE; ESCHERICHIA-COLI; IN-VIVO; POLYMERASE-ACTIVITY; CRYSTAL-STRUCTURE; GENERAL-APPROACH; ENERGY-TRANSFER; TRANSFER-RNAS AB A highly efficient cell-free translation system has been combined with suppressor tRNA technology to substitute nor-Tyr and 3-fluoro-Tyr in place of Tyr183 at the DNA polymerase active site of p66 of human immunodeficiency virus type I reverse transcriptase (HIV-1 RT). Supplementing the wild-type HIV-1 p51 RT subunit into this translation system permitted reconstitution of the biologically relevant p66/p51 heterodimer harboring Tyr analogs exclusively on the catalytically competent p66 subunit. Addition of an affinity tag at the p66 C-terminus allowed rapid, one-step purification of reconstituted and selectively mutated heterodimer HIV-1 RT via strep-Tactin-agarose affinity chromatography. The purified enzyme was demonstrated to be free of contaminating nucleases, allowing characterization of the DNA polymerase and ribonuclease H activities associated with HIV-1 RT. Preliminary characterization of HIV-1 RTnor-Tyr and HIV-1 RTm-fluoro-Tyr is presented. The success of this strategy will facilitate detailed molecular analysis of structurally and catalytically critical amino acids via their replacement with closely related, unnatural analogs. (C) 2004 Elsevier lnc. All rights reserved. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. Univ Virginia, Dept Chem, Charlottesville, VA USA. Sci Applicat Int Corp, Frederick, MD USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. EM slegrice@ncifcrf.gov NR 42 TC 9 Z9 9 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 2004 VL 38 IS 1 BP 37 EP 44 DI 10.1016/j.pep.2004.07.019 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 866MY UT WOS:000224778800006 PM 15477080 ER PT J AU Nallamsetty, S Kapust, RB Tozser, J Cherry, S Tropea, JE Copeland, TD Waugh, DS AF Nallamsetty, S Kapust, RB Tozser, J Cherry, S Tropea, JE Copeland, TD Waugh, DS TI Efficient site-specific processing of fusion proteins by tobacco vein mottling virus protease in vivo and in vitro SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE protease; TVMV protease; TEV protease; tobacco vein mottling virus; tobacco etch virus; affinity tag ID MALTOSE-BINDING PROTEIN; ESCHERICHIA-COLI; PURIFICATION; EXPRESSION; POLYPEPTIDES; DESIGN; FORM AB Affinity tags are widely used as vehicles for the production of recombinant proteins. Yet, because of concerns about their potential to interfere with the activity or structure of proteins, it is almost always desirable to remove them from the target protein. The proteases that are most often used to cleave fusion proteins are factor Xa, enterokinase, and thrombin, yet the literature is replete with reports of fusion proteins that were cleaved by these proteases at locations other than the designed site. It is becoming increasingly evident that certain viral proteases have more stringent sequence specificity. These proteases adopt a trypsin-like fold but possess an unconventional catalytic triad in which Cys replaces Ser. The tobacco etch virus (TEV) protease is the best-characterized enzyme of this type. TEV protease cleaves the sequence ENLYFQG/S between QG or QS with high specificity. The tobacco vein mottling virus (TVMV) protease is a close relative of TEV protease with a distinct sequence specificity (ETVRFQG/S). We show that, like TEV protease, TVMV protease can be used to cleave fusion proteins with high specificity in vitro and in vivo. We compared the catalytic activity of the two enzymes as a function of temperature and ionic strength, using an MBP-NusG fusion protein as a model substrate. The behavior of TVMV protease was very similar to that of TEV protease. Its catalytic activity was greatest in the absence of NaCl, but diminished only threefold with increasing salt up to 200 mM. We found that the optimum temperatures of the two enzymes are nearly the same and that they differ only two-fold in catalytic efficiency, both at room temperature and 4degreesC. Hence, TVMV protease may be a useful alternative to TEV protease when a recombinant protein happens to contain a sequence that is similar to a TEV protease recognition site or for protein expression strategies that involve the use of more than one protease. Published by Elsevier Inc. C1 NCI, Ctr Canc Res, Macromol Crystallog Lab, Frederick, MD USA. Univ Debrecen, Res Ctr Mol Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NCI, Ctr Canc Res, Lab Prot Dynam & Signaling, Frederick, MD USA. RP Waugh, DS (reprint author), NCI, Ctr Canc Res, Macromol Crystallog Lab, POB B, Frederick, MD USA. EM waughd@ncifcrf.gov RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 25 TC 63 Z9 74 U1 0 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 2004 VL 38 IS 1 BP 108 EP 115 DI 10.1016/j.pep.2004.08.016 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 866MY UT WOS:000224778800014 PM 15477088 ER PT J AU Harries, D Parsegian, VA AF Harries, D Parsegian, VA TI Gibbs adsorption isotherm combined with Monte Carlo sampling to see action of cosolutes on protein folding SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; SIMPLE LATTICE PROTEIN; AQUEOUS UREA SOLUTIONS; RANDOM COIL PROTEIN; GUANIDINE-HYDROCHLORIDE; STAPHYLOCOCCAL NUCLEASE; DENATURED STATE; CONSTANT-PH; SOLVENT DENATURATION; GLOBULAR-PROTEINS AB Driven by conditions set by smaller solutes, proteins fold and unfold. Experimentally, these conditions are stated as intensive variables pH and other chemical potentials - as though small solutes were infinite resources that come at an externally varied free energy cost. Computationally, the finite spaces of simulation allow only fixed numbers of these solutes. By combining the analytic Gibbs adsorption isotherm with the computational Monte Carlo sampling of polymer configurations, we have been able to overcome an inherent limitation of computer simulation. The idea is to compute analytically the free energy changes wrought by solutes on each particular configuration. Then numerical computation is needed only to sample the set of configurations as efficiently as when no bathing solute is present. For illustration, the procedure is applied to an idealized two-dimensional heteropolymer to yield lessons about the effect of cosolutes on protein stability. (C) 2004 Wiley-Liss, Inc. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Harries, D (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM harries@helix.nih.gov RI Harries, Daniel/F-7016-2012 OI Harries, Daniel/0000-0002-3057-9485 NR 70 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 2004 VL 57 IS 2 BP 311 EP 321 DI 10.1002/prot.20182 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 854TM UT WOS:000223926200008 PM 15340918 ER PT J AU Przytycka, T AF Przytycka, T TI Significance of conformational biases in Monte Carlo simulations of protein folding: Lessons from Metropolis-Hastings approach SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE protein folding; Metropolis-Hasting algorithm; detailed balance principle; biased sampling; hierarchical folding; minimalist models ID KNOWLEDGE-BASED POTENTIALS; LATTICE MODEL; PREDICTION; LINUS AB Despite significant effort, the problem of predicting a protein's three-dimensional fold from its amino-acid sequence remains unsolved. An important strategy involves treating folding as a statistical process, using the Markov chain formalism, implemented as a Metropolis Monte Carlo algorithm. A formal prerequisite of this approach is the condition of detailed balance, the plausible requirement that at equilibrium, the transition from state i to state j is traversed with the same probability as the reverse transition from state j to state i. Surprisingly, some relatively successful methods that use biased sampling fail to satisfy this requirement. Is this compromise merely a convenient heuristic that results in faster convergence? Or, is it instead a cryptic energy term that compensates for an incomplete potential function? I explore this question using Metropolis-Hasting Monte Carlo simulations. Results from these simulations suggest the latter answer is more likely. (C) 2004 Wiley-Liss, Inc. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Przytycka, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM przytyck@ncbi.nlm.nih.bov NR 23 TC 6 Z9 6 U1 0 U2 4 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 NOV 1 PY 2004 VL 57 IS 2 BP 338 EP 344 DI 10.1002/prot.20210 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 854TM UT WOS:000223926200011 PM 15340921 ER PT J AU Suh, SK Hood, BL Kim, BJ Conrads, TP Veenstra, TD Song, BJ AF Suh, SK Hood, BL Kim, BJ Conrads, TP Veenstra, TD Song, BJ TI Identification of oxidized mitochondria proteins in alcohol-exposed human hepatoma cells and mouse liver SO PROTEOMICS LA English DT Article DE alcohol; CYP2E1; cysteine oxidation; reactive oxygen species ID HUMAN CYTOCHROME P4502E1; OXIDATIVE STRESS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; MASS-SPECTROMETRY; INDUCED APOPTOSIS; ARACHIDONIC-ACID; TREATED RATS; PC12 CELLS; ETHANOL AB Heavy alcohol consumption can damage various cells and organs partly through production of reactive oxygen species (ROS) and mitochondrial dysfunction. Treatment with antioxidants can significantly reduce the degree of damage. Despite well established roles of ROS in alcohol-induced cell injury, the proteins that are selectively oxidized by ROS are poorly characterized. We hypothesized that certain cysteinyl residues of target proteins are oxidized by ROS upon alcohol exposure, and these modified proteins may play roles in mitochondrial dysfunction. A targeted proteomics approach utilizing biotin-N-maleimide (biotin-NM) as a specific probe to label oxidized cysteinyl residues was employed to investigate which mitochondrial proteins are modified during and after alcohol exposure. Human hepatoma HepG2 cells with transduced CYP2E1 (E47 cells) were used as a model to generate ROS through CYP2E1 -mediated ethanol metabolism. Following exposure to 100 mm ethanol for 4 and 8 h, the biotin-N M -labeled oxidized proteins were purified with agarose coupled to either streptavidin or monoclonal antibody against biotin. The purified proteins were resolved by twodimensional gel electrophoresis and protein spots that displayed differential abundances were excised from the gel, in-gel digested with trypsin and analyzed for identity utilizing either matrix-assisted laser desorption-time of flight mass spectrometry or microcapillary reversed-phase liquid chromatography-tandem mass spectrometry. The results demonstrate that heat shock protein 60, protein disulfide isomerase, mitochondrial aldehyde dehydrogenases, prohibitin, and other proteins were oxidized after alcohol exposure. The identity of some of the proteins purified with streptavidin-agarose was also confirmed by immunoblot analyses using the specific antibody to each target protein. This method was also used to identify oxidized mitochondrial proteins in the alcohol-fed mouse liver. These results suggest that exposure to ethanol causes oxidation of various mitochondrial proteins that may negatively affect their function and contribute to alcohol-induced mitochondrial dysfunction and cellular injury. C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. SAIC Frederick, NCI Frederick, Lab Proteom & Analyt Technol, Frederick, MD USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 5625 Fishers Lane,Rm 25-30, Rockville, MD 20852 USA. EM bjs@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 51 TC 53 Z9 54 U1 0 U2 1 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 NOV PY 2004 VL 4 IS 11 BP 3401 EP 3412 DI 10.1002/pmic.200400971 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 872QK UT WOS:000225223200014 PM 15449375 ER PT J AU Lamberti, JS Weisman, R Faden, DI AF Lamberti, JS Weisman, R Faden, DI TI Forensic assertive community treatment: Preventing incarceration of adults with severe mental illness SO PSYCHIATRIC SERVICES LA English DT Article ID JAIL DIVERSION PROGRAMS; CASE-MANAGEMENT PROGRAM; CRIMINAL-JUSTICE; PSYCHOPATHY CHECKLIST; DISORDERED OFFENDERS; ABILITY SCALE; ILL; DETAINEES; PREDICTION; RECIDIVISM AB Objective: Persons with severe mental illness are overrepresented in jails and prisons in the United States. A national survey was conducted to identify assertive community treatment programs that have been modified to prevent arrest and incarceration of adults with severe mental illness who have been involved with the criminal justice system. Methods: Members of the National Association of County Behavioral Health Directors (NACBHD) were surveyed to identify assertive community treatment programs serving persons with criminal justice histories and working closely with criminal justice agencies. Programs were identified that met three study criteria: all enrollees had a history of involvement with the criminal justice system, a criminal justice agency was the primary referral source, and a close partnership existed with a criminal justice agency to perform jail diversion. Senior representatives of each program were subsequently contacted, and a telephone survey was administered to gather information about the design and operation of the programs. Results: A total of 291 of 314 NACBHD members (93 percent) responded to the survey. Sixteen programs that met the study criteria were identified in nine states. The primary referral sources for 13 of these programs (81 percent) were local jails. Eleven programs (69 percent) incorporated probation officers as members of their assertive community treatment teams. Eight programs (50 percent) had a supervised residential component, with five providing residentially based addiction treatment. Eleven of the 16 programs have begun operating since 1999. Only three programs have published outcome data on program effectiveness. Conclusions: Forensic assertive community treatment is an emerging model for preventing arrest and incarceration of adults with severe mental illness who have substantial histories of involvement with the criminal justice system. Further research is needed to establish the structure, function, and effectiveness of this developing model of service delivery. C1 Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. Natl Inst Hlth, Bethesda, MD USA. RP Lamberti, JS (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM steve_lamberti@urmc.rochester.edu RI McCarthy, Jodie/B-5760-2012 NR 50 TC 77 Z9 78 U1 2 U2 19 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2004 VL 55 IS 11 BP 1285 EP 1293 DI 10.1176/appi.ps.55.11.1285 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 866MW UT WOS:000224778600013 PM 15534018 ER PT J AU Elman, I Rott, D Green, AI Langleben, DD Lukas, SE Goldstein, DS Breier, A AF Elman, I Rott, D Green, AI Langleben, DD Lukas, SE Goldstein, DS Breier, A TI Effects of pharmacological doses of 2-deoxyglucose on plasma catecholamines and glucose levels in patients with schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 08-12, 2002 CL SAN JUAN, PR SP Amer Coll Neuropsychopharmacol DE norepinephrine; dihydroxyphenylglycol; epinephrine; glucose; 2-deoxyglucose; glucoprivation; schizophrenia ID SYMPATHETIC NERVOUS-SYSTEM; DRUG-NAIVE PATIENTS; 2-DEOXY-D-GLUCOSE-INDUCED HYPERGLYCEMIA; ATYPICAL ANTIPSYCHOTICS; EQUIVALENT HYPOGLYCEMIA; CEREBROSPINAL-FLUID; INSULIN SENSITIVITY; CSF NOREPINEPHRINE; FAT DISTRIBUTION; PORTAL-VEIN AB Rationale: Several lines of evidence suggest that the pathophysiology of schizophrenia may be associated with altered noradrenergic and glucoregulatory function. Objective: The aim of this study was to investigate these alterations during a perturbed homeostatic state. Methods: Fifteen patients with schizophrenia and 13 healthy individuals were given a glucose deprivation challenge through administration of pharmacological doses of 2-deoxyglucose (2DG; 40 mg/kg), and their plasma was assayed over the next 60 min for concentrations of norepinephrine (NE), the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), epinephrine and glucose. Results: 2DG induced significant increases in plasma NE, epinephrine and glucose levels in both groups with significantly greater NE and glucose increments in patients than in controls. For DHPG, 2DG produced increases in patients and decreases in the control subjects. NE responses correlated positively and significantly with the DHPG and glucose responses in schizophrenics, but not in controls. Conclusions: These findings suggest that patients with schizophrenia have exaggerated NE and glucose responses to an acute metabolic perturbation. C1 McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. Harvard Med Sch, Belmont, MA 02478 USA. Medstar Cardiovasc Res Inst, Washington, DC USA. Dartmouth Coll Sch Med, Dept Psychiat, Concord, NH USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. NINDS, Bethesda, MD 20892 USA. Lilly Res Labs, Indianapolis, IN USA. RP Elman, I (reprint author), McLean Hosp, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM ielman@partners.org RI Langleben, Daniel/K-7407-2014 FU NIDA NIH HHS [DA00343, DA14410] NR 74 TC 8 Z9 9 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2004 VL 176 IS 3-4 BP 369 EP 375 DI 10.1007/s00213-004-1890-y PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 870IN UT WOS:000225050900017 PM 15179540 ER PT J AU Rutledge, T Reis, SE Olson, M Owens, J Kelsey, SF Pepine, CJ Mankad, S Rogers, WJ Merz, CNB Sopko, G Cornell, CE Sharaf, B Matthews, KA AF Rutledge, T Reis, SE Olson, M Owens, J Kelsey, SF Pepine, CJ Mankad, S Rogers, WJ Merz, CNB Sopko, G Cornell, CE Sharaf, B Matthews, KA TI Social networks are associated with lower mortality rates among women with suspected coronary disease: The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome evaluation study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE coronary artery disease; mortality; women; social networks ID SYNDROME EVALUATION WISE; ARTERY DISEASE; CHEST PAIN; CARDIOVASCULAR ACTIVITY; SOCIOECONOMIC-STATUS; HOST-RESISTANCE; SUPPORT; HEALTH; MEN; POPULATION AB Objective: To examine the association between social relationships measured by the Social Network Scale and coronary artery disease (CAD) risk and mortality among a sample of women with suspected CAD. Methods: Five hundred three women (mean age, 59 years) with suspected CAD warranting clinical investigation completed a diagnostic protocol including psychosocial testing, CAD risk factor assessment, and quantitative coronary angiography. Patients were subsequently followed for a mean of 2.3 years to track all-cause mortality. Results: Women reporting higher social network scores showed a consistent pattern of reduced coronary artery disease risk, including lower blood glucose levels (r = -0.11; p = .03), lower smoking rates (odds ratio [OR] 0.81; 95% confidence interval [CI] 0.71-0.93; p = .002), lower waist-hip ratios (r = 0.18; p < .01), and lower rates of hypertension (OR = 0.90; 95% Cl 0.81-0.99; p = .04) and diabetes (OR = 0.83-1 95% Cl = 0.73-0.94; p = .004). Based on quantitative angiogram findings, high social network scorers also had less severe CAD (mean angiogram stenosis value, 40.8 vs. 27.2 for low and high scoring social network groups, respectively; p < .001). Finally, mortality rates over follow-up showed a dose-response pattern in relation to quartile scorers on the Social Network Index, with low scorers showing more than twice the death rate of high scorers (relative risk = 2.4; p = .03). Conclusions: Among a cohort of women with suspected CAD, smaller social circles were associated with increased CAD risk factors and mortality, an effect that appeared to be explained largely by income level. The findings extend previous studies of social network effects on health by highlighting risk among women with suspected CAD, and suggest mechanisms for further study. C1 Univ Calif San Diego, San Diego, CA 92103 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Florida, Gainesville, FL USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Alabama, Birmingham, AL USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NHLBI, Bethesda, MD 20892 USA. Rhode Isl Hosp, Providence, RI USA. RP Rutledge, T (reprint author), VA San Diego Healthcare Syst, Med Ctr, Psychol Serv 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM Thomas.Rutledge@med.va.gov RI Reis, Steven/J-3957-2014 FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164] NR 29 TC 61 Z9 62 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2004 VL 66 IS 6 BP 882 EP 888 DI 10.1097/01.psy.0000145819.94041.52 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 874JY UT WOS:000225347900013 PM 15564353 ER PT J AU Gilbert, ES Koshurnikova, NA Sokolnikov, ME Shilnikova, NS Preston, DL Ron, E Okatenko, PV Khokhryakov, VF Vasilenko, EK Miller, S Eckerman, K Romanov, SA AF Gilbert, ES Koshurnikova, NA Sokolnikov, ME Shilnikova, NS Preston, DL Ron, E Okatenko, PV Khokhryakov, VF Vasilenko, EK Miller, S Eckerman, K Romanov, SA TI Lung cancer in Mayak workers SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; FORMER SOVIET-UNION; PRODUCTION-ASSOCIATION; NUCLEAR ENTERPRISE; PLUTONIUM WORKERS; MORTALITY; RADIATION; EXPOSURE; SMOKING; MODEL AB The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future. (C) 2004 by Radiation Research Society. C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. So Urals Biophys Inst, Ozyorsk, Chelyabinsk Reg, Russia. Radiat Res Fdn, Dept Stat, Hiroshima, Japan. Mayak Prod Assoc, Dept Radiat Safety, Ozyorsk, Russia. Univ Utah, Div Radiobiol, Salt Lake City, UT USA. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN USA. RP Gilbert, ES (reprint author), Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, 6120 Execut Blvd,MS 7238, Rockville, MD 20852 USA. EM gilberte@exchange.nih.gov FU NCI NIH HHS [N01 CP 11014] NR 31 TC 43 Z9 50 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2004 VL 162 IS 5 BP 505 EP 516 DI 10.1667/RR3259 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 870UI UT WOS:000225083500003 PM 15624305 ER PT J AU Yoshinaga, S Mabuchi, K Sigurdson, AJ Doody, MM Ron, E AF Yoshinaga, S Mabuchi, K Sigurdson, AJ Doody, MM Ron, E TI Cancer risks among radiologists and radiologic technologists: Review of epidemiologic studies SO RADIOLOGY LA English DT Review DE radiations, exposure to patients and personnel; radiations, injurious effects, neoplastic; radiology and radiologist, iatrogenic injury; review ID X-RAY WORKERS; ATOMIC-BOMB SURVIVORS; CURRENT MORTALITY-RATES; NATIONAL DOSE REGISTRY; RADIATION-EXPOSURE; UNITED-STATES; IONIZING-RADIATION; PHYSICIAN SPECIALISTS; BRITISH RADIOLOGISTS; CHINA AB Radiologists and radiologic technologists were among the earliest occupational groups exposed to ionizing radiation and represent a large segment of the working population exposed to radiation from human-made sources. The authors reviewed epidemiologic data on cancer risks from eight cohorts of over 270 000 radiologists and technologists in various countries. The most consistent finding was increased mortality due to leukemia among early workers employed before 1950, when radiation exposures were high. This, together with an increasing risk of leukemia with increasing duration of work in the early years, provided evidence of an excess risk of leukemia associated with occupational radiation exposure in that period. While findings on several types of solid cancers were less consistent, several studies provided evidence of a radiation effect for breast cancer and skin cancer. To date, there is no clear evidence of an increased cancer risk in medical radiation workers exposed to current levels of radiation doses. However, given a relatively short period of time for which the most recent workers have been followed up and in view of the increasing uses of radiation in modern medical practices, it is important to continue to monitor the health status of medical radiation workers. (C) RSNA, 2004. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Natl Inst Radiol Sci, Res Ctr Radiat Safety, Inage Ku, Chiba 2638555, Japan. RP Yoshinaga, S (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. EM yosinago@nirs.go.jp NR 51 TC 102 Z9 109 U1 3 U2 15 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2004 VL 233 IS 2 BP 313 EP 321 DI 10.1148/radiol.2332031119 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 864RK UT WOS:000224650400004 PM 15375227 ER PT J AU Zudova, D Wyrobek, AJ Bishop, J Marchetti, F AF Zudova, D Wyrobek, AJ Bishop, J Marchetti, F TI Impaired fertility in T-stock female mice after superovulation SO REPRODUCTION LA English DT Article ID GRISEOFULVIN-INDUCED ANEUPLOIDY; EARLY EMBRYO DEVELOPMENT; MARE SERUM GONADOTROPIN; IN-VITRO FERTILIZATION; METAPHASE-II OOCYTES; IMMATURE RATS; FETAL DEVELOPMENT; MOUSE OOCYTES; 1ST CLEAVAGE; GENETIC-VARIATION AB Superovulation of female mice with exogenous gonadotrophins is routinely used for increasing the number of eggs ovulated by each female in reproductive and developmental studies. We report an unusual effect of superovulation on fertilization in mice. In vivo matings of superovulated T-stock females with B6C3F1 males resulted in a two-fold reduction (P < 0.001) in the frequencies of fertilized eggs compared with control B6C3F1 matings. in addition, approximately 22 h after mating, only 15% of fertilized eggs recovered in T-stock females had reached the metaphase stage of the first cleavage division versus 87% in B6C3F1 females (P < 0.0001). Matings with T-stock males did not improve the reproductive performance of T-stock females. To investigate the possible cause(s) for the impaired fertilization and zygotic development, the experiments were repeated using in vitro fertilization. Under these conditions, the frequencies of fertilized eggs were not different in superovulated T-stock and B6C3F1 females (51.7 +/- 6.0 and 64.5 +/- 3.8%, P = 0.10). There was a seven-fold increase in the frequencies of fertilized eggs that completed the first cell cycle of development after in vitro versus in vivo fertilization in T-stock females. These results rule out an intrinsic deficiency of the T-stock oocyte as the main reason for the impaired fertility after in vivo matings, and suggest that superovulation of T-stock females may induce a hostile oviductal and uterine environment with dramatic effects on fertilization and zygotic development. C1 Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Marchetti, F (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, L-448,7000 East Ave, Livermore, CA 94550 USA. EM marchetti2@llnl.gov OI Marchetti, Francesco/0000-0002-9435-4867 FU NIEHS NIH HHS [Y01-ES-8016, ES09117] NR 48 TC 4 Z9 4 U1 0 U2 1 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD NOV PY 2004 VL 128 IS 5 BP 573 EP 581 DI 10.1530/rep.1.00333 PG 9 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 868MR UT WOS:000224918200010 PM 15509703 ER PT J AU Gochman, PA Greenstein, D Sporn, A Gogtay, N Nicolson, R Keller, A Lenane, M Brookner, F Rapoport, JL AF Gochman, PA Greenstein, D Sporn, A Gogtay, N Nicolson, R Keller, A Lenane, M Brookner, F Rapoport, JL TI Childhood onset schizophrenia: familial neurocognitive measures SO SCHIZOPHRENIA RESEARCH LA English DT Article DE childhood-onset; schizophrenia; neurocognitive; endophenotype ID SCHIZOTYPAL PERSONALITY-DISORDER; NEUROPSYCHOLOGICAL DYSFUNCTION; SPECTRUM DISORDERS; GENETIC RISK; PARENTS; PERFORMANCE; INTERVIEW; RELATIVES; SIBLINGS; CHILDREN AB Objective: Early onset disorders may have more salient familial/genetic etiology. Neurocognitive deficits which are seen in families of adult onset schizophrenic patients were examined in healthy family members of patients with childhood-onset schizophrenia (COS). Methods: Trail Making Tests (TMT) A and B, Wechsler Intelligence Scale-Revised Digit Span and Vocabulary subtests were administered to 67 parents and 24 siblings of patients with childhood-onset schizophrenia and 114 healthy community controls (CC) comparable in sex, age, and educational level. Results: COS siblings performed significantly more poorly than did controls on Trails Making Test B with a trend for poorer performance evident on Trails Making Test A. COS parents performed more poorly than controls only on Trails Making Test A. Conclusions: Healthy first-degree relatives of COS probands have subtle deficits in tests involving oculomotor/psychomotor speed, working memory and executive function. This provides further support for continuity between COS and later onset schizophrenia and for a familial/genetic factor associated with the illness. (C) 2004 Elsevier B.V. All rights reserved. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Gochman, PA (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Room 3N202, Bethesda, MD 20892 USA. EM peterg@codon.nih.gov RI Gogtay, Nitin/A-3035-2008; Nicolson, Robert/E-4797-2011 NR 26 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 1 PY 2004 VL 71 IS 1 BP 43 EP 47 DI 10.1016/j.schres.2004.01.012 PG 5 WC Psychiatry SC Psychiatry GA 859BW UT WOS:000224238100005 PM 15374571 ER PT J AU Warach, S Latour, LL AF Warach, S Latour, LL TI Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption SO STROKE LA English DT Article; Proceedings Paper CT 24th Princeton Conference on Cerebrovascular Disease CY APR 02-04, 2004 CL Baltimore, MD SP Amer Heart Assoc, Amer Stroke Assoc, Stroke Council, Astra Zeneca Pharmaceut, Centocor Inc, Janssen Ortho McNeil Johnson & Johnson, Mitsubishi Pharma, NINDS, Bristol Myers Squibb, Sanofi Synthelabo DE acute care; blood-brain barrier; stroke, hemorrhagic ID STROKE AB Loss of integrity of the blood-brain barrier (BBB) resulting from ischemia and reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and worse clinical outcome than would be expected from the beneficial effects of reperfusion. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in acute focal brain ischemia and tested associations with reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption was evident as delayed gadolinium enhancement of cerebrospinal fluid space on fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144 (33%) ischemic stroke patients. Reperfusion was found to be the strongest independent predictor of early BBB disruption (P=0.018) in multivariate analysis. HARM was associated with HT and worse clinical outcome (after adjustment for initial severity). It was also associated with more severe strokes at onset and greater age. Because the timing of the disruption was early enough (median estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by HARM may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. C1 NINDS, Bethesda, MD 20892 USA. RP Warach, S (reprint author), NINDS, 10 Ctr Dr,MSC 1063,Bldg 10,Rm B1D733, Bethesda, MD 20892 USA. EM warachs@ninds.nih.gov NR 8 TC 156 Z9 163 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2004 VL 35 IS 11 SU 1 BP 2659 EP 2661 DI 10.1161/01.STR.0000144051.32131.09 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 867PP UT WOS:000224854800014 PM 15472105 ER PT J AU DeGraba, TJ AF DeGraba, TJ TI Immunogenetic susceptibility of atherosclerotic stroke - Implications on current and future treatment of vascular inflammation SO STROKE LA English DT Article; Proceedings Paper CT 24th Princeton Conference on Cerebrovascular Disease CY APR 02-04, 2004 CL Baltimore, MD SP Amer Heart Assoc, Amer Stroke Assoc, Stroke Council, Astra Zeneca Pharmaceut, Centocor Inc, Janssen Ortho McNeil Johnson & Johnson, Mitsubishi Pharma, NINDS, Bristol Myers Squibb, Sanofi Synthelabo DE atherosclerosis; genetic susceptibility; inflammation; stroke; T-lymphocyte; therapeutics ID INTERCELLULAR-ADHESION MOLECULE-1; ACUTE CORONARY SYNDROMES; LOW-DENSITY-LIPOPROTEIN; GRADE CAROTID STENOSIS; TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; CHLAMYDIA-PNEUMONIAE; ISCHEMIC-STROKE; T-CELLS; PLAQUE DESTABILIZATION AB The understanding of the pathophysiology governing atherosclerosis supports a prominent role for inflammation pathways in plaque initiation and progression that result in stroke and myocardial infarction. Elevated levels of inflammatory markers in the blood, such as C-reactive protein and CD40 ligand/CD40, in concert with increased expression of adhesion molecules, chemokines, cytokines, matrix metalloproteinases (NIMP), and inflammatory cells in the plaque, characterize the symptomatic atherothrombotic state. Advances in predictive capabilities of vascular events using a number of these biomarkers are beginning to remodel our clinical practice in the use of medications such as statins and angiotensin receptor blockers for stroke prevention. Although the general inflammatory features of atherosclerosis are becoming widely recognized, factors resulting in individual variability in plaque formation and instability remain poorly defined. Emerging literature points toward several acquired and innate susceptibility factors in the immune pathways that may provide insight into why many plaques rapidly evolve from a "stable" to an "unstable" or symptomatic state. First, exposure of plaque memory T-lymphocytes to infectious or endogenous antigens may result in rapid clonal expansion of T-cell variable beta chain subtypes and stimulate macrophages to release MMPs, causing plaque destabilization. The effects of infectious agents can further be influenced by an individual's major histocompatibility complex class II molecule profiles, which can affect susceptibility to specific organisms. Second, functional polymorphisms of genes that regulate the immune pathway can predispose patients to a more robust inflammatory expression after risk factor exposure. Identification of a susceptibility gene profile and immunologic mediators that promote T-cell activation provides a unique opportunity for early identification of stroke risk and targets for future therapy. C1 NINDS, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. Henry Jackson Fdn, Comprehens Neurosci Program, Bethesda, MD USA. Natl Naval Med Res Inst, Clin Stroke Res Unit, Bethesda, MD USA. RP DeGraba, TJ (reprint author), Neurol Clin, 8901 Wisconsin Ave,Bldg 9,2nd Floor, Bethesda, MD 20889 USA. EM tjdegraba@bethesda.med.navy.mil NR 76 TC 44 Z9 50 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2004 VL 35 IS 11 SU 1 BP 2712 EP 2719 DI 10.1161/01.STR.0000143788.87054.85 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 867PP UT WOS:000224854800030 PM 15472106 ER PT J AU Gwinn-Hardy, K Dawson, V AF Gwinn-Hardy, K Dawson, V TI Genomics-proteomics and stroke - Introduction SO STROKE LA English DT Editorial Material ID ISCHEMIC CEREBROVASCULAR-DISEASE; BRAIN ARTERIOVENOUS-MALFORMATIONS; GENE MICROARRAY ANALYSIS; NITRIC-OXIDE SYNTHASE; APOLIPOPROTEIN-E; MYOCARDIAL-INFARCTION; CONFERS RISK; YOUNG-WOMEN; FACTOR-V; POLYMORPHISM C1 NINDS, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Dept Neurol, Inst Cell Engn, Baltimore, MD USA. RP Gwinn-Hardy, K (reprint author), NINDS, NIH, 6001 Execut Blvd 2142, Bethesda, MD 20892 USA. EM gwinnk@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009; OI Dawson, Valina/0000-0002-2915-3970 NR 43 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2004 VL 35 IS 11 SU 1 BP 2731 EP 2734 DI 10.1161/01.STR.0000143328.98154.33 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 867PP UT WOS:000224854800034 ER PT J AU Ren, G Quispe, J Leppla, SH Mitra, AK AF Ren, G Quispe, J Leppla, SH Mitra, AK TI Large-scale structural changes accompany binding of lethal factor to anthrax protective antigen: A cryo-electron microscopic study SO STRUCTURE LA English DT Article ID BACILLUS-ANTHRACIS; MAMMALIAN-CELLS; MEMBRANE TRANSLOCATION; ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; EDEMA FACTORS; TOXIN; PROTEIN; RESIDUES; CHANNEL AB Anthrax toxin (AT), secreted by Bacillus anthracis, is a three-protein cocktail of lethal factor (LF, 90 kDa), edema factor (EF, 89 kDa), and the protective antigen (PA, 83 kDa). Steps in anthrax toxicity involve (1) binding of ligand (EF/LF) to a heptamer of PA63 (PA63h) generated after N-terminal proteolytic cleavage of PA and, (2) following endocytosis of the complex, translocation of the ligand into the cytosol by an as yet unknown mechanism. The PA63h.LF complex was directly visualized from analysis of images of specimens suspended in vitrified buffer by cryo-electron microscopy, which revealed that the LF molecule, localized to the non-membrane-interacting face of the oligomer, interacts with four successive PA63 monomers and partially unravels the heptamer, thereby widening the central lumen. The observed structural reorganization in PA63h likely facilitates the passage of the large 90 kDa LF molecule through the lumen en route to its eventual delivery across the membrane bilayer. C1 Univ Auckland, Sch Biol Sci, Auckland 1020, New Zealand. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Mitra, AK (reprint author), Univ Auckland, Sch Biol Sci, 3 Symonds St, Auckland 1020, New Zealand. EM a.mitra@auckland.ac.nz RI Mitra, alok/P-7800-2016 OI Mitra, alok/0000-0003-0891-5697 FU NIGMS NIH HHS [R01-GM52567] NR 39 TC 18 Z9 19 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV PY 2004 VL 12 IS 11 BP 2059 EP 2066 DI 10.1016/j.str.2004.09.010 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 872ZD UT WOS:000225247200017 PM 15530370 ER PT J AU Richardson, MA Masse, LC Nanny, K Sanders, C AF Richardson, MA Masse, LC Nanny, K Sanders, C TI Discrepant views of oncologists and cancer patients on complementary/alternative medicine SO SUPPORTIVE CARE IN CANCER LA English DT Article DE attitudes; alternative; complementary medicine; communication ID TREATMENT DECISION-MAKING; STAGE BREAST-CANCER; ALTERNATIVE MEDICINE; THERAPY USE; ADVISING PATIENTS; WOMEN; PREVALENCE; PHYSICIANS; COMMUNICATION; CHEMOTHERAPY AB Goals: Complementary/ alternative medicine ( CAM) is widely used by patients but rarely discussed with oncologists. To understand reasons for the communication gap, this study compares physicians and patients on perceived reasons for CAM use and nondisclosure of use, reactions of physicians to disclosure, and expectations for CAM. Patients and methods: Cross-sectional studies assessed 82 physicians ( response 68.3%) and 244 of 374 outpatients ( response 65.2%) identified as CAM users at the MD Anderson Cancer Center. Data were summarized by frequency and compared using chi-square tests. Main results: Physicians were more likely ( p< 0.001) than patients to attribute CAM use to hope (χ(2) = 17.7), control (χ(2) = 17.5), incurable disease (χ(2) = 42.8), or a nontoxic approach (χ(2) = 50.9). Both physicians and patients agreed CAM could relieve symptoms/side effects, but physicians were less likely ( p< 0.001) than patients to expect that CAM improved immunity (chi(2) = 72.2) or quality of life (chi(2) = 17.1), cured disease (chi(2) = 42.5), or prolonged life (chi(2) = 58.4). Physicians and patients responded differently (p< 0.005) on reasons for nondisclosure. Physicians believed patients felt CAM discussions were unimportant (χ(2) = 7.9) and physicians would not understand (χ(2) = 48.1), discontinue treatment (χ(2) = 26.4), discourage or disapprove of the use (χ(2) = 131.7); patients attributed nondisclosure to their uncertainty of its benefit (χ(2) = 10.4) and never being asked about CAM (χ(2) = 9.9) by physicians. Physicians were more likely (χ(2) = 9.5, p< 0.002) to warn of risks and less likely (chi(2) = 23.5, p< 0.001) to encourage use than patients perceived. Conclusion: Oncologists and cancer patients hold discrepant views on CAM that may contribute to a communication gap. Nevertheless, physicians should ask patients about CAM use, discuss possible benefits, and advise of potential risks. C1 Natl Fdn Alternat Med, Washington, DC 20006 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. RP Richardson, MA (reprint author), Natl Fdn Alternat Med, 1629 K St NW,Suite 402, Washington, DC 20006 USA. EM marich@nfam.org FU NCI NIH HHS [5 U24 CA66826-03] NR 37 TC 71 Z9 71 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD NOV PY 2004 VL 12 IS 11 BP 797 EP 804 DI 10.1007/s00520-004-0677-3 PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 872CW UT WOS:000225185000009 PM 15378417 ER PT J AU Gourraud, PA Mano, S Barnetche, T Carrington, M Inoko, H Cambon-Thomsen, A AF Gourraud, PA Mano, S Barnetche, T Carrington, M Inoko, H Cambon-Thomsen, A TI Integration of microsatellite characteristics in the MHC region: a literature and sequence based analysis SO TISSUE ANTIGENS LA English DT Article DE bioinformatics; chromosome mapping/methods; genetic markers/genetics; HLA-antigens/genetics; human genome major histocompatibility complex/genetics; microsatellite; STR; tandem repeat sequences; variation (genetics)/genetics; VNTR ID CLASS-I REGION; HLA REGION; MARKERS; HAPLOTYPES; LOCI; MAP AB Reviews of microsatellite markers in the human leukocyte antigen region have been very useful in addressing the needs of the immunogenetics community. Nevertheless, characterization of the same microsatellite loci in different laboratories can lead to seemingly contradictory results, particularly in terms of nomenclature. Here we provide an update of previous reports, as well as a standardized characterization of primers for microsatellites located within the major histocompatibility complex (MHC). A uniform and extended inventory of 378 primer pairs from published reports was performed as well as a standardized characterization of the corresponding microsatellite loci according to the extended full-length consensus sequence of MHC region. The literature-based approach was complemented by a sequence-based analysis of each reported microsatellite locus. Iterative electronic polymerase chain reaction runs and an original algorithm that characterizes patterns of repeats within sequence were used. The sequence of primers was corrected according to the consensus sequence. Table of synonymous names for individual microsatellite loci is provided. C1 INSERM, Fac Med, U558, F-31000 Toulouse, France. Tokai Univ, Sch Med, Div Mol Life Sci, Kanagawa 2591100, Japan. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. RP Gourraud, PA (reprint author), INSERM, Fac Med, U558, 37 Allees Uvles Guesde, F-31000 Toulouse, France. EM gourraud@cict.fr RI Gourraud, Pierre-Antoine/O-3024-2015 FU NCI NIH HHS [N01-CO-12400] NR 15 TC 33 Z9 33 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2004 VL 64 IS 5 BP 543 EP 555 DI 10.1111/j.1399-0039.2004.00317.x PG 13 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 863XY UT WOS:000224598100002 PM 15496197 ER PT J AU Wetmore, BA Merrick, BA AF Wetmore, BA Merrick, BA TI Toxicoproteomics: Proteomics applied to toxicology and pathology SO TOXICOLOGIC PATHOLOGY LA English DT Review DE proteomics; toxicogenomics; toxicology; pathology; mass spectrometry; toxicity; microarray; biomarkers; systems biology ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; JET FUEL EXPOSURE; PROTEIN IDENTIFICATION TECHNOLOGY; CUTTING-EDGE TECHNOLOGY; HUMAN PLASMA PROTEOME; HUMAN SERUM PROTEOME; CODED AFFINITY TAGS; MASS-SPECTROMETRY; CEREBROSPINAL-FLUID; MOUSE-LIVER AB Global measurement of proteins and their many attributes in tissues and biofluids defines the field of proteomics. Toxicoproteomics, as part of the larger field of toxicogenomics, seeks to identify critical proteins and pathways in biological systems that are affected by and respond to adverse chemical and environmental exposures using global protein expression technologies. Toxicoproteomics integrates 3 disciplinary areas: traditional toxicology and pathology, differential protein and gene expression analysis, and systems biology. Key topics to be reviewed are the evolution of proteomics, proteomic technology platforms and their capabilities with exemplary studies from biology and medicine, a review of over 50 recent studies applying proteomic analysis to toxicological research, and the recent development of databases designed to integrate -Omics technologies with toxicology and pathology. Proteomics is examined for its potential in discovery of new biomarkers and toxicity signatures, in mapping serum, plasma, and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward an expanded understanding of protein expression during toxicity and environmental disease for the advancement of public health. C1 NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. RP Merrick, BA (reprint author), NIEHS, Natl Ctr Toxicogenom, D2-04,POB 12233, Res Triangle Pk, NC 27709 USA. EM merrick@niehs.nih.gov NR 221 TC 131 Z9 139 U1 7 U2 32 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2004 VL 32 IS 6 BP 619 EP 642 DI 10.1080/01926230490518244 PG 24 WC Pathology; Toxicology SC Pathology; Toxicology GA 887GJ UT WOS:000226293500002 PM 15580702 ER PT J AU Calderon-Garciduenas, L Reed, W Maronpot, RR Henriquez-Roldan, C Delgado-Chavez, R Calderon-Garciduenas, A Dragustinovis, I Franco-Lira, M Aragon-Flores, M Solt, AC Altenburg, M Torres-Jordon, R Swenberg, JA AF Calderon-Garciduenas, L Reed, W Maronpot, RR Henriquez-Roldan, C Delgado-Chavez, R Calderon-Garciduenas, A Dragustinovis, I Franco-Lira, M Aragon-Flores, M Solt, AC Altenburg, M Torres-Jordon, R Swenberg, JA TI Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution SO TOXICOLOGIC PATHOLOGY LA English DT Article DE brain; beta-amyloid; cyclooxygenase 2; inflammation; neuropathology; air pollution; Mexico City ID NEURONAL CYCLOOXYGENASE-2 EXPRESSION; INHALED ULTRAFINE PARTICLES; AMYLOID PRECURSOR PROTEIN; NF-KAPPA-B; BETA-PEPTIDE; RAT-BRAIN; DISEASE; ACCUMULATION; PLASTICITY; INDUCTION AB Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease. C1 Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Inst Nacl Pediat, Mexico City 14410, DF, Mexico. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Valparaiso, Dept Estadist, Valparaiso, Chile. Inst Nacl Cancerol, Dept Pathol, Mexico City, DF, Mexico. Hosp Especialidades No 25, IMSS, Monterrey, NL, Mexico. IMSS, Ctr Invest Biomed Noreste CIBIN, Monterrey, NL, Mexico. Univ Ejercito & Fuerza Aerea, Escuela Med Mil, Mexico City, DF, Mexico. Cent Mil Hosp, Dept Patol, Mexico City, DF, Mexico. Univ Nacl Autonoma Mexico, NUCE, Fac Med, Mexico City 04510, DF, Mexico. Univ Nacl Autonoma Mexico, Ctr Ciencias Atmosfera, Mexico City 04510, DF, Mexico. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. RP Swenberg, JA (reprint author), Univ N Carolina, Dept Environm Sci & Engn, CB 7431,253C Rosenau Hall, Chapel Hill, NC 27599 USA. EM james_swenberg@unc.edu FU NCI NIH HHS [P-30CA16086]; NIEHS NIH HHS [P30ES10126, T-32 ES07017] NR 41 TC 173 Z9 178 U1 5 U2 29 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2004 VL 32 IS 6 BP 650 EP 658 DI 10.1080/01926230490520232 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 887GJ UT WOS:000226293500004 PM 15513908 ER PT J AU Ward, JM Nikolov, NP Tschetter, JR Kopp, JB Gonzalez, FJ Kimura, S Siegel, RM AF Ward, JM Nikolov, NP Tschetter, JR Kopp, JB Gonzalez, FJ Kimura, S Siegel, RM TI Progressive glomerulonephritis and histiocytic sarcoma associated with macrophage functional defects in CYP1B1-deficient mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE CYP1B1; knockout mice; glomerulonephritis; mice; histiocytic sarcoma; macrophages; phagocytosis; autoimmune disease ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELL APOPTOSIS; CYTOCHROME P4501B1; GERMINAL-CENTERS; EXPRESSION; INDUCTION; PHAGOCYTOSIS; CYP1B1; GLAUCOMA; GENE AB The cytochrome P450 CYP1B1 enzyme metabolically activates polycyclic aromatic hydrocarbons and is a major P450 isoenzyme in human monocytes and macrophages. We have shown previously that mice deficient in CYP1B1 were resistant to induced tumors after 7,12-dimethylbenz[a]anthracene exposure. The pathology of aging CYP1B1 null mice on a B6; 129 background was studied in groups of 29 males and 30 females. By 12 months, 50% of the female mice had developed a unusual progressive glomerulonephritis while males had similar renal lesions later in life. This disease followed a sequence of proliferative, membranoproliferative and sclerotic glomerulonephritis. Anti-DNA antibodies were found in the blood of the mice along with immune deposits containing immunoglobulins in subepithelial locations of the glomerular basement membrane. The lesions were unlike those found in aging wild-type B6; 129 mice or mice of other strains. We found that macrophages from CYP1B1-null mice were impaired in the phagocytosis of apoptotic, necrotic, and opsonized cells. This suggests a generalized defect in the phagocytic activity of CYP1B1-null mouse macrophages. Male mice also developed a high incidence (62-64%) of histiocytic sarcomas. Our study provides evidence that deficiency of CYP1B1 can play a role in the development of glomerular disease, normal processing of catabolic DNA and tumors of the mononuclear phagocyte system. The function of CYP1B1 in histiocytes and macrophages may involve both self-tolerance and tumor suppression. C1 NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. SoBran Inc, Bethesda, MD 20892 USA. NIAMSD, DHHS, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NIDDKD, NIH, DHHS, Bethesda, MD 20892 USA. RP Ward, JM (reprint author), NIAID, Comparat Med Branch, NIH, Twinbrook 3,Room 2W-01A, Bethesda, MD 20892 USA. EM jw116y@nih.gov OI Tschetter, Jolynne/0000-0003-1743-1221; Kopp, Jeffrey/0000-0001-9052-186X FU NCI NIH HHS [N01-CO-56000] NR 47 TC 13 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2004 VL 32 IS 6 BP 710 EP 718 DI 10.1080/01926230490885706 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 887GJ UT WOS:000226293500010 PM 15580705 ER PT J AU Wyde, ME Braen, APJM Hejtmancik, M Johnson, JD Toft, JD Blake, JC Cooper, SD Mahler, J Vallant, M Bucher, JR Walker, NJ AF Wyde, ME Braen, APJM Hejtmancik, M Johnson, JD Toft, JD Blake, JC Cooper, SD Mahler, J Vallant, M Bucher, JR Walker, NJ TI Oral and dermal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces cutaneous papillomas and squamous cell carcinomas in female hemizygous Tg.AC transgenic mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE TCDD; Tg.AC mice; skin neoplasms ID V-HA-RAS; TOXICOLOGY PROGRAM-EVALUATION; MOUSE SKIN; IDENTIFYING CARCINOGENS; CHEMICAL CARCINOGENS; ALTERNATIVE MODELS; PREDICTIVE MODELS; COVALENT BINDING; PROMOTION; TUMORS AB Tg.AC mice develop epidermal papillomas in response to treatment with dermally applied nongenotoxic and complete carcinogens. The persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a multi-site rodent carcinogen and tumor promoter that induces the formation of papillomas in Tg.AC mice. To examine the dose-response relationship and compare dermal and oral routes of exposure for TCDD-induced skin papillomas, female Tg.AC mice were exposed dermally to average daily doses of 0, 2.1, 7.3, 15, 33, 52, 71, 152, and 326 ng TCDD/kg/day or 0, 75, 321, and 893 ng TCDD/kg body weight by gavage for 26 weeks. The incidence of cutaneous papillomas was increased in a dose-dependent manner, and tumors developed earlier with higher exposure to TCDD regardless of route of administration. Increased incidences of cutaneous squamous cell carcinomas were observed in mice exposed to dermal (greater than or equal to52 ng/kg) and oral (893 ng/kg) TCDD. Higher gavage doses than dermal exposure doses were required to induce papillomas and squamous cell carcinomas. Despite a linear correlation between administered dose and terminal skin concentrations, the incidence of tumor formation was lower in the gavage study than in the dermal study with respect to mean terminal skin TCDD concentrations. These studies demonstrate that, although Tg.AC mice are less responsive to TCDD by gavage than by dermal exposure, the induction of skin neoplasms is a response to systemic exposure and not solely a local response at the site of dermal application. Differences in response between the routes of exposure may reflect pharmacokinetic differences in the delivery of TCDD to the skin over the duration of the study. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Battelle Mem Inst, Columbus, OH 43201 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Walker, NJ (reprint author), NIEHS, MD D4-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM walker3@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 50 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2004 VL 82 IS 1 BP 34 EP 45 DI 10.1093/toxsci/kfh233 PG 12 WC Toxicology SC Toxicology GA 865LL UT WOS:000224704500005 PM 15282402 ER PT J AU Herr, DW Chanda, SM Graff, JE Barone, SS Beliles, RP Morgan, DL AF Herr, DW Chanda, SM Graff, JE Barone, SS Beliles, RP Morgan, DL TI Evaluation of sensory evoked potentials in Long Evans rats gestationally exposed to mercury (Hg-0) vapor SO TOXICOLOGICAL SCIENCES LA English DT Article DE mercury vapor; evoked potentials; sensory toxicity ID NERVE-CONDUCTION VELOCITY; ELEMENTAL MERCURY; INORGANIC MERCURY; PSYCHOPHYSIOLOGICAL RESEARCH; PERIPHERAL NEUROTOXICITY; CHLORALKALI WORKERS; SQUIRREL-MONKEYS; HOODED RATS; WATER MAZE; FLASH AB Mercury is known to alter neuronal function and has been shown to cross the placental barrier. These experiments were undertaken to examine if gestational exposure to mercury vapor (Hg-0) would result in alterations in sensory neuronal function in adult offspring. Dams were exposed to 0 or 4 mg/m(3) Hg-0 for 2 h/day from gestational days 6-15. This exposure paradigm has been shown to approximate a maximal tolerated dose of Hg-0 for the dams. Between postnatal days 140-168, male and female offspring (one of each gender/dam) were examined using a battery of sensory evoked potentials. Peripheral nerve action potentials, nerve conduction velocity, somatosensory evoked responses (cortical and cerebellar), brainstem auditory evoked responses, pattern evoked potentials, and flash evoked potentials were quantified. Gestational exposure to 4 mg/m(3) Hg-0 did not significantly alter any of the evoked responses, although there was a suggestion of a decrease in compound nerve action potential (CNAP) amplitudes in male animals for the 3 mA stimulus condition. However, this possible change in CNAP amplitudes was not replicated in a second experiment. All evoked potentials exhibited predictable changes as the stimulus was modified. This shows conclusively that the evoked responses were under stimulus control, and that the study had sufficient statistical power to detect changes of these magnitudes. These results indicate that gestational exposure to 4 mg/m(3) Hg-0 did not result in changes in responses evoked from peripheral nerves, or the somatosensory, auditory, or visual modalities. C1 US EPA, NHEERL, NTD, NPTB,ORD, Res Triangle Pk, NC 27711 USA. Roche Palo Alto LLC, Palo Alto, CA 94304 USA. NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, NCEA, ORD, Washington, DC 20460 USA. RP Herr, DW (reprint author), US EPA, NHEERL, NTD, NPTB,ORD, 109 TW Alexander Dr,MD B105-05, Res Triangle Pk, NC 27711 USA. EM Herr.david@epamail.epa.gov NR 75 TC 7 Z9 8 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2004 VL 82 IS 1 BP 193 EP 206 DI 10.1093/toxsci/kfh246 PG 14 WC Toxicology SC Toxicology GA 865LL UT WOS:000224704500021 PM 15310857 ER PT J AU Porter-Kelley, JM Gerald, NJ Engel, JC Ghedin, E Dwyer, DM AF Porter-Kelley, JM Gerald, NJ Engel, JC Ghedin, E Dwyer, DM TI LdARF1 in trafficking and structural maintenance of the trans-Golgi cisternal network in the protozoan pathogen Leishmania donovani SO TRAFFIC LA English DT Article DE episomal gene expression; gene transfection; green fluorescent protein-chimera; protozoan parasite; trafficking; trypanosomatid ID ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; CHOLERA-TOXIN; TRYPANOSOMA-BRUCEI; FACTOR-I; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL DOMAINS; ENDOCYTIC PATHWAYS; ACID-PHOSPHATASE; MEMBRANE AB Adenosine diphosphate ribosylation factors (ARFs) are small guanosine-5'-triphosphatases that are essential in vesicular trafficking and in the maintenance of the Golgi network. In this report, we identified a homolog of the mammalian ARF1 in the human pathogenic protozoan parasite, Leishmania donovani (Ld). Ld ARF1 is a 549 bp gene encoding a 183-amino acid deduced protein of similar to 20 kDa. We demonstrated by Southern blot analysis that there are at least two copies of ARF1 in the Ld genome. Moreover, Northern blot analysis revealed that Ld ARF1 is expressed on a 1.35 kb transcript in both the insect vector (promastigotes) and mammalian host (amastigotes) forms of this parasite. Fluorescent microscopy studies using Ld promastigotes episomally transfected with an ARF1::GFP (green fluorescent protein) chimeric construct showed that such chimeras appeared to localize to the Golgi region of these organisms. This observation was verified by immunoelectron microscopy using an anti-GFP antibody. Such studies also revealed that Ld ARF1::GFP chimeras localized to trans-Golgi vesicles, the flagellar pocket/reservoir and other vesicles located between the trans-Golgi network and flagellar pocket in these apically polarized cells. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching experiments revealed both the dynamic binding and releasing activity of Ld ARF1 from the Golgi network in these parasites. Further, episomal expression of a constitutively active ("on") ARF1 (Q71L mutation) resulted in the aberrant swelling and distended-structure of the trans-Golgi cisternae in these cells. These results show that Ld ARF1 is transiently associated with the Golgi network and plays a role in the structural maintenance of this organelle in these important human pathogens. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. Inst Genom Res, Dept Parasite Genom, Rockville, MD 20850 USA. George Washington Univ, Dept Microbiol & Trop Med, Washington, DC 20052 USA. RP Porter-Kelley, JM (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. FU PHS HHS [A135707] NR 50 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD NOV PY 2004 VL 5 IS 11 BP 868 EP 883 DI 10.1111/j.1600-0854.2004.00229.x PG 16 WC Cell Biology SC Cell Biology GA 860MA UT WOS:000224346500006 PM 15479452 ER PT J AU Borie, DC O'Shea, JJ Changelian, PS AF Borie, DC O'Shea, JJ Changelian, PS TI JAK3 inhibition, a viable new modality of immunosuppression for solid organ transplants SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID JANUS KINASE 3; SEVERE COMBINED IMMUNODEFICIENCY; ACUTE LYMPHOBLASTIC-LEUKEMIA; VERSUS-HOST DISEASE; COMMON GAMMA-CHAIN; CD8(+) T-CELLS; HOMEOSTATIC PROLIFERATION; RENAL-TRANSPLANTATION; ALLOGRAFT-REJECTION; SIGNAL-TRANSDUCTION AB The field of organ transplantation has had tremendous success because of the availability of immunosuppressive drugs that efficiently prevent acute organ rejection. Numerous and severe side effects are, however, associated with all current immunosuppressive therapies and justify a search for drugs with better efficacy and safety profiles. Janus kinase (JAK) 3, a tyrosine kinase that is crucial for mediating signals from the common gamma-chain of cytokine receptors, is peculiar in that its expression, contrarily to the targets of most current immunosuppressive drugs, is limited to cells that actively participate to the immune response to allografts. The recent demonstration in stringent preclinical models that JAK3 inhibition results in efficacy for the prevention of allograft rejection with a narrow side-effect profile might lead to a new era in the field of immunosuppression. C1 Stanford Univ, Sch Med, Dept Cardiothorac Surg, Transplantat Immunol Lab, Stanford, CA 94305 USA. Natl Inst Arthritis Musculoskeletal & Skin Dis, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Pfizer Global Res & Dev, Antibacterials Immunol & Canc, Groton, CT 06340 USA. RP Borie, DC (reprint author), Stanford Univ, Sch Med, Dept Cardiothorac Surg, Transplantat Immunol Lab, Stanford, CA 94305 USA. EM dborie@stanford.edu NR 74 TC 45 Z9 46 U1 0 U2 2 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 NOV PY 2004 VL 10 IS 11 BP 532 EP 541 DI 10.1016/j.molmed.2004.09.007 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 873HK UT WOS:000225270300003 PM 15519279 ER PT J AU Guhan, N Lu, B AF Guhan, N Lu, B TI Homer-PIKE complex: a novel link between mGluRI and PI 3-kinase SO TRENDS IN NEUROSCIENCES LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; RYANODINE RECEPTOR-TYPE-1; NEURONAL APOPTOSIS; NUCLEAR GTPASE; IP3 RECEPTORS; PROTEIN; ACTIVATION; MECHANISMS; MODULATION; PLASTICITY AB Metabotropic glutamate (mGlu) receptors, a family of G-protein-coupled receptors, are thought to signal through the phospholipase and inositol (1,4,5)-trisphosphate receptor system, or through the adenylyl cyclase and protein kinase C system. Rong et al. have recently identified a new phosphoinositide (PI) 3-kinase enhancer (PIKE-L) that links group I mGlu receptors (mGluRI) to PI 3-kinase through Homer proteins, adaptors that bind mGluRI. mGluRI agonists enhanced mGluRI-Homer-PIKE-L complex formation, leading to activation of PI 3-kinase and inhibition of staurosporine-induced neuronal apoptosis. These results reveal a novel antiapoptotic signaling mechanism that involves formation of an mGluRI signaling complex. C1 NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Lu, Bai/A-4018-2012 NR 27 TC 9 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 NOV PY 2004 VL 27 IS 11 BP 645 EP 648 DI 10.1016/tins.2004.08.011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 869GC UT WOS:000224970400001 PM 15474163 ER PT J AU Winterer, G Weinberger, DR AF Winterer, G Weinberger, DR TI Genes, dopamine and cortical signal-to-noise ratio in schizophrenia SO TRENDS IN NEUROSCIENCES LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; MESSENGER-RNA EXPRESSION; CEREBRAL BLOOD-FLOW; WORKING-MEMORY; PYRAMIDAL NEURONS; PHYSIOLOGICAL DYSFUNCTION; AUDITORY HALLUCINATIONS; D1 RECEPTORS; NORMAL BRAIN; MODULATION AB A large body of phenomenological evidence implicates abnormal connectivity of brain macrocircuitry and microcircuitry in schizophrenia. Recent discoveries of susceptibility genes for schizophrenia have zeroed in on the synaptic signaling machinery of cortical microcircuits as fundamental to disease causation and have militated for further revision of the role of dopamine in this illness. Dopamine, long implicated in psychosis and in antipsychotic drug effects, is crucial in optimizing signal-to-noise ratio of local cortical microcircuits. This action of dopamine is achieved principally by D1- and D2-receptor-mediated effects on pyramidal and local circuit neurons, which mediate neuronal excitability and recurrent inhibition and thus contribute to the stability of cortical representations of external and internal stimuli. In schizophrenia, an abnormal cortical dopamine D1/D2 activation ratio - in concert with, and in part related to, altered GABA and glutamate transmission appears to interfere crucially with this process. C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Univ Mainz, Dept Psychiat, Lab Mol Neuroimaging & Electrophysiol, D-55131 Mainz, Germany. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. EM weinberd@intra.nimh.nih.gov NR 73 TC 366 Z9 380 U1 4 U2 41 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 2004 VL 27 IS 11 BP 683 EP 690 DI 10.1016/j.tins.2004.08.0042 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 869GC UT WOS:000224970400007 PM 15474169 ER PT J AU Tsujino, H Jones, M Qin, JX Sitges, M Cardon, LA Morehead, AL Zetts, AD Bauer, F Kim, YJ Hang, XY Greenberg, N Thomas, JD Shiota, T AF Tsujino, H Jones, M Qin, JX Sitges, M Cardon, LA Morehead, AL Zetts, AD Bauer, F Kim, YJ Hang, XY Greenberg, N Thomas, JD Shiota, T TI Combination of pulsed-wave Doppler and real-time three-dimensional color Doppler echocardiography for quantifying the stroke volume in the left ventricular outflow tract SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE 3-D echocardiography; color Doppler; Doppler ultrasound; hemodynamics ID CARDIAC-OUTPUT; CLINICAL VALIDATION; ANIMAL-MODEL; QUANTIFICATION; ACCURACY; VELOCITY AB Real-time three-dimensional (3-D) color Doppler echocardiography (RT3D) is capable of quantifying flow. However, low temporal resolution limits its application to stroke volume (SV) measurements. The aim of the present study was, therefore, to develop a reliable method to quantify SV. In animal experiments, cross-sectional images of the LV outflow tract were selected from the RT3D data to calculate peak flow rates (Q(p3D)). Conventional pulsed-wave (PW) Doppler was performed to measure the velocity-time integral (VTI) and the peak velocity (V-p). By assuming that the flow is proportional to the velocity temporal waveform, SV was calculated as alpha x Q(p3D) x VTI/V-p, where a is a temporal correction factor. There was an excellent correlation between the reference flow meter and RT3D SV (mean difference = -1.3 mL, y = 1.05x -2.5, r = 0.94, p<0.01). The new method allowed accurate SV estimations without any geometric assumptions of the spatial velocity distributions. (C) 2004 World Federation for Ultrasound in Medicine Biology. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cardiovasc Imaging Ctr, Cleveland, OH 44195 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Shiota, T (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Cardiovasc Imaging Ctr, 9500 Euclid Ave,F15, Cleveland, OH 44195 USA. EM shiotat@ccf.org NR 18 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD NOV PY 2004 VL 30 IS 11 BP 1441 EP 1446 DI 10.1016/j.ultrasmebio.2004.08.027 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 879LP UT WOS:000225719600003 PM 15588954 ER PT J AU Goncalves, LF Espinoza, J Lee, W Mazor, M Romero, R AF Goncalves, LF Espinoza, J Lee, W Mazor, M Romero, R TI Three- and four-dimensional reconstruction of the aortic and ductal arches using inversion mode: a new rendering algorithm for visualization of fluid-filled anatomical structures SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article ID SPATIOTEMPORAL IMAGE CORRELATION; COLOR DOPPLER ULTRASOUND; FETAL HEART; ULTRASONOGRAPHY; ECHOCARDIOGRAPHY; DIAGNOSIS; DISPLAY; 3D C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), Wayne State Univ, NICHD, Hutzel Hosp, Dept Ob Gyn, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 24 TC 47 Z9 53 U1 0 U2 0 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 NOV PY 2004 VL 24 IS 6 BP 696 EP 698 DI 10.1002/uog.1754 PG 3 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 873IH UT WOS:000225272600024 PM 15521086 ER PT J AU Schmidt, AC Johnson, TR Openshaw, PJM Braciale, TJ Falsey, AR Anderson, LJ Wertz, GW Groothuis, JR Prince, GA Melero, JA Graham, BS AF Schmidt, AC Johnson, TR Openshaw, PJM Braciale, TJ Falsey, AR Anderson, LJ Wertz, GW Groothuis, JR Prince, GA Melero, JA Graham, BS TI Respiratory syncytial virus and other pneumoviruses: a review of the international symposium-RSV 2003 SO VIRUS RESEARCH LA English DT Review DE respiratory syncytial virus; molecular biology; cell biology; epidemiology; physiology; immunology; pathogenesis; treatment; anti-viral vaccine; animal model; metapneumovirus ID LUNG-TRANSPLANT RECIPIENTS; 2 DISTINCT SITES; FUSION PROTEIN; G-GLYCOPROTEIN; HOST-RANGE; VIRAL-INFECTION; RHESUS-MONKEYS; T-CELLS; VACCINE; TYPE-3 AB The Respiratory Syncytial Virus 2003 symposium took place from 8th-11th November 2003 in Stone Mountain, Georgia, and brought together more than 200 international investigators engaged in RSV research. RSV biology, pathogenesis, and clinical data, as well as RSV vaccines and antivirals, were addressed in the meeting, and this review will aim to briefly summarize and discuss the implications of new findings. The meeting also served as the inauguration of the Robert M. Chanock Award for lifetime achievement in RSV research, an award named in honor of the person who started the field of RSV research by recovering the first human RS virus from infants with severe bronchiolitis in 1956. (C) 2004 Elsevier B.V. All rights reserved. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Charite Univ Hosp, Dept Pediat Pulmonol & Immunol, Berlin, Germany. Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Sch Med, Dept Resp Med, London, England. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY USA. CDCP, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Resp & Enter Viruses Branch, Atlanta, GA USA. Univ Alabama, Dept Microbiol, Birmingham, AL USA. Abbott Labs, Abbott Pk, IL USA. Virion Syst Inc, Rockville, MD USA. Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid, Spain. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3017,Bldg 40,Room 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 53 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD NOV PY 2004 VL 106 IS 1 BP 1 EP 13 DI 10.1016/j.virusres.2004.06.008 PG 13 WC Virology SC Virology GA 874CL UT WOS:000225328400001 PM 15522442 ER PT J AU Lee, SY Lee, FS Moon, JS Kim, JI Park, JB Lee, JY Park, MJ Kim, J AF Lee, SY Lee, FS Moon, JS Kim, JI Park, JB Lee, JY Park, MJ Kim, J TI Transcriptional regulation of Zic3 by heterodimeric AP-1(c-Jun/c-Fos) during Xenopus development SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE activin; AP-1(c-Jun & c-fos); Xenopus development; Zic3 ID NEURAL CREST DEVELOPMENT; FIBROBLAST-GROWTH-FACTOR; C-JUN; MESODERM INDUCTION; AP-1; EMBRYOS; GENE; CELLS; BMP-4; TRANSFORMATION AB The heterodimeric c,-Jun/c-Fos, an activator protein-1 (AP-1) has been implicated in mesoderm induction (Dong et al., 1996; Kim et al., 1998) whereas the homodimer of c-Jun was reported to be involved in neural inhibition during the early development of Xenopus embryos. During the early vertebrate development AP-1 involvement in the neural induction is still not clearly understood. We report here that AP-1 has a role in Zic3 expression, a critical proneural gene and a primary regulator of neural and neural crest development (Nakata et al., 1997; Nakata et al., 1998). AP-1 was able to induce the Zic3 gene in a dose dependent manner but other homo-or hetero-dimeric proteins, such as. c-Jun/c-Jun, JunD/FosB or JunD/Fra-1 were not. The inhibition of AP-1 activity using morpholino antisenses of c-jun mRNAs blocked the Zic3 expression induced by activin. In addition, co-injection of c-jun mRNA rescued the down-regulated Zic3 expression. The promoter region of isolated Zic3 genomic DNA was found to possess several consensus-binding site of AP-1. Thus, in the functional assays, AP-1 could increase promoter activity of Zic3 gene. These findings suggest that proneural gene, Zic3 may be regulated by heterodimeric AP-1(c-Jun/c-Fos) and it may have a role in activin signaling for the regulation of neural specific gene, Zic3. C1 Hallym Univ, Coll Med, Dept Biochem, Kangwon Do 200702, South Korea. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700422, South Korea. RP Kim, J (reprint author), Hallym Univ, Coll Med, Dept Biochem, Kangwon Do 200702, South Korea. EM ibkim@hallym.ac.kr RI KIM, JONG-IL/D-1019-2011 OI KIM, JONG-IL/0000-0002-7240-3744 NR 32 TC 12 Z9 13 U1 0 U2 0 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD OCT 31 PY 2004 VL 36 IS 5 BP 468 EP 475 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 874OH UT WOS:000225359200009 PM 15557819 ER PT J AU Backman, CM Zhang, YJ Hoffer, BJ Tomac, AC AF Backman, CM Zhang, YJ Hoffer, BJ Tomac, AC TI Tetracycline-inducible expression systems for the generation of transgenic animals: a comparison of various inducible systems carried in a single vector SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE tetracycline-inducible; conditional gene regulation; single vector; conditional transgenics ID GENE-EXPRESSION; TIGHT CONTROL; BRAIN; RECOMBINATION; MICE AB The most often used tetracycline-regulated transgenic mice system requires the generation of two transgenic strains, one carrying an inducible promoter and the other a transactivator. In this study, we report the design of a universal and simplified regulatory gene delivery vector to facilitate the generation of conditional transgenic animals that integrate both the tetracycline regulatory and response elements in a single vector. The newly developed tetracycline reversed transactivator rtTA-M2 was used in all our constructs, based on its highly improved properties with respect to specificity, stability and inducibility. To minimize interference between the different tetracycline-inducible promoters used in this study (tetracycline-responsive element (TRE), TRE-tight, or Tk-tetO) and the rtTA-M2 transactivator, both elements were cloned in opposite directions and separated by a 5 kb human p53 intron. The functionality of this system was confirmed after in vitro transfection in a mammalian cell line. Overall induction by the tetracycline-responsive element promoter was significantly higher than that induced by the newly developed TRE-tight promoter. However, the TRE-tight promoter showed a significantly tighter expression with minimal background, and still maintained high induction levels. The minimal Tk-tetO promoter showed a very weak induction capacity. Our study demonstrates that this combination of elements, placed in a single vector is sufficient for delivering a functional tetracycline-inducible system to a mammalian cell tine. Moreover, additional modifications to this regulatory gene delivery system, such as the introduction of specific cloning sites and selection markers, have been designed with the idea of creating a simplified and universal inducible system to facilitate the generation of conditional transgenic, knock-out, and knock-in animals. Published by Elsevier B.V. C1 NIDA, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Tomac, AC (reprint author), NIDA, Cellular Neurobiol Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM atomac@intra.nida.nih.gov RI backman, cristina/C-1276-2013 NR 14 TC 21 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 30 PY 2004 VL 139 IS 2 BP 257 EP 262 DI 10.1016/j.jneumeth.2004.05.012 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 869GD UT WOS:000224970500015 PM 15488239 ER PT J AU Copersino, ML Serper, MR Vadhan, N Goldberg, BR Richarme, D Chou, JCY Stitzer, M Cancro, R AF Copersino, ML Serper, MR Vadhan, N Goldberg, BR Richarme, D Chou, JCY Stitzer, M Cancro, R TI Cocaine craving and attentional bias in cocaine-dependent schizophrenic patients SO PSYCHIATRY RESEARCH LA English DT Article DE substance abuse; schizophrenia; Stroop test; comorbidity ID SELECTIVE ATTENTION; COGNITIVE BIASES; STROOP TASK; DRUG-ABUSE; ADDICTION; ALCOHOL; CUES; HALOPERIDOL; ACTIVATION; STIMULI AB Cocaine craving has been implicated as a major factor underlying addiction and drug relapse. From a cognitive viewpoint, craving may reflect, in part, attentional processing biased in favor of drug-related cues and stimuli. Schizophrenic individuals (SZ), however, abuse cocaine in high numbers but typically manifest baseline cognitive deficits that impair their ability to selectively allocate their attentional resources. In this study, we examined the relationship between attentional bias and craving in patients with cocaine dependence (COC; n=20), schizophrenic patients comorbid for cocaine dependence (COC+SZ; n=23), and two other comparison groups using a modified version of the Stroop test to include cocaine-relevant words. Results revealed that only the COC patients demonstrated Stroop interference on the cocaine-related words. Moreover, COC patients' attentional processing biases were significantly associated with their cocaine craving severity ratings. COC+SZ patients, in contrast, did not demonstrate Stroop interference and manifested significantly fewer craving symptoms than their COC counterparts. These results suggest that COC+SZ patients' inability to selectively encode their drug-use experience may limit and shape their subjective experience. of craving cocaine and motivation for cocaine use. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Hofstra Univ, Dept Psychol, Hempstead, NY 11549 USA. Natl Inst Drug Abuse, Intramural Res Program, NIH, US Dept HHS, Baltimore, MD USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. RP Serper, MR (reprint author), Hofstra Univ, Dept Psychol, Hauser Hall, Hempstead, NY 11549 USA. EM mark.serper@nyu.edu OI Cancro, Robert/0000-0003-1553-2168 NR 50 TC 47 Z9 48 U1 4 U2 11 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 OCT 30 PY 2004 VL 128 IS 3 BP 209 EP 218 DI 10.1016/j.psychres.2004.07.006 PG 10 WC Psychiatry SC Psychiatry GA 878DY UT WOS:000225627900001 PM 15541777 ER PT J AU Pejsa, V Grgurevic, I Kujundzic, M Martinovic, M Stancic, V Donley, K Pavletic, S AF Pejsa, V Grgurevic, I Kujundzic, M Martinovic, M Stancic, V Donley, K Pavletic, S TI No adverse effect of ABVD chemotherapy in a patient with chronic hepatitis C and Hodgkin's disease SO WIENER KLINISCHE WOCHENSCHRIFT LA English DT Article DE hepatitis C; Hodgkin's disease; chemotherapy ID CELL LYMPHOPROLIFERATIVE DISORDERS; VIRUS-INFECTION; LIVER DYSFUNCTION; HIGH PREVALENCE; LYMPHOMA; CANCER AB There is insufficient information on the effects of chemotherapy protocols for Hodgkin's disease (HD) and the course of coexisting hepatitis C virus (HCV) infection. A single literature case reported a patient with HID who developed fulminant hepatitis and hepatic coma after receiving chemotherapy. The case described here is of a female patient previously exposed to prolonged war stress, complicated by intravenous drug abuse and chronic hepatitis C. One year after diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II, clinical stage IIIB). The patient received six cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete remission of HD. There was no hepatitis flare either during or after chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on the course of HCV infection in this patient who was successfully treated for HD. Because concurrent HCV infection and HID is extremely rare, we discuss here the possibility of the synergistic contribution of chronic war stress and hepatitis C infection in the pathogenesis of HD. C1 Univ Zagreb, Dubrava Univ Hosp, Div Hematol, Dept Internal Med, Zagreb 10000, Croatia. Univ Zagreb, Dubrava Univ Hosp, Div Gastroenterol & Hepatol, Dept Internal Med, Zagreb 10000, Croatia. Univ Zagreb, Univ Hosp Sisters Mercy, Dept Internal Med, Div Hematol, Zagreb, Croatia. Natl Canc Inst, Bethesda, MD USA. RP Pejsa, V (reprint author), Univ Zagreb, Dubrava Univ Hosp, Div Hematol, Dept Internal Med, Av Gojka Suska 6, Zagreb 10000, Croatia. EM vpejsa@kbd.hr NR 16 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0043-5325 J9 WIEN KLIN WOCHENSCHR JI Wien. Klin. Wochen. PD OCT 30 PY 2004 VL 116 IS 19-20 BP 695 EP 697 DI 10.1007/s00508-004-0247-1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 871EK UT WOS:000225112000012 PM 15941081 ER PT J AU Hygge-Blakeman, K Brumovsky, P Hao, JX Xu, XJ Hokfelt, T Crawley, JN Wiesenfeld-Hallin, Z AF Hygge-Blakeman, K Brumovsky, P Hao, JX Xu, XJ Hokfelt, T Crawley, JN Wiesenfeld-Hallin, Z TI Galanin over-expression decreases the development of neuropathic pain-like behaviors in mice after partial sciatic nerve injury SO BRAIN RESEARCH LA English DT Article DE galanin over-expression; neuropathy; nociception; spinal cord ID DORSAL-ROOT GANGLIA; SPINAL REFLEX EXCITABILITY; PRIMARY SENSORY NEURONS; C-FIBER STIMULATION; INTRATHECAL GALANIN; PERIPHERAL AXOTOMY; ALZHEIMERS-DISEASE; TRANSGENIC MICE; FLEXOR REFLEX; RAT AB The neuropeptide galanin may have a role in modulation of nociception, particularly after peripheral nerve injury. Here we assessed the development of neuropathic pain-like behaviors in mice overexpressing galanin under the dopamine-hydroxylase promoter. Unoperated galanin over-expressing mice exhibited a moderately reduced sensitivity to noxious heat. Both galanin over-expressing mice and wild-type controls developed mechanical and heat hypersensitivity after photochemically induced partial sciatic nerve ischemic injury. The magnitude and persistence of such pain-like behaviors were significantly less, and recovery was faster in galanin over-expressing mice compared to wild types. However, the recovery from toe-spread deficits did not differ between galanin over-expressing and wild-type mice after a crush injury to the sciatic nerve. Thus, early recovery in pain-like response is unlikely to result from accelerated regeneration in the galanin overexpressing mice. Immunohistochemical analysis showed that galanin is over-expressed both in small and large dorsal root ganglion cells in the transgene mouse, whereas large galanin-positive neurons were never seen in wild-type mice. The present results in general support an inhibitory role of galanin in nociception and indicate that increased availability of galanin in spinal dorsal horn at the time or shortly after nerve injury may reduce the development of pain-like behaviors in mice. (C) 2004 Elsevier B.V. All rights reserved. C1 Huddinge Univ Hosp, Div Clin Neurophysiol, S-14186 Huddinge, Sweden. Karolinska Inst, Dept Neurosci, Div Chem Neurotransmiss, Stockholm, Sweden. NIMH, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. RP Wiesenfeld-Hallin, Z (reprint author), Huddinge Univ Hosp, Div Clin Neurophysiol, S-14186 Huddinge, Sweden. EM zsuzsanna.wiesenfeld-hallin@labmed.ki.se RI Brumovsky, Pablo/A-6477-2009 NR 46 TC 30 Z9 31 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 29 PY 2004 VL 1025 IS 1-2 BP 152 EP 158 DI 10.1016/j.brainres.2004.07.078 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 865DM UT WOS:000224682700018 PM 15464755 ER PT J AU Kamhawi, S Ramalho-Ortigao, M Pham, VM Kumar, S Lawyer, PG Turco, SJ Barillas-Mury, C Sacks, DL Valenzuela, JG AF Kamhawi, S Ramalho-Ortigao, M Pham, VM Kumar, S Lawyer, PG Turco, SJ Barillas-Mury, C Sacks, DL Valenzuela, JG TI A role for insect galectins in parasite survival SO CELL LA English DT Article ID LEISHMANIA-MAJOR PROMASTIGOTES; SAND FLY INTERACTIONS; DEVELOPMENTAL MODIFICATION; VECTORIAL COMPETENCE; TRYPANOSOMA-RANGELI; RHODNIUS-PROLIXUS; LIPOPHOSPHOGLYCAN; LECTIN; IDENTIFICATION; DOMAINS AB Insect galectins are associated with embryonic development or immunity against pathogens. Here, we show that they can be exploited by parasites for survival in their insect hosts. PpGalec, a tandem repeat galectin expressed in the midgut of the sand fly Phlebotomus papatasi, is used by Leishmania major as a receptor for mediating specific binding to the insect midgut, an event crucial for parasite survival, and accounts for species-specific vector competence. PpGalec is thus identified as a key molecule controlling vector competence for the most widely distributed form of cutaneous leishmaniasis in the Old World. In addition, these studies demonstrate the feasibility of using midgut receptors for parasite ligands as target antigens for transmission-blocking vaccines. C1 NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Dept Mol & Cellular Biochem, Lexington, KY 40502 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jvalenzuela@niaid.nih.gov RI Ramalho-Ortigao, Marcelo/E-8225-2011 FU NIAID NIH HHS [AI20941] NR 51 TC 132 Z9 137 U1 4 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 29 PY 2004 VL 119 IS 3 BP 329 EP 341 DI 10.1016/j.cell.2004.10.009 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868IW UT WOS:000224908300005 PM 15543683 ER PT J AU Yedavalli, VSRK Neuveut, C Chi, YH Kleiman, L Jeang, KT AF Yedavalli, VSRK Neuveut, C Chi, YH Kleiman, L Jeang, KT TI Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function SO CELL LA English DT Article ID CONSTITUTIVE TRANSPORT ELEMENT; IMMUNODEFICIENCY-VIRUS REV; NUCLEAR-PORE COMPLEX; MESSENGER-RNA; D RETROVIRUS; SACCHAROMYCES-CEREVISIAE; TRANSLATION INITIATION; CELLULAR-PROTEINS; CRM1; TYPE-1 AB A single transcript in its unspliced and spliced forms directs the synthesis of all HIV-1 proteins. Although nuclear export of intron-containing cellular transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev protein to overcome this restriction for viral transcripts. Previously, CRM1 was identified as a cellular cofactor for Rev-dependent export of intron-containing HIV-1 RNA. Here, we present evidence that Rev/CRM1 activity utilizes the ATP-dependent DEAD box RNA helicase, DDX3. We show that DDX3 is a nucleo-cytoplasmic shuttling protein, which binds CRM1 and localizes to nuclear membrane pores. Knockdown of DDX3 using either antisense vector or dominant-negative mutants suppressed Rev-RRE-function in the export of incompletely spliced HIV-1 RNAs. Plausibly, DDX3 is the human RNA helicase which functions in the CRM1 RNA export pathway analogously to the postulated role for Dbp5p in yeast mRNA export. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA. McGill AIDS Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Chi, Ya-Hui/B-1080-2010; Jeang, Kuan-Teh/A-2424-2008 NR 61 TC 299 Z9 308 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD OCT 29 PY 2004 VL 119 IS 3 BP 381 EP 392 DI 10.1016/j.cell.2004.09.029 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868IW UT WOS:000224908300009 PM 15507209 ER PT J AU Canagarajah, B Leskow, FC Ho, JYS Mischak, H Saidi, LF Kazanietz, MG Hurley, JH AF Canagarajah, B Leskow, FC Ho, JYS Mischak, H Saidi, LF Kazanietz, MG Hurley, JH TI Structural mechanism for lipid activation of the Rac-specific GAP, beta 2-chimaerin SO CELL LA English DT Article ID PROTEIN-KINASE-C; PHORBOL ESTER RECEPTOR; CYSTEINE-RICH REGION; CRYSTAL-STRUCTURE; N-CHIMAERIN; SUBCELLULAR-LOCALIZATION; INDUCED TRANSLOCATION; MEMBRANE-BINDING; NIH 3T3-CELLS; DOMAIN AB The lipid second messenger diacylglycerol acts by binding to the C1 domains of target proteins, which translocate to cell membranes and are allosterically activated. Here we report the crystal structure at 3.2 Angstrom resolution of one such protein, beta2-chimaerin, a GTPase-activating protein for the small GTPase Rac, in its inactive conformation. The structure shows that in the inactive state, the N terminus of beta2-chimaerin protrudes into the active site of the RacGAP domain, sterically blocking Rac binding. The diacylglycerol and phospholipid membrane binding site on the C1 domain is buried by contacts with the four different regions of beta2-chimaerin: the N terminus, SH2 domain, RacGAP domain, and the linker between the SH2 and C1 domains. Phospholipid binding to the C1 domain triggers the cooperative dissociation of these interactions, allowing the N terminus to move out of the active site and thereby activating the enzyme. C1 NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov RI Mischak, Harald/E-8685-2011 FU NCI NIH HHS [R01-CA74197] NR 60 TC 87 Z9 88 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 29 PY 2004 VL 119 IS 3 BP 407 EP 418 DI 10.1016/j.cell.2004.10.012 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868IW UT WOS:000224908300011 PM 15507211 ER PT J AU Gonzalez-Navarro, H Nong, ZX Amar, MJA Shamburek, RD Najib-Fruchart, J Paigen, BJ Brewer, HB Santamarina-Fojo, S AF Gonzalez-Navarro, H Nong, ZX Amar, MJA Shamburek, RD Najib-Fruchart, J Paigen, BJ Brewer, HB Santamarina-Fojo, S TI The ligand-binding function of hepatic lipase modulates the development of atherosclerosis in transgenic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; RECEPTOR-RELATED PROTEIN; IN-VIVO EVIDENCE; HUMAN APO-B; APOLIPOPROTEIN-E; DEFICIENT MICE; LDL RECEPTOR; CHYLOMICRON REMNANTS; TRIGLYCERIDE LIPASE AB To investigate the separate contributions of the lipolytic versus ligand-binding function of hepatic lipase (HL) to plasma lipoprotein metabolism and atherosclerosis, we compared mice expressing catalytically active wild-type HL (HL-WT) and inactive HL (HL-S145G) with no endogenous expression of mouse apoE or HL (E-KO x HL-KO, where KO is knockout). HL-WT and HL-S145G reduced plasma cholesterol ( by 40 and 57%, respectively), non-high density lipoprotein cholesterol ( by 48 and 61%, respectively), and apoB (by 36 and 44%, respectively) (p < 0.01), but only HL-WT decreased high density lipoprotein cholesterol (by 67%) and apoA-I (by 54%). Compared with E-KO x HL-KO mice, both active and inactive HL lowered the pro-atherogenic lipoproteins by enhancing the catabolism of autologous I-125-apoB very low density/intermediate density lipoprotein (VLDL/IDL) ( fractional catabolic rates of 2.87 &PLUSMN; 0.04/day for E-KO x HL-KO, 3.77 &PLUSMN; 0.03/day for E-KO x HL-WT, and 3.63 &PLUSMN; 0.09/day for E-KO x HL-S145G mice) and I-125-apoB-48 low density lipoprotein (LDL) ( fractional catabolic rates of 5.67 &PLUSMN; 0.34/day for E-KO x HL-KO, 18.88 &PLUSMN; 1.72/day for E-KO x HL-WT, and 9.01 &PLUSMN; 0.14/day for E-KO x HL-S145G mice). In contrast, the catabolism of apoE-free, I-131-apoB-100 LDL was not increased by either HL-WT or HL-S145G. Infusion of the receptor-associated protein ( RAP), which blocks LDL receptor-related protein function, decreased plasma clearance and hepatic uptake of I-131-apoB-48 LDL induced by HL-S145G. Despite their similar effects on lowering proatherogenic apoB-containing lipoproteins, HL-WT enhanced atherosclerosis by up to 50%, whereas HL-S145G markedly reduced aortic atherosclerosis by up to 96% (p < 0.02) in both male and female E-KO x HL-KO mice. These data identify a major receptor pathway ( LDL receptor-related protein) by which the ligand-binding function of HL alters remnant lipoprotein uptake in vivo and delineate the separate contributions of the lipolytic versus ligand-binding function of HL to plasma lipoprotein size and metabolism, identifying an anti-atherogenic role of the ligand-binding function of HL in vivo. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Inst Pasteur, F-59019 Lille, France. RP Santamarina-Fojo, S (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10,Rm 7N115,10 Ctr Dr,MSC 1666, Bethesda, MD 20892 USA. EM silvia@mdb.nhlbi.nih.gov NR 63 TC 25 Z9 27 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 OCT 29 PY 2004 VL 279 IS 44 BP 45312 EP 45321 DI 10.1074/jbc.M406495200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900005 PM 15304509 ER PT J AU Jeong, JS Rouault, TA Levine, RL AF Jeong, JS Rouault, TA Levine, RL TI Identification of a heme-sensing domain in iron regulatory protein 2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAGNETIC CIRCULAR-DICHROISM; OXIDIZED PROTEINS; MICROSOMAL CYTOCHROME-P-450; OXIDATIVE MODIFICATION; DEPENDENT DEGRADATION; HIF-ALPHA; PROTEASOME; BINDING; IRP2; METABOLISM AB Iron regulatory protein 2 coordinates the cellular regulation of iron metabolism by binding to iron-responsive elements in mRNA. The protein is synthesized constitutively but is rapidly degraded when iron stores are replete. The mechanisms that prevent degradation during iron deficiency or promote degradation during iron sufficiency are not delineated. Iron regulatory protein 2 contains a domain not present in the closely related iron regulatory protein 1, and we found that this domain binds heme with high affinity. A cysteine within the domain is axially liganded to the heme, as occurs in cytochrome P450. The protein-bound heme reacts with molecular oxygen to mediate the oxidation of cysteine, including beta-elimination of the sulfur to yield alanine. This covalent modification may thus mark the protein molecule for degradation by the proteasome system, providing another mechanism by which heme can regulate the level of iron regulatory protein 2. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Rm 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 NR 46 TC 29 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 OCT 29 PY 2004 VL 279 IS 44 BP 45450 EP 45454 DI 10.1074/jbc.M407562200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900021 PM 15316013 ER PT J AU Daniel, R Ramcharan, J Rogakou, E Taganov, KD Greger, JG Bonner, W Nussenzweig, A Katz, RA Skalka, AM AF Daniel, R Ramcharan, J Rogakou, E Taganov, KD Greger, JG Bonner, W Nussenzweig, A Katz, RA Skalka, AM TI Histone H2AX is phosphorylated at sites of retroviral DNA integration but is dispensable for postintegration repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAKS; GENOMIC INSTABILITY; V(D)J RECOMBINATION; IONIZING-RADIATION; DAMAGE; CELLS; TRANSDUCTION; CHECKPOINT; VIRUS; GAMMA-H2AX AB The histone variant H2AX is rapidly phosphorylated (denoted gammaH2AX) in large chromatin domains ( foci) flanking double strand DNA ( dsDNA) breaks that are produced by ionizing radiation or genotoxic agents and during V(D)J recombination. H2AX-deficient cells and mice demonstrate increased sensitivity to dsDNA break damage, indicating an active role for gammaH2AX in DNA repair; however, gammaH2AX formation is not required for V(D)J recombination. The latter finding has suggested a greater dependence on gammaH2AX for anchoring free broken ends versus ends that are held together during programmed breakage-joining reactions. Retroviral DNA integration produces a unique intermediate in which a dsDNA break in host DNA is held together by the intervening viral DNA, and such a reaction provides a useful model to distinguish gammaH2AX functions. We found that integration promotes transient formation of gammaH2AX at retroviral integration sites as detected by both immunocytological and chromatin immunoprecipitation methods. These results provide the first direct evidence for the association of newly integrated viral DNA with a protein species that is an established marker for the onset of a DNA damage response. We also show that H2AX is not required for repair of the retroviral integration intermediate as determined by stable transduction. These observations provide independent support for an anchoring model for the function of gammaH2AX in chromatin repair. C1 Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Skalka, AM (reprint author), Fox Chase Canc Ctr, Inst Canc Res, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM AM_skalka@fccc.edu FU NCI NIH HHS [CA06927, CA98090, CA71515]; NIAID NIH HHS [AI40385] NR 35 TC 39 Z9 52 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 29 PY 2004 VL 279 IS 44 BP 45810 EP 45814 DI 10.1074/jbc.M407886200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900065 PM 15308627 ER PT J AU Nagiec, MJ Lei, B Parker, SK Vasil, ML Matsumoto, M Ireland, RM Beres, SB Hoe, NP Musser, JM AF Nagiec, MJ Lei, B Parker, SK Vasil, ML Matsumoto, M Ireland, RM Beres, SB Hoe, NP Musser, JM TI Analysis of a novel prophage-encoded Group A Streptococcus extracellular phospholipase A(2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLETE GENOME SEQUENCE; SEROTYPE M3 STRAIN; PYOGENES; INFECTIONS; EXPRESSION; MECHANISM; EVOLUTION; EMERGENCE; ENZYMES; ONTARIO AB Group A Streptococcus ( GAS) is an important human pathogen that causes many types of infections, including pharyngitis and severe invasive diseases. We recently sequenced the genome of a serotype M3 strain and identified a prophage-encoded secreted phospholipase A(2) designated SlaA. To study SlaA structure-activity relationships, 20 site-specific mutants were constructed by alanine-replacement mutagenesis and purified to apparent homogeneity. Enzymatic activity was greatly reduced by alanine replacement of amino acid residues previously described as crucial in the catalytic mechanism of secreted phospholipase A(2). Similarly, substitution of five residues in an inferred Ca2+-binding loop and three residues in the inferred active site region resulted in loss of activity of 76.5% or greater relative to the wild-type enzyme. Analysis of enzyme substrate specificity confirmed SlaA as a phospholipase A(2), with activity against multiple phospholipid head groups and acyl chains located at the sn-2 position. PCR analysis of 1,189 GAS strains representing 48 M protein serotypes commonly causing human infections identified the slaA gene in 129 strains of nine serotypes (M1, M2, M3, M4, M6, M22, M28, M75, and st3757). Expression of SlaA by strains of these serotypes was confirmed by Western immunoblot. SlaA production increased rapidly and substantially on co-culture with Detroit 562 human pharyngeal epithelial cells. Together, these data provide new information about a novel extracellular enzyme that participates in GAS-human interactions. C1 Baylor Coll Med, Dept Pathol, Ctr Human Bacterial Pathogenesis Res, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. RP Musser, JM (reprint author), Baylor Coll Med, Dept Pathol, Ctr Human Bacterial Pathogenesis Res, 1 Baylor Plaza, Houston, TX 77030 USA. EM musser@bcm.tmc.edu NR 36 TC 27 Z9 29 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 OCT 29 PY 2004 VL 279 IS 44 BP 45909 EP 45918 DI 10.1074/jbc.M405434200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900075 PM 15304506 ER PT J AU Gardiner, EJ Hunter, CA Lu, XJ Willett, P AF Gardiner, EJ Hunter, CA Lu, XJ Willett, P TI A structural similarity analysis of double-helical DNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE sequence-dependent DNA; structural similarity; promoter recognition; DNA flexibility; data fusion ID CONFORMATIONAL MAPS; DATA FUSION; SEQUENCE; PROTEIN; RECOGNITION; COMBINATION AB A database of the structural properties of all 32,896 unique DNA octamer sequences has been calculated, including information on stability, the minimum energy conformation and flexibility. The contents of the database have been analysed using a variety of Euclidean distance similarity measures. A global comparison of sequence similarity with structural similarity shows that the structural properties of DNA are much less diverse than the sequences, and that DNA sequence space is larger and more diverse than DNA structure space. Thus, there are many very different sequences that have very similar structural properties, and this may be useful for identifying DNA motifs that have similar functional properties that are not apparent from the sequences. On the other hand, there are also small numbers of almost identical sequences that have very different structural properties, and these could give rise to false-positives in methods used to identify function based on sequence alignment. A simple validation test demonstrates that structural similarity can differentiate between promoter and non-promoter DNA. Combining structural and sequence similarity improves promoter recall beyond that possible using either similarity measure alone, demonstrating that there is indeed information available in the structure of double-helical DNA that is not readily apparent from the sequence. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England. Univ Sheffield, Dept Informat Studies, Sheffield S1 4DP, S Yorkshire, England. NCI, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. RP Gardiner, EJ (reprint author), Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England. EM e.gardiner@sheffield.ac.uk NR 26 TC 9 Z9 9 U1 0 U2 1 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 OCT 29 PY 2004 VL 343 IS 4 BP 879 EP 889 DI 10.1016/j.jmb.2004.08.092 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 864TP UT WOS:000224656100007 PM 15476807 ER PT J AU Rigden, DJ Galperin, MY AF Rigden, DJ Galperin, MY TI The DxDxDG motif for calcium binding: Multiple structural contexts and implications for evolution SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE calcium; EF-hand; protein structure; structure motifs; evolution ID EF-HAND PROTEINS; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; SECONDARY STRUCTURE; METAL-BINDING; ALPHA-AMYLASE; PROTECTIVE ANTIGEN; SEQUENCE; DOMAIN; SITE AB Calcium ions regulate many cellular processes and have important structural roles in living organisms. Despite the great variety of calcium-binding proteins (CaBPs), many of them contain the same Ca2+-binding helix-loop-helix structure, referred to as the EF-hand. In the canonical EF-hand, the loop contains three calcium-binding aspartic acid residues, which form the DxDxDG sequence motif, and is flanked by two a-helices. Recently, other CaBPs containing the same motif, but lacking one or both helices, have been described. Here, structural motif searches were used to analyse the full diversity of structural context in the known set of DxDxDG-containing CaBPs, including those where the structural resemblance of a given DxDxDG motif to that of EF-hands had not been noted. The results obtained indicate that the EF-hand represents but one, among many, structural context for the DxDxDG-like Ca2+-binding loops. While the structural similarity of the binuclear calcium-binding sites in anthrax protective antigen and human thrombospondin suggests that they are homologous, evolutionary relationships for mononuclear sites are harder to discern. The possible scenarios for the evolution of DxDxDG motif-containing calcium-binding loops in a variety of non-homologous proteins suggested loop transplant as a mechanism perhaps responsible for much of the diversity in structural contexts of present day DxDxDG-type CaBPs. Additionally, while it can be shown that existence of a DxDxDG sequence is not enough to confer a conformation suitable for calcium binding, local convergent evolution may still have a role. The analysis presented here has consequences for the prediction of calcium binding from sequence alone. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Rigden, DJ (reprint author), Univ Liverpool, Sch Biol Sci, Crown St, Liverpool L69 7ZB, Merseyside, England. EM drigden@liverpool.ac.uk RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 NR 69 TC 60 Z9 63 U1 0 U2 11 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 OCT 29 PY 2004 VL 343 IS 4 BP 971 EP 984 DI 10.1016/j.jmb.2004.08.077 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 864TP UT WOS:000224656100014 PM 15476814 ER PT J AU Xiao, XS Antony, S Kohlhagen, G Pommier, Y Cushman, M AF Xiao, XS Antony, S Kohlhagen, G Pommier, Y Cushman, M TI Novel autoxidative cleavage reaction of 9-fluoredenes discovered during synthesis of a potential DNA-threading indenoisoquinoline SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID TOPOISOMERASE-I INHIBITORS; BIOLOGICAL EVALUATION; CAMPTOTHECIN; CHLORIDE; DESIGN; CHEMISTRY; OXIDATION; POSITION; OXYGEN; RINGS AB The indenoisoquinolines are a novel class of cytotoxic non-camptothecin topoisomerase I inhibitors. A potential DNA-threading agent was designed by attaching different amine side chains on the lactam nitrogen as well as on the C11 position of the indenoisoquinoline ring system. It was hypothesized that substituents on the lactam nitrogen could protrude out toward the DNA major groove while those on the C11 project out toward the DNA minor groove in the ternary "cleavage complex." Compound 4 was synthesized in order to test this DNA-threading scenario. It was found unexpectedly that an alkenyl substituent on the C11 position was autoxidatively cleaved under basic conditions to afford a ketone. A possible mechanism for this unusual oxidative cleavage was proposed on the basis of the studies of a 9-fluoredene model compound. The proposed mechanism was further supported by computational studies. Although the designed compound 4 showed potent cytotoxicities in various cancer cell lines, it was less potent than its nonthreading counterparts and was not a topoisomerase I inhibitor. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm & Pharm Sci, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm & Pharm Sci, W Lafayette, IN 47907 USA. EM cushman@pharmacy-purdue.edu FU NCI NIH HHS [U01 CA089566, N01-CO-56000] NR 31 TC 10 Z9 10 U1 0 U2 3 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 OCT 29 PY 2004 VL 69 IS 22 BP 7495 EP 7501 DI 10.1021/jo048808f PG 7 WC Chemistry, Organic SC Chemistry GA 865MT UT WOS:000224707900012 PM 15497974 ER PT J AU Birnbaum, SG Yuan, PX Wang, M Vijayraghavan, S Bloom, AK Davis, DJ Gobeske, KT Sweatt, JD Manji, HK Arnsten, AFT AF Birnbaum, SG Yuan, PX Wang, M Vijayraghavan, S Bloom, AK Davis, DJ Gobeske, KT Sweatt, JD Manji, HK Arnsten, AFT TI Protein kinase C overactivity impairs prefrontal cortical regulation of working memory SO SCIENCE LA English DT Article ID BIPOLAR DISORDER; ALPHA-1-ADRENERGIC AGONIST; AUDITORY HALLUCINATIONS; CORTEX; SCHIZOPHRENIA; PERFORMANCE; MONKEYS AB The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder. C1 Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RP Arnsten, AFT (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06520 USA. EM amy.arnsten@yale.edu OI Sweatt, J. David/0000-0003-3567-485X FU NIA NIH HHS [AG06036]; NIMH NIH HHS [P50 MH068789] NR 18 TC 162 Z9 170 U1 0 U2 10 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 OCT 29 PY 2004 VL 306 IS 5697 BP 882 EP 884 DI 10.1126/science.1100021 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 869FS UT WOS:000224969400050 PM 15514161 ER PT J AU Doyle, AES Goodman, JE Silber, PM Yager, JD AF Doyle, AES Goodman, JE Silber, PM Yager, JD TI Catechol-O-methyltransferase low activity genotype (COMTLL) is associated with low levels of COMT protein in human hepatocytes SO CANCER LETTERS LA English DT Article DE val108met COMT; gene polymorphism; enzyme activity; human hepatocytes ID BREAST-CANCER RISK; METHYL TRANSFERASE; PARKINSONS-DISEASE; POLYMORPHISM; GENE; PHARMACOGENETICS; ERYTHROCYTES; VARIANT; ALLELE AB A single nucleotide polymorphism in the COMT (catechol-O-methyltransferase) gene that alters the amino acid sequence at codon 108 of S-COMT from val to met (val108met polymorphism) has been associated with a number of diseases and neuropsychiatric disorders. Several studies have shown that the met108 allele (COMTL) is associated with three to four-fold lower levels of COMT activity, compared to the val108 allele (COMTH), in extracts of human erythrocytes, liver and kidney tissue. We hypothesized that the differences in COMT activity observed in these studies were due to differing levels of COMT protein in cells and tissues with varying COMT genotypes. In order to address this, we obtained hepatocytes from 31 Caucasian female donors and determined their COMT genotype, COMT activity and COMT protein levels. We found that both cytosolic COMT activity and cytosolic COMT protein levels are lower in hepatocytes from COMTLL individuals, and that COMT activity levels correlate with COMT protein levels. Therefore, lower COMT activity seen in tissues and cells with the COMTLL genotype is likely due to lower COMT protein levels compared with tissues and cells from COMTHH individuals. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Baltimore, MD 21205 USA. NCI, Human Carcinogenesis Lab, NIH, Baltimore, MD USA. In Vitro Technol Inc, Baltimore, MD USA. RP Yager, JD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Room 7032,615 N Wolfe St, Baltimore, MD 21205 USA. EM jyager@jhsph.edu FU NCI NIH HHS [R01CA77550]; NIEHS NIH HHS [T32ESO7141, P30ES03819] NR 21 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 28 PY 2004 VL 214 IS 2 BP 189 EP 195 DI 10.1016/j.canlet.2004.06.033 PG 7 WC Oncology SC Oncology GA 859CN UT WOS:000224240000007 PM 15363545 ER PT J AU Yang, XHR Wacholder, S Xu, ZY Dean, M Clark, V Gold, B Brown, LM Stone, BJ Fraumeni, JF Caporaso, NE AF Yang, XHR Wacholder, S Xu, ZY Dean, M Clark, V Gold, B Brown, LM Stone, BJ Fraumeni, JF Caporaso, NE TI CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women SO CANCER LETTERS LA English DT Article DE CYP1A1 I462V; GSTM1; lung cancer; Chinese women ID S-TRANSFERASE GENES; POOLED ANALYSIS; AIR-POLLUTION; SUSCEPTIBILITY; SMOKING; ASSOCIATION; POPULATION; ADENOCARCINOMA; CARCINOGENS; SHENYANG AB We examined CYP1A1 (1462V) and GSTM1 null polymorphisms in 200 female cases and 144 female controls selected from a population-based case-control study of lung cancer conducted in northeast China, where the rates of lung cancer among Chinese women are especially high. The CYP1A1 codon 462 point mutation in exon 7 (I462V) causes an Ile-Val substitution near the heme binding site. This mutation correlates with inducibility of aryl hydrocarbon hydrolase (AHH) activity, which activates polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke and in indoor air pollution from coal-burning stoves, a risk factor for lung cancer in this study population. We found that the CYP1A1 I462V genotype (combined ile/val and val/val) was significantly associated with lung cancer risk. The odds ratio (OR) was 2.5 (95% confidence interval [CI], 1.55-4.03) after adjustment for significant risk factors such as age, ever smoking status, family history of cancer, and eye irritation when cooking. The association was more pronounced among non-smokers (OR= 3.67; 95% Cl, 1.85-7.28) than among smokers (OR= 1.74, 95% CI, 0.85-3.54). In contrast. we did not find a significant association with the GSTM1 null genotype. In summary, our case-control study of lung cancer among women in northeast China revealed an elevated risk associated with the CYP1A1 I462V genotype, but no interaction with smoking or indoor air pollution was found. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Liaoning Publ Hlth & Anti Epidem Stn, Shenyang, Peoples R China. NCI, Lab Genet Divers, Frederick, MD 21702 USA. RP Yang, XHR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM royang@mail.nih.gov OI Dean, Michael/0000-0003-2234-0631 NR 29 TC 42 Z9 50 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 28 PY 2004 VL 214 IS 2 BP 197 EP 204 DI 10.1016/j.canlet.2004.06.040 PG 8 WC Oncology SC Oncology GA 859CN UT WOS:000224240000008 PM 15363546 ER PT J AU Perry, JL Goldsmith, MR Peterson, MA Beratan, DN Wozniak, G Ruker, F Simon, JD AF Perry, JL Goldsmith, MR Peterson, MA Beratan, DN Wozniak, G Ruker, F Simon, JD TI Structure of the ochratoxin A binding site within human serum albumin SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID ASPERGILLUS OCHRACEUS WILH; CRYSTAL-STRUCTURE; PROTEIN-BINDING; MYCOTOXINS; MECHANISM; WARFARIN; REVEALS; SYSTEM; MODEL; FOOD AB The binding site of ochratoxin A (OTA) within domain 2A of human serum albumin (HSA) is examined by theoretical simulations and site-directed mutagenesis experiments. The calculated binding constant, based on docking experiments and theoretical affinity constants derived from the empirical free energy of binding as implemented in AutoDock 3.0, for the OTA dianion (3.7 x 10(6) M-1) is in good agreement with experimental value of 5.2 x 10(6) M-1. The carboxy terminus of OTA associates with R218 and R222 of the protein. Binding is reduced by over an order of magnitude for the mutant R218A in both experiments and theoretical simulations. The carbonyl of the lactone and the phenolic group of OTA are in close proximity to R257. The experimental binding constant of OTA to the R257A mutant is 1.6 x 10(5) M-1, over an order of magnitude smaller than for the wild-type protein. The predicted binding constant based on a comparison of the lowest-energy conformer from docking studies performed in AutoDock 3.0 of OTA to the R257A mutant (8.3 x 10(4) M-1) is also in good agreement with the experimental result. R257 clearly plays an important role in the binding of the isocoumarin ring of OTA by serving as a proton acceptor and stabilizing the binding through the creation of an ion pair with the phenoxide group on OTA. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Duke Univ, Dept Chem, Durham, NC 27708 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Univ Nat Resources & Appl Life Sci, BOKU, Inst Appl Microbiol, A-1190 Vienna, Austria. RP Simon, JD (reprint author), NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. EM jsimon@duke.edu RI Beratan, David/C-5098-2011 NR 40 TC 10 Z9 10 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD OCT 28 PY 2004 VL 108 IS 43 BP 16960 EP 16964 DI 10.1021/jp0480652 PG 5 WC Chemistry, Physical SC Chemistry GA 865EP UT WOS:000224685600051 ER PT J AU Kawakubo, H Carey, JL Brachtel, E Gupta, V Green, JE Walden, PD Maheswaran, S AF Kawakubo, H Carey, JL Brachtel, E Gupta, V Green, JE Walden, PD Maheswaran, S TI Expression of the NF-kappa B-responsive gene BTG2 is aberrantly regulated in breast cancer SO ONCOGENE LA English DT Article DE BTG2; breast cancer; cell cycle; cyclin D1; NF-kappa B ID MULLERIAN-INHIBITING SUBSTANCE; CYCLIN D1 TRANSCRIPTION; NERVE GROWTH-FACTOR; CELL-GROWTH; DOWN-REGULATION; TIS21 PROTEIN; DNA-DAMAGE; IN-VIVO; CARCINOMA; PC3 AB BTG2, a p53-inducible antiproliferative gene, is stimulated in breast cancer cells by activation of nuclear factor kappa B (NF-kappaB). In rat mammary glands, BTG2 is expressed in epithelial cells and levels decreased during pregnancy and lactation but recovered during involution. Estrogen and progestin suppress BTG2 expression, suggesting that these steroids, which stimulate proliferation and lobuloalveolar development of mammary epithelial cells, may downregulate BTG2 in the mammary gland during pregnancy. Consistent with the report that BTG2 inhibits cyclin D1 expression, suppression of BTG2 mRNA in the mammary gland during gestation, and by estrogen and progestin, correlated with stimulation of cyclin D1. Ectopic expression of BTG2 inhibited breast cancer cell growth by arresting cells in the G1 phase, an effect reversed by cyclin D1. BTG2 expression was very low or undetectable in human breast cancer cell lines compared with nontumorigenic mammary epithelial cells, and nuclear expression of BTG2 was absent in 65% of human breast tumors compared with adjacent matched normal glands. Spontaneous mammary tumors arising in a mouse model with targeted expression of the early region of the SV40 large tumor Ag demonstrated loss of BTG2 protein very early during the tumorigenic process. Thus deregulation of BTG2 may be an important step in the development of mammary tumors. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Urol, New York, NY 10016 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Jackson 904,55 Fruit St, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA84441, CA89138] NR 44 TC 48 Z9 51 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 28 PY 2004 VL 23 IS 50 BP 8310 EP 8319 DI 10.1038/sj.onc.1208008 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 866CC UT WOS:000224749500013 PM 15378000 ER PT J AU Guarne, A Ramon-Maiques, S Wolff, EM Ghirlando, R Hu, XJ Miller, JH Yang, W AF Guarne, A Ramon-Maiques, S Wolff, EM Ghirlando, R Hu, XJ Miller, JH Yang, W TI Structure of the MutL C-terminal domain: a model of intact MutL and its roles in mismatch repair SO EMBO JOURNAL LA English DT Article DE ATPase; dimerization; DNA binding; MutL; UvrD ID DNA-BINDING PROPERTIES; ESCHERICHIA-COLI; HELICASE-II; CRYSTAL-STRUCTURE; YEAST MSH2-MSH6; ATPASE ACTIVITY; DISTINCT ROLES; GENE-PRODUCT; PROTEIN MUTS; IN-VIVO AB MutL assists the mismatch recognition protein MutS to initiate and coordinate mismatch repair in species ranging from bacteria to humans. The MutL N-terminal ATPase domain is highly conserved, but the C-terminal region shares little sequence similarity among MutL homologs. We report here the crystal structure of the Escherichia coli MutL C-terminal dimerization domain and the likelihood of its conservation among MutL homologs. A 100-residue proline-rich linker between the ATPase and dimerization domains, which generates a large central cavity in MutL dimers, tolerates sequence substitutions and deletions of one-third of its length with no functional consequences in vivo or in vitro. Along the surface of the central cavity, residues essential for DNA binding are located in both the N- and C-terminal domains. Each domain of MutL interacts with UvrD helicase and is required for activating the helicase activity. The DNA-binding capacity of MutL is correlated with the level of UvrD activation. A model of how MutL utilizes its ATPase and DNA-binding activities to mediate mismatch-dependent activation of MutH endonuclease and UvrD helicase is proposed. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Inst Mol Biol, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 5,Rm B1-03, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 55 TC 108 Z9 109 U1 2 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 OCT 27 PY 2004 VL 23 IS 21 BP 4134 EP 4145 DI 10.1038/sj.emboj.7600412 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 873SO UT WOS:000225301500002 PM 15470502 ER PT J AU Tan, NS Michalik, L Di-Poi, N Ng, CY Mermod, N Roberts, AB Desvergne, B Wahli, W AF Tan, NS Michalik, L Di-Poi, N Ng, CY Mermod, N Roberts, AB Desvergne, B Wahli, W TI Essential role of Smad3 in the inhibition of inflammation-induced PPAR beta/delta expression SO EMBO JOURNAL LA English DT Article DE PPAR; Smad3; TGF-beta 1; wound healing ID GROWTH-FACTOR-BETA; TGF-BETA; TRANSCRIPTIONAL ACTIVATION; DIFFERENTIAL REGULATION; DENDRITIC CELLS; IN-VIVO; GENE; FIBROBLASTS; INDUCTION; MICE AB Wound healing proceeds by the concerted action of a variety of signals that have been well identified. However, the mechanisms integrating them and coordinating their effects are poorly known. Herein, we reveal how PPARbeta/delta (PPAR: peroxisome proliferator-activated receptor) follows a balanced pattern of expression controlled by a crosstalk between inflammatory cytokines and TGF-beta1. Whereas conditions that mimic the initial inflammatory events stimulate PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced PPARbeta/delta transcription, as seen in the late re-epithelialization/remodeling events. This TGF-beta1/Smad3 action involves an inhibitory effect on AP-1 activity and DNA binding that results in an inhibition of the AP-1-driven induction of the PPARbeta/delta promoter. As expected from these observations, wound biopsies from Smad3-null mice showed sustained PPARbeta expression as compared to those of their wild-type littermates. Together, these findings suggest a mechanism for setting the necessary balance between inflammatory signals, which trigger PPARbeta/delta expression, and TGF-beta1/Smad3 that governs the timely decrease of this expression as wound healing proceeds to completion. C1 Univ Lausanne, Ctr Integrat Genom, NCCR Frontiers Genet, CH-1015 Lausanne, Switzerland. Univ Lausanne, Inst Biotechnol, Ctr Biotechnol, UNIL EPFL, Lausanne, Switzerland. Natl Canc Inst, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD USA. RP Wahli, W (reprint author), Univ Lausanne, Ctr Integrat Genom, NCCR Frontiers Genet, Biol Bldg, CH-1015 Lausanne, Switzerland. EM walter.wahli@cig.unil.ch RI Wahli, Walter/B-1398-2009; Di-Poi, Nicolas/O-2378-2015; Desvergne, Beatrice/C-8892-2016 OI Wahli, Walter/0000-0002-5966-9089; Di-Poi, Nicolas/0000-0002-3313-3016; Desvergne, Beatrice/0000-0001-5483-288X NR 40 TC 55 Z9 62 U1 0 U2 2 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 OCT 27 PY 2004 VL 23 IS 21 BP 4211 EP 4221 DI 10.1038/sj.emboj.7600437 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 873SO UT WOS:000225301500009 PM 15470497 ER PT J AU Polzin, RG Benlhabib, H Trepel, J Herrera, JE AF Polzin, RG Benlhabib, H Trepel, J Herrera, JE TI E2F sites in the Op18 promoter are required for high level of expression in the human prostate carcinoma cell line PC-3-M SO GENE LA English DT Article DE NT1; stathmin ID STATHMIN EXPRESSION; MITOTIC SPINDLE; DOWN-REGULATION; LEUKEMIC-CELLS; ONCOPROTEIN-18; PROLIFERATION; GENES; PHOSPHORYLATION; OVEREXPRESSION; IDENTIFICATION AB Op18 (Oncoprotem 18, Stathmin) is an important mitotic regulator that is highly expressed in many cancers including the metastatic prostate carcinoma cell line PC-3-M. Recent studies indicate that antisense-mediated down-regulation of Op18 can inhibit cellular proliferation. However, the transcriptional mechanisms responsible for its normal regulation and for its high level of expression in proliferating cells remain poorly understood. In the study presented here, we have characterized transcription factor binding sites that together account for nearly 80% of the Op18 expression in PC-3-M cells. The 5' flanking region of the Op18 gene contains four putative E2F sites located at -700 (site 1), -28 (site 2), -19 (site 3), and +720 (site 4) relative to the transcriptional start site. E2F has been implicated in both the c-Jun-mediated up-regulation and the doxorubicin-induced repression of Op18 expression. We have used promoter-reporter assays and mobility shift assays to functionally examine each of these E2F sites. Mutagenesis studies indicate that all sites contribute to the basal expression of Op18. Mutagenesis of either site 1 or 4 reduced the reporter activity by 40%, mutagenesis of site 2 reduced reporter activity by 20%, and mutations in site 3 had no effect on reporter activity. Combinatorial mutagenesis indicates that site 1 and 4 function independently, whereas site 2 functions synergistically with either site 3 or 4. Mobility shift assays indicate that all elements bind factors in the nuclear extracts of PC-3-M cells. Characterization of the sites show that site 1, though a positive element, is not E2F specific; sites 2 and 3 may contain an overlapping binding site for E2F and NF1; and site 4, which resides in intron 1, is the only site shown to interact exclusively with E2F. These studies suggest that the overexpression of Op18 in PC-3-M cells is mediated predominately through the E2F family of transcription factors. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. RP Herrera, JE (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, 321 Church St SE,6-155 Jackson Hall, Minneapolis, MN 55455 USA. EM herre009@tc.umn.edu NR 29 TC 18 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 27 PY 2004 VL 341 BP 209 EP 218 DI 10.1016/j.gene.2004.06.052 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 866HR UT WOS:000224765100020 PM 15474303 ER PT J AU Fisahn, A Contractor, A Traub, RD Buhl, EH Heinemann, SF McBain, CJ AF Fisahn, A Contractor, A Traub, RD Buhl, EH Heinemann, SF McBain, CJ TI Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations SO JOURNAL OF NEUROSCIENCE LA English DT Article DE kainate receptors; gamma oscillations; interneurons; hippocampus; knock-out mice; epilepsy ID TEMPORAL-LOBE EPILEPSY; MOSSY-FIBER SYNAPSES; NETWORK OSCILLATIONS; SYNAPTIC-TRANSMISSION; KAINIC ACID; GLUR6-DEFICIENT MICE; PYRAMIDAL CELLS; CA3 REGION; IN-VITRO; INTERNEURONS AB Kainate receptors (KARs) play an important role in synaptic physiology, plasticity, and pathological phenomena such as epilepsy. However, the physiological implications for neuronal networks of the distinct expression patterns of KAR subunits are unknown. Using KAR knock-out mice, we show that subunits glutamate receptor (GluR) 5 and GluR6 play distinct roles in kainate-induced gamma oscillations and epileptiform burst activity. Ablation of GluR5 leads to a higher susceptibility of the network to the oscillogenic and epileptogenic effects of kainate, whereas lack of GluR6 prevents kainate-induced gamma oscillations or epileptiform bursts. Based on experimental and simulated neuronal network data as well as the consequences of GluR5 and GluR6 expression for cellular and synaptic physiology, we propose that the functional interplay of GluR5-containing KARs on axons of interneurons and GluR6-containing KARs in the somatodendritic region of both interneurons and pyramidal cells underlie the oscillogenic and epileptogenic effects of kainate. C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Univ Leeds, Sch Biomed Sci, Leeds LS2 9NQ, W Yorkshire, England. Univ Oxford, MRC, Anat Neuropharmacol Unit, Oxford OX1 3TH, England. RP Fisahn, A (reprint author), Karolinska Inst, Nobel Inst Neurophysiol, Dept Neurosci, Retzius Vag 8,A3-5, SE-17177 Stockholm, Sweden. EM Andre.Fisahn@neuro.ki.se OI Contractor, Anis/0000-0002-5131-2536 FU NINDS NIH HHS [NS28709] NR 55 TC 127 Z9 130 U1 1 U2 12 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 OCT 27 PY 2004 VL 24 IS 43 BP 9658 EP 9668 DI 10.1523/JNEUROSCI.2973-04.2004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 866CD UT WOS:000224749600021 PM 15509753 ER PT J AU Wang, J Boja, ES Oubrahim, H Chock, PB AF Wang, J Boja, ES Oubrahim, H Chock, PB TI Testis brain ribonucleic acid-binding protein/translin possesses both single-stranded and double-stranded ribonuclease activities SO BIOCHEMISTRY LA English DT Article ID MALE GERM-CELLS; FUNCTIONAL GENOMIC ANALYSIS; PROTAMINE-2 MESSENGER-RNA; 3' UNTRANSLATED REGION; TB-RBP; MAMMALIAN-CELLS; GENE-EXPRESSION; CHROMOSOMAL TRANSLOCATIONS; INTERCELLULAR BRIDGES; CRYSTAL-STRUCTURE AB RNA interference (RNAi) is a biological process in which animal and plant cells destroy double-stranded RNA (dsRNA) and consequently the mRNA that shares sequence homology to the dsRNA. Although it is known that the enzyme Dicer is responsible for the digestion of dsRNA into similar to22 bp fragments, the mechanism through which these fragments are associated with the RNA-induced silencing complex (RISC) is mostly unknown. To find protein components in RISC that interact with the similar to22 bp fragment, we synthesized a P-32- and photoaffinity moiety-labeled 22 bp dsRNA fragment and used it as bait to fish out protein(s) directly interacting with the dsRNA fragment. One of the proteins that we discovered by mass spectrometric analysis was TB-RBP/translin. Further analysis of this DNA/RNA binding protein showed that it possesses both ssRNase and dsRNase activities but not DNase activity. The protein processes long dsRNA mainly into similar to25 bp fragments by binding to the open ends of dsRNA and cutting it with almost no turnover due to its high affinity toward the products. The activity requires physiological ionic strength. However, with single-stranded RNA as substrate, the digestion appeared to be more complete. Both ssRNase and dsRNase activities are inhibited by high levels of common RNase inhibitors. Interestingly, both activities can be enhanced greatly by EDTA. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM bchock@nih.gov NR 51 TC 16 Z9 18 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 26 PY 2004 VL 43 IS 42 BP 13424 EP 13431 DI 10.1021/bi048847l PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 864GQ UT WOS:000224622400020 PM 15491149 ER PT J AU Yokoyama, F Suzuki, N Haruki, M Nishi, N Oishi, S Fujii, N Utani, A Kleinman, HK Nomizu, M AF Yokoyama, F Suzuki, N Haruki, M Nishi, N Oishi, S Fujii, N Utani, A Kleinman, HK Nomizu, M TI Cyclic peptides from the loop region of the laminin alpha 4 chain LG4 module show enhanced biological activity over linear peptides SO BIOCHEMISTRY LA English DT Article ID CELL-BINDING SEQUENCES; G-DOMAIN; MOUSE LAMININ; SYNTHETIC PEPTIDES; IDENTIFICATION; EXPRESSION; ADHESION; HEPARIN; SITE; SYNDECAN-4 AB Laminins, heterotrimeric glycoproteins in the basement membrane, are involved in diverse biological activities. So far, five alpha, three beta, and three gamma chains have been identified, and at least 15 laminin isoforms exist composed of various combinations of the different three chains. The major cell-surface receptors for laminins are integrins and proteoglycans, such as dystroglycans and syndecans. Previously, we reported that synthetic peptide A4G82 (TLFLAHGRLVFM, mouse laminin alpha4 chain residues 1514-1525) showed strong cell attachment and syndecan binding activities. On the basis of the crystal structure of the LG module and sequence alignment, A4G82 is located in the connecting loop region between beta-strands E and F in the laminin alpha4 chain LG4 module. Here, we have focused on the structural importance of this E-F loop region for the biological activity of the alpha4 chain LG4 module. To determine the importance of the loop structure, we synthesized peptide A4G82X (cyclo-A4G82X, Cys-TLFLAHGRLVFX-Cys, X= norleucine), which was cyclized via disulfide bridges at both the N- and C-termini. The cyclic peptides derived from A4G82X inhibited the heparin binding activity of the alpha4 chain G domain and promoted HT-1080 cell attachment better than the corresponding linear peptides. We determined FLAHGRLVFX as a minimal sequence of cyclo-A4G82X important for cell adhesion and heparin binding using a series of truncated peptides. Moreover, HT-1080 cell attachment to the cyclic peptides was more efficiently blocked by heparin than cell attachment to the linear peptides. Furthermore, the cyclic peptides showed significantly enhanced syndecan-2-mediated cell attachment activity. These results indicate that the activity of A4G82 is highly conformation-dependent, suggesting that the E-F loop structure is crucial for its biological activity. C1 Tokyo Univ Pharm & Life Sci, Sch Pharmaceut Sci, Lab Clin Biochem, Hachioji, Tokyo 1920392, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 0600810, Japan. Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto 6068501, Japan. Chiba Univ, Sch Med, Dept Dermatol, Chiba 2608670, Japan. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Nomizu, M (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharmaceut Sci, Lab Clin Biochem, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. EM nomizu@ps.toyaku.ac.jp RI Oishi, Shinya/C-1350-2011 OI Oishi, Shinya/0000-0002-2833-2539 NR 39 TC 21 Z9 24 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 26 PY 2004 VL 43 IS 42 BP 13590 EP 13597 DI 10.1021/bi049009u PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 864GQ UT WOS:000224622400036 PM 15491165 ER PT J AU Katori, T Tocchetti, CG Miranda, KM Mancardi, D Toscano, JP Wink, DA Hogg, N Paolocci, N AF Katori, T Tocchetti, CG Miranda, KM Mancardi, D Toscano, JP Wink, DA Hogg, N Paolocci, N TI S-nitrosoglutathione does not reproduce in vivo positive inotropy induced by nitroxyl donors SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Arizona, Tucson, AZ USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 142 BP 31 EP 31 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500141 ER PT J AU Wang, H Rubin, JS Patterson, C AF Wang, H Rubin, JS Patterson, C TI A role for Wnt signaling in vascular development: Expansion of vascular progenitors SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NCI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 147 BP 32 EP 32 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500146 ER PT J AU Lammerding, J Hsiao, J Schulze, PC Stewart, CL Lee, RT AF Lammerding, J Hsiao, J Schulze, PC Stewart, CL Lee, RT TI Emerin-deficient cells have normal nuclear mechanics but impaired mechanotransduction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 MIT, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 209 BP 44 EP 45 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500208 ER PT J AU Brewer, HB Alaupovic, P Kostner, G Asztalos, B Schaefer, E Rothblat, G Akeefe, H Conner, A Perlman, T Kunas, G Bellotti, M AF Brewer, HB Alaupovic, P Kostner, G Asztalos, B Schaefer, E Rothblat, G Akeefe, H Conner, A Perlman, T Kunas, G Bellotti, M TI Selective plasma HDL delipidation and reinfusion: A unique new approach for acute HDL therapy in the treatment of cardiovascular disease SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Graz Univ, Graz, Austria. Tufts Univ, Sch Med, Boston, MA 02111 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Lipid Sci, Pleasanton, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 241 BP 51 EP 52 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500240 ER PT J AU Kodavanti, UP Schladweiler, MC Gilmour, PS McGee, JK Watkinson, WP Jaskot, RH Richards, JR Ledbetter, AD Costa, DL Graff, DW Cascio, WE Rowan, WH Nyska, A AF Kodavanti, UP Schladweiler, MC Gilmour, PS McGee, JK Watkinson, WP Jaskot, RH Richards, JR Ledbetter, AD Costa, DL Graff, DW Cascio, WE Rowan, WH Nyska, A TI Paradoxical role of zinc in cardiac injury: A potential link environmental zinc exposure and cardiovascular morbidity SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 US EPA, Res Triangle Pk, NC 27711 USA. Astra Zeneca, Macclesfield, Cheshire, England. US EPA, Chapel Hill, NC USA. Univ N Carolina, Greenville, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1917 BP 56 EP 56 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500262 ER PT J AU Gaussin, V Morley, GE Cox, L Liu, J Hong, C Depre, C Myers, D Tian, YM Emile, L Mishina, Y Behringer, RR Hanks, MC Zwijsen, A Huylebroeck, D Fishman, GI Schneider, MD Burch, JB AF Gaussin, V Morley, GE Cox, L Liu, J Hong, C Depre, C Myers, D Tian, YM Emile, L Mishina, Y Behringer, RR Hanks, MC Zwijsen, A Huylebroeck, D Fishman, GI Schneider, MD Burch, JB TI ALK3 deletion targeted to the atrioventricular canal results in defects compatible with Ebstein's anomaly SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NYU, Sch Med, New York, NY USA. VIB, Louvain, Belgium. Katholieke Univ Leuven, Louvain, Belgium. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Procter & Gamble Co, Mason, OH 45202 USA. Baylor Coll Med, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 272 BP 59 EP 59 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500275 ER PT J AU Tipparaju, SM Kumar, R Liu, SQ Bhatnagar, A AF Tipparaju, SM Kumar, R Liu, SQ Bhatnagar, A TI Pryidine coenzyme binding to Kv beta proteins imparts redox-sensitivity to Kv channels SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Louisville, Louisville, KY 40292 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 286 BP 62 EP 62 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500289 ER PT J AU Stabile, E Kinnaird, T la Sala, A Watkins, C Clavijo, L Zbinden, S Epstein, SE Burnett, MS AF Stabile, E Kinnaird, T la Sala, A Watkins, C Clavijo, L Zbinden, S Epstein, SE Burnett, MS TI CD8+T cells regulate the arteriogenic response to ischemia by ilnfiltrating the site of collateral vessel development and recruiting CD4+mononuclear cells through the expression of IL-16 SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Washington Hosp Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD USA. RI la Sala, Andrea/A-3228-2009 OI la Sala, Andrea/0000-0003-1268-6516 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 331 BP 71 EP 71 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500333 ER PT J AU Vinogradova, TM Lyashkov, A Zhu, WZ Maltsev, V Lakatta, EG AF Vinogradova, TM Lyashkov, A Zhu, WZ Maltsev, V Lakatta, EG TI Constitutive protein kinase A activation generates rhythmic call oscillations in rabbit sinoatrial nodal cells that modulate intrinsic, spontaneous beating SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 398 BP 85 EP 85 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500400 ER PT J AU Chakir, K Zhang, SJ Rhee, MH Blumer, K Lefkowitz, RJ Xiao, RP AF Chakir, K Zhang, SJ Rhee, MH Blumer, K Lefkowitz, RJ Xiao, RP TI Use-dependent beta 2-adrenergic receptor-GI coupling requires RGS and beta-ARK/PKA-mediated receptor phosphorylation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIA, GRC, NIH, Baltimore, MD 21224 USA. Washington Univ, Sch Med, St Louis, MO USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 433 BP 92 EP 92 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500434 ER PT J AU Myers, DC Gaussin, V Mishina, Y Behringer, R Hanks, M Burch, J Schneider, M Danik, S Fishman, G Morley, G AF Myers, DC Gaussin, V Mishina, Y Behringer, R Hanks, M Burch, J Schneider, M Danik, S Fishman, G Morley, G TI Optical mapping of bypass tracts in mice with AV canal-targeted deletion of ALK3 SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NIH, Res Triangle Pk, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Procter & Gamble Pharm, Mason, OH USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 474 BP 100 EP 100 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500475 ER PT J AU El-Bizri, N Wang, LL Merklinger, SL Desai, K Rountree, RB Mishina, Y Rabinovitch, M AF El-Bizri, N Wang, LL Merklinger, SL Desai, K Rountree, RB Mishina, Y Rabinovitch, M TI Transgenic mice with arterial smooth muscle cell-specific conditional deletion of the bone morphogenetic protein type IA receptor (BMPRIA/ALK3) are hyporesponsive to hypoxia SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Stanford Univ, Palo Alto, CA 94304 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 624 BP 132 EP 132 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500624 ER PT J AU Wang, XXJ Liu, JB Chen, QH Dong, X Wawrousek, EF Li, FQ Horak, K AF Wang, XXJ Liu, JB Chen, QH Dong, X Wawrousek, EF Li, FQ Horak, K TI Impairment of the ubiquitin-proteasome system by misfolded cytoplasmic protein in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ S Dakota, Sioux Falls, SD 57069 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 764 BP 160 EP 160 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500763 ER PT J AU Seubert, JM Goralski, K Sinal, CJ Murphy, E Zeldin, DC AF Seubert, JM Goralski, K Sinal, CJ Murphy, E Zeldin, DC TI Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Dalhousie Univ, Halifax, NS B3H 3J5, Canada. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 808 BP 169 EP 169 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783500805 ER PT J AU Brochet, DX Yang, DM Cheng, HP AF Brochet, DX Yang, DM Cheng, HP TI Visualization of calcium depletion of the sarcoplasmic reticulum in rabbit ventricular myocytes SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIA, Lab Cardiovasc, Sci, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 929 BP 194 EP 195 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501088 ER PT J AU Maltsev, VA Bogdanov, KY Vinogradova, TM Spurgeon, HA Stern, MD Lakatta, EG AF Maltsev, VA Bogdanov, KY Vinogradova, TM Spurgeon, HA Stern, MD Lakatta, EG TI Membrane depolarizations produced by individual local Ca2+ releases are elementary events in regulation of sinoatrial nodal cell beating rate SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIA, GRC, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 934 BP 195 EP 196 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501093 ER PT J AU Pi, YQ Song, LS Kim, SJ Guatimosim, S Niiyama, S Kudej, RK Hittinger, L Ghaleh, B Yatani, A Cheng, HP Vatner, DE Lederer, WJ Vatner, SF AF Pi, YQ Song, LS Kim, SJ Guatimosim, S Niiyama, S Kudej, RK Hittinger, L Ghaleh, B Yatani, A Cheng, HP Vatner, DE Lederer, WJ Vatner, SF TI Increase in spontaneous Ca2+ sparks with depressed myocyte function in canine severe left ventricular hypertrophy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Maryland, Med Biotech Ctr, Baltimore, MD 21201 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NIA, NIH, Bethesda, MD 20892 USA. RI Lederer, William/B-1285-2010 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 935 BP 196 EP 196 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501094 ER PT J AU Imahashi, K Schneider, MD Steenbergen, C Murphy, E AF Imahashi, K Schneider, MD Steenbergen, C Murphy, E TI Modulation of voltage-dependent anion channel (VDAC) by Bcl-2 reduces mitochondrial ATP uptake and hydrolysis and mimics protective effects of diazoxide during ischemia SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Baylor Coll Med, Houston, TX 77030 USA. Duke Univ, Sch Med, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 971 BP 203 EP 203 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501130 ER PT J AU Morrison, RR Teng, B Qin, W Oldenburg, PJ Schnermann, JB Mustafa, SJ AF Morrison, RR Teng, B Qin, W Oldenburg, PJ Schnermann, JB Mustafa, SJ TI Impaired tolerance to ischemia-reperfusion in A(1) adenosine receptor knockout hearts SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Brody Sch Med, Greenville, NC USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 987 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501146 ER PT J AU Faraday, N Becker, LC Yanek, LR Moy, TF Chiles, K Kerns, M Hasan, AA Becker, DM AF Faraday, N Becker, LC Yanek, LR Moy, TF Chiles, K Kerns, M Hasan, AA Becker, DM TI In vitro tests of aspirin resistance are poorly correlated and identify distinct subgroups with aspirin resistance SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1037 BP 217 EP 217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501196 ER PT J AU Remaley, AT Stonik, J Thomas, F Demosky, S Neufeld, EB Brewer, BH AF Remaley, AT Stonik, J Thomas, F Demosky, S Neufeld, EB Brewer, BH TI Asymmetry in lipid affinity of multillelical amphipathic peptides: an important structural determinant for specificity of ABCA1-dependent cholesterol efflux by peptides SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1164 BP 243 EP 243 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501322 ER PT J AU Mattiussi, S Matsumoto, K Martelli, F Yamada, K Capogrossi, MC Gaetano, C AF Mattiussi, S Matsumoto, K Martelli, F Yamada, K Capogrossi, MC Gaetano, C TI Evidence for a paxillin specialized function in flow directional remodeling of human endothelial cells SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Inst Dermopat Immacolata, Rome, Italy. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1178 BP 245 EP 245 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501336 ER PT J AU Moon, C Krawczyk, M Paik, D Lakatta, EG Talan, MI AF Moon, C Krawczyk, M Paik, D Lakatta, EG Talan, MI TI Recombinant human erythropoietin (rhEPO) to reduce acute experimental myocardial infarction: Therapeutic window and dose responses in rats SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIA, Baltimore, MD 21224 USA. Hanyang Univ, Seoul 133791, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1277 BP 266 EP 267 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501434 ER PT J AU Liu, LJ Joyce, C Vaisman, B Fruchart-Najib, J Santamarina-Fojo, S Brewer, B AF Liu, LJ Joyce, C Vaisman, B Fruchart-Najib, J Santamarina-Fojo, S Brewer, B TI Selective hepatic expression of ABCA1 in ABCA1-K0 mice identifies liver ABCA1 as the major source of plasma HDL-C SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Inst Pasteur, F-59019 Lille, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1300 BP 272 EP 272 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501457 ER PT J AU Basso, F Wu, J Freeman, L Tansey, T Amar, MJ Joyce, C Thomas, F Santamarina-Fojo, S Brewer, BH AF Basso, F Wu, J Freeman, L Tansey, T Amar, MJ Joyce, C Thomas, F Santamarina-Fojo, S Brewer, BH TI Inhibition of fractional intestinal cholesterol absorption by zetia alters hepatic cholesterol balance in E-KO x ABCG5-G8-Tg and LDLr-KO x ABCG5-G8-Tg mice SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1307 BP 273 EP 273 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501464 ER PT J AU Tong, HY Bernstein, D Murphy, E Steenbergen, C AF Tong, HY Bernstein, D Murphy, E Steenbergen, C TI The protective effect of the beta-adrenergic receptor is through PKA-mediated switching of coupling of the receptor from Gs to Gi SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Stanford Univ, Stanford, CA 94305 USA. Duke Univ, Med Ctr, Durham, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1442 BP 301 EP 301 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501598 ER PT J AU Chun, THH Sabeh, F Ota, I Allen, ED Murphy, H McDonagh, K Holmbeck, K Birkedal-Hansen, H Weiss, SJ AF Chun, THH Sabeh, F Ota, I Allen, ED Murphy, H McDonagh, K Holmbeck, K Birkedal-Hansen, H Weiss, SJ TI MT1-MMP-dependent neovessel formation within the confines of the 3-dimensional extracellular matrix SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Univ Michigan, Ann Arbor, MI 48109 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1458 BP 305 EP 305 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501614 ER PT J AU Potteaux, S Combadiere, C Esposito, B Casanova, S Merval, R Ardouin, P Gao, JL Murphy, PM Tedgui, A Mallat, Z AF Potteaux, S Combadiere, C Esposito, B Casanova, S Merval, R Ardouin, P Gao, JL Murphy, PM Tedgui, A Mallat, Z TI Targeted disruption of the chemokine receptor CCR1 in bone marrow cells enhances atherosclerotic lesion development and inflammation in LDL receptor-deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 INSERM, U541, Paris, France. INSERM, U543, Paris, France. Inst Gustave Roussy, Villejuif, France. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1494 BP 312 EP 312 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501649 ER PT J AU Chen, KH Guo, XM Tang, J Xiao, RP AF Chen, KH Guo, XM Tang, J Xiao, RP TI Dysregulation of a novel hyperplasia suppressor gene triggers vascular proliferative disorders SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 GRC, NIA, NIH, Baltimore, MD USA. Inst Cardiovasc Sci, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1516 BP 317 EP 317 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501670 ER PT J AU Hill, JM Syed, MA Arai, AE Powell, TM Paul, JD Zalos, G Read, EJ Khuu, H Leitman, SF Horne, MK Csako, G Dunbar, CE Cannon, RO AF Hill, JM Syed, MA Arai, AE Powell, TM Paul, JD Zalos, G Read, EJ Khuu, H Leitman, SF Horne, MK Csako, G Dunbar, CE Cannon, RO TI Outcomes of granulocyte colony-stimulating factor administration to patients with severe coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 1681 BP 352 EP 352 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783501832 ER PT J AU Blaufox, AD Sleeper, LA Bradley, DJ Breitbart, RE Hordof, A Kanter, RJ Stephenson, E Stylianou, M Vetter, V Saul, JP AF Blaufox, AD Sleeper, LA Bradley, DJ Breitbart, RE Hordof, A Kanter, RJ Stephenson, E Stylianou, M Vetter, V Saul, JP CA Pediatric Heart Network Investigat TI Association of functional status and heart rate and rhythm at rest and in response to exercise in 508 Fontan patients 6-18 years of age SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Med Univ S Carolina, Charleston, SC 29425 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Utah, Primary Childrens Med Ctr, Salt Lake City, UT USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Columbia Univ, Childrens Hosp New York, New York, NY USA. Duke Univ, Durham, NC USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. NHLBI, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2078 BP 442 EP 442 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502391 ER PT J AU Mohiddin, SA Tripodi, D Kent, K McAreavey, D Plehn, J Fananapazir, L AF Mohiddin, SA Tripodi, D Kent, K McAreavey, D Plehn, J Fananapazir, L TI Randomized therapy for obstructive hyperthrophic cardiomyopathy: Long-term outcome of dual-chamber pacemaker and alcohol septal ablation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2423 BP 517 EP 517 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783502742 ER PT J AU Hodges, M Bailey, JJ AF Hodges, M Bailey, JJ TI Testing the tests: Relative sensitivities of 7 tests used to stratify post-myocardial infarction patients SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Minneapolis Heart Inst Fdn, Minneapolis, MN USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2699 BP 580 EP 580 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503153 ER PT J AU Ingkanisorn, WP Rhoads, KL Hirsch, GA Block, M Lowrey, T Syed, MA Arai, AE AF Ingkanisorn, WP Rhoads, KL Hirsch, GA Block, M Lowrey, T Syed, MA Arai, AE TI Sensitivity of dipyridamole CMR for the assessment of intermediate severity coronary artery stenosis SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2833 BP 609 EP 609 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503287 ER PT J AU Syed, MA Carlson, K Murphy, M Arai, AE AF Syed, MA Carlson, K Murphy, M Arai, AE TI Safety of magnetic resonance imaging in the first few days after primary angioplasty/stenting for acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2832 BP 609 EP 609 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503286 ER PT J AU Najjar, SS Bottomley, PA Schulman, SP Waldron, MM Gerstenblith, G Weiss, RG AF Najjar, SS Bottomley, PA Schulman, SP Waldron, MM Gerstenblith, G Weiss, RG TI Does right-shifting hemoglobin-oxygen dissociation attenuate exercise-induced ischemia in patients with coronary artery disease? SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Johns Hopkins Univ, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2835 BP 610 EP 610 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503289 ER PT J AU Spaeder, J Najjar, S Gerstenblith, G Hefter, G Kern, L Gottlieb, S Kasper, E AF Spaeder, J Najjar, S Gerstenblith, G Hefter, G Kern, L Gottlieb, S Kasper, E TI Rapid titration of carvedilol in patients with CHF: A randomized trial of automated telemedicine versus frequent outpatient clinic SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Johns Hopkins Univ, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2004 VL 110 IS 17 SU S MA 2966 BP 638 EP 638 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866OT UT WOS:000224783503417 ER EF