FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bohr, VA AF Bohr, VA TI Deficient DNA repair in the human progeroid disorder, Werner syndrome SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE Werner syndrome; RecQ helicases; DNA repair ID DEPENDENT PROTEIN-KINASE; WRN HELICASE ACTIVITY; BASE EXCISION-REPAIR; FUNCTIONAL INTERACTION; RECQ HELICASES; HOMOLOGOUS RECOMBINATION; POLYMERASE DELTA; TELOMERES; INTERACTS; COMPLEX AB The study of how DNA repair mechanisms change with aging is central to our understanding of the aging process. Here, I review the molecular functions of a key aging protein, Werner protein (WRN), which is deficient in the premature aging disorder, Werner syndrome (WS). This protein plays a significant role in DNA repair, particularly in base excision repair and in recombination. WRN may be a key regulatory factor in these processes and may also play a role in coordinating them. WRN belongs to the RecQ helicase family of proteins, often referred to as the guardians of the genome. These proteins appear to integrate with the more classic DNA repair pathways and proteins. Published by Elsevier B.V. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 50 TC 37 Z9 38 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 4 PY 2005 VL 577 IS 1-2 BP 252 EP 259 DI 10.1016/j.mrfmmm.2005.03.021 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 954OR UT WOS:000231164900021 PM 15916783 ER PT J AU Lee, JY Hennighausen, L AF Lee, JY Hennighausen, L TI The transcription factor Stat3 is dispensable for pancreatic beta-cell development and function SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Stat3; Pdx1-Cre; RIP-Cre; islets of langerhans; beta-cells; glucose homeostasis ID GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; MICE; OVEREXPRESSION; GLUCOKINASE; ISLETS; LIVER; MASS AB The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. Gorogawa, Y. Fujitani, H. Kaneto, Y. Hazama, H. Watada, Y. Miyamoto, K. Takeda, S. Akira, M. Magnuson, Y. Yamasaki, Y. Kajimoto, M. Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. Biophys. Res. Commun. 319 (2004) 1159; Y. Cui, L. Huang, F. Elefteriou, G. Yang, J. Shelton, J. Giles, O. Oz, T. Pourbahrami, C. Lu, J. Richardson, G. Karsenty, C. Li, Essential role of STAT3 in body weight and glucose homeostasis, Mol. Cell. Biol. 24 (2004) 258]. However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. We have addressed this issue through the inactivation of Stat3 from pancreatic (3-cells using a Pdx1-Cre transgene. Complete loss of Stat3 was observed in islets from mice, which carry two (foxed Stat3 alleles and the Pdx1-Cre transgene. However, these mice did not develop glucose intolerance or obesity over a period of 6 months, demonstrating that Stat3 is dispensable for the generation and physiology of beta-cells. Similarly, mice that express only the Pdx1-Cre transgene display a normal physiology. In contrast, mice that expressed only the RIP-Cre transgene developed glucose intolerance as early as 6 weeks of age. The finding that RIP-Cre transgenic mice in a C57B/6 dominated background develop glucose intolerance is important as this line has been used in several studies. Published by Elsevier Inc. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM hennighausen@nih.gov NR 15 TC 23 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 2 PY 2005 VL 334 IS 3 BP 764 EP 768 DI 10.1016/j.bbrc.2005.06.162 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 955LB UT WOS:000231226300005 PM 16026757 ER PT J AU Song, LS Pi, Y Kim, SJ Yatani, A Guatimosim, S Kudej, RK Zhang, QX Cheng, HP Hittinger, L Ghaleh, B Vatner, DE Lederer, WJ Vatner, SF AF Song, LS Pi, Y Kim, SJ Yatani, A Guatimosim, S Kudej, RK Zhang, QX Cheng, HP Hittinger, L Ghaleh, B Vatner, DE Lederer, WJ Vatner, SF TI Paradoxical cellular Ca2+ signaling in severe but compensated canine left ventricular hypertrophy SO CIRCULATION RESEARCH LA English DT Article DE hypertrophy; Ca2+ sparks; E-C coupling; myocyte contractility; Ca2+ handling ID INTRACELLULAR CALCIUM TRANSIENTS; INDUCED HEART-FAILURE; SARCOPLASMIC-RETICULUM; CARDIAC-HYPERTROPHY; RYANODINE RECEPTOR; TRANSVERSE TUBULES; T-TUBULES; MYOCYTES; RELEASE; SPARKS AB In conscious dogs with severe left ventricular (LV) hypertrophy ( H) ( doubling of LV/body weight), which developed gradually over 1 to 2 years after aortic banding, baseline LV function was well compensated. The LV was able to generate twice the LV systolic pressure without an increase in LV end-diastolic pressure, or decrease in LV dP/dt or LV wall thickening. However, LV myocytes isolated from LVH dogs exhibited impaired contraction at baseline and in response to Ca2+. There was no change in L- type Ca2+ channel current (I-Ca) density but the ability of I-Ca to trigger Ca2+ release from the sarcoplasmic reticulum (SR) was reduced. Immunoblot analysis revealed a 68% decrease in SERCA2a, and a 35% decrease in the number of ryanodine receptors (RyR2), with no changes in protein level of calsequestrin, Na+/Ca2+ exchanger or phospholamban (PLB), but with both RyR2 and PLB hyperphosphorylated. Spontaneous Ca2+ sparks in LVH cells were found to have prolonged duration but similar intensities despite the reduced SR Ca2+ load. A higher Ca2+ spark rate was observed in LVH cells, but this is inconsistent with the reduced SR Ca2+ content. However, Ca2+ waves were found to be less frequent, slower and were more likely to be aborted in Ca2+ challenged LVH cells. These paradoxical observations could be accounted for by a nonuniform SR Ca2+ distribution, RyR2 hyperphosphorylation in the presence of decreased global SR Ca2+ load. We conclude that severe LVH with compensation masks cellular and subcellular Ca2+ defects that remain likely contributors to the limited contractile reserve of LVH. C1 Univ Med & Dent New Jersey, Dept Cell Biol & Mol Med, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Cardiovasc Res Inst, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil. Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Baltimore, MD USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Vatner, SF (reprint author), Univ Med & Dent New Jersey, Dept Cell Biol & Mol Med, New Jersey Med Sch, 185 S Orange Ave,MSB G609, Newark, NJ 07103 USA. EM lederer@umbi.umd.edu; vatnersf@umdnj.edu RI Lederer, William/B-1285-2010; Song, Long-Sheng/D-5899-2012 FU Intramural NIH HHS; NHLBI NIH HHS [2PO1HL59139, 1PO1HL69020, 2R01HL036974, 2R01HL33107, 5P01HL067849, 5P01HL070709, 5R01HL025675, 5R01HL62442, 5R01HL65182, 5R01HL65183, HL65182, HL65183]; NIA NIH HHS [2R01AG14121, AG023137] NR 38 TC 42 Z9 45 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 2 PY 2005 VL 97 IS 5 BP 457 EP 464 DI 10.1161/01.RES.0000179722.79295.d4 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 960OC UT WOS:000231602000009 PM 16051885 ER PT J AU Kuznetsova, SA Day, AJ Mahoney, DJ Rugg, MS Mosher, DF Roberts, DD AF Kuznetsova, SA Day, AJ Mahoney, DJ Rugg, MS Mosher, DF Roberts, DD TI The n-terminal module of thrombospondin-1 interacts with the link domain of TSG-6 and enhances its covalent association with the heavy chains of inter-alpha-trypsin inhibitor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-STIMULATED GENE-6; NECROSIS-FACTOR-ALPHA; BINDING PROTEIN TSG-6; SMOOTH-MUSCLE CELLS; COLLAGEN-INDUCED ARTHRITIS; INFLAMMATORY T-CELLS; HYALURONAN-BINDING; EXTRACELLULAR-MATRIX; IN-VIVO; HEPARIN-BINDING AB We recently found that leukocytes from thrombospondin-1 (TSP1)-deficient mice exhibit significant reductions in cell surface CD44 relative to those from wild type mice. Because TSG-6 modulates CD44-mediated cellular interactions with hyaluronan, we examined the possibility that TSP1 interacts with TSG-6. We showed that recombinant full-length human TSG-6 (TSG-6Q) and the Link module of TSG-6 (Link_TSG6) bind I-125-TSP1 with comparable affinities. Trimeric recombinant constructs containing the N-modules of TSP1 or TSP2 inhibit binding of TSP1 to TSG-6Q and Link_TSG6, but other recombinant regions of TSP1 do not. Therefore, the N-modules of both TSP1 and TSP2 specifically recognize the Link module of TSG-6. Heparin, which binds to these domains of both proteins, strongly inhibits binding of TSP1 to Link_TSG6 and TSG-6Q, but hyaluronan does not. Inhibition by heparin results from its binding to TSP1, because heparin also inhibits TSP1 binding to Link_TSG6 mutants deficient in heparin binding. Removal of bound Ca2+ from TSP1 reduces its binding to full-length TSG-6. Binding of TSP1 to Link_TSG6, however, is enhanced by chelating divalent cations. In contrast, divalent cations do not influence binding of the N-terminal region of TSP1 to TSG-6Q. This implies that divalent cation dependence is due to conformational effects of calcium-binding to the C-terminal domains of TSP1. TSP1 enhances covalent modification of the inter-alpha-trypsin inhibitor by TSG-6 and transfer of its heavy chains to hyaluronan, suggesting a physiological function of TSP1 binding to TSG-6 in regulation of hyaluronan metabolism at sites of inflammation. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Biochem, MRC, Immunochem Unit, Oxford OX1 3QU, England. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10 Rm 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Day, Anthony/O-1658-2015 OI Roberts, David/0000-0002-2481-2981; Day, Anthony/0000-0002-1415-3134 FU Intramural NIH HHS; Medical Research Council [MC_U138274352] NR 99 TC 23 Z9 24 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 SEP 2 PY 2005 VL 280 IS 35 BP 30899 EP 30908 DI 10.1074/jbc.M500701200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958ZX UT WOS:000231487800031 PM 16006654 ER PT J AU Huang, KT Keszler, A Patel, N Patel, RP Patel, RP Gladwin, MT Kim-Shapiro, DB Hogg, N AF Huang, KT Keszler, A Patel, N Patel, RP Patel, RP Gladwin, MT Kim-Shapiro, DB Hogg, N TI The reaction between nitrite and deoxyhemoglobin - Reassessment of reaction kinetics and stoichiometry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-NITROSOGLUTATHIONE; HEMOGLOBIN HYBRIDS; OXIDE; NO; REDUCTION; OXIDATION; OXYGEN; CYCLE AB Recent evidence suggests that the reaction between nitrite and deoxygenated hemoglobin provides a mechanism by which nitric oxide is synthesized in vivo. This reaction has been previously defined to follow second order kinetics, although variable product stoichiometry has been reported. In this study we have re-examined this reaction and found that under fully deoxygenated conditions the product stoichiometry is 1: 1 ( methemoglobin: nitrosylhemoglobin), and unexpectedly, the kinetics deviate substantially from a simple second order reaction and exhibit a sigmoidal profile. The kinetics of this reaction are consistent with an increase in reaction rate elicited by heme oxidation and iron-nitrosylation. In addition, conditions that favor the "R" conformation show an increased rate over conditions that favor the "T" conformation. The reactivity of nitrite with heme is clearly more complex than has been previously realized and is dependent upon the conformational state of the hemoglobin tetramer, suggesting that the nitrite reductase activity of hemoglobin is under allosteric control. C1 Wake Forest Univ, Sch Med, Dept Biomed Engn, Winston Salem, NC USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, NIH, Bethesda, MD 20892 USA. Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. RP Kim-Shapiro, DB (reprint author), Wake Forest Univ, Sch Med, Dept Biomed Engn, Winston Salem, NC USA. EM shapiro@wfu.edu; shapiro@wfu.edu FU NHLBI NIH HHS [HL58091, R01 HL058091, R01HL70146]; NIBIB NIH HHS [EB001980]; NIGMS NIH HHS [GM55792, T32GM08361] NR 23 TC 189 Z9 192 U1 1 U2 12 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 SEP 2 PY 2005 VL 280 IS 35 BP 31126 EP 31131 DI 10.1074/jbc.M501496200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958ZX UT WOS:000231487800058 PM 15837788 ER PT J AU Rhee, DK Marcelino, J Al-Mayouf, S Schelling, DK Bartels, CF Cui, YJ Laxer, R Goldbach-Mansky, R Warman, ML AF Rhee, DK Marcelino, J Al-Mayouf, S Schelling, DK Bartels, CF Cui, YJ Laxer, R Goldbach-Mansky, R Warman, ML TI Consequences of disease-causing mutations on lubricin protein synthesis, secretion, and post-translational processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUPERFICIAL ZONE PROTEIN; BOVINE SYNOVIAL-FLUID; ARTICULAR-CARTILAGE; LUBRICATING FACTOR; GENE-EXPRESSION; GROWTH-FACTOR; 2-CHAIN FORM; VITRONECTIN; DOMAIN; BINDING AB Lubricin, a protein product of the gene PRG4, is a secreted mucin-like proteoglycan that is a major lubricant in articulating joints. Mutations in PRG4 cause the autosomal recessive, human disorder camptodactyly-arthropathycoxa vara-pericarditis syndrome. We developed rabbit polyclonal antibodies against human lubricin to determine the consequence of disease-causing mutations at the protein level and to study the protein's normal post-translational processing. Antiserum generated against an epitope in the amino-terminal portion of lubricin detected protein in wild-type synovial fluid and in conditioned media from wild-type cultured synoviocytes. However, the antiserum did not detect lubricin in synovial fluid or cultured synoviocytes from several patients with frameshift or nonsense mutations in PRG4. Antiserum generated against an epitope in the protein's carboxyl-terminal, hemopexin-like domain identified a post-translational cleavage event in wild-type lubricin, mediated by a subtilisin-like proprotein convertase (SPC). Interestingly, in contrast to wild-type lubricin, one disease-causing mutation that removes the last 8 amino acids of the protein, including a conserved cysteine residue, was not cleaved within the hemopexin-like domain when expressed in COS-7 cells. This suggests that formation of an intrachain disulfide bond is required for SPC-mediated cleavage and that SPC-mediated cleavage is essential to protein function. C1 Case Western Reserve Univ, Dept Genet, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Human Genet, Sch Med, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Rheumatol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON M5G 1X8, Canada. NIAMS, NIH, Bethesda, MD 20892 USA. RP Warman, ML (reprint author), Case Western Reserve Univ, Dept Genet, Sch Med, Rm BRB-719,2109 Adelbert Rd, Cleveland, OH 44106 USA. EM mlw14@case.edu OI Al-Mayouf, Sulaiman/0000-0003-0142-6698 FU NIAMS NIH HHS [AR050180]; NICHD NIH HHS [HD07104, HD07518]; NIGMS NIH HHS [GM07250, GM08613] NR 31 TC 38 Z9 41 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 SEP 2 PY 2005 VL 280 IS 35 BP 31325 EP 31332 DI 10.1074/jbc.M505401200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958ZX UT WOS:000231487800080 PM 16000300 ER PT J AU Goren, MB Sokoloski, EA Fales, HM AF Goren, MB Sokoloski, EA Fales, HM TI 2-methyl-(1Z,3E)-butadiene-1,3,4-tricarboxylic acid, "isoprenetricarboxylic acid" SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CONFIGURATIONS AB The synthesis of the title compound 7 from ethyl glyoxylate and dimethyl and diethyl-methylglutaconate is described along with its physical properties that suggest its inability to assume a cis-dienoid structure due to steric hindrance between the methyl and carboxyl groups. C1 NHLBI, Lab Appl Mass Spectrometry, Bethesda, MD 20892 USA. RP Fales, HM (reprint author), NHLBI, Lab Appl Mass Spectrometry, Bldg 10, Bethesda, MD 20892 USA. EM hrnfales@helix.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 2 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 SEP 2 PY 2005 VL 70 IS 18 BP 7429 EP 7431 DI 10.1021/jo0507892 PG 3 WC Chemistry, Organic SC Chemistry GA 960EO UT WOS:000231573200052 PM 16122270 ER PT J AU Caudle, RM Perez, FM Del Valle-Pinero, AY Iadarola, MJ AF Caudle, Robert M. Perez, Federico M. Del Valle-Pinero, Arseima Y. Iadarola, Michael J. TI Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation SO MOLECULAR PAIN LA English DT Article AB Background: Spinal cord N-methyl-D-aspartate ( NMDA) receptors are intimately involved in the development and maintenance of central sensitization. However, the mechanisms mediating the altered function of the NMDA receptors are not well understood. In this study the role of phosphorylation of NR1 splice variants and NR2 subunits was examined following hind paw inflammation in rats. We further examined the level of expression of these proteins following the injury. Results: Lumbar spinal cord NR1 subunits were found to be phosphorylated on serine residues within two hours of the induction of hind paw inflammation with carrageenan. The enhanced NR1 serine phosphorylation reversed within six hours. No phosphorylation on NR1 threonine or tyrosine residues was observed. Likewise, no NR2 subunit phosphorylation was observed on serine, threonine or tyrosine residues. An analysis of NR1 and NR2 protein expression demonstrated no change in the levels of NR1 splice variants or NR2A following the inflammation. However, spinal cord NR2B expression was depressed by the hind paw inflammation. The expression of NR2B remained depressed for more than one week following initiation of the inflammation. Conclusion: These data suggest that NR1 serine phosphorylation leads to an initial increase in NMDA receptor activity in the spinal cord following peripheral injury. The suppression of NR2B expression suggests compensation for the enhanced nociceptive activity. These data indicate that spinal cord NMDA receptors are highly dynamic in the development, maintenance and recovery from central sensitization following an injury. Thus, chronic pain therapies targeted to NMDA receptors should be designed for the exact configuration of NMDA receptor subunits and post-translational modifications present during specific stages of the disease. C1 Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg & Diagnost Sci, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Neurosci, McKnight Brain Inst, Gainesville, FL 32610 USA. Natl Inst Dent & Craniofacial Res, Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Caudle, RM (reprint author), Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg & Diagnost Sci, Gainesville, FL 32610 USA. EM caudle@ufl.edu; fperez@dental.ufl.edu; delvalle@ufl.edu; miadarola@dir.nidcr.nih.gov NR 37 TC 40 Z9 42 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD SEP 2 PY 2005 VL 1 AR 25 DI 10.1186/1744-8069-1-25 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V43NN UT WOS:000202941900001 PM 16137337 ER PT J AU McVeigh, ER Guttman, MA Kellman, P Raval, AN Lederman, RJ AF McVeigh, ER Guttman, MA Kellman, P Raval, AN Lederman, RJ TI Real-time, interactive MRI for cardiovascular interventions SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT 5th International Interventional MRI Symposium CY OCT 15-16, 2004 CL Boston, MA DE MRI; intervention; real-time; therapy ID VENA-CAVA FILTER; GUIDED CORONARY CATHETERIZATION; MAGNETIC-RESONANCE FLUOROSCOPY; ARTERY STENT PLACEMENT; ANIMAL-MODEL; INTRAVASCULAR PROCEDURES; CARDIAC-CATHETERIZATION; ENDOVASCULAR PROCEDURES; BALLOON ANGIOPLASTY; SWINE MODEL C1 NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP McVeigh, ER (reprint author), NHLBI, Lab Cardiac Energet, NIH, Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM emcveigh@nih.gov FU Intramural NIH HHS [Z01 HL004608-08] NR 74 TC 17 Z9 17 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2005 VL 12 IS 9 BP 1121 EP 1127 DI 10.1016/j.acra.2005.05.024 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 958QT UT WOS:000231463500008 PM 16112512 ER PT J AU Hama, Y Uematsu, M Kosuda, S AF Hama, Y Uematsu, M Kosuda, S TI Portal vein gas after concurrent chemoradiotherapy for advanced oesophageal carcinoma SO ACTA CLINICA BELGICA LA English DT Article DE Esophageal neoplasms; complications; radiation; drug therapy; patient care AB Portal vein gas is a rare but potentially lethal condition commonly caused by mucosal damage, bowel distention and sepsis. However, the association between portal vein gas and concurrent chemoradiotherapy has not been documented. We present the case of a 56-year old woman with portal vein gas revealed on computed tomography (CT) after concurrent chemoradiotherapy for advanced oesophageal carcinoma. The portal vein gas totally disappeared 10 days later without any specific treatment. This case demonstrates that the option of close observation for portal vein gas after concurrent chemoradiotherapy is appropriate for consideration. If physical examination, CT findings and laboratory data are unremarkable, it is essential that the patient undergoes close observation and repeated follow-up CT. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Natl Def Med Coll, Dept Radiol, Tokorozawa, Saitama 3590042, Japan. RP Hama, Y (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM yjhama2005@yahoo.co.jp NR 4 TC 0 Z9 0 U1 0 U2 1 PU ACTA CLINICA BELGICA PI GHENT PA UNIV HOSPITAL GENT, DE PINTELAAN 185, RENAL DIVISION, B-9000 GHENT, BELGIUM SN 0001-5512 J9 ACTA CLIN BELG JI Acta Clin. Belg. PD SEP-OCT PY 2005 VL 60 IS 4 BP 198 EP 200 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 983UL UT WOS:000233257500007 PM 16279401 ER PT J AU Ramagopal, UA Dauter, Z Thirumuruhan, R Fedorov, E Almo, SC AF Ramagopal, UA Dauter, Z Thirumuruhan, R Fedorov, E Almo, SC TI Radiation-induced site-specific damage of mercury derivatives: phasing and implications SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID SULFUR ANOMALOUS SIGNAL; X-RAY-DIFFRACTION; PROTEIN CRYSTALS; IN-HOUSE; ABSORPTION-EDGE; MACROMOLECULAR CRYSTALLOGRAPHY; SUBSTRUCTURE SOLUTION; RESOLUTION; REFINEMENT; SCATTERING AB The behavior of mercury-derivatized triclinic crystals of a 60 kDa protein target from the New York Structural GenomiX Research Consortium provides novel insights into the mechanism of heavy-atom-specific radiation damage and its potential exploitation for de novo structure solution. Despite significant anomalous signal, structure solution by classic SAD and MAD phasing approaches was not successful. A detailed analysis revealed that significant isomorphic variation of the diffracted intensities was induced by X-ray irradiation. These intensity changes allowed the crystal structure to be solved by the radiation-damage-induced phasing ( RIP) technique. Inspection of the crystal structure and electron-density maps demonstrated that the covalent S - Hg bonds at all four derivatized cysteine sites were much more susceptible to radiation-induced cleavage than other bonds typically present in native proteins. A simple diagnostic is described to identify the fingerprint of such decay at the time of data collection/processing. The rapid radiation-induced decomposition of mercury adducts is consistent with the difficulties frequently associated with the experimental phasing of mercury derivatives and suggests a straightforward solution to overcome this limitation by radiation-damage-induced phasing with anomalous scattering (RIPAS). These results indicate that historically recalcitrant and newly emerging difficulties associated with Hg phasing should be revisited. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. Argonne Natl Lab, Natl Canc Inst, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Ctr Synchrotron Biosci, Bronx, NY 10461 USA. RP Ramagopal, UA (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM acharya@bnl.gov; almo@aecom.yu.edu FU NIGMS NIH HHS [1P50 GM62529] NR 52 TC 35 Z9 36 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP PY 2005 VL 61 BP 1289 EP 1298 DI 10.1107/S0907444905022316 PN 9 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 955QZ UT WOS:000231243400015 PM 16131763 ER PT J AU Carucci, DJ AF Carucci, DJ TI Advances in malaria genomics since MIM Arusha, 2002 SO ACTA TROPICA LA English DT Article; Proceedings Paper CT 4th Multilateral Initative on Malaria Pan-African Conference CY NOV 14-18, 2005 CL Yaounde, CAMEROON DE malaria; genomics; vaccines; drugs ID PLASMODIUM-FALCIPARUM; LIFE-CYCLE; SEQUENCE; PROTEINS; PROTEOME AB The promise of new interventions against malaria and other infectious diseases of global health importance derived from pathogen genomic sequence data may only be realized through the coordinated effort of genomic and post-genomics scientists. vaccine and drug developers along with lab- and field-based investigators. With the availability of the genome and the genomes of related species, post-genomics research can now be applied to the development of new interventions against malaria and may provide a more complete understanding of complex parasite biology. The vast amount of data that are generated through these new approaches must be organized, assembled and made accessible in a useful manner, By establishing a set of "credentials" for each gene in the genome, which captures information about gene expression, diversity, function and other information, the time and resources needed to test and evaluate candidate drugs and vaccines can he substantially reduced and a more complete picture of parasite biology can be created. (c) 2005 Elsevier B.V. All rights reserved. C1 Fdn Natl Inst Hlth, Grand Challenges Global Hlth, Bethesda, MD 20814 USA. RP Carucci, DJ (reprint author), Fdn Natl Inst Hlth, Grand Challenges Global Hlth, 45 Ctr Dr,3An44, Bethesda, MD 20814 USA. EM dcarucci@fnih.org NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-706X J9 ACTA TROP JI Acta Trop. PD SEP PY 2005 VL 95 IS 3 BP 260 EP 264 DI 10.1016/j.actatropica.2005.06.010 PG 5 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 964MX UT WOS:000231886300012 PM 16018960 ER PT J AU Zou, SG Wolkow, CA AF Zou, Sige Wolkow, Catherine A. TI Invertebrate models for studying human aging SO AGE LA English DT Editorial Material C1 NIA, Gerontol Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Zou, SG (reprint author), NIA, Gerontol Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. EM zous@grc.nia.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2005 VL 27 IS 3 BP III EP IV DI 10.1007/s11357-005-5137-6 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 121PM UT WOS:000243169500001 ER PT J AU Ashton, E Vosvick, M Chesney, M Gore-Felton, C Koopman, C O'Shea, K Maldonado, J Bachmann, MH Israelski, D Flamm, J Spiegel, D AF Ashton, E Vosvick, M Chesney, M Gore-Felton, C Koopman, C O'Shea, K Maldonado, J Bachmann, MH Israelski, D Flamm, J Spiegel, D TI Social support and maladaptive coping as predictors of the change in physical health symptoms among persons living with HIV/AIDS SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-OF-LIFE; METASTATIC BREAST-CANCER; EARLY HIV-1 INFECTION; GAY MEN; ANTIRETROVIRAL THERAPY; DEPRESSIVE SYMPTOMS; CLINICAL PROGRESSION; PSYCHOSOCIAL FACTORS; MEDICAL OUTCOMES AB This study examined social support and maladaptive coping as predictors of HIV-related health symptoms. Sixty-five men and women living with HIV/AIDS completed baseline measures assessing coping strategies, social support, and HIV-related health symptoms. The sample was primarily low-income and diverse with respect to gender, ethnicity, and sexual orientation. Three, 6, and 12 months after completing baseline assessments, physical health symptoms associated with HIV disease were assessed. After controlling for demographic characteristics, CD4 T-cell count, and baseline HIV-related health symptoms, individuals reporting lower increase in HIV-related health symptoms used less venting (expressing emotional distress) as a strategy for coping with HIV. However, when satisfaction with social support was added to the model, the use of this coping strategy was no longer significant, and individuals reporting more satisfying social support were more likely to report lower increase in their HIV-related health symptoms, suggesting that social support is a robust predictor of health outcomes over time independent of coping style and baseline medical status. These findings provide further evidence that social support can buffer deleterious health outcomes among individuals with a chronic illness. Future research needs to examine mediating pathways that can explain this relationship. C1 Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. Univ N Texas, Dept Hlth Psychol & Behav Med, Denton, TX 76203 USA. Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. San Mateo Cty Hlth Ctr, San Mateo, CA USA. Stanford Positive Care Clin, Palo Alto, CA USA. So Calif Permanente Med Grp, Sacramento, CA USA. RP Koopman, C (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. EM koopman@stanford.edu RI Bachmann, Michael/N-9339-2016 OI Bachmann, Michael/0000-0002-0204-3720 FU NIMH NIH HHS [MH54930] NR 70 TC 56 Z9 58 U1 2 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2005 VL 19 IS 9 BP 587 EP 598 DI 10.1089/apc.2005.19.587 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 966YI UT WOS:000232058300006 PM 16164385 ER PT J AU Aberg, JA Zackin, RA Brobst, SW Evans, SR Alston, BL Henry, WK Glesby, MJ Torriani, FJ Yang, YJ Owens, SI Fichtenbaum, CJ AF Aberg, JA Zackin, RA Brobst, SW Evans, SR Alston, BL Henry, WK Glesby, MJ Torriani, FJ Yang, YJ Owens, SI Fichtenbaum, CJ CA ACTG 5087 Study Team TI A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS Clinical Trials Group Study 5087 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT 11th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2004 CL San Francisco, CA ID REACTIVE PROTEIN-LEVELS; CARDIOVASCULAR RISK; INSULIN-RESISTANCE; CORONARY ATHEROSCLEROSIS; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; FAT REDISTRIBUTION; METABOLIC SYNDROME; METFORMIN THERAPY; INHIBITORS AB There is a paucity of information on the safety and efficacy of lipid-lowering therapy for dyslipidemia associated with human immunodeficiency virus (HIV) and antiretroviral therapy. Our objective was to determine whether fenofibrate and pravastatin were equivalent for the treatment of combined dyslipidemia in HIV as measured by a composite of the National Cholesterol Education Project (NCEP) goals based on absolute values for low-density lipoprotein (LDL), triglycerides (TG), and high-density lipoprotein (HDL) and to compare the safety of these agents through 48 weeks. This was a randomized, open-label trial with subjects assigned to fenofibrate 200 mg (n = 88) or pravastatin 40 mg (n = 86) daily. Subjects who failed to reach the NCEP composite goal on monotherapy by week 12 received both drugs. The composite goal at week 12 was achieved in 1% of fenofibrate and 5% of pravastatin subjects. At week 16, 69/88 subjects on fenofibrate added pravastatin (FP) and 67/86 subjects on pravastatin added fenofibrate (PF). At week 48, 7% FP subjects and 3% PF subjects achieved the composite goal. Median changes in LDL/HDL/TG/non-HDL were -8/+5/-144/-50 and -14/+2/-66/-34 mg/dl in subjects receiving FP and PF, respectively. There were few adverse events and no rhabdomyolysis reported. Combination therapy with fenofibrate and pravastatin for HIV-related dyslipidemia provides substantial improvements in lipid parameters and appears safe, but is unlikely to achieve all NCEP targets for lipid levels. C1 NYU, New York, NY 10016 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Social & Sci Syst Inc, Silver Spring, MD 20910 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Frontier Sci & Technol Res Fdn Inc, Chestnut Hill, MA 02467 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. NIAID, Bethesda, MD 20892 USA. RP Aberg, JA (reprint author), NYU, Bellevue Hosp Ctr, AIDS Clin Trials Unit, Bellevue C&D Bldg,Rm 550,501 1st Ave, New York, NY 10016 USA. EM judith.aberg@med.nyu.edu FU NCRR NIH HHS [RR00044, RR00046, RR00096]; NIAID NIH HHS [AI46381, AI25859, AI25868, AI25897, AI25903, AI25924, AI27661, AI27664, AI27665, AI27666, AI27670, AI27675, AI34832, AI34853, AI38855, AI38858, AI46383, AI46386, AI46730] NR 38 TC 73 Z9 74 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2005 VL 21 IS 9 BP 757 EP 767 DI 10.1089/aid.2005.21.757 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 973NA UT WOS:000232528300003 PM 16218799 ER PT J AU Dawson, DA Grant, BF Ruan, WJ AF Dawson, DA Grant, BF Ruan, WJ TI The association between stress and drinking: Modifying effects of gender and vulnerability SO ALCOHOL AND ALCOHOLISM LA English DT Article ID ALCOHOL-USE; PERCEIVED STRESS; SUBSTANCE USE; LIFE-EVENTS; PERSONALITY; CONSUMPTION; ADULTHOOD; MODEL; MOOD AB Aims: To assess the relationship between number and type of past-year stressful experiences and alcohol consumption, with a focus on how gender, poverty, and psychological vulnerability moderate this association. Methods: Data from 26 946 US past-year drinkers 18 years of age and over, interviewed in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), were used to construct multivariate linear regression models predicting six measures of drinking pattern and volume. Results: There was a consistent positive relationship between number of past-year stressors experienced and all measures of heavy drinking. Frequency of heavy (5+ drinks for men; 4+ drinks for women) drinking increased by 24% with each additional stressor reported by men and by 13% with each additional stressor reported by women. In contrast, the frequency of moderate drinking (< 5 drinks for men; < 4 drinks for women) decreased as stress levels increased. Job-related and legal sources of stress were more strongly associated with alcohol consumption than were social and health-related stress. Men showed a stronger association than women between the number of stressors and the most consumption measures; they also responded more strongly to the presence of any legal and job-related stress. Having an income below the poverty level intensified the effects of job-related stress, but having a mood or anxiety disorder did not affect any of the associations between stress and consumption. Conclusions: Stress does not so much lead individuals to drink more often as to substitute larger quantities of alcohol on the days when they do drink. Treatment and brief interventions aimed at problem drinkers might benefit from addressing the issue of tension alleviation and the development of alternative coping mechanisms. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3083,5635 Fishers Lane MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov NR 24 TC 114 Z9 117 U1 3 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD SEP-OCT PY 2005 VL 40 IS 5 BP 453 EP 460 DI 10.1093/alcalc/agh176 PG 8 WC Substance Abuse SC Substance Abuse GA 957IN UT WOS:000231363600019 PM 15972275 ER PT J AU Tran, DQ AF Tran, DQ TI Susceptibility to mycobacterial infections due to interferongamma and interleukin-12 pathway defects SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID GAMMA RECEPTOR; DEFICIENCY; MUTATION; DOMINANT; CONSEQUENCES AB A case of interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway defect is presented. Pathophysiology, clinical characteristics, diagnostic test, and case management are reviewed. Clinical Pearls and Pitalls include: (1) A high probability of a defect in the IFN-gamma/IL-12 cascade exists in patients with disseminated or recurrent infection due to poorly pathogenic mycobacteria or systemic infections caused by non-typhi Salmonella species that are persistent (aid recurrent despite antibiotic therapy. (2) Although less frequent, patients with impaired IFN-gamma/IL-12 mediated immunity are more susceptible to cytomegalovirus, human herpesvirus 8, herpes simplex virus, Listeria monocytogenes, and Histoplasma capsulatum. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Tran, DQ (reprint author), NIAID, NIH, 9000 Rockville Pike,10-11N315 MSC 1892, Bethesda, MD 20892 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2005 VL 26 IS 5 BP 418 EP 421 PG 4 WC Allergy SC Allergy GA 978XR UT WOS:000232906800017 PM 16450579 ER PT J AU Miller, MR Gergen, P Honour, M Zhan, CL AF Miller, MR Gergen, P Honour, M Zhan, CL TI Burden of illness for children and where we stand in measuring the quality of this health care SO AMBULATORY PEDIATRICS LA English DT Article DE adolescent; child; emergency medicine; health care; hospitals; infant; inpatients; outpatients; quality indicators; quality of health care AB Context.-Measures of health care quality for children are not as well developed as those for adults. It is also unclear the extent to which the current pool of measures address common causes of illness and health care utilization for children. Objective.-The goal of this study was to create lists of high-priority conditions for children based on different vantage points for defining burden relative to both inpatient and outpatient care for children. These high-priority conditions were then cross-tabulated with all known existing quality measures for pediatric health care. Data.-High-prevalence conditions for children were identified by using the 2000 National Ambulatory Medical Care Survey, 2000 National Hospital Ambulatory Medical Care Survey, 1999 Medical Expenditure Panel Survey, 2000 Healthcare Cost and Utilization Project's State Inpatient Databases, and 2000 Healthcare Cost and Utilization Project's State Ambulatory Surgery Databases. Burden assessments were done using frequencies of visits, charges, in-hospital deaths. Existing quality measures for children were identified from a recent compendium of such measures and a search of the National Quality Measures Clearinghouse. Results.-There are numerous and large gaps in existing quality-of-care measures for children relative to high-burden conditions in both the inpatient and outpatient setting. With the ever increasing efforts to measure and even publicly report on health care, efforts for children need to include focus on building a representative repertoire of quality measures for the high-burden conditions children experience. C1 Johns Hopkins Univ, Childrens Ctr, Dept Pediat, Baltimore, MD 21287 USA. NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, Rockville, MD USA. RP Miller, MR (reprint author), Johns Hopkins Univ, Childrens Ctr, Dept Pediat, 600 N Wolfe St, Baltimore, MD 21287 USA. EM mmille21@jhmi.edu NR 15 TC 13 Z9 13 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD SEP-OCT PY 2005 VL 5 IS 5 BP 268 EP 278 DI 10.1367/A04-229R.1 PG 11 WC Pediatrics SC Pediatrics GA 967VJ UT WOS:000232119000003 PM 16167849 ER PT J AU Wattendorf, DJ Muenke, M AF Wattendorf, DJ Muenke, M TI Prader-Willi syndrome SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID DIAGNOSTIC-CRITERIA; DEATH AB To complement the 2005 Annual Clinical Focus on medical genomics, AFP is publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the type of care they might require in the future. This review discusses Prader-Willi syndrome. C1 Med Genet Branch, NHGRI, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), Med Genet Branch, NHGRI, NIH, 35 Convent Dr-MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov NR 8 TC 23 Z9 26 U1 0 U2 2 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD SEP 1 PY 2005 VL 72 IS 5 BP 827 EP 830 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 962DF UT WOS:000231710500012 PM 16156341 ER PT J AU Fisher, SD Easley, KA Orav, EJ Colan, SD Kaplan, S Starc, TJ Bricker, JT Lai, WW Moodie, DS Sopko, G Lipshultz, SE AF Fisher, SD Easley, KA Orav, EJ Colan, SD Kaplan, S Starc, TJ Bricker, JT Lai, WW Moodie, DS Sopko, G Lipshultz, SE CA Pediat Pulm Cardiovascular Complic TI Mild dilated cardiomyopathy and increased left ventricular mass predict mortality: The prospective (PCHIV)-C-2-H-2 multicenter study SO AMERICAN HEART JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CARDIOVASCULAR COMPLICATIONS; PEDIATRIC PULMONARY; INFECTED CHILDREN; HIV; (PC2)-C-2; INFANTS AB Background Many HIV-infected children die with cardiac abnormalities. We sought to understand the course of these HIV-associated abnormalities and their impact on all-cause mortality. Methods We describe longitudinal changes in left ventricular (LV) structure and function and mortality in 185 children vertically infected with HIV. Serial cardiac data were obtained from 0.1 to 10 years of age. Age- or body surface area-adjusted z scores were calculated for 10 echocardiographic outcomes. Results Median age at first echocardiogram was 2 years (range 0.2-9.4 years); median follow-up was 3.6 years (range 0-6.3 years). The 5-year cumulative incidence of congestive heart failure was 12.3%. Mean fractional shortening z scores declined from -0.65 at 1 year of age to -1.47 at 3 years of age without further decline between 3 and 10 years of age. Among children with 2 echocardiograms performed in the first year of follow-up, mild LV dysfunction (fractional shortening of <-2 SD on both echocardiograms) was present in 29 (18%) of 158 children. For these 29 children, the 5-year mortality was 55.4%. Left ventricular mass z scores were elevated at 1 year (mean z score 0.68, P<.001) and remained elevated throughout follow-up. In the 8 children with LV mass z score of >2 SD on both initial and follow-up echocardiograms, the 5-year mortality was 75%. Conclusion In HIV-infected children, LV structure and function progressively deteriorated in the first 3 years of life, resulting in subsequent persistent mild LV dysfunction and increased LV mass. Chronic mild depression of LV function and elevated LV mass were associated with higher all-cause mortality. C1 Midatlantic Cardiol Associates, Baltimore, MD USA. Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Sch Med, Los Angeles, CA USA. Columbia Univ, Presbyterian Hosp, Coll Phys & Surg, Dept Pediat,Div Pediat Cardiol, New York, NY USA. Univ Kentucky, Dept Pediat, Lexington, KY USA. Mt Sinai Sch Med, Dept Pediat, Div Pediat Cardiol, New York, NY USA. Oschner Clin, Dept Pediat, New Orleans, LA USA. NHLBI, Bethesda, MD 20892 USA. Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33101 USA. RP Lipshultz, SE (reprint author), Univ Miami, Miller Sch Med, Dept Pediat D820, POB 016820, Miami, FL 33101 USA. EM slipshultz@med.miami.edu RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [RR-00071, M01 RR000533, RR-00533, RR-00188, K01 RR000188, M01 RR000071, M01 RR000188, M01 RR000645, RR-00645, RR-00865, RR-00043, M01 RR000865, M01 RR000043]; NHLBI NIH HHS [N01-HR-96042, N01-HR-96039, N01 HR096043, N01 HR096037, N01-HR-96040, N01-HR-96041, N01-HR-96038] NR 16 TC 38 Z9 38 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2005 VL 150 IS 3 BP 439 EP 447 DI 10.1016/j.ahj.2005.06.012 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 970WQ UT WOS:000232343500015 PM 16169321 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Undue inducement: Nonsense on stilts? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE undue inducement; coercion; exploitation; research ethics; payment ID CLINICAL-RESEARCH; DEVELOPING-COUNTRIES; INCENTIVES; ETHICS C1 NIH, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Bethesda, MD 20892 USA. NR 17 TC 64 Z9 64 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD SEP-OCT PY 2005 VL 5 IS 5 BP 9 EP 13 DI 10.1080/15265160500244959 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 980LH UT WOS:000233019500003 PM 16179296 ER PT J AU Miller, FG AF Miller, FG TI The case for a code of ethics for bioethicists: Some reasons for skepticism SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD SEP-OCT PY 2005 VL 5 IS 5 BP 50 EP 52 DI 10.1080/15265160500245436 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 980LH UT WOS:000233019500019 PM 16179312 ER PT J AU Visser, M Kritchevsky, SB Newman, AB Goodpaster, BH Tylavsky, FA Nevitt, MC Harris, TB AF Visser, M Kritchevsky, SB Newman, AB Goodpaster, BH Tylavsky, FA Nevitt, MC Harris, TB CA Health Aging Body Composition TI Lower serum albumin concentration and change in muscle mass: the Health, Aging and Body Composition Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE sarcopenia; dual-energy X-ray absorptiometry; body composition; aging; protein; inflammation ID CORONARY-HEART-DISEASE; SKELETAL-MUSCLE; OLDER PERSONS; ELDERLY MEN; WOMEN; MORTALITY; RISK; INTERLEUKIN-6; ACTIVATION; PROTEIN AB Background: Low albumin concentrations in older persons increase the risk of poor health outcomes, including functional decline. Objective: The aim of the study was to investigate the association between serum albumin concentration and skeletal muscle loss (sarcopenia) in old age. Design: Serum albumin concentration was measured in 1882 black and white men and women aged 70-79 y participating in the Health, Aging and Body Composition Study. Five-year changes in appendicular skeletal muscle mass (ASMM), total-body fat-free mass (FFM), and trunk lean mass (TLM) were measured by using dual-energy X-ray absorptiometry. Confounders included health and lifestyle factors, which are markers of inflammation and protein intake. Results: A low albumin concentration (< 38 g/L) was observed in 21.2% of the study participants. After adjustment for confounders, the mean (+/- SE) change in ASMM was -82 +/- 26 g per 3-g/L lower albumin concentration (P = 0.002). This association remained after persons with a low albumin concentration (< 38 g/L) were excluded. The decline in ASMM in subjects with low albumin concentrations was almost 30% higher (-930 +/- 56 g) than that in those with albumin concentrations >= 42 g/L (-718 38 g; P < 0.01). The association between albumin and change in ASMM remained after additional adjustment for weight change. A weak association was observed for FFM, whereas no association was observed for TLM, which suggests a specific role of albumin in skeletal muscle change. Conclusions: Lower albumin concentrations, even above the clinical cutoff of 38 g/L, are associated with future loss of ASMM in older persons. Low albumin concentration may be a risk factor for sarcopenia. C1 Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, NL-1081 HV Amsterdam, Netherlands. Vrije Univ Amsterdam, Inst Res Extramural Med, Med Ctr, NL-1081 HV Amsterdam, Netherlands. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. NIA, Dept Biometry, Lab Epidemiol, Bethesda, MD 20892 USA. RP Visser, M (reprint author), Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM marjolein.visser@falw.vu.nl RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2106, N01-AG-6-2101, N01-AG-6-2103] NR 36 TC 85 Z9 86 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 531 EP 537 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900008 PM 16155264 ER PT J AU Sahyoun, NR Anderson, AL Kanaya, AM Koh-Banerjee, P Kritchevsky, SB de Rekeneire, N Tylavsky, FA Schwartz, AV Lee, JS Harris, TB AF Sahyoun, NR Anderson, AL Kanaya, AM Koh-Banerjee, P Kritchevsky, SB de Rekeneire, N Tylavsky, FA Schwartz, AV Lee, JS Harris, TB TI Dietary glycemic index and load, measures of glucose metabolism, and body fat distribution in older adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE glycemic index; glycemic load; glucose metabolism; insulin resistance; body composition; older adults ID ADIPOSE-TISSUE; YOUNG-ADULTS; FIBER INTAKE; CARBOHYDRATE; RISK; WOMEN; INSULIN; ASSOCIATION; TOLERANCE; AMERICAN AB Background: Recent evidence suggests that the rate of carbohydrate digestion and absorption may influence the development of type 2 diabetes. Objective: The aim of this study was to examine associations of dietary glycemic index and glycemic load with predictors of type 2 diabetes in older adults. Design: This study evaluated cross-sectional relations of dietary glycemic index and glycemic load with measures of glucose metabolism and body fat distribution in participants of the Health, Aging and Body Composition Study, a prospective cohort study of adults aged 70 - 80 y (n = 2248). Results: In men, dietary glycemic index was positively associated with 2-h glucose (P for trend = 0.04) and fasting insulin (P for trend = 0.004), inversely associated with thigh intramuscular fat (P for trend = 0.02), and not significantly associated with fasting glucose, glycated hemoglobin, or visceral abdominal fat. Dietary glycemic load was inversely associated in men with visceral abdominal fat (P for trend = 0.02) and not significantly associated with fasting glucose, 2-h glucose, glycated hemoglobin, fasting insulin, or thigh intramuscular fat. In women, although dietary glycemic index and load were not significantly related to any measures of glucose metabolism or body fat distribution. the association between dietary glycemic index and 2-h glucose was nearly significant (P for trend = 0.06). Conclusion: The findings of this cross-sectional study indicate an association between dietary glycemic index and selected predictors of type 2 diabetes in older adults, particularly in men. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Wake Forest Univ, J Paul Sticht Ctr Aging, Winston Salem, NC 27109 USA. Social & Sci Syst, Silver Spring, MD USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Bethesda, MD 20892 USA. RP Sahyoun, NR (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM nsahyoun@umd.edu RI Sahyoun, Nadine/G-2608-2011 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106, N01-AG-6-2102] NR 25 TC 32 Z9 34 U1 1 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 547 EP 552 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900010 PM 16155266 ER PT J AU Lee, JS Kritchevsky, SB Harris, TB Tylavsky, F Rubin, SM Newman, AB AF Lee, JS Kritchevsky, SB Harris, TB Tylavsky, F Rubin, SM Newman, AB TI Short-term weight changes in community-dwelling older adults: the health, aging, and body composition weight change substudy SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE weight-change intention; short-term weight change; community-dwelling elderly; Health ABC Study ID FOOD-INTAKE; AGE; PREDICTORS; ANOREXIA; MEN; ASSOCIATION; OVERWEIGHT; DIAGNOSIS; WOMEN; DIET AB Background: The frequency and short-term natural history of weight loss in community-dwelling older adults have not been described. Unintentional weight loss may be more likely to continue than intentional weight loss. Objectives: The present substudy described the frequency of a >= 5% loss or gain in body weight in community-dwelling older adults at an annual examination of the Health, Aging, and Body Composition (Health ABC) Study and 6 mo later. The weight-management practices used by the participants were also described. Design: A total of 522 older adults with either a >= 5% weight gain (n = 116) or a >= 5% weight loss (n = 17 1) in the previous year were compared with a random sample of weight-stable older adults (< 5% weight loss or gain, n = 235) at the fourth annual visit of the ongoing Health ABC Study. The participants' weight-loss intention and weight-management practices were assessed by an interview. The participants' weight was reassessed 6 mo later. Results: Compared with the weight-stable participants, the participants who had lost or gained weight at the substudy baseline were more likely to have subsequent weight changes. The direction of the subsequent weight change, however, was more likely toward either maintenance of or recovery from the previous weight change. Only 4% of the participants who gained weight and 11% of those who lost weight continued to gain or lose weight, respectively. Continued weight loss was more common in the participants with unintentional weight loss than in those with intentional weight loss, but the difference was not significant. Conclusions: Weight changes were common, but most participants, including those who unintentionally lost weight, maintained their weight change or resolved their weight change in 6 mo. Unintentional weight loss appears less likely to resolve than other weight changes. C1 Univ Pittsburgh, Pittsburgh, PA 15213 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Lee, JS (reprint author), Univ Pittsburgh, 130 N Bellefield Ave, Pittsburgh, PA 15213 USA. EM jung-sun.lee@mail.cscc.unc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 35 TC 9 Z9 10 U1 1 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 644 EP 650 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900023 PM 16155279 ER PT J AU Freudenheim, JL Ritz, J Smith-Warner, SA Albanes, D Bandera, EV van den Brandt, PA Colditz, G Feskanich, D Goldbohm, RA Harnack, L Miller, AB Rimm, E Rohan, TE Sellers, TA Virtamo, J Willett, WC Hunter, DJ AF Freudenheim, JL Ritz, J Smith-Warner, SA Albanes, D Bandera, EV van den Brandt, PA Colditz, G Feskanich, D Goldbohm, RA Harnack, L Miller, AB Rimm, E Rohan, TE Sellers, TA Virtamo, J Willett, WC Hunter, DJ TI Alcohol consumption and risk of lung cancer: a pooled analysis of cohort studies SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE alcohol consumption; diet; epidemiology; lung neoplasms; meta-analysis ID CHRONIC ETHANOL-CONSUMPTION; BREAST-CANCER; DIETARY CAROTENOIDS; NEW-YORK; MORTALITY; METAANALYSIS; SMOKING; WOMEN; RAT; FAT AB Background: Although smoking is the primary cause of lung cancer. much is unknown about lung cancer etiology, including risk determinants for nonsmokers and modifying factors for smokers. Objective: We hypothesized that alcohol consumption contributes to lung cancer risk. Design: We conducted a pooled analysis using standardized exposure and covariate data from 7 prospective studies with 399 767 participants and 3 137 lung cancer cases. Study-specific relative risks (RRs) and CIs were estimated and then combined to calculate pooled multivariate RRs by using a random-effects model. Results: We found a slightly greater risk for the consumption of >= 30 alcohol/d than for that of 0 alcohol/d in men (RR: 1.21; 95% CI: 0.91. 1.61: P for trend = 0.03) and in women (RR: 1.16; 95% CI: 0.94. 1.43: P for trend = 0.03). In male never smokers, the RR for consumption of >= 15 g alcohol/d rather than 0 g alcohol/d was 6.38 (95% CI: 2.74,14.9; P for trend < 0.001). In women, there were few never-smoking cases and no evidence of greater risk (RR: 1.35; 95% CI: 0.64 2.87). Because of possible residual confounding by smoking, we performed sensitivity analyses by reclassifying the never smokers in the highest drinking category as former smokers. Resulting associations for alcohol consumption were somewhat attenuated, but P for trend = 0.05 for men, which was near the original P = 0.03. Conclusions: A slightly greater risk of lung cancer was associated with the consumption of >= 30 g alcohol/d than with no alcohol consumption. Alcohol consumption was strongly associated with,greater risk in male never smokers. Residual confounding by smoking may explain part of the observed relation. C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. TNO, Nutr & Food Res Inst, Dept Epidemiol, NL-3700 AJ Zeist, Netherlands. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Freudenheim, JL (reprint author), SUNY Buffalo, Dept Social & Prevent Med, 270 Farber Hall, Buffalo, NY 14214 USA. EM jfreuden@buffalo.edu RI Bandera, Elisa/M-4169-2014; Albanes, Demetrius/B-9749-2015; Colditz, Graham/A-3963-2009 OI Bandera, Elisa/0000-0002-8789-2755; Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, CA78548]; NIAAA NIH HHS [AA 09802] NR 60 TC 54 Z9 58 U1 2 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 657 EP 667 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900025 PM 16155281 ER PT J AU Murabito, JM Evans, JC D'Agostino, RB Wilson, PWF Kannel, WB AF Murabito, JM Evans, JC D'Agostino, RB Wilson, PWF Kannel, WB TI Temporal trends in the incidence of intermittent claudication from 1950 to 1999 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cardiovascular diseases; intermittent claudication; mortality ID PERIPHERAL ARTERIAL-DISEASE; CORONARY-HEART-DISEASE; HIGH-RISK PATIENTS; BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; LEG SYMPTOMS; FRAMINGHAM; PREVALENCE AB Declines in coronary disease and stroke mortality have occurred, but it remains unclear whether intermittent claudication (IC) incidence and mortality rates have changed. The authors sought to examine long-term trends for IC in the community. Cases of IC among Framingham Study participants aged >= 40 years were classified according to date of onset from the 1950s to the 1990s. IC was defined as the presence of exertional calf discomfort that was relieved with rest. Age- and sex-adjusted incidence rate ratios were estimated using log-linear Poisson regression, and 10-year survival was calculated using the Kaplan-Meier method. IC occurred in 668 participants (286 women). The age- and sex-adjusted incidence rate of IC fell from 282 per 100,000 person-years during the period 1950-1969 to 225 per 100,000 person-years in the 1990s. The decline in IC incidence across time periods was significant (p for trend = 0.01), with an initial increase in the 1970s being followed by declines of 16% in the 1980s and 18% in the 1990s. Approximately 40% of persons with IC died within 10 years of diagnosis, with no significant change occurring during the study period. IC incidence has declined since 1950, but mortality has remained high and unchanged. Factors contributing to the declining incidence of IC need clarification. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Sect Gen Internal Med, Boston, MA 02118 USA. Boston Univ, Stat & Consulting Unit, Boston, MA 02215 USA. Med Univ S Carolina, Dept Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Diabet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med Genet, Charleston, SC 29425 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM Murabito@bu.edu OI Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [N01-HC-25195] NR 47 TC 25 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2005 VL 162 IS 5 BP 430 EP 437 DI 10.1093/aje/kwi217 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 957IP UT WOS:000231363800006 PM 16076834 ER PT J AU Loftis, JM Rifai, MA Hauser, P AF Loftis, JM Rifai, MA Hauser, P TI Depression and sustained viral response in patients with hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIMH, Off Clin Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 277 BP S114 EP S114 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853500278 ER PT J AU Oxentenko, AS Vierkant, RA Pardi, DS Farley, DR Dozois, EJ Hartman, TE Hough, DM Petersen, WO Klabunde, C Sharpe, K Bond, JH Smith, RA Levin, B Pope, JB Schroy, PC Limburg, PJ AF Oxentenko, AS Vierkant, RA Pardi, DS Farley, DR Dozois, EJ Hartman, TE Hough, DM Petersen, WO Klabunde, C Sharpe, K Bond, JH Smith, RA Levin, B Pope, JB Schroy, PC Limburg, PJ TI Follow-up of positive colorectal cancer screening tests: Data from the second national colorectal cancer roundtable (NCCRT) trainee survey SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Mayo Clin, Coll Med, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. ACS, Atlanta, GA USA. VA Med Ctr, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Louisiana State Univ, Shreveport, LA 71105 USA. BMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 1060 BP S386 EP S386 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502317 ER PT J AU Oxentenko, AS Vierkant, RA Pardi, DS Farley, DR Dozios, EJ Hartman, TE Hough, DM Petersen, WO Klabunde, C Sharpe, K Bond, JH Smith, RA Levin, B Pope, JB Schroy, PC Limburg, PJ AF Oxentenko, AS Vierkant, RA Pardi, DS Farley, DR Dozios, EJ Hartman, TE Hough, DM Petersen, WO Klabunde, C Sharpe, K Bond, JH Smith, RA Levin, B Pope, JB Schroy, PC Limburg, PJ TI Recognition of patients at increased risk for colorectal cancer: Data from the second national colorectal cancer roundtable (NCCRT) trainee survey SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Mayo Clin, Coll Med, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. ACS, Atlanta, GA USA. VA Med Ctr, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Louisiana State Univ, Shreveport, LA 71105 USA. BMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 1059 BP S385 EP S385 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502316 ER PT J AU Sabouni, D Rifai, MA AF Sabouni, D Rifai, MA TI Interferon-alpha treatment of hepatitis C patients with psychiatric disorders: A case series on evidence-based, risk-benefit assessment SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Univ Virginia, Sch Med, Vet Affairs Med Ctr, Roanoke Salem Program, Charlottesville, VA 22903 USA. NIMH, Off Clin Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 566 BP S214 EP S215 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853501174 ER PT J AU Sabouni, D Rifai, MA Moles, JK Van Der Linden, BJ AF Sabouni, D Rifai, MA Moles, JK Van Der Linden, BJ TI Hepatitis C treatment eligibility and outcomes in patients with psychiatric illness SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 NIMH, NIH, Off Clin Director, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Vet Affairs Med Ctr, Roanoke Salem Program, Charlottesville, VA 22908 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 287 BP S117 EP S118 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853500288 ER PT J AU Drilea, SK Reid, BC Li, CH Hyman, JJ Manski, RJ AF Drilea, SK Reid, BC Li, CH Hyman, JJ Manski, RJ TI Dental visits among smoking and nonsmoking US adults in 2000 SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE dental visits; smoking; oral diseases; dental care; health education ID TOOTH LOSS; PERIODONTAL-DISEASE; CIGARETTE-SMOKING; ORAL-CANCER; RISK; TOBACCO AB Objective: To examine dental visits among smoking and nonsmoking adults in a nationally representative sample. Methods: Logistic regression analysis was performed, using a sample of 15,250 US adults from the Medical Expenditure Panel Survey Household Component 2000. Results: Currentsmokers were less likely to report dental visits (32.9%) than were nonsmokers (45.0%) during 2000. Differ- ences were statistically significant even after accounting for other predictors of dental care use. Conclusions: Efforts to optimize the oral health of smokers and reduce serious oral diseases may benefit from addressing this lower use of dental services among smokers. C1 NIDCR, CDC, Data Resource Ctr, Rockville, MD 20850 USA. Univ Maryland, Sch Dent, Dept Hlth Promot & Policy, Hlth Serv Res Program, Baltimore, MD 21201 USA. NIDCR, NIH, Bethesda, MD USA. Univ Maryland, Sch Dent, Dept Hlth Promot & Policy, Hlth Serv Res Div, Baltimore, MD 21201 USA. RP Drilea, SK (reprint author), NIDCR, CDC, Data Resource Ctr, 2101 Gaither Rd,Suite 600, Rockville, MD 20850 USA. EM susan.drilea@ngc.com NR 23 TC 22 Z9 22 U1 0 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD SEP-OCT PY 2005 VL 29 IS 5 BP 462 EP 471 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 958XK UT WOS:000231481300009 PM 16201863 ER PT J AU Nyholt, DR Morley, KI Ferreira, MAR Medland, SE Boomsma, DI Heath, AC Merikangas, KR Montgomery, GW Martin, NG AF Nyholt, DR Morley, KI Ferreira, MAR Medland, SE Boomsma, DI Heath, AC Merikangas, KR Montgomery, GW Martin, NG TI Genomewide significant linkage to migrainous headache on chromosome 5q21 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL HEMIPLEGIC MIGRAINE; SEROTONIN TRANSPORTER GENE; CA2+ CHANNEL GENE; TYPICAL MIGRAINE; SUSCEPTIBILITY LOCUS; QUANTITATIVE-TRAIT; RECEPTOR GENES; DIAGNOSTIC-CRITERIA; COMPLEX TRAITS; LATENT CLASS AB Familial typical migraine is a common, complex disorder that shows strong familial aggregation. Using latent-class analysis (LCA), we identified subgroups of people with migraine/severe headache in a community sample of 12,245 Australian twins (60% female), drawn from two cohorts of individuals aged 23-90 years who completed an interview based on International Headache Society criteria. We report results from genomewide linkage analyses involving 756 twin families containing a total of 790 independent sib pairs ( 130 affected concordant, 324 discordant, and 336 unaffected concordant for LCA-derived migraine). Quantitative-trait linkage analysis produced evidence of significant linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13. In addition, we replicated previously reported typical-migraine susceptibility loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding which potentially implicates ATP1A2 in familial typical migraine for the first time. Linkage analyses of individual migraine symptoms for our six most interesting chromosomes provide tantalizing hints of the phenotypic and genetic complexity of migraine. Specifically, the chromosome 1 locus is most associated with phonophobia; the chromosome 5 peak is predominantly associated with pulsating headache; the chromosome 6 locus is associated with activity-prohibiting headache and photophobia; the chromosome 8 locus is associated with nausea/vomiting and moderate/severe headache; the chromosome 10 peak is most associated with phonophobia and photophobia; and the chromosome 13 peak is completely due to association with photophobia. These results will prove to be invaluable in the design and analysis of future linkage and linkage disequilibrium studies of migraine. C1 Queensland Inst Med Res, PO Off Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4067, Australia. Univ Queensland, Dept Psychol, St Lucia, Qld 4067, Australia. Free Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA. NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Nyholt, DR (reprint author), Queensland Inst Med Res, PO Off Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. EM daleN@qimr.edu.au RI Montgomery, Grant/B-7148-2008; Morley, Katherine/A-2986-2011; Nyholt, Dale/C-8384-2013; Ferreira, Manuel/D-3609-2013; Medland, Sarah/C-7630-2013 OI Montgomery, Grant/0000-0002-4140-8139; Morley, Katherine/0000-0002-2725-5535; Martin, Nicholas/0000-0003-4069-8020; Medland, Sarah/0000-0003-1382-380X FU NIAAA NIH HHS [AA014041, AA013320, AA013326, AA07728, AA11998, P50 AA011998, R01 AA007535, R01 AA007728, R01 AA010249, R01 AA013320, R01 AA013326, R01 AA014041, R37 AA007728] NR 77 TC 63 Z9 64 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2005 VL 77 IS 3 BP 500 EP 512 DI 10.1086/444510 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 956QE UT WOS:000231314100016 PM 16080125 ER PT J AU Choh, AC Czerwinski, SA Lee, M Demerath, EW Wilson, AF Towne, B Siervogel, RM AF Choh, AC Czerwinski, SA Lee, M Demerath, EW Wilson, AF Towne, B Siervogel, RM TI Quantitative genetic analysis of blood pressure response during the cold pressor test SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE genetic epidemiology; cardiovascular disease reactivity; cold pressor test; blood pressure; pleiotropy ID CARDIOVASCULAR RISK-FACTORS; RACIAL-DIFFERENCES; LINKAGE ANALYSIS; HYPERTENSION; TRAITS; HERITABILITY; REACTIVITY; PREDICTOR; STRESS; FAMILY AB Background: The genetic association between blood pressure (BP) at rest and during the cold pressor test (CPT) is not well characterized. The purpose of this study was to examine the genetic architecture of BP during the CPT, and to determine whether BP at rest and during the CPT share common genetic influences. Methods: In 419 individuals distributed across four large families, variance components methods were used to estimate heritabilities of resting BP and CPT BP, along with genetic correlations among BP traits. The CPT consisted of immersion of the left foot in 4 C water while the participant was supine. Blood pressure reactivity (Delta BP) was defined as BP at 15 to 30 sec and 45 to 60 sec of foot immersion minus resting BP. Results: Significant (P < .05) heritabilities were found for supine BP (h(SBP)(2) = 0.35), CPT BP (h(SBP)(2) = 0.27 and 0.33, h(DBP)(2) = 0.18 and 0.30), and Delta SBP (h(SBP)(2) = 0.12 and 0.37) but not for Delta DBP. Bivariate analyses detected significant (P < .05) genetic correlations between resting SBP and CPT SBP that were different from 0 and 1. Genetic correlations between resting DBP and CPT DBP were not significantly different from 1. Genetic correlations between resting SBP and Delta SBP were not significant. Conclusions: Measures of BP at rest and during cold immersion are significantly influenced by additive genetic effects. These genetic influences are only partially shared between SBP at rest and SBP during cold immersion, suggesting that a somewhat different set of genes may influence SBP during cold immersion. Unique sets of genes also appear to influence Delta SBP independent of those influencing resting SBP. C1 Wright State Univ, Sch Med, Lifespan Hlth Res Ctr, Kettering, OH 45420 USA. NHGRI, Natl Inst Hlth, Baltimore, MD USA. RP Choh, AC (reprint author), Wright State Univ, Sch Med, Lifespan Hlth Res Ctr, 3171 Res Blvd, Kettering, OH 45420 USA. EM audrey.choh@wright.edu RI Wilson, Alexander/C-2320-2009 FU NHLBI NIH HHS [HL 070167, HL 69995, R01 HL069995, R01 HL070167] NR 29 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD SEP PY 2005 VL 18 IS 9 BP 1211 EP 1217 DI 10.1016/j.amjhyper.2004.11.041 PN 1 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 970EP UT WOS:000232288300014 PM 16182112 ER PT J AU Menon, V Greene, T Pereira, AA Wang, XL Beck, GJ Kusek, JW Collins, AJ Levey, AS Sarnak, MJ AF Menon, V Greene, T Pereira, AA Wang, XL Beck, GJ Kusek, JW Collins, AJ Levey, AS Sarnak, MJ TI Relationship of phosphorus and calcium-phosphorus product with mortality in CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE calcium-phosphorus product; cardiovascular disease; chronic kidney disease (CKD); mineral metabolism; phosphorus ID STAGE RENAL-DISEASE; CHRONIC-HEMODIALYSIS PATIENTS; CARDIOVASCULAR OUTCOMES; VASCULAR CALCIFICATION; PARATHYROID-HORMONE; MINERAL METABOLISM; SERUM PHOSPHORUS; RISK; PHOSPHATE; ASSOCIATION AB Background Abnormalities of mineral metabolism are prevalent in patients with kidney failure and are associated with increased risk for cardiovascular events. There are limited data investigating relationships of phosphorus and calcium-phosphorus product with outcomes in patients with chronic kidney disease (CKD) stages 3 to 4. Methods: Serum phosphorus and calcium were measured at baseline in 840 participants from the randomized cohort of the Modification of Diet in Renal Disease Study. Survival status until December 31, 2000, was obtained from the National Death Index. Cox models were performed to assess the relationship of serum phosphorus level and calcium-phosphorus product with all-cause and cardiovascular disease (CVD) mortality. Results Mean serum phosphorus level was 3.8 +/- 0.7 mg/dL (1.23 +/- 0.23 mmol/L), calcium-phosphorus product was 34.7 +/- 6.3 mg(2)/dL(2), and glomerular filtration rate (GFR) was 33 +/- 12 mL/min/1.73 m(2) (0.55 +/- 0.20 mL/s/1.73 m(2)). All-cause and CVD mortality rates were 25% and 15%. Serum phosphorus level was not related to all-cause mortality in multivariable models (P=0.46). In unadjusted analysis, serum phosphorus level was associated with (hazard ratio [HR] per 1 mg/dL increase, 1.34; 95% confidence interval [CI], 1.05 to 1.71; P=0.02) increased risk for CVD mortality, but this association was partly attenuated and not statistically significant after adjustment for GFR and other confounders (HR, 1.27; 95% CI, 0.94 to 1.73; P=0.12). Calcium-phosphorus product was not associated with all-cause mortality in unadjusted (P=0.23) or multivariate analysis (P=0.35). Calcium-phosphorus product was related to CVD mortality in unadjusted (HR per 10 mg(2)/dL(2) increase, 1.30; 95% CI, 1.01 to 1.69; P=0.04) analysis, but this association was not statistically significant after adjustment for GFR and other confounders (HR, 1.22; 95% CI, 0.89 to 1.66; P=0.23). Conclusion: In the Modification of Diet in Renal Disease Study cohort, serum phosphorus level and calcium-phosphorus product were not statistically associated with all-cause or CVD mortality after adjustment for GFR; however larger studies with additional statistical power are needed to evaluate these relationships, especially in the context of current practice patterns in patients with CKD. C1 Tufts New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. RP Sarnak, MJ (reprint author), Tufts New England Med Ctr, Dept Med, Div Nephrol, 750 Washington St,NEMC 391, Boston, MA 02111 USA. EM msarnak@tufts-nemc.org FU NIDDK NIH HHS [1 K23 DK67303, 1 K23 DK02904, UO1 DK 35073] NR 24 TC 73 Z9 74 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2005 VL 46 IS 3 BP 455 EP 463 DI 10.1053/j.ajkd.2005.05.025 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 964AF UT WOS:000231847500009 PM 16129207 ER PT J AU Thom, EA Klebanoff, MA AF Thom, EA Klebanoff, MA TI Issues in clinical trial design: Stopping a trial early, and the large and simple trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE research methods; clinical trial; biostatics; study monitoring ID BROAD-SPECTRUM ANTIBIOTICS; PREVENT PRETERM DELIVERY; RANDOMIZED-TRIAL; WEEKLY COURSES; PREGNANT-WOMEN; CORTICOSTEROIDS; METRONIDAZOLE; SINGLE; RISK AB During the conduct of a clinical trial, a primary function of the Data Safety and Monitoring Committee is to select the trial conduct and the accumulating data to determine whether the trial should continue or be discontinued earlier than planned. Reasons for early discontinuation of a trial include: evidence of benefit, evidence of harm, and evidence of futility. More than l of these elements will often be present. These principles will be illustrated with examples from National Institute of Child Health and Human Development-Maternal-Fetal Medicine Units clinical trials. The "large and simple clinical trial'' is a study design rarely undertaken in the United States but commonly used elsewhere. The principles of this type of trial will be introduced and contrasted with those of the "conventional clinical trial." (c) 2005 Mosby, Inc. All rights reserved. C1 George Washington Univ, Ctr Biostat, Rockville, MD USA. NICHHD, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Thom, EA (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD USA. FU NICHD NIH HHS [U01-HD36801] NR 23 TC 5 Z9 5 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 619 EP 625 DI 10.1016/j.ajog.2005.05.061 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IM UT WOS:000232013300005 PM 16150252 ER PT J AU Althuis, MD Scoccia, B Lamb, EJ Moghissi, KS Westhoff, CL Mabie, JE Brinton, LA AF Althuis, MD Scoccia, B Lamb, EJ Moghissi, KS Westhoff, CL Mabie, JE Brinton, LA TI Melanoma, thyroid, cervical, and colon cancer risk after use of fertility drugs SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ovulation induction; clomiphene; gonadotropins; cancer; infertility ID OVULATION-STIMULATING DRUGS; IN-VITRO FERTILIZATION; INFERTILE WOMEN; BREAST-CANCER; REPRODUCTIVE FACTORS; REPLACEMENT THERAPY; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; CLOMIPHENE CITRATE; FEMALE HORMONES AB Objective: This study was undertaken to evaluate melanoma, thyroid, colon, and cervical cancer risks after clomiphene or gonadotropins. Study design: Retrospective cohort of 8422 women (155,527 women-years) evaluated for infertility (1965-1988). Through 1999, cancers were ascertained by questionnaire, cancer and death registries. Poisson regression estimated adjusted rate ratios (RRs). Results: Clomiphene use did not significantly increase risk of melanoma (RR = 1.66; 95% CI, 0.9- 3.1), thyroid (RR = 1.42; 95% CI, 0.5-3.7), cervical (RR = 1.61; 95% CI, 0.5-4.7), or colon cancer (RR = 0.83; 95% CI, 0.4-1.9). We found no relationship between clomiphene dose or cycles of use and cancer risk at any site. Clomiphene use may impart stronger effects on risks of melanoma (RR 2.00; 95% CI, 0.9-4.6) and thyroid cancer among women who remained nulliparous (RR 4.23; 95% CI, 1.0- 17.1). Gonadotropins did not increase cancer risk for these sites. Conclusion: Fertility drugs do not appear to have strong effects on these cancers. Nonetheless, follow-up should be pursued to assess long-term risks and to monitor effects among women who remain nulliparous. (c) 2005 Mosby, Inc. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Stanford Univ, Stanford, CA 94305 USA. Wayne State Univ, Detroit, MI 48202 USA. Columbia Univ, New York, NY 10027 USA. Informat Management Serv Inc, Rockville, MD USA. RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7068, Bethesda, MD 20892 USA. EM brintoni@exchange.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 30 TC 25 Z9 26 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 668 EP 674 DI 10.1016/j.ajog.2005.01.091 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IM UT WOS:000232013300011 PM 16150258 ER PT J AU Albright, TS Gehrich, AP Davis, GD Sabi, FL Buller, JL AF Albright, TS Gehrich, AP Davis, GD Sabi, FL Buller, JL TI Arcus tendineus fascia pelvis: A further understanding SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE arcus tendineus fascia pelvis; white line; anatomy; rectovaginal septum; rectovaginal fascia ID STRESS URINARY-INCONTINENCE; RECTOVAGINAL SEPTUM; PROLAPSE; ANATOMY; REPAIR AB Objective: The study was undertaken to further define the anatomy of the arcus tendineus fascia pelvis (ATFP). Study design: Thirty cadavers were dissected to find the average length, SD, and range of, the ATFP. Comparisons were made to height and pelvis type. The average distance between the ischial spine and the attachment of the fascia of the rectovaginal septum (RVF) to the ATFP was measured. Results: The average length, SD, and range in centimeters for the ATFP are 9.0, 0.70, and 7 to 10.5, respectively. The length of the ATFP increased With height. No associations could be made regarding pelvis type. The average distance between the ischial spine and the attachment of the RVF to the ATFP is 2.15 cm with a SD and range of 0.21 and 1.75 to 2.5, respectively. Conclusion: In this study, an average length for the ATFP is established and the distance between the ischial spine and the attachment of the RVF to the ATFP is redefined. (c) 2005 Mosby, Inc. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Natl Capital Consortium, Div Female Pelv Med & Reconstruct Surg,NIH, Bethesda, MD 20814 USA. RP Albright, TS (reprint author), Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Natl Capital Consortium, Div Female Pelv Med & Reconstruct Surg,NIH, Bethesda, MD 20814 USA. NR 20 TC 13 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 677 EP 681 DI 10.1016/j.ajog.2005.02.129 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IM UT WOS:000232013300013 PM 16150260 ER PT J AU Vink, J Auth, J Abebe, DT Brenneman, DE Spong, CY AF Vink, J Auth, J Abebe, DT Brenneman, DE Spong, CY TI Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine release in a mouse model of fetal alcohol syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE alcohol; spatial learning; proinflammatory cytokine ID DEPENDENT NEUROTROPHIC FACTOR; OXIDATIVE STRESS; PRENATAL EXPOSURE; FREE-RADICALS; WATER-MAZE; ETHANOL; PROTEIN; MEMORY; RAT; NEUROTOXICITY AB Objective: Previously, the novel peptides NAPVSIPQ and SALLRSIPA were shown to prevent alcohol-induced fetal death and growth abnormalities in a mouse model of fetal alcohol syndrome. This study evaluated whether these peptides could prevent long-term alcohol-induced learning abnormalities. In addition, because specific cytokines are known to effect long-term potentiation, a model of learning at the molecular level, we studied the effect of these novel peptides on tumor necrosis factor-alpha, interleukin-6, and interferon-gamma levels. Study design: We used a well-characterized mouse model of fetal alcohol syndrome. Pregnant mice were injected on day 8 with alcohol (0.03 mL/kg) or placebo. Pretreatment with NAPVSIPQ + SALLRSIPA (20 mu g) or placebo was given 30 minutes before alcohol. Embryos were removed after 6 hours, at which time cytokine, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma levels were measured with enzyme-linked immunoassays. To test spatial learning, adult offspring from litters that were treated with alcohol, control, NAPVSIPQ + SALLRSIPA then alcohol, or NAPVSIPQ + SALLRSIPA alone were evaluated for latency to find a hidden platform in the Morris water maze. Results: Alcohol treatment increased tumor necrosis factor-alpha levels versus control levels (50.0 +/- 3.5 pg/mL vs 32.7 +/- 2.4 pg/mL; P <= .001). NAPVSIPQ + SALLRSIPA pretreatment prevented this increase (39.9 9 +/- 2.8 pg/mL; P < .01), with levels similar to control (P = .1). Similarly, alcohol increased interleukin-6 levels versus control levels (22.6 +/- 1.4 pg/mL vs 17.3 +/- 0.6 pg/mL; P < .001), and NAPVSIPQ + SALLRSIPA prevented this increase (19.1 +/- 1.0 pg/mL; P < .02), with levels similar to control levels (P = .2). Interferon-gamma levels were not different among the 3 groups (alcohol, 14.6 + 4.9 pg/mL; control, 17.9 +/- 6.6 pg/mL; alcohol + NAPVSIPQ + SALLRSIPA, 13.6 +/- 4.9 pg/mL; P = .2). In the Morris water maze, alcohol-treated groups did not learn over the 7-day trial compared with the control group (P = .001). Groups that were pretreated with NAPVSIPQ + SALLRSIPA then alcohol learned significantly, which was similar to the control group. Groups that were treated with only NAPVSIPQ + SALLRSIPA learned significantly earlier, with the shortest latency once learning commenced. C1 NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Vink, J (reprint author), NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bldg 9,1W116,MSC 0925,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jyv5y@virginia.edu NR 30 TC 40 Z9 41 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 825 EP 829 DI 10.1016/j.ajog.2005.02.101 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IM UT WOS:000232013300034 PM 16150281 ER PT J AU Kim, YM Romero, R Oh, SY Kim, CJ Kilburn, BA Armant, DR Nien, JK Gomez, R Mazor, M Saito, S Abrahams, VM Mor, G AF Kim, YM Romero, R Oh, SY Kim, CJ Kilburn, BA Armant, DR Nien, JK Gomez, R Mazor, M Saito, S Abrahams, VM Mor, G TI Toll-like receptor 4: A potential link between "danger signals," the innate immune system and preeclampsia? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE toll-like receptor; toll-like receptor-4; toll-like receptor-2; NF-kappa B; tumor necrosis factor-alpha; preeclampsia; danger signal; trophoblast migration; placental bed biopsy; pregnancy; innate immunity ID PERIPHERAL-BLOOD LEUKOCYTES; HUMAN TROPHOBLAST CELLS; TOLL-LIKE RECEPTOR-2; SPIRAL ARTERIES; MODEL; PREGNANCIES; MEMBRANES; LABOR AB Objective: Toll-like receptors (TLRs) recognize microbial ligands and host products released during tissue damage, the so-called "danger signals." This study was conducted to determine whether changes in TLR-4 and TLR-2 expression can be detected in the trophoblasts at the placental bed of women with and without preeclampsia. Study design: Placental bed biopsies were obtained from women with: (1) normal term pregnancies with and without labor (each n = 20); (2) preeclampsia who delivered preterm (n = 15); and (3) preterm labor and intact membranes (PTL) with and without chorioamnionitis (each n = 15). The expression pattern of TLR-4 and TLR-2 in the trophoblasts was analyzed by double immunohistochemistry. Results: (1) The median percentage of TLR-4 positive interstitial trophoblasts was significantly higher in preeclamptic patients than in patients with PTL without or with histologic chorioamnionitis (P =.0002 and P =.02, respectively). (2) The median percentage of TLR-2 positive interstitial trophoblasts was not different among study groups (P >.05). (3) TLR-4 positive trophoblasts were also frequently immunoreactive to activated nuclear factor-kappa B, tumor. necrosis factor-alpha, and M30 (a specific apoptosis antigen for trophoblast). (4) Lipopolysaccharide treatment inhibited migration of trophoblast cell lines in vitro. Conclusion: TLR-4 protein expression is increased in interstitial trophoblasts of patients with preeclampsia. We propose that "danger signals" at the feto-maternal interface, recognized by trophoblasts through TLR-4, may play a key role in creating a local abnormal cytokine milieu. This suggests a novel mechanism that links activation of the innate immune system through TLR-4 and preeclampsia. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Pontificia Univ Catolica Chile, Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. Toyama Med & Pharmaceut Univ, Dept Obstet & Gynecol, Toyama, Japan. Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA. RP Kim, YM (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NR 19 TC 95 Z9 105 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 921 EP 927 DI 10.1016/j.ajog.2005.06.053 PN 2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700004 PM 16157088 ER PT J AU Toso, L Poggi, S Park, J Einat, H Roberson, R Dunlap, V Woodard, J Abebe, D Spong, CY AF Toso, L Poggi, S Park, J Einat, H Roberson, R Dunlap, V Woodard, J Abebe, D Spong, CY TI Inflammatory-mediated model of cerebral palsy with developmental sequelae SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE cerebral palsy; periventricular leukomalacia; lipopolysaccharide; rat ID INDUCED PRETERM BIRTH; DEVELOPING RAT-BRAIN; PERIVENTRICULAR LEUKOMALACIA; WEIGHT; LABOR; MICE; CHILDREN; DELIVERY; INJURY; MOUSE AB Objective: Cerebral palsy (CP) is characterized by motor deficits. There is increasing evidence that CP may result from inflammatory and infection-mediated white matter damage. Our objective was to develop an inflammatory model for CP based on chronic lipopolysaccharide (LPS) exposure with a recognizable phenotype in offspring. Study design: On gestational days 15, 17, and 19 (similar to 28-36 wks human gestation; rat length of gestation is 21 days), pregnant rats were intracervically injected with 0.15 mg/kg LPS (in 0.1 mL saline) or 0.1 mL saline for controls. Neonatal tests for sensory-motor milestones were performed on postnatal days I to 21 (LPS n = 25; control n = 26). Adult males were tested at 8 weeks on open field and rotarod for motor activity. Immunohistochemistry studies were performed to assess olygodendrocyte (OL) damage. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA) with P <.05 considered significant. Results: Immunohistochemistry revealed a decrease in the immature OL marker PLP on day 21 (P =.03) in LPS-exposed offspring, and an increase of the mature OL marker CNP on day 21 and at 8 weeks (P <.01, P <.001). LPS-exposed offspring were delayed achieving 3 motor milestones: negative geotaxis (P <.05), cliff aversion (P <.01), and surface righting (P =.05). They were also delayed in eye opening (P <.01). There was no difference between the 2 groups for the other tests. There was a trend towards decreased mean speed in LPS-exposed adults in open field testing (P =.08), but no differences observed in rotarod testing. Conclusion: Using an animal model for CP that mimics a chronic intrauterine inflammation that results in decreased levels of PLP, a marker for early oligodendrocytes consistent with white matter damage, we have demonstrated a phenotype relevant to the human CP manifestations in the neonatal period. Nevertheless, adult animals were able to compensate to the damage. Further refinement is needed to improve the understanding of pathogenesis, as well as allow for testing preventative therapies. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. INOVA Alexandria Hosp, Perinatal Diagnost Ctr, Alexandria, VA USA. RP Toso, L (reprint author), NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bldg 9,Rm 1W125,9 Mem Dr,MSC 0925, Bethesda, MD 20892 USA. EM laura_toso@hotmail.com RI Einat, Haim/A-7203-2009 NR 31 TC 18 Z9 19 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 933 EP 941 DI 10.1016/j.ajog.2005.05.072 PN 2 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700006 PM 16157090 ER PT J AU Hong, JS Santolaya-Forgas, J Romero, R Espinoza, J Goncalves, LF Kim, YM Edwin, S Yoon, BH Nien, JK Hassan, S Mazor, M AF Hong, JS Santolaya-Forgas, J Romero, R Espinoza, J Goncalves, LF Kim, YM Edwin, S Yoon, BH Nien, JK Hassan, S Mazor, M TI Maternal plasma osteoprotegerin concentration in normal pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE osteoprotegerin; osteoporosis in pregnancy; maternal bone remodeling; fetal skeleton mineralization; calcium homeostasis ID CALCIUM HOMEOSTASIS; BONE TURNOVER; OSTEOCLAST DIFFERENTIATION; INDUCED OSTEOPOROSIS; BIOCHEMICAL MARKERS; LACTATION; METABOLISM; LIGAND; PUERPERIUM; ACTIVATION AB Objective: Pregnancy is associated with major changes in calcium metabolism because the neonatal skeleton contains approximately 30 g of calcium, which are largely deposited in the third trimester. Osteoprotegerin (OPG) acts as a decoy receptor for the "Receptor Activator of Nuclear Factor-kappa B Ligand" (RANKL), which is an essential factor for bone remodeling. This study was conducted to determine whether there were changes in maternal plasma OPG concentration during normal pregnancy. Study design: A cross-sectional study was performed in 433 patients of reproductive age (40 nonpregnant and 393 pregnant). Pregnant patients were classified into 4 groups according to gestational age: group 1: 11 to 14 weeks (n = 100); group 2: 15 to 18 weeks (n = 99); group 3: 27 to 30 weeks (n = 100); and group 4: 37 to 42 weeks (n = 94). Plasma OPG concentrations were measured with the use of a sensitive and specific immunoassay. Nonparametric statistics were used for analysis. Results: OPG was detected in the plasma of all women tested. The median OPG concentration was significantly higher in term patients than in those in early pregnancy (median: 6.63 pmol/L [range: 1.57-25.57] vs median: 3.98 pmol/L [range: 0.41-13.71], P <.001). There was no significant difference in plasma OPG concentrations between nonpregnant women and those in groups I or 2 (nonpregnant women median: 3.86 pmol/L [range: 1.64-15.29] vs group I median: 3.98 pmol/L [range: 0.41-13.71] vs group 2 median: 3.87 pmol/L [range: 1.14-69.83], P =.75). Conclusion: The median maternal plasma OPG concentration is higher in the third trimester than in the first trimester of pregnancy. OPG may be involved in the regulation of bone turnover during pregnancy. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Hong, JS (reprint author), NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Yoon, Bo Hyun/H-6344-2011 FU NICHD NIH HHS [Z01 HD002400-14] NR 25 TC 17 Z9 19 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1011 EP 1015 DI 10.1016/j.ajog.2005.06.051 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700019 PM 16157103 ER PT J AU Landon, MB Leindecker, S Spong, CY Hauth, JC Bloom, S Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG AF Landon, MB Leindecker, S Spong, CY Hauth, JC Bloom, S Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG CA Natl I Child Hlth Human Dev TI The MFMU Cesarean Registry: Factors affecting the success of trial of labor after previous cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE trial of labor; cesarean delivery; dystocia ID VAGINAL BIRTH; COST-EFFECTIVENESS; SECTION AB Objective: The purpose of this study was to determine which factors influence the likelihood of successful trial of labor (TOL) after 1 previous cesarean delivery (CD). Study design: We performed a multicenter 4-year prospective observational study (1999-2002) of all women with previous CD undergoing TOL. Women with term singleton pregnancies with 1 previous low transverse CD or unknown incision were included for analysis. Results: Fourteen thousand five hundred twenty-nine women underwent TOL, with 10,690 (73.6%) achieving successful VBAC. Women with previous vaginal birth had an 86.6% success rate compared with 60.9% in women without such a history (odds ratio [OR] 4.2; 95% Cl 3.8-4.5; P <.001). TOL success rates were affected by previous indication for CD, need for induction or augmentation, cervical dilation on admission, birth weight, race, and maternal body mass index. Multivariate logistic regression analysis identified as predictive of TOL success: previous vaginal delivery (OR 3.9; 95% CI 3.6-4.3), previous indication not being dystocia (CPD/FTP) (OR 1.7; 95% Cl 1.5-1.8), spontaneous labor (OR 1.6; 95% CI 1.5-1.8), birth weight <4000 g (OR 2.0; 95% CI 1.8-2.3), and Caucasian race (OR 1.8, 95% CI 1.6-1.9) (all P <.001). The overall TOL success rate in obese women (BMI >= 30) was lower (68.4%) than in nonobese women (79.6%) (P <.001), and when combined with induction and lack of previous vaginal delivery, successful VBAC occurred in only 44.2% of cases. Conclusion: Previous vaginal delivery including previous VBAC is the greatest predictor for successful TOL. Previous indication as dystocia, need for labor induction,or a maternal BMI >= 30 significantly lowers success rates. (C) 2005 Mosby, Inc. All rights reserved. C1 Ohio State Univ, Coll Med & Publ Hlth, Dept Obstet & Gynecol, Columbus, OH 43210 USA. George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, Houston, TX USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. RP Landon, MB (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Dept Obstet & Gynecol, 1654 Upham Dr,Means Hall 5th Floor, Columbus, OH 43210 USA. EM landon.1@osu.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD34208, HD19897, HD21410, HD21414, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 14 TC 121 Z9 132 U1 1 U2 13 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1016 EP 1023 DI 10.1016/j.ajog.2005.05.066 PN 2 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700020 PM 16157104 ER PT J AU Endres, M Toso, L Roberson, R Park, J Abebe, D Poggi, S Spong, CY AF Endres, M Toso, L Roberson, R Park, J Abebe, D Poggi, S Spong, CY TI Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE fetal alcohol syndrome; pregnancy; alcohol; prevention; neuroprotection; mental retardation ID DEPENDENT NEUROTROPHIC FACTOR; ETHANOL; EXPOSURE; PEPTIDE; GROWTH; SYSTEM AB Objective: Prenatal alcohol exposure results in fetal death and neurobehavioral complications including learning impairment. Previously synthetic peptides derived from activity-dependent neurotrophic factor have been shown to prevent aspects of alcohol-induced damage in pregnancy. The objective of this work was to evaluate whether activity-dependent neurotrophic factor-12 could prevent alcohol-induced damage in a model of fetal alcohol syndrome. Study design: Using a well-characterized model, C57B16/J mice on gestational day 8 were treated with placebo, alcohol (30% volume/volume alcohol 0.03 mL/kg), alcohol plus activity-dependent neurotrophic factor-12 30 minutes prior to alcohol, or activity-dependent neurotrophic factor-12 alone. Fetal death was assessed on gestational day 18 (25 litters were evaluated: alcohol, n = 5; placebo, n = 9; alcohol plus activity-dependent neurotrophic factor-12, n = 11). Neonatal behavior tests were performed on postnatal days 1 through 21 with the offspring of 12 dams (alcohol, n = 16; placebo, n = 46; alcohol plus activity-dependent neurotrophic factor-12, n = 23; and activity-dependent neurotrophic factor-12, n = 35). Adult males were tested in the Morris water maze for learning assessment and with the hole punch activity test for exploratory activity. Statistical analysis included Kruskal-Wallis and analysis of variance. Results: Fetal death was greater in alcohol (67% +/- 13%) vs placebo (8.4% +/- 3%, P<.001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced fetal death (2.2% +/- 8.1%) with levels similar to control (P =.12). Alcohol exposure caused a delay in achieving developmental milestones, with alcohol achieving milestones later than all other groups (all P <.001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced milestone delays. In the Morris water maze, the placebo learned, decreasing their latency to find the hidden platform over 70% (P<.01), Alcohol plus activity-dependent neurotrophic factor-12 also significantly learned, with a learning curve not different from placebo (all P>.5) and significantly better than alcohol on days 4, 6, and 7 (all P <.05). Alcohol exposure resulted in significantly less time in hole punch activity (P<.02) than control. Activity-dependent neurotrophic factor-12 pretreatment prevented the alcohol-induced decline, with levels the same as control (P =.1). Conclusion: The novel peptide activity-dependent neurotrophic factor-12 prevents alcohol-induced fetal death and developmental and learning abnormalities in a model of fetal alcohol syndrome. This demonstrates that a single treatment with a peptide is efficacious and may be of value in the prevention of alcohol-induced damage. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. INOVA Alexandria Hosp, Perinatal Diagnost Ctr, Alexandria, VA USA. RP Toso, L (reprint author), NICHHD, Unit Perinatal & Dev Neurobiol, NIH, 9 Mem Dr, Bethesda, MD 20892 USA. EM tosol@mail.nih.gov NR 18 TC 23 Z9 23 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1028 EP 1034 DI 10.1016/j.ajog.2005.05.052 PN 2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700022 PM 16157106 ER PT J AU Rouse, DJ Leindecker, S Landon, M Bloom, SL Varner, MW Moawad, AH Spong, CY Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M O'Sullivan, MJ Sibai, BM Langer, O AF Rouse, DJ Leindecker, S Landon, M Bloom, SL Varner, MW Moawad, AH Spong, CY Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M O'Sullivan, MJ Sibai, BM Langer, O CA Natl Inst Child Hlth Human Dev Mat TI The MFMU Cesarean Registry: Uterine atony after primary cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE cesarean delivery; uterine atony ID RISK-FACTORS; HEMORRHAGE AB Objective: The purpose of this study was to define independent risk factors for uterine atony after primary cesarean delivery, and to assess their overall association with atony in the study cohort. Study design: This. was a 13-university center prospective observational study. All women who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Trained and certified research nurses performed systematic data abstraction. The definition of atony required both the clinical diagnosis and the use of methergine or a prostaglandin preparation. Risk factors for uterine atony were assessed in univariable and multivariable logistic regression analyses, and these analyses then used to inform an assessment of the association of the various risk factors with the occurrence of uterine atony in the overall cohort. Results: Twenty-three thousand, three hundred and ninety pregnancies were analyzed. Uterine atony occurred in 1416 women (6%). Several variables were independently associated with atony in a multivariable model, including multiple gestation (odds ratio [OR] 2.40, 95% CI 1.95-2.93), maternal Hispanic race (2.21, 1.90-2.57), induced or augmented labor for > 18 hours (2.23, 1.92-2.60), infant birth weight >4500 g (2.05, 1.53-2.69), and clinically diagnosed chorioamnionitis (1.80, 1.55-2.09). However, because the various risk factors were not very powerful, approximately half of the cases of atony were associated with the 2/3 of women lacking a given risk factor or combination of risk factors. Conclusion: Although certain risk factors and uterine atony were clearly associated, the associations are of limited practical clinical use. (C) 2005 Mosby, Inc. All rights reserved. C1 Univ Alabama, Dept Obstet & Gynecol, Ctr Res Womens Hlth, Birmingham, AL 35294 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Chicago, IL 60637 USA. NICHHD, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Rouse, DJ (reprint author), Univ Alabama, Dept Obstet & Gynecol, Ctr Res Womens Hlth, Birmingham, AL 35294 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801] NR 9 TC 33 Z9 34 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1056 EP 1060 DI 10.1016/j.ajog.2005.07.077 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700027 PM 16157111 ER PT J AU Mari, G Zimmermann, R Moise, KJ Deter, RL AF Mari, G Zimmermann, R Moise, KJ Deter, RL TI Correlation between middle cerebral artery peak systolic velocity and fetal hemoglobin after 2 previous intrauterine transfusions SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE fetal anemia; red cellalloimmunization; middle cerebral artery; peak systolic velocity; ultrasound; intrauterine transfusion ID RED-CELL ALLOIMMUNIZATION; DOPPLER ULTRASONOGRAPHY; ANEMIA; PREDICTION; PREVENTION; ULTRASOUND; DIAGNOSIS; TRIAL AB Objective: The middle cerebral artery peak systolic velocity (MCA-PSV) has been successfully used for timing the first 2 transfusions in fetuses at risk for anemia because of maternal red cell alloimmunization. The objective of this study was to assess whether the correlation between the MCA-PSV and fetal hemoglobin is maintained in fetuses that had undergone 2 previous intrauterine transfusions. Study design: Doppler measurement of MCA-PSV was performed before cordocentesis in 39 fetuses. The timing of the third transfusion was based on traditional criteria. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). Anemia was defined as mild (hemoglobin <0.84 MoM for a given gestational age, moderate (hemoglobin <0.65 MoM), and severe (hemoglobin <0.55 MoM). Regression analysis was used to assess the correlation between the MCA-PSV MoM and fetal hemoglobin MoM. Results: Gestational age at Doppler study ranged from 22 to 35 weeks. Six fetuses (15%) had normal hemoglobin concentration; 21 (53%) had mild anemia; 7 (20%) had moderate anemia; and 5 (12%) had severe anemia. There was a linear correlation between fetal hemoglobin (y) and the MCA-PSV (x): y = 1.185-0.341x. Conclusion: Previously, concerns have been expressed about the accuracy of Doppler prediction of anemia after previous transfusions. Our data suggest that there is a good correlation between the MCA-PSV and fetal hemoglobin in fetuses that have undergone 2 previous transfusions. Our findings expand the clinical situation in which Doppler can be used to monitor red cell alloimmunized pregnancies. (C) 2005 Mosby, Inc. All rights reserved. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. RP Mari, G (reprint author), Hutzel Womens Hosp, Rush Ctr PRB Obstet & Gynecol, 4th Floor,3990 John R, Detroit, MI 48201 USA. EM gmari@med.wayne.edu NR 19 TC 31 Z9 42 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1117 EP 1120 DI 10.1016/j.ajog.2005.06.078 PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700038 PM 16157122 ER PT J AU Spong, CY Meis, PJ Thom, EA Sibai, B Dombrowski, MP Moawad, AH Hauth, JC Iams, JD Varner, MW Caritis, SN O'Sullivan, MJ Miodovnik, M Leveno, KJ Conway, D Wapner, RJ Carpenter, M Mercer, B Ramin, SM Thorp, JM Peaceman, AM Gabbe, S AF Spong, CY Meis, PJ Thom, EA Sibai, B Dombrowski, MP Moawad, AH Hauth, JC Iams, JD Varner, MW Caritis, SN O'Sullivan, MJ Miodovnik, M Leveno, KJ Conway, D Wapner, RJ Carpenter, M Mercer, B Ramin, SM Thorp, JM Peaceman, AM Gabbe, S CA Natl Inst Child Hlth Human Dev Mat TI Progesterone for prevention of recurrent preterm birth: Impact of gestational age at previous delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE progesterone; preterm birth; prevention; recurrent preterm birth ID PREDICTION; RISK AB Objective: Preterm birth occurs in 1 of 8 pregnancies and may result in significant morbidity and mortality. 17-alpha hydroxyprogesterone caproate (17-OHP caproate) has been found to be efficacious in reducing the risk of subsequent preterm delivery in women who have had a previous spontaneous preterm birth (sPTB). This analysis was undertaken to evaluate if 17-OHP caproate therapy works preferentially depending on the gestational age at previous spontaneous delivery. We hypothesized that treatment with 17-OHP caproate is more effective in prolonging pregnancy depending on the gestational age of the earliest previous preterm birth (20-27.9, 28-33.9 vs 34-36.9 weeks). Study design: This was a secondary analysis of 459 women with a previous sPTB enrolled in a randomized controlled trial evaluating 17-OHP caproate versus placebo. Effectiveness of 17-OHP caproate for pregnancy prolongation was evaluated based on gestational age at earliest previous delivery according to clinically relevant groupings (20-27.9, 28-33.9, and 34-36.9 weeks). Statistical analysis included the chi-square, Fisher exact, and Kruskal-Wallis tests, logistic regression, and survival analysis using proportional hazards. Results: Gestational age at earliest previous delivery was similar between women treated with 17-OHP caproate or placebo (P = .1). Women with earliest delivery at 20 to 27.9 weeks and at 28 to 33.9 weeks delivered at significantly more advanced gestational age if treated with 17-OHP caproate than with placebo (median 37.3 vs 35.4 weeks, P = .046 and 38.0 vs 36.7 weeks, P = .004, respectively) and were less likely to deliver <37 weeks (42% vs 63%, P = .026 and 34% vs 56%, P = .005, respectively). Those with earliest delivery at 34 to 36.9 weeks were not significantly different between 17-OHP caproate or control. Conclusion: 17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall, and especially for women with a previous spontaneous PTB at <34 weeks. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHHD, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Tennessee, Memphis, TN USA. Wayne State Univ, Detroit, MI USA. Univ Chicago, Chicago, IL 60637 USA. Univ Alabama Birmingham, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Utah, Salt Lake City, UT USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Miami, Miami, FL 33152 USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Univ Texas San Antonio, SW Med Ctr, Dallas, TX USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Brown Univ, Providence, RI 02912 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Texas San Antonio, Houston, TX USA. Univ N Carolina, Chapel Hill, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Vanderbilt Univ, Nashville, TN USA. RP Spong, CY (reprint author), NICHHD, Bethesda, MD 20892 USA. RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NCRR NIH HHS [M01-RR-000080]; NICHD NIH HHS [HD27905, HD21410, HD21414, HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40500, HD40512, HD40544, HD40560] NR 14 TC 50 Z9 52 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1127 EP 1131 DI 10.1016/j.ajog.2005.05.077 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700040 PM 16157124 ER PT J AU Kim, GJ Romero, R Kuivaniemi, H Tromp, G Haddad, R Kim, YM Kim, MR Nien, JK Hong, JS Espinoza, J Santolaya, J Yoon, BH Mazor, M Kim, CJ AF Kim, GJ Romero, R Kuivaniemi, H Tromp, G Haddad, R Kim, YM Kim, MR Nien, JK Hong, JS Espinoza, J Santolaya, J Yoon, BH Mazor, M Kim, CJ TI Expression of bone morphogenetic protein 2 in normal spontaneous labor at term, preterm labor, and preterm premature rupture of membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE parturition; chorioamniotic membrane; immunohistochemistry; real-time quantitative reverse-transcriptase polymerase chain reaction; BMP-2; preterm labor; preterm premature rupture of membranes (PPROM) ID PARTURITION; DEFICIENT; CYTOKINES AB Objective: Genome-wide screening studies of the chorioamniotic membranes unexpectedly identified an increase in the expression of bone morphogenetic protein 2 in spontaneous labor at term. The objective of this study was to determine whether bone morphogenetic protein 2 messenger RNA and protein expression are altered in the chorioamniotic membranes of patients with term labor, preterm labor, and preterm premature rupture of membranes. Study design: Chorioamniotic membranes were obtained from patients at term (with and without labor), with preterm labor (with and without histologic chorioamnionitis), and with preterm premature rupture of membranes (with and without histologic chorioamnionitis). The expression of bone morphogenetic protein 2 was studied by real-time quantitative reverse transcriptase-polymerase chain reaction (n = 88) and immunohistochemistry (n = 124). Nonparametric statistics were used for analysis. Primary amnion cells obtained from women at term not in labor were treated with bone morphogenetic protein 2 to examine whether there was increased prostaglandin E2 expression. Results: The median bone morphogenetic protein 2 messenger RNA and protein expression were significantly higher in the membranes of patients with spontaneous labor at term than in those of patients not in labor at term (P < .001 for both). Bone morphogenetic protein 2 messenger RNA and protein expression were increased in patients with preterm labor with histologic chorioamnionitis than in those without histologic chorioamnionitis (P < .05 and P < .001, respectively). There was no difference in bone morphogenetic protein 2 messenger RNA and protein expression in patients with preterm premature rupture of membranes, regardless of chorioamnionitis (P = .13 and P = .08, respectively). There was a correlation between bone morphogenetic protein 2 and cyclooxygenase 2 protein expression in chorioamniotic membranes (R = .34; P < .001). Conclusion: Bone morphogenetic protein 2 messenger RNA and protein expression are increased in the chorioamniotic membranes of patients with spontaneous labor at term and patients with preterm labor associated with histologic chorioamnionitis. Its expression pattern and biologic effects strongly suggest that bone morphogenetic protein 2 is involved in human parturition. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Kim, GJ (reprint author), NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RI Yoon, Bo Hyun/H-6344-2011; Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NICHD NIH HHS [Z01 HD002400-14] NR 17 TC 5 Z9 5 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1137 EP 1143 DI 10.1016/j.ajog.2005.06.032 PN 2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700042 PM 16157126 ER PT J AU Sibai, B Meis, PJ Klebanoff, M Dombrowski, MP Weiner, SJ Moawad, AH Northen, A Iams, JD Varner, MW Caritis, SN O'Sullivan, MJ Miodovnik, M Leveno, KJ Conway, D Wapner, RJ Carpenter, M Mercer, B Ramin, SM Thorp, JM Peaceman, AM Gabbe, S AF Sibai, B Meis, PJ Klebanoff, M Dombrowski, MP Weiner, SJ Moawad, AH Northen, A Iams, JD Varner, MW Caritis, SN O'Sullivan, MJ Miodovnik, M Leveno, KJ Conway, D Wapner, RJ Carpenter, M Mercer, B Ramin, SM Thorp, JM Peaceman, AM Gabbe, S CA Natl Inst Child Hlth Human Dev TI Plasma CRH measurement at 16 to 20 weeks' gestation does not predict preterm delivery in women at high-risk for preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE CRH levels; prediction; preterm delivery ID CORTICOTROPIN-RELEASING HORMONE; MATERNAL SERUM; ALPHA-FETOPROTEIN; BINDING-PROTEIN; MECHANISMS; MARKERS; BIRTH; LABOR AB Objective: The purpose of this study was to examine the utility of a single second- trimester plasma corticotropin-relasing hormone measurement as a marker for preterm delivery in women at high risk for preterm delivery. Study design: This is an analysis of data from a multicenter placebo-con trolled trial designed to evaluate the role of 17 alpha hydroxyprogesterone caproate (17P) in the prevention of recurrent preterm birth. Women with a documented history of a previous spontaneous preterm birth at < 37 weeks were enrolled (16-20 wks) and randomly assigned in a 2 to I ratio to weekly injections of 17P or matching placebo. Blood was collected before treatment in 170 patients (113 assigned 17P and 57 placebo) who were enrolled at I I of the 19 centers. Plasma levels of corticotropin-releasing hormone were compared between those who delivered preterm and those delivering at term. Data were analyzed using the Wilcoxon rank-sum test. Results: The overall rates of preterm birth in this cohort of 170 patients were 35.9% at < 37 weeks (31.9% progesterone, 43.9% placebo), and 19.4% at < 35 weeks (18.6% vs 2 1. 1 %). The median levels of corticotropin-releasing hormone were similar between those delivering at < 37 weeks and those delivering >= 37 weeks (0.39 ng/mL vs 0.37 ng/mL, P = .08). In addition, there were no differences in corticotropin-releasing hormone levels among those who delivered at < 35 weeks or >= 35 weeks (0.36 vs 0.38, P =.90). Moreover, there were no differences in corticotropin-releasing hormone levels among those in the placebo group who delivered at < 37 or >= 37 weeks (0.40 vs 0.41, P = .72) and at < 35 or >= 35 weeks (P = .64). Conclusion: A single measurement of corticotropin- releasing hormone at 16 to 20 weeks' gestation is not a good biomarker for recurrent preterm delivery in patients at high risk for this complication. (C) 2005 Mosby, Inc. All rights reserved. C1 Univ Cincinnati, Sch Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. NICHHD, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, Houston, TX USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA. RP Sibai, B (reprint author), Univ Cincinnati, Sch Med, Dept Obstet & Gynecol, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM baha.sibai@uc.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD21414, HD27860, HD27861, HD21410, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40500, HD40512, HD40544, HD40560] NR 16 TC 21 Z9 21 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 1181 EP 1186 DI 10.1016/j.ajog.2005.06.036 PN 2 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700050 PM 16157134 ER PT J AU Stambolian, D Ciner, EB Reider, LC Moy, C Dana, D Owens, R Schlifka, M Holmes, T Ibay, G Bailey-Wilson, JE AF Stambolian, D Ciner, EB Reider, LC Moy, C Dana, D Owens, R Schlifka, M Holmes, T Ibay, G Bailey-Wilson, JE TI Genome-wide scan for myopia in the Old Order Amish SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID LINKAGE ANALYSIS; SIB-PAIR; LOCUS; POPULATION; PREVALENCE; GENE; MAPS; IDENTIFICATION; PREDICTORS; CLONING AB PURPOSE: To identify myopia susceptibility genes influencing common myopia in 34 Old Order Amish families, a genetically well,defined founder population. DESIGN: A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia. METHODS: Extended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research (CIDR). Linkage analyses were conducted with parametric (autosomal dominant, fixed penetrance model) and nonparametric methods. Model-free linkage analysis was also performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models). RESULTS: Under the fixed penetrance model, the maximum two-point heterogeneity LOD score (HLOD) was 1.59 at D20S451 and the maximum multipoint HLOD was 1.92 at D6S1021. The nonparametric maximum multipoint (NPL) at D3S2427 had a P-value of .0005. Under the model-free analysis, multipoint heterogeneity LOD scores of 2.03 were observed on both chromosomes 8 (under a recessive model between D8S1130 and D8S1106) and X (under a recessive model between DXS6800 and DXS6789). Reanalyses of chromosomes 3, 6, 8, 20, and X using the best penetrance models resulted in maximum multipoint HLODs of 1.84 at D3S3053; 1.84 at D3S2427; 2.04 at D8S1130; and 2.34 at DXS6800. CONCLUSIONS: The locus on chromosome 8p23 independently confirms a report by Hammond and associates mapping a myopia quantitative trait loci (QTL) to this region. C1 Univ Penn, Stellar Chance Labs, Dept Ophthalmol, Philadelphia, PA 19104 USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. Owens Optometr, Lancaster, PA USA. NHGRI, NIH, Baltimore, MD USA. RP Stambolian, D (reprint author), Univ Penn, Stellar Chance Labs, Dept Ophthalmol, Room 313,422 Curie Blvd, Philadelphia, PA 19104 USA. EM stamboli@mail.med.upenn.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NEI NIH HHS [EY 12226]; NHGRI NIH HHS [N01 HG 65403] NR 47 TC 34 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2005 VL 140 IS 3 BP 469 EP 476 DI 10.1016/j.ajo.2005.04.014 PG 8 WC Ophthalmology SC Ophthalmology GA 965DC UT WOS:000231929300015 PM 16084785 ER PT J AU Dogru, M Stern, ME Smith, JA Foulks, GN Lemp, MA Tsubota, K AF Dogru, M Stern, ME Smith, JA Foulks, GN Lemp, MA Tsubota, K TI Changing trends in the definition and diagnosis of dry eyes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID BREAK-UP TIME C1 Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo, Japan. Tokyo Dent Coll, Ichikawa Hosp, Dept Ophthalmol, Tokyo, Japan. Allergan Pharmaceut Inc, Irvine, CA USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA. Georgetown Univ, Washington, DC USA. RP Tsubota, K (reprint author), Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Shinanomachi 35, Tokyo, Japan. EM muratodooru@yahoo.com NR 15 TC 28 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2005 VL 140 IS 3 BP 507 EP 508 DI 10.1016/j.ajo.2005.04.034 PG 2 WC Ophthalmology SC Ophthalmology GA 965DC UT WOS:000231929300021 PM 16139002 ER PT J AU Oh, YS Turner, RJ AF Oh, YS Turner, RJ TI Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Alzheimer's disease; gamma-secretase; beta-amyloid; intramembranous protease; transmembrane topology ID DISEASE-ASSOCIATED PRESENILINS; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MEMBRANE TOPOLOGY; SUBCELLULAR-LOCALIZATION; CULTURED-CELLS; BIOGENESIS; ELEGANS; GENES; MICE AB The polytopic membrane protein presenilin 1 (PS1) is a component of the gamma-secretase complex that is responsible for the intramembranous cleavage of several type I transmembrane proteins, including the beta-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset familial Alzheimer's disease. PS1 contains 10 hydrophobic regions (HRs) sufficiently long to be alpha-helical membrane spanning segments. Most topology models for PS1 place its COOH terminal similar to 40 amino acids, which include HR 10, in the cytosolic space. However, several recent observations suggest that HR 10 may be integrated into the membrane and involved in the interaction between PS1 and APP. We have applied three independent methodologies to investigate the location of HR 10 and the extreme COOH terminus of PS1. The results from these methods indicate that HR 10 spans the membrane and that the COOH terminal amino acids of PS1 lie in the extracytoplasmic space. C1 Natl Inst Dental & Craniofacial Res, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Oh, YS (reprint author), Natl Inst Dental & Craniofacial Res, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1A01,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. EM yoh@mail.nih.gov FU NIDCR NIH HHS [Z01 DE000415-20] NR 30 TC 15 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 2005 VL 289 IS 3 BP C576 EP C581 DI 10.1152/ajpcell.00636.2004 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 955EI UT WOS:000231207800009 PM 15843437 ER PT J AU McConville, P Spencer, RG Lakatta, EG AF McConville, P Spencer, RG Lakatta, EG TI Temporal dynamics of inotropic, chronotropic, and metabolic responses during beta(1)- and beta(2)-AR stimulation in the isolated, perfused rat heart SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE receptors; adrenergic; metabolism; myocardial oxygen consumption; inotropy; chronotropy; phosphorus-31 nuclear magnetic resonance; rat heart; adrenergic receptor ID BETA(2)-ADRENERGIC RECEPTORS; VENTRICULAR MYOCYTES; ENERGY-METABOLISM; CELLS; CAMP; CA2+; BETA-1-ADRENOCEPTOR; PHOSPHORYLATION; PROTEINS; INCREASE AB During the beta- adrenergic receptor ( beta- AR)- mediated stress response in the heart, the relations between functional responses and metabolism are ill defined, with the distinction between beta(1)- and beta(2)- AR subtypes creating further complexity. Specific outstanding questions include the temporal relation between inotropic and chronotropic responses and their metabolic correlates. We sought to elucidate the relative magnitudes and temporal dynamics of the response to beta(1)- and beta(2)- AR stimulation and the energy expenditure and bioenergetic state related to these responses in the isolated perfused rat heart. Inotropic [ left ventricular developed pressure ( LVDP) and dP/ dt], chronotropic [ heart rate ( HR)], and metabolic responses were measured during beta(1)- ( n = 9; agonist: norepinephrine) and beta(2)- ( n = 9; agonist: zinterol) AR stimulation. Myocardial oxygen consumption ( MV. O-2) was measured using fiberoptic oximetry, and high- energy phosphate levels and intracellular pH were measured using P-31 NMR spectroscopy. A multiple- dose protocol was used, with near- maximal beta-AR stimulation at the highest doses. In both beta(1) and beta(2) groups, there were dose- dependent increases in LVDP, dP/ dt, HR, and MVO2. The inotropic response showed more rapid onset, washout, and variation during dose than did the chronotropic response and was closely correlated with MVO2. This suggests that the myocardial bioenergetic state is more closely related to the inotropic response than to the chronotropic response. In addition, beta(1)- AR stimulation resulted in a greater magnitude and rate of onset of inotropic and MVO2 responses than did beta(2)- AR stimulation during maximal stimulation. However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during beta(1)- than during beta(2)- AR stimulation. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Nucl Magnet Resonance Unit, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov NR 21 TC 7 Z9 10 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2005 VL 289 IS 3 BP E412 EP E418 DI 10.1152/ajpendo.00049.2004 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 957SZ UT WOS:000231394900009 PM 15840637 ER PT J AU Xie, GF Drachenberg, C Yamada, M Wess, J Raufman, JP AF Xie, GF Drachenberg, C Yamada, M Wess, J Raufman, JP TI Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M-1 and M-3 muscarinic receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE carbamylcholine; cholecystokinin; chief cells; gastric glands; knock-out mice; in situ hybridization ID GUINEA-PIG STOMACH; ACETYLCHOLINE-RECEPTORS; KNOCKOUT MICE; ACID-SECRETION; DEFICIENT MICE; M1 RECEPTOR; RAT STOMACH; GLANDS; MUCOSA; LOCALIZATION AB Muscarinic cholinergic mechanisms play a key role in stimulating gastric pepsinogen secretion. Studies using antagonists suggested that the M-3 receptor subtype (M3R) plays a prominent role in mediating pepsinogen secretion, but in situ hybridization indicated expression of M-1 receptor (M1R) in rat chief cells. We used mice that were deficient in either the M-1 (M1R-/-) or M-3 (M3R-/-) receptor or that lacked both receptors (M1/3R-/-) to determine the role of M1R and M3R in mediating cholinergic agonist-induced pepsinogen secretion. Pepsinogen secretion from murine gastric glands was determined by adapting methods used for rabbit and rat stomach. In wild-type (WT) mice, maximal concentrations of carbachol and CCK caused a 3.0- and 2.5- fold increase in pepsinogen secretion, respectively. Maximal carbachol-induced secretion from M1R-/- mouse gastric glands was decreased by 25%. In contrast, there was only a slight decrease in carbachol potency and no change in efficacy when comparing M3R-/- with WT glands. To explore the possibility that both M1R and M3R are involved in carbachol-mediated pepsinogen secretion, we examined secretion from glands prepared from M1/3R-/- double-knockout mice. Strikingly, carbachol-induced pepsinogen secretion was nearly abolished in glands from M1/3R-/- mice, whereas CCK-induced secretion was not altered. In situ hybridization for murine M1R and M3R mRNA in gastric mucosa from WT mice revealed abundant signals for both receptor subtypes in the cytoplasm of chief cells. These data clearly indicate that, in gastric chief cells, a mixture of M-1 and M-3 receptors mediates cholinergic stimulation of pepsinogen secretion and that no other muscarinic receptor subtypes are involved in this activity. The development of a murine secretory model facilitates use of transgenic mice to investigate the regulation of pepsinogen secretion. C1 Univ Maryland, Div Gastroenterol & Hepatol, Sch Med, Vet Affairs Maryland Hlth Care Syst, Baltimore, MD 21201 USA. Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Raufman, JP (reprint author), Univ Maryland, Div Gastroenterol & Hepatol, Sch Med, Vet Affairs Maryland Hlth Care Syst, 22 G Greene St,N3W62, Baltimore, MD 21201 USA. EM jraufman@medicine.umaryland.edu NR 39 TC 17 Z9 19 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2005 VL 289 IS 3 BP G521 EP G529 DI 10.1152/ajpgi.00105.2004 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 954BU UT WOS:000231129900018 PM 15933222 ER PT J AU Ashikaga, H Mickelsen, SR Ennis, DB Rodriguez, I Kellman, P Wen, H McVeigh, ER AF Ashikaga, H Mickelsen, SR Ennis, DB Rodriguez, I Kellman, P Wen, H McVeigh, ER TI Electromechanical analysis of infarct border zone in chronic myocardial infarction SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE electromechanical mapping; magnetic resonance imaging ID ACUTELY ISCHEMIC-MYOCARDIUM; VENTRICULAR-TACHYCARDIA; STIMULATED ECHOES; CANINE HEART; MRI; DOGS; DEFORMATION; CONTRACTION; DYSFUNCTION; PERFUSION AB To test the hypothesis that alterations in electrical activation sequence contribute to depressed systolic function in the infarct border zone, we examined the anatomic correlation of abnormal electromechanics and infarct geometry in the canine post-myocardial infarction (MI) heart, using a high-resolution MR-based cardiac electromechanical mapping technique. Three to eight weeks after an MI was created in six dogs, a 247-electrode epicardial sock was placed over the ventricular epicardium under thoracotomy. MI location and geometry were evaluated with delayed hyperenhancement MRI. Three- dimensional systolic strains in epicardial and endocardial layers were measured in five short-axis slices with motion- tracking MRI (displacement encoding with stimulated echoes). Epicardial electrical activation was determined from sock recordings immediately before and after the MRscans. The electrodes and MR images were spatially registered to create a total of 160 nodes per heart that contained mechanical, transmural infarct extent, and electrical data. The average depth of the infarct was 55% (SD 11), and the infarct covered 28% (SD 6) of the left ventricular mass. Significantly delayed activation (> mean + 2SD) was observed within the infarct zone. The strain map showed abnormal mechanics, including abnormal stretch and loss of the transmural gradient of radial, circumferential, and longitudinal strains, in the region extending far beyond the infarct zone. We conclude that the border zone is characterized by abnormal mechanics directly coupled with normal electrical depolarization. This indicates that impaired function in the border zone is not contributed by electrical factors but results from mechanical interaction between ischemic and normal myocardium. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Ashikaga, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,B1D416, Bethesda, MD 20892 USA. EM ashikagah@nhlbi.nih.gov RI Rodriguez, Ignacio/B-1006-2015; Wen, Han/G-3081-2010 OI Rodriguez, Ignacio/0000-0002-4262-2516; Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [Z01 HL004609-08]; NHLBI NIH HHS [Z01 HL004609] NR 40 TC 35 Z9 36 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2005 VL 289 IS 3 BP H1099 EP H1105 DI 10.1152/ajp.00423.2005 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 955EK UT WOS:000231208000019 PM 15908463 ER PT J AU Seubert, JM Xu, F Graves, JP Collins, JB Sieber, SO Paules, RS Kroetz, DL Zeldin, DC AF Seubert, JM Xu, F Graves, JP Collins, JB Sieber, SO Paules, RS Kroetz, DL Zeldin, DC TI Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE soluble epoxide hydrolase; hypertension; arachidonic acid; elastase; real-time polymerase chain reaction ID SOLUBLE EPOXIDE HYDROLASE; BLOOD-PRESSURE; ARTERIAL STIFFNESS; EPOXYEICOSATRIENOIC ACIDS; INSULIN-RESISTANCE; PULSE PRESSURE; AORTIC-WALL; MICROARRAY; IDENTIFICATION; PATTERNS AB Development of hypertension stems from both environmental and genetic factors wherein the kidney plays a central role. Spontaneously hypertensive rats (SHR) and the nonhypertensive Wistar-Kyoto (WKY) controls are widely used as a model for studying hypertension. The present study examined the renal gene expression profiles between SHR and WKY at a prehypertensive stage ( 3 wk of age) and hypertensive stage ( 9 wk of age). Additionally, age-related changes in gene expression patterns were examined from 3 to 9 wk in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together, and quadruplicate hybridizations were performed using the National Institute of Environmental Health Sciences Rat version 2.0 Chip, which contains similar to 6,700 genes. Twenty two genes were found to be differentially expressed between SHR and WKY at 3 wk of age, and 104 genes were differentially expressed at 9 wk of age. Soluble epoxide hydrolase (Ephx2) was found to be significantly upregulated in SHR at both time points and was the predominant outlier. Conversely, elastase 1 (Ela1) was found to be the predominant gene downregulated in SHR at both time points. Analysis of profiles at 3 vs. 9 wk of age identified 508 differentially expressed genes in WKY rats. In contrast, only 211 genes were found to be differentially expressed during this time period in SHR. The altered gene expression patterns observed in the age-related analysis suggested significant differences in the vascular extracellular matrix system between SHR and WKY kidney. Together, our data highlight the complexity of hypertension and the numerous genes involved in and affected by this condition. C1 NIEHS, Natl Ctr Toxicogenom, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Microarray Grp, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. RP Zeldin, DC (reprint author), NIEHS, Natl Ctr Toxicogenom, Div Intramural Res, POB 12233, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU NHLBI NIH HHS [HL-53994] NR 54 TC 22 Z9 22 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 2005 VL 289 IS 3 BP F552 EP F561 DI 10.1152/ajprenal.00354.2004 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 954BM UT WOS:000231129100011 PM 15798089 ER PT J AU Zhang, Z Ferraris, JD Irarrazabal, CE Dmitrieva, NI Park, JH Burg, MB AF Zhang, Z Ferraris, JD Irarrazabal, CE Dmitrieva, NI Park, JH Burg, MB TI Ataxia telangiectasia-mutated, a DNA damage-inducible kinase, contributes to high NaCl-induced nuclear localization of transcription factor TonEBP/OREBP SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ataxia telangiectasia-mutated kinase; tonicity; responsive enhancer/osmotic response element binding protein; wortmannin; AT cells ID ENHANCER-BINDING PROTEIN; KIDNEY-CELLS; IN-VIVO; PHOSPHORYLATION; HYPERTONICITY; ACTIVATION; ATM; P53; UREA; HYPEROSMOLALITY AB Zhang, Zheng, Joan D. Ferraris, Carlos E. Irarrazabal, Natalia I. Dmitrieva, Jong-Hwan Park, and Maurice B. Burg. Ataxia telangiectasia-mutated, a DNA damage-inducible kinase, contributes to high NaCl-induced nuclear localization of transcription factor TonEBP/OREBP. Am J Physiol Renal Physiol 289: F506 - F511, 2005. First published April 19, 2005; doi: 10.1152/ ajprenal. 00417.2004. - High NaCl activates the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/ OREBP) by increasing its abundance and transactivation, the latter signaled by a variety of protein kinases. In addition, high NaCl causes TonEBP/OREBP to translocate into the nucleus, but little is known about the signals directing this translocation. The result is increased transcription of protective genes, including those involved in accumulation of organic osmolytes. High NaCl also damages DNA, and DNA damage activates ataxia telangiectasia-mutated (ATM) kinase through autophosphorylation on serine 1981. We previously found that ATM is involved in the high NaCl-induced increase in TonEBP/OREBP transactivation. The purpose of the present studies was to test whether ATM is also involved in high NaCl-induced TonEBP/OREBP nuclear translocation. We quantified TonEBP/OREBP in nuclear and cytoplasmic extracts from cultured cells by Western blot analysis. In COS-7 cells, wortmannin, an inhibitor of ATM, reduces high NaCl-induced nuclear translocation of TonEBP/OREBP. We used AT cells (in which ATM is inactive) to test the specificity of this effect. Nuclear translocation of native TonEBP/OREBP and of its recombinant NH(2)-terminal rel homology domain, which contains the nuclear localization signal, is reduced in AT cells and is restored when the cells are reconstituted with functional ATM. In conclusion, activation of ATM contributes to high NaCl-induced nuclear translocation of TonEBP/OREBP. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Zhang, Z (reprint author), Virginia Commonwealth Univ, Ctr Med, Dept Nephrol, Sanger Hall,Rms 8-056 & 8-063,1101 E Marshall St, Richmond, VA 23298 USA. EM zzhang3@vcu.edu RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 NR 26 TC 30 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 2005 VL 289 IS 3 BP F506 EP F511 DI 10.1152/ajprenal.00417.2004 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 954BM UT WOS:000231129100004 PM 15840767 ER PT J AU McClure, EB Treland, JE Snow, J Schmajuk, M Dickstein, DP Towbin, KE Charney, DS Pine, DS Leibenluft, E AF McClure, EB Treland, JE Snow, J Schmajuk, M Dickstein, DP Towbin, KE Charney, DS Pine, DS Leibenluft, E TI Deficits in social cognition and response flexibility in pediatric bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CONTINUOUS PERFORMANCE-TEST; PREFRONTAL CORTEX; SUSTAINED ATTENTION; FACIAL EXPRESSIONS; INHIBITORY CONTROL; RATING-SCALE; RECOGNITION; MANIA; ADOLESCENTS; AMYGDALA AB Objective: Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility. Method: Forty outpatients with pediatric bipolar disorder and 22 comparison subjects ( no differences in age, gender, and IQ) completed measures of social cognition ( the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility stop and stop-change tasks), and motor inhibition ( continuous performance tasks). Results: Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures ( pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder. Conclusions: Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP McClure, EB (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr,Room 102,MSC 2670, Bethesda, MD 20892 USA. EM erin.mcclure@nih.gov RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 NR 52 TC 122 Z9 124 U1 2 U2 15 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2005 VL 162 IS 9 BP 1644 EP 1651 DI 10.1176/appi.ajp.162.9.1644 PG 8 WC Psychiatry SC Psychiatry GA 959ZT UT WOS:000231559300011 PM 16135623 ER PT J AU Shannon, C Schwandt, ML Champoux, M Shoaf, SE Suomi, SJ Linnoila, M Higley, JD AF Shannon, C Schwandt, ML Champoux, M Shoaf, SE Suomi, SJ Linnoila, M Higley, JD TI Maternal absence and stability of individual differences in CSF5-HIAA concentrations in rhesus monkey infants SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-of-Primatologists CY JUN 21-24, 1995 CL SCOTTSDALE, AZ SP Amer Soc Primatologists ID POLYUNSATURATED FATTY-ACIDS; DIMINISHED SOCIAL COMPETENCE; LOCALLY WEIGHTED REGRESSION; NONHUMAN PRIMATE MODEL; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; HUMAN-MILK; ELECTROCHEMICAL DETECTION; MONOAMINE METABOLITES; HOMOVANILLIC-ACID AB Objective: Early life events often lead to deficits in CNS serotonin function, which underlie a number of reoccurring psychopathological disorders. Studies using rhesus macaques have demonstrated that early maternal deprivation reduces CNS serotonin turnover, as measured by cisternal CSF 5-HIAA concentrations. In addition, individual differences in CSF 5-HIAA remain stable from the first year of life through adulthood. The purpose of this study was to assess 1) the impact of rearing environment on the early development (< 6 months of age) of the serotonin system, and 2) at what stage of early development individual differences in CSF 5-HIAA concentrations stabilize. Method: The subjects were 256 infant rhesus macaques reared in three different conditions ( mother-reared, peer-reared, and surrogate/peer-reared). Cisternal CSF was obtained at 14, 30, 60, 90, 120, and 150 days of age. Results: No differences in CSF 5-HIAA concentrations were observed between peer only- and surrogate/peer-reared infants, and these groups combined exhibited lower 5-HIAA concentrations than mother-reared infants throughout early development. CSF 5-HIAA concentrations declined with increasing age regardless of rearing condition. Within each rearing condition, individual differences in CSF 5-HIAA concentrations remained stable from 14 to 150 days of age. Conclusions: Early maternal deprivation reduces CNS serotonin turnover, and individual differences in CSF 5-HIAA concentrations are trait-like and appear to stabilize in infancy. C1 NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. NIH Anim Ctr, Clin Studies Lab, Poolesville, MD 20837 USA. RP Higley, JD (reprint author), NIH Anim Ctr, Comparat Ethol Lab, Bldg 112,POB 529, Poolesville, MD 20837 USA. EM higleyd@exchange.nih.gov RI Schwandt, Melanie/L-9866-2016 NR 47 TC 62 Z9 62 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2005 VL 162 IS 9 BP 1658 EP 1664 DI 10.1176/appi.ajp.162.9.1658 PG 7 WC Psychiatry SC Psychiatry GA 959ZT UT WOS:000231559300013 PM 16135625 ER PT J AU Bohl, DL Storch, GA Ryschkewitsch, C Gaudreault-Keener, M Schnitzler, MA Major, EO Brennan, DC AF Bohl, DL Storch, GA Ryschkewitsch, C Gaudreault-Keener, M Schnitzler, MA Major, EO Brennan, DC TI Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE antibody; BK; C7; donor; HLA; kidney transplant; polyoma ID POLYOMAVIRUS BK; JC-VIRUS; ALLOGRAFT RECIPIENTS; NATIVE KIDNEYS; NEPHROPATHY; INFECTION; CYTOMEGALOVIRUS; PANCREAS; URINE; RISK AB In a previous study, we performed serial BK virus (BKV), polymerase chain reaction (PCR) and detected active BKV infection in 70 (35.4%) of 198 renal transplant recipients. In the current study, pre-transplant donor and recipient samples were analyzed for BKV antibody titer and HLA alleles. Donor antibody titer was inversely proportional to onset of viruria, p < 0.001, directly proportional to duration of viruria, p = 0.014 and directly proportional to peak urine viral titer p = 0.005. Recipient pairs receiving kidneys from the same donor were concordant for BKV infection, p = 0.017, and had matched sequences of segments of the NCCR and VP1 genes that tended to vary among recipients of kidneys from different donors. We did not see an association of HLA A, B, or DR, HLA allele mismatches or total HLA mismatches and BK infection. However, all 11 recipients with sustained BK viremia received kidneys from donors lacking HLA C7, and 10 recipients also lacked C7. These findings derive from the largest and most comprehensive prospective study of BKV infection in renal transplant recipients performed to date. Our data support donor origin for early BKV infection in kidney transplant recipients, and suggest that a specific HLA C locus may be associated with failure to control BKV infection. C1 Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. St Louis Univ, Dept Internal Med, St Louis, MO 63103 USA. St Louis Univ, Ctr Outcomes Res, St Louis, MO 63103 USA. RP Brennan, DC (reprint author), Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. EM brennand@msnotes.wustl.edu FU NIDDK NIH HHS [K25-DK-02916-03]; PHS HHS [1 K24-02886] NR 36 TC 142 Z9 147 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2005 VL 5 IS 9 BP 2213 EP 2221 DI 10.1111/j.1600-6143.2005.01000.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 952RR UT WOS:000231023700015 PM 16095500 ER PT J AU O'Meara, WP McKenzie, FE Magill, AJ Forney, JR Permpanich, B Lucas, C Gasser, RA Wongsrichanalai, C AF O'Meara, WP McKenzie, FE Magill, AJ Forney, JR Permpanich, B Lucas, C Gasser, RA Wongsrichanalai, C TI Sources of variability in determining malaria parasite density by microscopy SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CASE DEFINITIONS; CLINICAL MALARIA; DIAGNOSIS; DEVICES AB Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. USN, Med Ctr Detachment, Lima, Peru. USN, Med Res Unit 2, Jakarta, Indonesia. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov; mckenzel@mail.nih.gov; Alan.magill@na.amedd.army.mil; John.Forney@usma.edu; clucas@nmrcd.med.naqvy.mil; rgasser@erols.com; chansuda@namru2.org FU Intramural NIH HHS [Z99 TW999999] NR 14 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2005 VL 73 IS 3 BP 593 EP 598 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 965ZX UT WOS:000231990500024 PM 16172488 ER PT J AU Chung, EJ Lee, S Sausville, EA Ryan, Q Karp, JE Gojo, I Telford, WG Lee, MJ Kong, HS Trepel, JB AF Chung, EJ Lee, S Sausville, EA Ryan, Q Karp, JE Gojo, I Telford, WG Lee, MJ Kong, HS Trepel, JB TI Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE HDAC; pharmacodynamic analysis; multiparameter; flow cytometry ID LEUKEMIA-CELLS; TUBULIN ACETYLATION; CANCER-THERAPY; APOPTOSIS; TARGET; HSP90; TRANSCRIPTION; DEPSIPEPTIDE; EXPRESSION AB Histone deacetylase ( HDAC) inhibitors are a promising new class of anticancer drug. The aim of this study was to develop a versatile and sensitive technique for the pharmacodynamic (PD) assessment of HDAC inhibitor activity as monotherapy and in combination therapy. A multiparameter flow cytometric assay was developed initially in healthy donor lymphocytes and leukemia cell lines, and then tested in peripheral blood of solid tumor patients and in bone marrow aspirates of leukemia patients on phase I trials of the HDAC inhibitor MS-275. A technique was developed that allows highly sensitive single parameter determination of HDAC inhibitor activity in as little as 50 mu l of whole blood. Multiparameter analysis enabled correlation on a single cell basis of protein acetylation with biologically relevant markers including cell lineage antigens, an apoptosis marker, and PD markers of other anti-cancer agents. The level of protein acetylation can be readily detected and quantified in peripheral blood or in bone marrow aspirates by flow cytometric analysis. The technique described has significant advantages for the PD assessment of HDAC inhibitors as monotherapy and as a component of combination therapy trials. C1 NCI, Med Oncol Clin Res Unit, CCR, NIH, Bethesda, MD 20892 USA. NCI, Clin Trials Unit, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Maryland, Med Ctr, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Trepel, JB (reprint author), NCI, Med Oncol Clin Res Unit, CCR, NIH, Bldg 10,Rm 12N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM trepel@helix.nih.gov FU Intramural NIH HHS NR 38 TC 14 Z9 14 U1 1 U2 2 PU ASSN CLINICAL SCIENTISTS PI MIDDLEBURY PA PO BOX 1287, MIDDLEBURY, VT 05753 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD FAL PY 2005 VL 35 IS 4 BP 397 EP 406 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 978VV UT WOS:000232902000004 PM 16254255 ER PT J AU Broderick, JP Brott, T DeGraba, T Fagan, SC Frankel, MR Grotta, JC Haley, EC Hamilton, S Kwiatkowski, T Levine, SR Lewandowski, CA Lin, Y Libman, R Lu, M Lyden, P Marler, JR Morgenstern, L Patel, S Sanders, C Tilley, BC AF Broderick, JP Brott, T DeGraba, T Fagan, SC Frankel, MR Grotta, JC Haley, EC Hamilton, S Kwiatkowski, T Levine, SR Lewandowski, CA Lin, Y Libman, R Lu, M Lyden, P Marler, JR Morgenstern, L Patel, S Sanders, C Tilley, BC CA Natl Inst Neurological Disorders S TI Recombinant tissue plasminogen activator for minor strokes: The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Experience SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE ISCHEMIC-STROKE; T-PA; THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; TRIAL; HEMIPARESIS; IMPROVEMENT; DIAGNOSIS; ACCURACY; SCALE AB Study objective: Acute ischemic stroke patients eligible for tissue plasminogen activator and with less severe neurologic deficits, although still generally benefiting from therapy, may have a different risk-benefit profile than all eligible acute stroke patients. We address whether patients with a minor stroke should receive tissue plasminogen activator, analyze minor stroke syndromes in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, and define what constitutes a "minor stroke." Methods: The NINDS rt-PA Stroke Study included 624 patients with acute ischemic stroke within 180 minutes of symptom onset within a randomized, double-blind, placebo-controlled trial. To explore the relationship among stroke severity, thrombolytic therapy, and stroke outcome, we defined minor strokes (5 specified definitions) based on the standardized data available at treatment decision, including National Institutes of Health Stroke Scale score. We studied prespecified clinical outcomes, including 3-month favorable outcome (global statistic) defined from a set of standardized clinical scales, dichotomized clinical outcome at 3 months (good=modified Rankin Scale <= 2, bad=modified Rankin Scale > 2), and risk of symptomatic intracerebral hemorrhage. Results: For each of the 5 definitions of minor stroke, adjusted odds ratios for treatment benefit were consistently 2.0 with the lower 95% confidence limit, ranging from 1.4 to 1.5, and the upper 95% confidence limit, ranging from 2.7 to 2.9. There were less frequent "bad" outcomes (modified Rankin Scale > 2) after therapy with tissue plasminogen activator than placebo. Symptomatic intracerebral hemorrhage within 36 hours of treatment had a frequency in the tissue plasminogen activator-treated subjects, ranging from 0% to 4%, depending on minor stroke definition. Conclusion: Recognizing the limitations of post hoc subgroup analyses, we could not detect a difference in the beneficial effects of tissue plasminogen activator in patients with minor stroke syndromes compared to the overall treatment effects in the entire cohort. Our data suggest that the risk-benefit ratio for using tissue plasminogen activator in minor-stroke patients favors treatment in eligible patients. C1 Mt Sinai Sch Med, Stroke Program, Dept Neurol, New York, NY 10029 USA. Univ Cincinnati, Ctr Stroke Res, Cincinnati, OH USA. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. NINDS, Ctr Neurosci, Bethesda, MD 20892 USA. Med Coll Georgia, Clin Pharm Program, Augusta, GA 30912 USA. Emory Sch Med, Dept Neurol, Atlanta, GA USA. Univ Texas, Med Ctr, Dept Neurol, Houston, TX USA. Univ Virginia, Hlth Syst, Dept Neurol, Charlottesville, VA USA. Stanford Univ, Sch Med, Dept Neurol, Palo Alto, CA 94304 USA. Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Pk, NY 11042 USA. Henry Ford Hosp, Dept Emergency Med, Detroit, MI 48202 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Henry Ford Hlth Syst Biostat & Res Epidemiol, Detroit, MI USA. Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA. Henry Ford Hosp, Div MRI WCB, Detroit, MI 48202 USA. Genentech Inc, San Francisco, CA USA. RP Levine, SR (reprint author), Mt Sinai Sch Med, Stroke Program, Dept Neurol, Box 1137,1 Gustave L Levy Pl, New York, NY 10029 USA. EM steven.levine@mssm.edu RI Fagan, Susan /D-3281-2009 NR 27 TC 44 Z9 44 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 BP 243 EP 252 DI 10.1016/j.annemergmed.2005.02.013 PG 10 WC Emergency Medicine SC Emergency Medicine GA 960ZT UT WOS:000231632400007 ER PT J AU Reed, D Birnbaum, A Brown, LH Fleg, JL O'Connor, RE Peberdy, MA Van Ottingham, L Hallstrom, AP AF Reed, D Birnbaum, A Brown, LH Fleg, JL O'Connor, RE Peberdy, MA Van Ottingham, L Hallstrom, AP CA P A D Trial Investigators TI Location of cardiac arrests in the public access defibrillation trial SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Upstate Med Univ, Trial Investigators, Syracuse, NY USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NHLBI, Clin Trials Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Christana Care Hlth Syst, Newark, DE USA. Virginia Commonwealth Univ, Dept Med, Hlth Syst, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S75 EP S75 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000269 ER PT J AU Shaw, GJ Meunier, JM Cheng, JY Holland, CK AF Shaw, GJ Meunier, JM Cheng, JY Holland, CK TI Duty cycle dependence of ultrasound enhanced thrombolysis in an in-vitro human clot model SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Univ Cincinnati, Cincinnati, OH USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S27 EP S27 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000093 ER PT J AU Abbott, KC Bernet, VJ Agodoa, LY Yuan, CM AF Abbott, KC Bernet, VJ Agodoa, LY Yuan, CM TI Differing manifestations of hepatitis C and tacrolimus on hospitalized diabetes mellitus occurring after kidney transplantation SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE diabetic ketoacidosis; hyperglycemic hyperosmolar syndrome; nonketotic hyperosmolar coma; graft loss; African American; female; hepatitis C; rejection; cyclosporine; tacrolimus; hospitalization; complications; USRDS ID RENAL-ALLOGRAFT RECIPIENTS; INTERFERON-ALPHA THERAPY; INSULIN-RESISTANCE; LIVER-TRANSPLANT; UNITED-STATES; SUDDEN ONSET; RISK-FACTORS; KETOACIDOSIS; IMMUNOSUPPRESSION; ASSOCIATION AB PURPOSE: Previous studies suggest the association of recipient hepatitis C seropositivity (HCV +) and use of tacrolimus (TAC) with post-transplant diabetes mellitus (PTDM) may differ by manifestations of type I or type II diabetes, but this has not been assessed in the era of current immunosuppression. METHODS: We performed a retrospective cohort study of 10,342 Medicare primary renal transplantation recipients without evidence of diabetes at the time of listing in the United States Renal Data System between January 1, 1998 and July 31, 2000, followed until December 31, 2000. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for time to DKA or HHS, stratified by diabetes status at the time of transplant. RESULTS: In Cox regression analysis, use of TAC at discharge was independently associated with shorter time to DKA (AHR, 1.88; 95% CI, 1.05-3.37, p = 0.034) but not HHS. In contrast, recipient HCV+ was independently associated with shorter time to HHS (AHR, 3.90; 1.59-9.60, P = .003), but not DKA. There was no interaction between TAC and HCV+ for either outcome. CONCLUSION: These results confirm earlier findings that TAC and HCV+ may mediate the risk of PTDM through different mechanisms, even in the modern era. C1 Walter Reed Army Med Ctr, Serv Nephrol, Dept Med, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Endocrinol, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Dept Med, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 26 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2005 VL 15 IS 8 BP 558 EP 563 DI 10.1016/j.annepidem.2004.10.003 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963MG UT WOS:000231807800002 PM 16118000 ER PT J AU Koster, A Penninx, BWJH Bosma, H Kempen, GIJM Newman, AB Rubin, SM Satterfield, S Atkinson, HH Ayonayon, HN Rosano, C Yaffe, K Harris, TB Rooks, RN Van Eijk, JT Kritchevsky, SB AF Koster, A Penninx, BWJH Bosma, H Kempen, GIJM Newman, AB Rubin, SM Satterfield, S Atkinson, HH Ayonayon, HN Rosano, C Yaffe, K Harris, TB Rooks, RN Van Eijk, JT Kritchevsky, SB TI Socioeconomic differences in cognitive decline and the role of biomedical factors SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE aged; cognition; educational status; income; longitudinal studies; socioeconomic factors ID C-REACTIVE PROTEIN; METABOLIC SYNDROME; RISK-FACTORS; CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; ALZHEIMER-DISEASE; WHITEHALL-II; LIFE-STYLE; MIDDLE-AGE; HEALTH AB PURPOSE: This study examines the association between socioeconomic status and cognitive decline in a community-based cohort of well-functioning older adults and seeks to determine whether this link could be explained by biomedical factors. METHODS: Data are from 2574 men and women aged 70 to 79 years from Pittsburgh, PA, and Memphis, TN, participating in the Health, Aging and Body Composition study (Health ABC). Three indicators of socioeconomic status were used: education, income, and ownership of financial assets. Cognitive decline over 4 years was defined as a decrease of five points or more in the Modified Mini-Mental State Examination (3MS) score. Biomedical factors measured at baseline, included heart disease, cerebrovascular disease, diabetes, hypertension, poor pulmonary function, and high serum levels of inflammatory markers. RESULTS: Adjusted odds ratios were significantly higher in those with low education, low income, and few assets. Odds ratios ranged from 1.51 to 2.16 in the lowest socioeconomic groups. Additional adjustment for biomedical factors reduced the odds ratios of cognitive decline by an average of 2% for education, 5% for income, and 8% for the number of assets. CONCLUSIONS: Low socioeconomic status predicts a decline in cognitive function in older adults and this relationship is not mediated by biomedical factors. C1 Univ Maastricht, Dept Hlth Care Studies, Sect Med Sociol, NL-6200 MD Maastricht, Netherlands. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. VU Univ Med Ctr, Dept Psychiat, Amsterdam, Netherlands. Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Kent State Univ, Dept Sociol, Kent, OH USA. RP Koster, A (reprint author), Univ Maastricht, Dept Hlth Care Studies, Sect Med Sociol, POB 616, NL-6200 MD Maastricht, Netherlands. EM a.koster@zw.unimaas.nl RI Koster, Annemarie/E-7438-2010; Bosma, Hans/A-6184-2013; Newman, Anne/C-6408-2013; Kempen, Gertrudis/H-5978-2016; OI Newman, Anne/0000-0002-0106-1150; Kempen, Gertrudis/0000-0002-7053-2198; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Kritchevsky, Stephen/0000-0003-3336-6781 NR 51 TC 40 Z9 40 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2005 VL 15 IS 8 BP 564 EP 571 DI 10.1016/j.annepidem.2005.02.008 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963MG UT WOS:000231807800003 PM 15922627 ER PT J AU Kung, HC Pearson, JL Wei, R AF Kung, HC Pearson, JL Wei, R TI Substance use, firearm availability, depressive symptoms, and mental health service utilization among white and African American suicide decedents aged 15 to 64 years SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE suicide; risk factors; race ID MORTALITY FOLLOWBACK SURVEY; RISK-FACTORS; UNITED-STATES; COCAINE; PREVENTION; SMOKING; GENDER; OLDER; RACE; LIFE AB PURPOSE: We investigated whether the substance use problems of excessive alcohol consumption and marijuana use, firearm availability, depressive symptoms, and mental health service utilization, differed among white and African American suicide decedents compared with natural cause-of-death decedents. METHODS: The subjects were a representative sample of 22,957 deceased individuals aged 15 years or older from the 1993 US National Mortality Followback Survey (NMFS). A matched case-control study was constructed for suicide decedents aged 15 to 64 years, with natural death controls frequency matched to cases by age and gender. Conditional logistic regression analysis was used to examine the associations of risk factors with suicide by race. RESULTS: When compared with natural causes of death, suicide deaths among white decedents were associated with use of mental health services, heavy drinking, marijuana use, depression symptoms, and firearm availability. Suicides by African American decedents were associated only with use of mental health services, marijuana, and firearm availability. The interaction of mental health service use and marijuana use was significant only for white suicide decedents. CONCLUSION: This study contributes to the limited understanding of how risk factors unique to suicide differ, and possibly interact, among African American and white decedents. Similarities and differences in risk factors should be considered in suicide prevention planning efforts. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NIMH, NIH, Bethesda, MD USA. RP Kung, HC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 7813, Hyattsville, MD 20782 USA. EM hckO@cdc.gov NR 51 TC 26 Z9 26 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2005 VL 15 IS 8 BP 614 EP 621 DI 10.1016/j.annepidem.2004.09.011 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963MG UT WOS:000231807800009 PM 16118006 ER PT J AU Meschia, JF Brott, TG Brown, RD Crook, R Worrall, BB Kissela, B Brown, WM Rich, SS Case, LD Evans, EW Hague, S Singleton, A Hardy, J AF Meschia, JF Brott, TG Brown, RD Crook, R Worrall, BB Kissela, B Brown, WM Rich, SS Case, LD Evans, EW Hague, S Singleton, A Hardy, J CA SWISS Investigators ISGS Investigators MSGD Investigators TI Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke SO ANNALS OF NEUROLOGY LA English DT Article ID LINKAGE ANALYSIS; PDE4 INHIBITORS; CONFERS RISK; GENE; POPULATION; MODULATION; EXPRESSION; MORTALITY; DISEASE; MODELS AB Risk for ischemic stroke is mediated by both environmental and genetic factors. Although several environmental exposures have been implicated, relatively little is known about the genetic basis of predisposition to this disease. Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5A-P). A collection of North American sibling pairs concordant for ischemic stroke and two cohorts of prospectively ascertained North American ischemic stroke cases and control subjects were used for evaluation of PDE4D and ALOX5A-P. Although no evidence supported linkage of ischemic stroke with either of the two candidate genes, single-nucleotide polymorphisms and haplotypic associations were observed between PDE4D and ischemic stroke. There was no evidence of association between variants of ALOX5AP and ischemic stroke. These data suggest that common variants in PDE4D may contribute to the genetic risk for ischemic stroke in multiple populations. C1 Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Mayo Clin, Neurosci Res Dept, Jacksonville, FL USA. Univ Virginia, Dept Neurol & Hlth Evaluat Sci, Charlottesville, VA USA. Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Meschia, JF (reprint author), Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM meschia.james@mayo.edu RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; OI Kissela, Brett/0000-0002-9773-4013 FU NINDS NIH HHS [R01 NS039987, R01 NS042733, R01-NS39987, R01-NS42733] NR 29 TC 88 Z9 95 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2005 VL 58 IS 3 BP 351 EP 361 DI 10.1002/ana.20585 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961RJ UT WOS:000231679200004 PM 16130105 ER PT J AU Lonser, RR Vortmeyer, AO Butman, JA Glasker, S Finn, MA Ammerman, JM Merrill, MJ Edwards, NA Zhuang, ZP Oldfield, EH AF Lonser, RR Vortmeyer, AO Butman, JA Glasker, S Finn, MA Ammerman, JM Merrill, MJ Edwards, NA Zhuang, ZP Oldfield, EH TI Edema is a precursor to central nervous system peritumoral cyst formation SO ANNALS OF NEUROLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; HIPPEL-LINDAU-DISEASE; RECEPTOR INHIBITOR SU5416; SURGICAL-MANAGEMENT; FACTOR EXPRESSION; TUMOR-TISSUE; BRAIN-TUMORS; SPINAL-CORD; FACTOR VEGF AB Despite the common occurrence and frequent clinical effects of peritumoral cysts in the central nervous system (CNS), the mechanism underlying their development and evolution is not understood. Because they commonly produce peritumoral cysts and because serial magnetic resonance imaging (MRI) is obtained in von Hippel-Lindau disease patients, hemangioblastomas provide an opportunity to examine the pathophysiology of CNS peritumoral cyst formation. Serial MRI was correlated with the clinical findings in 16 von Hippel-Lindau disease patients with 22 CNS hemangioblastomas (11 spinal cord; 11 cerebellar) that were associated with the appearance and evolution of peritumoral cysts. Hemangioblastoma-associated cyst wall histomorphological analysis was performed on postmortem tissues from three von Hippel-Lindau disease patients (not in the clinical series). Comparative proteomic profiling was performed on peritumoral cyst fluid and serum. Vascular endothelial growth factor levels were determined in peritumoral cysts. MRI dearly showed peritumoral edema that developed and slowly and progressively evolved into enlarging hemangioblastoma-associated cysts in all tumors (mean follow-up, 130 +/- 38 months; mean +/- standard deviation). Postcontrast MRI demonstrated convective leakage of gadolinium into cysts. Mean time required for edema to evolve into a cyst was 36 +/- 23 months (range, 8-72 months). Thirteen (59%) hemangioblastoma-cysts became symptomatic (mean time to symptom formation after cyst development, 35 +/- 32 months; range, 3-102 months) and required resection. Protein profiles of cyst fluid and serum were similar. Mean cyst fluid vascular endothelial growth factor concentration was 1.5ng/ml (range, 0-5.4ng/ml). Histology of the cyst walls was consistent with reactive gliosis. CNS peritumoral cyst formation is initiated by increased tumor vascular permeability, increased interstitial pressure in the tumor, and plasma extravasation with convective distribution into the surrounding tissue. When the delivery of plasma from the tumor exceeds the capacity of the surrounding tissue to absorb the extravasated fluid, edema (with its associated increased interstitial pressure) and subsequent cyst formation occur. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Neuroradiol Sect, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 31 TC 38 Z9 39 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2005 VL 58 IS 3 BP 392 EP 399 DI 10.1002/ana.20584 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961RJ UT WOS:000231679200008 PM 16130092 ER PT J AU Olthoff, KM Merion, RM Ghobrial, RM Abecassis, MM Fair, EH Fisher, RA Freise, CE Kam, I Pruett, TL Everhart, JE Hulbert-Shearon, TE Gillespie, BW Emond, JC AF Olthoff, KM Merion, RM Ghobrial, RM Abecassis, MM Fair, EH Fisher, RA Freise, CE Kam, I Pruett, TL Everhart, JE Hulbert-Shearon, TE Gillespie, BW Emond, JC CA A2ALL Study Grp TI Outcomes of 385 adult-to-adult living donor liver transplant recipients - A report from the A2ALL consortium SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 125th Annual Meeting of the American-Surgical-Association CY APR 14-16, 2005 CL Palm Beach, FL SP Amer Surg Assoc ID RIGHT HEPATIC LOBE; SINGLE-CENTER EXPERIENCE/; FOR-SIZE GRAFT; SURVIVAL; VOLUME; MELD; DISEASE; UTILITY; MODEL AB Objective: The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of peri-operative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). Summary Background Data: Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure. Methods: Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure. Results: Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors. Conclusions: This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience. C1 Univ Michigan, Dept Surg, Ann Arbor, MI 48103 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48103 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC USA. Virginia Commonwealth Univ, Dept Surg, Richmond, VA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Colorado, Dept Surg, Denver, CO 80202 USA. Univ Virginia, Dept Surg, Charlottesville, VA USA. NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. Columbia Presbyterian Med Ctr, Dept Surg, New York, NY 10032 USA. RP Merion, RM (reprint author), Univ Michigan, Dept Surg, 315 W Huron St,Suite 240, Ann Arbor, MI 48103 USA. EM kim.olthoff@uphs.upenn.edu; merionb@umich.edu RI Abecassis, Michael/F-7977-2011 FU NIDDK NIH HHS [U01 DK062496, U01 DK062444, U01 DK062467, U01 DK062483, U01 DK062484, U01 DK062494, U01 DK062498, U01 DK062505, U01 DK062531, U01 DK062536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, U01-DK62536] NR 58 TC 207 Z9 213 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2005 VL 242 IS 3 BP 314 EP 325 DI 10.1097/01.sla.0000179646.37145.cf PG 12 WC Surgery SC Surgery GA 962QV UT WOS:000231748200003 PM 16135918 ER PT J AU Bihl, T Vassina, E Boettger, MK Goldbach-Mansky, R Seitz, M Villiger, PM Simon, HU AF Bihl, T Vassina, E Boettger, MK Goldbach-Mansky, R Seitz, M Villiger, PM Simon, HU TI The T348M mutated form of cryopyrin is associated with defective lipopolysaccharide-induced interleukin 10 production in CINCA syndrome SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Editorial Material ID CIAS1 MUTATIONS; ACTIVATION; APOPTOSIS C1 Univ Bern, Dept Pharmacol, CH-3010 Bern, Switzerland. Univ Bern, Inselspital, Dept Rheumatol Clin Immunol Allergol, CH-3010 Bern, Switzerland. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Simon, HU (reprint author), Univ Bern, Dept Pharmacol, Friedbuehlstr 49, CH-3010 Bern, Switzerland. EM hus@pki.unibe.ch RI Vassina, Ekaterina/A-9218-2012; OI Simon, Hans-Uwe/0000-0002-9404-7736 NR 7 TC 6 Z9 7 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 2005 VL 64 IS 9 BP 1380 EP 1381 DI 10.1136/ard.2004.031179 PG 2 WC Rheumatology SC Rheumatology GA 955ER UT WOS:000231208700033 PM 16100350 ER PT J AU Liu, YY Woo, JH Neville, DM AF Liu, YY Woo, JH Neville, DM TI Overexpression of an anti-CD3 immunotoxin increases expression and secretion of molecular chaperone BiP/Kar2p by Pichia pastoris SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID UNFOLDED-PROTEIN RESPONSE; GLUCOSE-REGULATED PROTEINS; SINGLE-CHAIN IMMUNOTOXIN; T-CELL IMMUNOTOXIN; ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE; DIPHTHERIA-TOXIN; ALPHA-FACTOR; TRANSMEMBRANE PROTEIN; IN-VIVO AB We previously reported that the secretory capacity of Pichia pastoris is limited with respect to the secretion of a 96.5-kDa bivalent anti-CD3 immunotoxin; double-copy expression generated more translation products than single-copy expression but did not increase the secretion of the immunotoxin. In Saccharomyces cerevisiae heterologous protein secretion has been reported to increase the expression of molecular chaperones, most prominently BiP/Kar2p. We therefore investigated the relationships between immunotoxin secretion and Kar2p expression in P. pastoris. We found that expression of the immunotoxin in P. pastoris increased the expression of Kar2p to levels that surpassed the retrieval capacity of the cell, leading to secretion of Kar2p into the medium. The level of Kar2p secretion was correlated with the copy number of the immunotoxin gene. Intracellular Kar2p was found to bind exclusively to the unprocessed immunotoxin containing the prosequence of alpha-factor in the endoplasmic reticulum. These results show that Kar2p is intimately involved in immunotoxin secretion in P. pastoris. The limited capacity of P. pastoris to retain a sufficiently high level of intracellular Kar2p may be a factor restricting the production of the immunotoxin. C1 NIMH, Sect Biophys Chem, Mol Biol Lab, Bethesda, MD 20892 USA. RP Liu, YY (reprint author), NIMH, Sect Biophys Chem, Mol Biol Lab, Bldg 10,Rm 3D46,10 Ctr Dr, Bethesda, MD 20892 USA. EM yyliu@mail.nih.gov NR 48 TC 12 Z9 14 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2005 VL 71 IS 9 BP 5332 EP 5340 DI 10.1128/AEM.71.9.5332-5340.2005 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 964RE UT WOS:000231897400051 PM 16151122 ER PT J AU Hassan, R Kreitman, RJ Pastan, I Willingham, MC AF Hassan, R Kreitman, RJ Pastan, I Willingham, MC TI Localization of mesothelin in epithelial ovarian cancer SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE mesothelin; ovarian cancer; immunohistochemistry ID MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; MOLECULAR-CLONING; IN-VITRO; EXPRESSION; CARCINOMAS; AFFINITY; HER2; K1 AB Mesothelin is a cell surface glycoprotein that is present on normal mesothelial cells and overexpressed in several cancers. On immunohistochemical examination of a limited number of ovarian tumors, increased mesothelin expression has been previously noted. The authors evaluated mesothelin expression in 48 patients with ovarian cancer who were screened for participation in phase I studies of a recombinant immunotoxin targeting mesothelin. Eligibility criteria for participation in the studies included mesothelin expression by more than 30% of accessible tumor cells. Sections of formalin-fixed paraffin-embedded tumor specimens were evaluated for mesothelin expression by immunohistochemistry using the anti-mesothelin monoclonal antibody K1. Between September 2000 and January 2003, 48 ovarian tumors were analyzed for mesothelin positivity. Mesothelin positivity was noted in 34 of the 48 cases evaluated (71%). These results show that mesothelin is expressed in most epithelial ovarian cancers and that mesothelin expression in ovarian cancers can be evaluated in archival material. Patients whose tumors express mesothelin could be eligible for participation in clinical trials of novel agents targeting mesothelin. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov NR 18 TC 68 Z9 71 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD SEP PY 2005 VL 13 IS 3 BP 243 EP 247 DI 10.1097/01.pai.00000141545.36485.d6 PG 5 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 959UD UT WOS:000231543900005 PM 16082249 ER PT J AU Miligi, L Costantini, AS Benvenuti, A Veraldi, A Tumino, R Ramazzotti, V Vindigni, C Amadori, D Fontana, A Rodella, S Stagnaro, E Crosignani, P Vineis, P AF Miligi, Lucia Seniori Costantini, Adele Benvenuti, Alessandra Veraldi, Angela Tumino, Rosario Ramazzotti, Valerio Vindigni, Carla Amadori, Dino Fontana, Arabella Rodella, Stefania Stagnaro, Emanuele Crosignani, Paolo Vineis, Paolo TI Personal use of hair dyes and hematolymphopoletic malignancies SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Article DE hair dye; hematolymphopoietic malignancies; leukemia; non-Hodgkin's lymphoma ID MULTICENTER CASE-CONTROL; NON-HODGKINS-LYMPHOMA; HEMATOPOIETIC CANCER; MULTIPLE-MYELOMA; BLADDER-CANCER; UNITED-STATES; RISK; LEUKEMIA; CARCINOGENICITY; IDENTIFICATION AB In the context of a population-based case-control study in Italy, the authors investigated the possible association between the personal use of hair dyes and non-Hodgkin's lymphoma (NHL), leukemia, multiple myeloma, and Hodgkin's disease. They collected all incident cases of hematolymphopoietic malignancies; the control group was formed with a random sample of the general population. Overall, the authors interviewed 2,737 research subjects and 1,779 control subjects. Among women, the authors found no association between ever using hair dyes and the risk of hematotynnphopoietic malignancies. However, for permanent hair dyes, the authors observed a slightly increased risk of lymphocytic leukemia (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 0.8-2.2) and of follicular subtypes of NHL (OR = 1.3; 95% CI = 0.8-2.0). Women who used black hair dye colors were at an increased risk of developing leukemia (OR = 1.9; 95% CI = 1.0-3.4), in particular chronic lymphocytic leukemia (OR - 3.0; 95% Cl - 1.1-7.5). In spite of the lack of information on the timing and frequency of hair dye use and the imprecision of the ORs, associations were suggested between leukemia and permanent black hair dye use and follicular NHL and the use of permanent hair dyes. C1 Ist Toscano Tumori, Unit Environm & Occupat Epidemiol, Ctr Study & Canc Prevent, I-30135 Florence, Italy. Registro Tumori Azienda Osped Civile MP Arezzo, Ragusa, Italy. Natl Canc Inst, Rome, Italy. Natl Canc Inst, Genoa, Italy. Natl Canc Inst, Milan, Italy. Univ Siena, Dipartimento Oncol Anat Patol, I-53100 Siena, Italy. Ist Oncol Romagnolo, Dept Med Oncol, Forli, Italy. Local Hlth Unit, Novara, Italy. Az Osped, Verona, Italy. Agenzia Reg Sanita, Florence, Italy. Univ Turin, Turin, Italy. Univ London Imperial Coll Sci & Technol, London, England. RP Miligi, L (reprint author), Ist Toscano Tumori, Unit Environm & Occupat Epidemiol, Ctr Study & Canc Prevent, Via San Salvi 12, I-30135 Florence, Italy. EM l.miligi@cspo.it FU NCI NIH HHS [CA51086] NR 25 TC 12 Z9 15 U1 2 U2 10 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PD SEP-OCT PY 2005 VL 60 IS 5 BP 249 EP 256 DI 10.3200/AEOH.60.5.249-256 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 130NZ UT WOS:000243807600003 PM 17290845 ER PT J AU Bailer, UF Frank, GK Henry, SE Price, JC Meltzer, CC Weissfeld, L Mathis, CA Drevets, WC Wagner, A Hoge, J Ziolko, SK McConaha, CW Kaye, WH AF Bailer, UF Frank, GK Henry, SE Price, JC Meltzer, CC Weissfeld, L Mathis, CA Drevets, WC Wagner, A Hoge, J Ziolko, SK McConaha, CW Kaye, WH TI Altered brain serotonin 5-HT1A receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [Carbonyl(11)C]WAY-100635 SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 24th Congress of the Collegium-Internationale-Neuro-Psychopharmacologicum CY JUN 20-24, 2004 CL Paris, FRANCE SP Collegium Int Neuro Psychopharmacol ID ANTERIOR CINGULATE CORTEX; OBSESSIVE COMPULSIVE SCALE; TERM WEIGHT RESTORATION; EATING DISORDER SCALE; BULIMIA-NERVOSA; PREFRONTAL CORTEX; 1A RECEPTOR; ANXIETY DISORDERS; FUNCTIONAL NEUROANATOMY; CONTROLLED FAMILY AB Context: Previous studies have shown that women with anorexia nervosa (AN), when ill and after recovery, have alterations of serotonin (5-HT) neuronal activity and core eating disorder symptoms, such as anxiety. Objective: To further characterize the 5-HT system in AN, we investigated 5-HT1A receptor activity using positron emission tomography imaging because this receptor is implicated in anxiety and feeding behavior. Design, Setting, and Participants: To avoid the confounding effects of malnutrition, we studied 13 women who had recovered from restricting-type AN (mean age, 23.3 +/- 5.2 years) and 12 women who had recovered from bulimia-type AN (mean age, 28.6 +/- 7.3 years) (> 1 year normal weight, regular menstrual cycles, no bingeing or purging). These subjects were compared with 18 healthy control women (mean age, 25.1 +/- 5.8 years). Intervention: The 5-HT1A receptor binding was measured using positron emission tomography imaging and a specific 5-HT1A receptor antagonist, [carbonyl-C-11]WAY-100635. Main Outcome Measure: Specific 5-HT1A receptor binding was assessed using the binding potential measure. Binding potential values were derived using both the Logan graphical method and compartmental modeling. The binding potential in a region of interest was calculated with the formula: binding potential = distribution volume of the region of interest minus distribution volume of the cerebellum. Results: Women recovered from bulimia-type AN had significantly (P < .05) increased [C-11]WAY-100635 binding potential in cingulate, lateral and mesial temporal, lateral and medial orbital frontal, parietal, and prefrontal cortical regions and in the dorsal raphe compared with control women. No differences were found for women recovered from restricting-type AN relative to controls. For women recovered from restricting-type AN, the 5-HT1A postsynaptic receptor binding in mesial temporal and subgenual cingulate regions was positively correlated with harm avoidance. Conclusions: We observed increased 5-HT, receptor binding in women who had recovered from bulimia-type AN but not restricting-type AN. However, 5-HT1A receptor binding was associated with a measure of anxiety in women recovered from restricting-type AN. These data add to a growing body of evidence showing that altered serotonergic function and anxiety symptoms persist after recovery from AN. These psychobiological alterations may be trait related and may contribute to the pathogenesis of AN. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Presbyterian Univ Hosp, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Hosp Vienna, Dept Gen Psychiat, A-1090 Vienna, Austria. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Dept Child & Adolescent Psychiat, San Diego, CA 92103 USA. RP Kaye, WH (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Dept Psychiat, Iroquois Bldg,Suite 600,3811 O Hara St, Pittsburgh, PA 15213 USA. EM kayewh@msx.upmc.edu RI Mathis, Chester/A-8607-2009 FU NIMH NIH HHS [MH42984, MH46001, T32-MH18399]; NIMHD NIH HHS [K05-MD01894] NR 96 TC 93 Z9 96 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2005 VL 62 IS 9 BP 1032 EP 1041 DI 10.1001/archpsyc.62.9.1032 PG 10 WC Psychiatry SC Psychiatry GA 961RU UT WOS:000231680300011 PM 16143735 ER PT J AU Bauer, CR Langer, JC Shankaran, S Bada, HS Lester, B Wright, LL Krause-Steinrauf, H Smeriglio, VL Finnegan, LP Maza, PL Verter, J AF Bauer, CR Langer, JC Shankaran, S Bada, HS Lester, B Wright, LL Krause-Steinrauf, H Smeriglio, VL Finnegan, LP Maza, PL Verter, J TI Acute neonatal effects of cocaine exposure during pregnancy SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID INFANT-DEATH-SYNDROME; MATERNAL LIFE-STYLE; FULL-TERM INFANTS; PRENATAL COCAINE; INTRAVENTRICULAR HEMORRHAGE; INUTERO EXPOSURE; EARLY-CHILDHOOD; BIRTH-WEIGHT; DRUG-USE; GROWTH AB Objective: To identify associations between cocaine-exposure during pregnancy and medical conditions in newborn infants from birth through hospital discharge. Design: Multisite, prospective, randomized study. Setting: Brown University, University of Miami, University of Tennessee (Memphis), and Wayne State University. Subjects: A total of 717 cocaine-exposed infants and 7442 nonexposed infants. Main Outcome Measures: Results of physical examination and conditions observed during hospitalization. Results: Cocaine-exposed infants were about 1.2 weeks younger, weighed 536 g less, measured 2.6 cm shorter, and had head circumference 1.5 cm smaller than nonexposed infants (all P <.001). Results did not confirm previously reported abnormalities. Central and autonomic nervous system symptoms were more frequent in the exposed group: jittery/tremors (adjusted odds ratio, 2.17; 99% confidence interval, 1.44-3.29), high-pitched cry (2.44; 1.06-5.66), irritability (1.81; 1.18-2.80), excessive suck (3.58; 1.63-7-88), hyperalertness (7.78; 1.72-35.06), and autonomic instability (2.64; 1.17-5.95). No differences were detected in organ systems by ultrasound examination. Exposed infants had more infections (3.09; 1.76-5.45), including hepatitis (13.46; 7.46-24.29), syphilis (8.84; 3.74-20.88), and human immunodeficiency virus exposure (12.37; 2.20-69.51); were less often breastfed (0.26; 0.15-0.44); had more child protective services referrals (48.92; 28.77-83.20); and were more often not living with their biological mother (18.70; 10.53-33.20). Conclusions: Central and autonomic nervous system symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually transient and may be a true cocaine effect. Abnormal anatomic outcomes previously reported were not confirmed. increased infections, particularly sexually transmitted diseases, pose a serious public health challenge. Exposure increased involvement of child protective services and out-of-home placement. C1 Univ Miami, Sch Med, Dept Pediat, Miami, FL 33101 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. Univ Tennessee, Coll Med, Dept Pediat, Memphis, TN 38163 USA. Women & Infants Hosp Rhode Isl, Brown Med Sch, Dept Pediat, Providence, RI USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Natl Inst Drug Abuse, Bethesda, MD USA. Ctr Subst Abuse Treatment, Washington, DC USA. Adm Children Youth & Families, Washington, DC USA. RP Bauer, CR (reprint author), Univ Miami, Sch Med, Dept Pediat, R-131,POB 016960, Miami, FL 33101 USA. FU NICHD NIH HHS [U01 HD 198977, U10 HD 279045, U10 HD 213853, U01 HD 2367902, U10 HD 21397, U10 HD 214154] NR 47 TC 77 Z9 84 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2005 VL 159 IS 9 BP 824 EP 834 DI 10.1001/archpedi.159.9.824 PG 11 WC Pediatrics SC Pediatrics GA 961HX UT WOS:000231653800005 PM 16143741 ER PT J AU Waldmann, TA AF Waldmann, TA TI Targeting the interleukin-15 system in rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID RECEPTOR-BETA-CHAIN; IL-15 RECEPTOR; T-CELLS; HUMANIZED ANTIBODY; IN-VIVO; PROLIFERATION; HOMEOSTASIS; ACTIVATION; EXPRESSION; MIGRATION C1 NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, CCR, NIH, 10 Ctr Dr,MSC 1374,Bldg 10,Room 4N115, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov NR 21 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 BP 2585 EP 2588 DI 10.1002/art.21363 PG 4 WC Rheumatology SC Rheumatology GA 967UC UT WOS:000232115700001 PM 16142738 ER PT J AU Oddis, CV Rider, LG Reed, AM Ruperto, N Brunner, HI Koneru, B Feldman, BM Giannini, EH Miller, FW AF Oddis, CV Rider, LG Reed, AM Ruperto, N Brunner, HI Koneru, B Feldman, BM Giannini, EH Miller, FW CA Int Myositis Assessment Clinical S TI International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INCLUSION-BODY MYOSITIS; INTRAVENOUS GAMMA-GLOBULIN; TERM FOLLOW-UP; JUVENILE DERMATOMYOSITIS; REFRACTORY POLYMYOSITIS; ADULT PATIENTS; IMMUNOGLOBULIN THERAPY; OUTCOME ASSESSMENT; PLASMA-EXCHANGE; CLINICAL-TRIALS C1 Univ Pittsburgh, Pittsburgh, PA 15261 USA. Natl Inst Environm Hlth Sci, NIH, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. IRCCS, Genoa, Italy. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. RP Oddis, CV (reprint author), Univ Pittsburgh, S703 Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15261 USA. EM oddis@dom.pitt.edu RI Feldman, Brian/A-8586-2011; Song, Yeong Wook/J-2765-2012; OI Harris-Love, Michael/0000-0002-1842-3269; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIAMS NIH HHS [AR-48349-01] NR 45 TC 67 Z9 68 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 BP 2607 EP 2615 DI 10.1002/art.21291 PG 9 WC Rheumatology SC Rheumatology GA 967UC UT WOS:000232115700005 PM 16142757 ER PT J AU Aletaha, D Ward, MM Machold, KP Nell, VPK Stamm, T Smolen, JS AF Aletaha, D Ward, MM Machold, KP Nell, VPK Stamm, T Smolen, JS TI Remission and active disease in rheumatoid arthritis - Defining criteria for disease activity states SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-PRACTICE; RADIOGRAPHIC PROGRESSION; ACTIVITY INDEX; ACTIVITY SCORE; THERAPY; METHOTREXATE; RA; INTERVENTION AB Objective. Several composite scores are available to assess the activity of rheumatoid arthritis (RA). Criteria for remission and active RA based on these continuous scores are important for use in clinical practice and clinical trials. We aimed to reevaluate or to define such criteria for the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). Methods. We sampled patient profiles from an observational RA database that included clinical and laboratory variables. Thirty-five rheumatology experts classified these profiles into 1 of 4 categories: remission, low, moderate, or high disease activity. Cutoff values were estimated by mapping scores on the DAS28 and SDAI to these ratings, and analyses of agreement (kappa statistics) and a diagnostic testing approach (receiver operating characteristic curves) were used to validate the estimates. The final criteria were validated using 2 observational cohorts (a routine cohort of 767 patients and an inception cohort of 91 patients). Results. Results from the 3 analyses were very similar and were integrated. The criteria for separating remission, low, moderate, and high disease activity based on the SDAI were scores of 3.3, 11, and 26, respectively; those based on the DAS28 were scores of 2.4, 3.6, 5.5, respectively. In the routine cohort, these cutoff values showed substantial agreement (weighed kappa = 0.70) and discriminated between groups of patients with clearly different functional capacities (P < 0.001). In the inception cohort, these cutoff scores differentiated responders (those with a 20% response on the American College of Rheumatology improvement criteria) from nonresponders (P < 0.01), as well as patients with and without radiologic progression (P < 0.05). Conclusion. New criteria for levels of RA disease activity were determined and internally validated. These criteria, which are based on current and explicit expert judgment, are valuable in this era of rapidly advancing therapeutic approaches. C1 Med Univ Vienna, Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. Lainz Hosp, Vienna, Austria. RP Aletaha, D (reprint author), Univ Vienna, Dept Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM aletaha@meduniwien.ac.at NR 47 TC 230 Z9 244 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 BP 2625 EP 2636 DI 10.1002/art.21235 PG 12 WC Rheumatology SC Rheumatology GA 967UC UT WOS:000232115700007 PM 16142705 ER PT J AU Nagayoshi, R Nagai, T Matsushita, K Sato, K Sunahara, N Matsuda, T Nakamura, T Komiya, S Onda, M Matsuyama, T AF Nagayoshi, R Nagai, T Matsushita, K Sato, K Sunahara, N Matsuda, T Nakamura, T Komiya, S Onda, M Matsuyama, T TI Effectiveness of anti-folate receptor beta antibody conjugated with truncated Pseudomonas exotoxin in the targeting of rheumatoid arthritis synovial macrophages SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FOLATE RECEPTOR; ACTIVATED MACROPHAGES; FOLIC-ACID; INFLAMMATION; IMMUNOTOXIN; EXPRESSION; INDUCTION; CELLS; TRANSDUCTION; DESTRUCTION AB Objective. To define the distribution of folate receptor beta (FR beta)-expressing cells in various tissues, including rheumatoid arthritis (RA) synovial tissues, and to verify the effects of an immunotoxin composed of an anti-FR beta monoclonal antibody (mAb) and truncated Pseudomonas exotoxin A (PEA) on apoptosis and tumor necrosis factor alpha (TNF alpha) production by adherent synovial mononuclear cells from RA patients. Methods. Anti-FRO mAb were produced by immunizing mice with FR beta-transfected murine pre-B cells. The distribution of the FR beta antigen was examined by immunohistochemical analysis using anti-FR beta mAb and macrophage-specific anti-CD163 mAb. Anti-FR beta mAb was chemically crosslinked with truncated PEA. FR beta-expressing macrophages were produced by the transfection of adenovirus vector containing the FR beta gene. Apoptotic cells were detected by staining with propidium iodide. TNF alpha was measured by enzyme-linked immunosorbent assay. Results. FR beta-expressing cells were not present in peripheral blood leukocytes and their activated cells. In all of the tissues examined, most FR beta-expressing cells were CD163+. The immunotoxin significantly induced the apoptosis of FR beta-transfected macrophages and adherent RA synovial mononuclear cells and inhibited TNF alpha production by adherent RA synovial mononuclear cells. Conclusion. We demonstrated the limited distribution of FR beta-expressing cells in various tissues. The immunotoxin targeting FR beta-expressing cells will provide a therapeutic tool for rheumatoid synovitis. C1 Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Immunol, Kagoshima 890854, Japan. Kagoshima Red Cross Hosp, Kagoshima, Japan. Kumamoto Orthopaed Hosp, Kumamoto, Japan. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Matsuyama, T (reprint author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Immunol, 8-3501 Sakuragaoka, Kagoshima 890854, Japan. EM matuyama@m.kufm.kagoshima-u.ac.jp NR 39 TC 39 Z9 42 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 BP 2666 EP 2675 DI 10.1002/art.21228 PG 10 WC Rheumatology SC Rheumatology GA 967UC UT WOS:000232115700011 PM 16142741 ER PT J AU Aletaha, D Smolen, JS Ward, MM AF Aletaha, D Smolen, JS Ward, MM TI Functional limitation in rheumatoid arthritis (RA): How much is reversible? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Univ Vienna, Vienna, Austria. Lainz Hosp, Vienna, Austria. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S327 EP S328 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801349 ER PT J AU Aletaha, D Machold, KP Nell, VPK Smolen, JS AF Aletaha, D Machold, KP Nell, VPK Smolen, JS TI Impact of rheumatoid arthritis (RA) core set measures on rheumatologists' judgment of disease activity SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Med Univ Vienna, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S124 EP S125 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800266 ER PT J AU Bachen, EA Chesney, MA Criswell, LA AF Bachen, EA Chesney, MA Criswell, LA TI Prevalence of mood and anxiety disorders in women with SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NCCAM, NIH, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mills Coll, Oakland, CA 94613 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S381 EP S381 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802008 ER PT J AU Barron, KS Emerson, SU Rowley, AH Shulman, ST St Claire, M Burklow, TR Doroshow, RW Purcell, RH AF Barron, KS Emerson, SU Rowley, AH Shulman, ST St Claire, M Burklow, TR Doroshow, RW Purcell, RH TI Attempt to transmit a putative Kawasaki disease agent to chimpanzees. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAID, NIH, Bethesda, MD 20892 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. BIOQUAL Inc, Rockville, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S303 EP S303 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801278 ER PT J AU Basu, D Weisman, MH Davis, JC Nichols, DR Ward, MM Reveille, JD AF Basu, D Weisman, MH Davis, JC Nichols, DR Ward, MM Reveille, JD TI HLA-B27 negative are similar to HLA-B27 positive patients with ankylosing spondylitis in radiographic, functional and clinical severity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston, TX USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S211 EP S211 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801018 ER PT J AU Blair, JM Blair, J Fiorentino, N Marini, J Morris, D Schimel, D Lipsky, P AF Blair, JM Blair, J Fiorentino, N Marini, J Morris, D Schimel, D Lipsky, P TI Rapid development of osteoarthritis in mice with Osteogenesis Imperfecta SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S719 EP S719 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803487 ER PT J AU Canna, S Paul, SM Hildenbrand, H Jain, M Smith, MR Comis, L Goldbach-Mansky, R AF Canna, S Paul, SM Hildenbrand, H Jain, M Smith, MR Comis, L Goldbach-Mansky, R TI Functional characteristics of children with neonatal onset multisystem inflammatory disease (NOMID). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S666 EP S666 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803344 ER PT J AU Canna, S Gelabert, A Jones, J Dailey, NJ Kastner, D Reynolds, J Goldbach-Mansky, R AF Canna, S Gelabert, A Jones, J Dailey, NJ Kastner, D Reynolds, J Goldbach-Mansky, R TI Bone density and metabolism in patients with NOMID after 12 months of treatment with the IL-1 receptor-antagonist anakinra/kinereto (R) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Bethesda, MD USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S723 EP S723 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803496 ER PT J AU Canna, S Gelabert, A Aksentijevich, I Radin, A Papadopoulos, J Barham, B Wilson, M Hawkins, P Kastner, D Goldbach-Mansky, R AF Canna, S Gelabert, A Aksentijevich, I Radin, A Papadopoulos, J Barham, B Wilson, M Hawkins, P Kastner, D Goldbach-Mansky, R TI Treatment of 4 patients with cryopyrin-associated periodic syndromes with the long-acting Il-1 inhibitor Il-1 trap. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Bethesda, MD USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. UCL Royal Free & Univ Coll Med Sch, London, England. RI Hawkins, Philip/C-5573-2008 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S274 EP S274 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801200 ER PT J AU Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM AF Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM TI Analysis of an adjuvant-induced arthitis quatitative trait locus on chromosome 10-Aia5: Arthritis severity controlled by a distal portion of Aia5 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 VA, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. NIAMS, NIH, Bethesda, MD USA. MedImmune Inc, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S157 EP S158 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800354 ER PT J AU Christopher-Stine, L Levine, SM Plotz, PH Pahlajani, NH Astor, BC Gelber, AC AF Christopher-Stine, L Levine, SM Plotz, PH Pahlajani, NH Astor, BC Gelber, AC TI Sensitivity and specificity of magnetic resonance imaging in discriminating dermatomyositis and polymyositis from muscular dystrophy and normal controls SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S314 EP S314 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801311 ER PT J AU Cid, MC Hoffman, MP Hernandez-Rodriguez, J Segarral, M Sanchez, M Vilardell, C Garcia-Martinez, A Canete, JD Urbano-Marquez, A Kleinman, HK AF Cid, MC Hoffman, MP Hernandez-Rodriguez, J Segarral, M Sanchez, M Vilardell, C Garcia-Martinez, A Canete, JD Urbano-Marquez, A Kleinman, HK TI Genes related to the maintenance of inflammatory lesions in giant cell arteritis. Association between increased CCL-2 (MCP-1) expression and persistence of disease activity SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Barcelona, Hosp Clin, IDIBAPS, Barcelona, Spain. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S219 EP S219 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801039 ER PT J AU Clegg, DO Reda, DJ Harris, CL Klein, MA AF Clegg, DO Reda, DJ Harris, CL Klein, MA CA GAIT Invest TI The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): The glucosamine/chondroitin arthritis intervention trial SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Utah, Salt Lake City, UT USA. VACSP, Hines, IL USA. VACSP, Albuquerque, NM USA. NIH, NCCAM, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S256 EP S256 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801151 ER PT J AU Davis, JC Ward, MM Learch, T Reveille, J Weisman, M AF Davis, JC Ward, MM Learch, T Reveille, J Weisman, M TI Radiographic severity in patients with long-standing ankylosing spondylitis is associated with multiple factors including male gender, age and history of smoking. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. Univ Texas, Houston, TX USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S635 EP S636 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803257 ER PT J AU Finckh, A Cooper, GS Chibnik, LB Costenbader, KH Fraser, PA Karlson, EW AF Finckh, A Cooper, GS Chibnik, LB Costenbader, KH Fraser, PA Karlson, EW TI Occupational exposures and risk of systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIEHS, Durham, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S733 EP S734 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803523 ER PT J AU Fischer, RT Slota, R Longo, N Lugar, P Sohn, HW Illei, G Phillips, T Lipsky, P Grammer, A AF Fischer, RT Slota, R Longo, N Lugar, P Sohn, HW Illei, G Phillips, T Lipsky, P Grammer, A TI Functional and phenotypic characterization of anergic B cells circulating in the periphery of patients with systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S204 EP S204 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800490 ER PT J AU Gergely, P Pullmann, R Stancato, C Otvos, L Koncz, A Blazsek, A Poor, G Brown, KE Phillips, PE Perl, A AF Gergely, P Pullmann, R Stancato, C Otvos, L Koncz, A Blazsek, A Poor, G Brown, KE Phillips, PE Perl, A TI Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 SUNY Syracuse, Syracuse, NY 13210 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. ORFI, Budapest, Hungary. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S208 EP S208 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801010 ER PT J AU Gregersen, PK Chen, W Lee, AT Seldin, MF Li, WT Kern, M Remmers, EF Criswell, LA Kastner, DL Amos, CI AF Gregersen, PK Chen, W Lee, AT Seldin, MF Li, WT Kern, M Remmers, EF Criswell, LA Kastner, DL Amos, CI TI Genome wide linkage scan of 748 affected sibling pair families with rheumatoid arthritis using the illumina linkage IV set of similar to 5,600 SNP markers. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 N Shore LIJ Res Inst, Manhasset, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Davis, Davis, CA USA. NIAMSD, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S448 EP S448 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802199 ER PT J AU Harris-Love, M Joe, G Abbett, K Koziol, D AF Harris-Love, M Joe, G Abbett, K Koziol, D TI Performance-based assessment of functional limitation and muscle endurance: Reliability of the adult myositis assessment tool. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Ithaca Coll, Ithaca, NY 14850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S434 EP S434 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802160 ER PT J AU Huber, A Dugan, E Lachenbruch, P Feldman, BM Perez, M Zemel, L Lindsley, C Rennebohm, R Wallace, C Passo, M Reed, AM Bowyer, S Ballinger, S Miller, F Rider, L AF Huber, A Dugan, E Lachenbruch, P Feldman, BM Perez, M Zemel, L Lindsley, C Rennebohm, R Wallace, C Passo, M Reed, AM Bowyer, S Ballinger, S Miller, F Rider, L TI Reliability of the cutaneous assessment tool (CAT) in juvenile dermatomyositis (JDM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 IWK Hlth Ctr, Halifax, NS, Canada. NIEHS, NIH, Bethesda, MD USA. RI Feldman, Brian/A-8586-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S314 EP S315 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801312 ER PT J AU Hunter, DJ Zhang, YQ Niu, JB Felson, DT Kwoh, CK Newman, A Kritchevsky, S Harris, T Nevitt, M AF Hunter, DJ Zhang, YQ Niu, JB Felson, DT Kwoh, CK Newman, A Kritchevsky, S Harris, T Nevitt, M TI Patella malalignment and its consequences: The health ABC study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Pittsburgh, Pittsburgh, PA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Wake Forest Univ, Salem, NC USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S686 EP S686 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803398 ER PT J AU Illei, GG Jacobs, G Austin, H Ward, M AF Illei, GG Jacobs, G Austin, H Ward, M TI Accuracy of glomerular filtration rate (GFR) prediction equations in patients with immune-mediated glomerulonephritides (GN). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S382 EP S382 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802010 ER PT J AU Illei, GG Phillips, TM Yarboro, C Pham, TH Sun, HW Lipsky, PE AF Illei, GG Phillips, TM Yarboro, C Pham, TH Sun, HW Lipsky, PE TI Analysis of multiple serum cytokines and chemokines in SLE patients demonstrates that they highly correlate to each other and fails to identify a principal effector molecule. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S205 EP S205 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801002 ER PT J AU Lapteva, L Steele, S Manzano, M Van der Veen, JW Yarboro, CH Lipsky, PE Volpe, B Diamond, B Marenco, S Illei, GG AF Lapteva, L Steele, S Manzano, M Van der Veen, JW Yarboro, CH Lipsky, PE Volpe, B Diamond, B Marenco, S Illei, GG TI MRI and proton magnetic resonance spectroscopy imaging (H-MRSI) in patients with systemic lupus erythematosus (SLE) and cognitive dysfunction (CdysF). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. NIMH, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Columbia Univ, New York, NY USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S379 EP S379 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802002 ER PT J AU Lapteva, L Oroszi, G Davis, E Yarboro, CH Lipsky, PE Goldman, D Hu, XZ Lipsky, R Illei, GG AF Lapteva, L Oroszi, G Davis, E Yarboro, CH Lipsky, PE Goldman, D Hu, XZ Lipsky, R Illei, GG TI The Met66 variant of the functional Val66Met polymorphism in the brain-derived neurotrophic factor gene confers protection against cognitive dysfunction in systemic lupus erythematosus (SLE) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, NIAMS, Bethesda, MD 20892 USA. NIH, NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S200 EP S200 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800476 ER PT J AU Levine, SM Plotz, PH Casciola-Rosen, L Rosen, A AF Levine, SM Plotz, PH Casciola-Rosen, L Rosen, A TI The N-terminal domain of Jo-1 is conformationally mobile: Implications for immunogenicity in myositis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S264 EP S264 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801172 ER PT J AU Ling, SM Patel, D Zhan, M Taub, D Muller, D Bathon, J Hochberg, M Abernethy, D Metter, E Ferrucci, L AF Ling, SM Patel, D Zhan, M Taub, D Muller, D Bathon, J Hochberg, M Abernethy, D Metter, E Ferrucci, L TI Changes in selected proteins associated with osteoarthritis development in the Baltimore longitudinal study of aging (BLSA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIA, Intramural Res Program, Baltimore, MD 21224 USA. Univ N Carolina, Chapel Hill, NC USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S255 EP S256 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801150 ER PT J AU Lugar, P Slota, R Fischer, R Phillips, T Brescia, AM Lipsky, P Grammer, AC AF Lugar, P Slota, R Fischer, R Phillips, T Brescia, AM Lipsky, P Grammer, AC TI Gene expression, phenotypic and proteornic profile of Ig-secretin plasma cells in the periphery of patients with active SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S286 EP S286 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801230 ER PT J AU Magalnick, M Wilson, M Yao, L Goldbach-Mansky, R Duryea, J AF Magalnick, M Wilson, M Yao, L Goldbach-Mansky, R Duryea, J TI Computer tool to measure carpal volumes on hand CT scans to detect erosive changes in patients with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S114 EP S114 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800237 ER PT J AU Mamyrova, G Carrick, D O'Hanlon, T Malley, J Reed, A Sherry, D Wallace, C James-Newton, L Zemel, L Perez, M Lindsley, C Miller, F Rider, L AF Mamyrova, G Carrick, D O'Hanlon, T Malley, J Reed, A Sherry, D Wallace, C James-Newton, L Zemel, L Perez, M Lindsley, C Miller, F Rider, L CA Childhood Myositis Heterogeneity TI Relative importance of immunogenetic risk and protective factors for the development of juvenile dermatomyositis (JDM) in European American (EA) patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, DHHS, Bethesda, MD USA. NIH, CIT, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S308 EP S309 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801295 ER PT J AU Mamyrova, G O'Hanlon, T Carrick, D Malley, J Miller, F Rider, L AF Mamyrova, G O'Hanlon, T Carrick, D Malley, J Miller, F Rider, L CA Childhood Myositis Heterogeneity TI DRB1*0301 and the second hypervariable region DRB1 motif, (70)QKRGR(74) are HLA risk factors for dermatomyositis (DM) in African-American (AA) patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, DHHS, Bethesda, MD USA. NIH, CIT, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S308 EP S308 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801294 ER PT J AU Martins, DC Zhang, W Zhang, X He, LS Lipsky, PE Grammer, AC AF Martins, DC Zhang, W Zhang, X He, LS Lipsky, PE Grammer, AC TI TNF receptor-associated factor 2 (TRAF2) is an important adaptor in activation of nuclear factor (NF-kB) and activation protein (AP-1) pathways in human B cells. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S287 EP S287 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801234 ER PT J AU Mavragani, CP Patronas, N Dalakas, M Moutsopoulos, HM AF Mavragani, CP Patronas, N Dalakas, M Moutsopoulos, HM TI Strong association of homozygous Mthfr mutations and autoimmune thyroiditis in patients with Ms-like disease who do not fulfill the diagnostic criteria for multiple sclerosis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Hosp Special Surg, New York, NY 10021 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S245 EP S245 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801118 ER PT J AU Moini, B Harris-Love, M Pokrovnichka, A Pahlajani, N Plotz, P AF Moini, B Harris-Love, M Pokrovnichka, A Pahlajani, N Plotz, P TI Distribution of muscle weakness as measured by the manual muscle test in subjects with myositis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S434 EP S435 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802161 ER PT J AU Nagai, T Tanaka, M Tsuneyoshi, Y Matsushita, K Komiya, S Onda, M Matsuyama, T AF Nagai, T Tanaka, M Tsuneyoshi, Y Matsushita, K Komiya, S Onda, M Matsuyama, T TI Effectiveness of recombinant anti-folate receptor-beta immunotoxin to damage rheumatoid arthritis synovial macrophages. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima 890, Japan. Natl Canc Inst, Mol Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S559 EP S560 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803032 ER PT J AU Neogi, T Nevitt, M LaValley, MP Niu, J Hunter, DJ Terkeltaub, R Carbone, L Chen, H Guermazi, A Felson, DT AF Neogi, T Nevitt, M LaValley, MP Niu, J Hunter, DJ Terkeltaub, R Carbone, L Chen, H Guermazi, A Felson, DT TI Chondrocalcinosis is not associated with increased risk of cartilage loss in knees with osteoarthritis: Results from two prospective longitudinal MRI studies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Boston Univ, Boston, MA 02215 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Tennessee, Memphis, TN 38163 USA. NIA, Bethesda, MD 20892 USA. OARG, San Francisco, CA USA. RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S68 EP S68 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800106 ER PT J AU Nichols, DR Weisman, MH Davis, JC Basu, D Ward, MM Reveille, JD AF Nichols, DR Weisman, MH Davis, JC Basu, D Ward, MM Reveille, JD TI Ankylosing spondylitis in African Americans: A clinical and genetic analysis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston, TX USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S394 EP S395 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802045 ER PT J AU Paul, SM Hildenbrand, H Jain, M Smith, MR Canna, S Comis, L Wiggs, E AF Paul, SM Hildenbrand, H Jain, M Smith, MR Canna, S Comis, L Wiggs, E TI Functional outcomes of treatment of neonatal onset multisystern inflammatory disease (NOMID) with anakinra: Preliminary results SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S536 EP S537 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802452 ER PT J AU Reveille, JD Ward, MM Davis, JC Weisman, MH AF Reveille, JD Ward, MM Davis, JC Weisman, MH TI HLA-B, DRB1, DQA1, DQB1 and DPB1 alleles do not affect radiographic severity in ankylosing spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston, TX USA. NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S644 EP S645 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803283 ER PT J AU Reveille, JD Zhang, G Weisman, MH Bruckel, J Inman, RD Khan, MA Schumacher, HR Maksymowych, WP Martin, TM Rosenbaum, JT Yu, DT Davis, JC Ward, MM Jin, L AF Reveille, JD Zhang, G Weisman, MH Bruckel, J Inman, RD Khan, MA Schumacher, HR Maksymowych, WP Martin, TM Rosenbaum, JT Yu, DT Davis, JC Ward, MM Jin, L TI Evidence for involvement of the neural cell adhesion cell (NCAM)-1 gene in susceptibility to ankylosing spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston, TX USA. Univ Cincinnati, Ctr Genome Informat, Cincinnati, OH USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Spondylitis Assoc Amer, Sherman Oaks, CA USA. Univ Toronto, Toronto, ON, Canada. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Alberta, Edmonton, AB, Canada. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S389 EP S389 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802031 ER PT J AU Rider, L Villalba, M Adams, E Joe, G Harris-Love, M Hill, S James-Newton, L Hicks, J Plotz, P Lachenbruch, P Miller, F AF Rider, L Villalba, M Adams, E Joe, G Harris-Love, M Hill, S James-Newton, L Hicks, J Plotz, P Lachenbruch, P Miller, F CA JDM Dis Activity Collaborative TI Validity of the myositis disease activity assessment tool (MDAAT) for assessing extra-muscular disease activity in adult and juvenile idiopathic inflammatory myopathies (IIM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, JDM Dis Act Collaborat Study Grp, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S315 EP S315 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801313 ER PT J AU Saleh, AS Najjar, SS Muller, D Gelber, AC Ferrucci, L Ling, SM AF Saleh, AS Najjar, SS Muller, D Gelber, AC Ferrucci, L Ling, SM TI Aging joints and vessels: Is hand osteoarthritis associated with increased arterial stiffness? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Aging Intramural, Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S514 EP S514 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802386 ER PT J AU Shirota, Y Yarboro, C Sims, G Fritsch, R Ettinger, R Valencia, X Fischer, R Grammer, A Pham, TH Lipsky, PE Illei, GG AF Shirota, Y Yarboro, C Sims, G Fritsch, R Ettinger, R Valencia, X Fischer, R Grammer, A Pham, TH Lipsky, PE Illei, GG TI The impact of in vivo anti IL-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, DHHS, NIH, Bethesda, MD USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S697 EP S697 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803429 ER PT J AU Skapenko, A Niedobitek, GU Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, A Niedobitek, GU Kalden, JR Lipsky, PE Schulze-Koops, H TI Cytokine control of human inflammation in vivo. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Erlangen Nurnberg, Erlangen, Germany. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S48 EP S48 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800046 ER PT J AU Valencia, X Vogt, SL Simone, J Yarboro, C Illei, G Lipsky, PE AF Valencia, X Vogt, SL Simone, J Yarboro, C Illei, G Lipsky, PE TI Defective suppressor function of CD4+CD25hi T regulatory cells in active SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIDCR, NIH, Bethesda, MD USA. NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. NIAMS, OCD, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S614 EP S615 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803195 ER PT J AU Vegosen, L Weinberg, C O'Hanlon, T Targoff, I Koneru, B Mamyrova, G Miller, F Rider, L AF Vegosen, L Weinberg, C O'Hanlon, T Targoff, I Koneru, B Mamyrova, G Miller, F Rider, L CA Childhood Myositis Heterogeneity TI Seasonal birth patterns in subgroups of myositis suggest a role for perinatal environmental factors in etiology SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S228 EP S228 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801067 ER PT J AU Ward, MM Reveille, JD Davis, JC Weisman, M AF Ward, MM Reveille, JD Davis, JC Weisman, M TI Specific occupational activities associated with functional limitations in patients with long-standing ankylosing spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. Univ Texas, HSC, Houston, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S212 EP S212 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801021 ER PT J AU Ward, MM Guthrie, LC AF Ward, MM Guthrie, LC TI Comparison of patients' judgments of improvement in rheumatoid arthritis with ACR and EULAR response criteria. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S127 EP S127 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800274 ER PT J AU Xu, H Wilson, M Goldbach-Mansky, R AF Xu, H Wilson, M Goldbach-Mansky, R TI Metabolic and endocrine changes in patients with erosive rheumatoid arthritis (RA) enrolled in a treatment controlled trial of the anti-TNF-alpha antibody infliximab. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S144 EP S144 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800312 ER PT J AU Yin, HE Yu, MX Zhang, FC AF Yin, HE Yu, MX Zhang, FC TI Vasoactive intestinal peptide and beta-endorphin exert neuro-immune regulation on collagen induced arthritis rats by down-regulating NF-kB activity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Peking Union Med Coll, Beijing, Peoples R China. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S155 EP S155 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800346 ER PT J AU Zhang, W Fischer, R He, LS Pisitkun, P Gaffney, P Behrens, T Lipsky, PE Grammer, AC AF Zhang, W Fischer, R He, LS Pisitkun, P Gaffney, P Behrens, T Lipsky, PE Grammer, AC TI An SLE-associated mutation in CD40 alters human B cell function. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, B Cell Biol Grp, NIH, DHHS, Bethesda, MD USA. NIAMS, Flow Cytometry Sect, Off Sci & Tehcno, NIH,DHHS, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Mol Cellular Dev Biol & Genet, Minneapolis, MN 55455 USA. NIAMS, Autoimmun Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S287 EP S288 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801235 ER PT J AU Hedetniemi, J Gaunt, EE AF Hedetniemi, J Gaunt, EE TI ASM, NIAID survey USBSL-3 laboratories SO ASM NEWS LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. Constella Hlth Sci, Lab Sci, Durham, NC USA. RP Hedetniemi, J (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD SEP PY 2005 VL 71 IS 9 BP 399 EP 401 PG 3 WC Microbiology SC Microbiology GA 004FG UT WOS:000234736800007 ER PT J AU Carey, JB Carey, MA Allshire, A Van Pelt, FN AF Carey, JB Carey, MA Allshire, A Van Pelt, FN TI Tipping the balance towards tolerance: The basis for therapeutic immune modulation by gold? SO AUTOIMMUNITY LA English DT Article DE Rheumatoid arthritis; gold; regulatory T-cells; autoimmunh bystander suppression ID REGULATORY T-CELLS; LYMPH-NODE ASSAY; RHEUMATOID-ARTHRITIS; TUMOR REJECTION; II COLLAGEN; RESPONSES; INDUCTION; ANTIGENS; MECHANISMS; MICE AB Gold salts have long been used in the treatment of rheumatoid arthritis. However, the basis for their therapeutic immune-modulating properties has never been satisfactorily explained. Furthermore, treatments are often marred by the development of adverse immune reactions such as hypersensitivity and even exacerbation of autoimmunity. We would like to propose a hypothesis to explain the basis for both the beneficial and adverse immune-modulating effects of gold in the treatment of rheumatoid arthritis. If accepted, this hypothesis will allow for the development of safer and more effective treatments with gold salts. The principle underlying this hypothesis also has broader implications for how immune hypersensitivity and tolerance are perceived. C1 Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. Natl Univ Ireland Univ Coll Cork, Environm Res Inst, Cork, Ireland. NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Van Pelt, FN (reprint author), Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. EM f.vanpelt@ucc.ie NR 35 TC 1 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD SEP PY 2005 VL 38 IS 6 BP 393 EP 397 DI 10.1080/08916930500193531 PG 5 WC Immunology SC Immunology GA 983PM UT WOS:000233244600001 PM 16278143 ER PT J AU Bossert, JM Busch, RF Gray, SM AF Bossert, JM Busch, RF Gray, SM TI The novel group II metabotropic glutamate agonist, LY379268, attenuates discrete cue-induced reinstatement of heroin seeking SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S55 EP S55 DI 10.1097/00008877-200509001-00173 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300170 ER PT J AU Desai, RI Newman, AH Katz, JL AF Desai, RI Newman, AH Katz, JL TI Antagonism of the stimulant effects of cocaine by the dopamine transporter ligand, JHW007 SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIDA, Medicat Discovery Res Branch, Psychobiol Sect, NIH, Baltimore, MD USA. NIDA, Medicat Discovery Res Branch, Med Chem Sect, NIH, Baltimore, MD USA. EM rdesai@intra.nida.nih.gov 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S78 EP S78 DI 10.1097/00008877-200509001-00244 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300241 ER PT J AU Heilig, M AF Heilig, M TI Neuropeptide Y in anxiety and alcoholism SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIAAA, NIH, Bethesda, MD USA. EM markus.heilig@mail.nih.gov 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S4 EP S4 DI 10.1097/00008877-200509001-00011 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300011 ER PT J AU Holmes, A AF Holmes, A TI Galanin; A novel therapeutic target for stress-related disorders? SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIAAA, Sect Behav Sci & Genet, 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S4 EP S4 DI 10.1097/00008877-200509001-00012 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300012 ER PT J AU Lipska, BK AF Lipska, BK TI Neonatal disconnection of the hippocampus alters prefrontal cortical function: Implications for schizophrenia SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIMH, CBDB, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S7 EP S7 DI 10.1097/00008877-200509001-00021 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300021 ER PT J AU Manji, HK AF Manji, HK TI Impairments of cellular plasticity and resilience in severe mood disorders: Therapeutic implications SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIMH, Mol Pathophysiol 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S5 EP S5 DI 10.1097/00008877-200509001-00014 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300014 ER PT J AU Preston, KL Schmittner, J Epstein, DH AF Preston, KL Schmittner, J Epstein, DH TI Comparison of two schedules of lottery-based abstinence reinforcement in polydrug users in methadone maintenance therapy SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 Natl Inst Drug Abuse, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, Baltimore, MD 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S63 EP S63 DI 10.1097/00008877-200509001-00198 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300195 ER PT J AU Shaham, Y AF Shaham, Y TI Stress and relapse to drug-taking behavior: An update SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society CY SEP 09-12, 2005 CL Barcelona, SPAIN SP European Behav Pharmacol Soc C1 NIDA, NIH, Baltimore, MD USA. EM yshaham@intra.nida.nih.gov 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 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2005 VL 16 SU 1 BP S17 EP S17 DI 10.1097/00008877-200509001-00053 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 974PG UT WOS:000232603300051 ER PT J AU Koonin, EV AF Koonin, EV TI Paralogs and mutational robustness linked through transcriptional reprogramming SO BIOESSAYS LA English DT Article ID HIGHLY EXPRESSED GENES; EVOLUTIONARY RATE; SELECTION; PROTEINS AB A recent analysis of genome-wide expression patterns and regulatory motif content of paralogous yeast genes(l) strongly suggests that mutational robustness (backup) between paralogous genes is achieved via transcriptional reprogramming of one paralog to compensate for the loss or silencing of the other. BioEssays 27:865-868,2005. Published 2005 Wiley Periodicals, Inc. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM koonin@ncbi.nim.nih.gov NR 21 TC 8 Z9 9 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD SEP PY 2005 VL 27 IS 9 BP 865 EP 868 DI 10.1002/bies.20296 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 960OV UT WOS:000231603900001 PM 16108060 ER PT J AU Hart, S Fischer, OM Prenzel, N Zwick-Wallasch, E Schneider, M Hennighausen, L Ullrich, A AF Hart, S Fischer, OM Prenzel, N Zwick-Wallasch, E Schneider, M Hennighausen, L Ullrich, A TI GPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways SO BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT Annual Fall Meeting of the German-Society-for-Biochemistry-and-Molecular-Biology CY SEP, 2005 CL Berlin, GERMANY SP German Soc Biochem & Mol Biol DE ADAM; breast cancer; cross-talk; HB-EGF; shedding; sphingosine kinase (SPHK) ID GROWTH-FACTOR-RECEPTOR; PROTEIN-COUPLED RECEPTOR; CANCER-CELLS; LYSOPHOSPHATIDIC ACID; PLASMINOGEN-ACTIVATOR; KINASE ACTIVATION; OVARIAN-CANCER; HB-EGF; PROLIFERATION; INVASION AB The epidermal growth factor receptor (EGFR) plays a key role in the regulation of important cellular processes under normal and pathophysiological conditions such as cancer. In human mammary carcinomas the EGFR is involved in regulating cell growth, survival, migration and metastasis and its activation correlates with the lack of response in hormone therapy. Here, we demonstrate in oestrogen receptor-positive and -negative human breast cancer cells and primary mammary epithelial cells a cross-communication between G protein-coupled receptors (GPCRs) and the EGFR. We present evidence that specific inhibition of ADAM15 or TACE blocks GPCR-induced and proHB-EGF-mediated EGFR tyrosine phosphorylation, downstream mitogenic signalling and cell migration. Notably, activation of the PI3K downstream mediator PKB/Akt by GPCR ligands involves the activity of sphingosine kinase (SPHK) and is independent of EGFR signal transactivation. We conclude that GPCR-induced chemotaxis of breast cancer cells is mediated by EGFR-dependent and -independent signalling pathways, with both parallel pathways having to act in concert to achieve a complete migratory response. C1 Max Planck Inst Biochem, Dept Mol Biol, D-82152 Martinsried, Germany. U3 Pharma AG, D-82152 Martinsried, Germany. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Ullrich, A (reprint author), Max Planck Inst Biochem, Dept Mol Biol, Klopferspitz 18A, D-82152 Martinsried, Germany. EM ullrich@biochem.mpg.de NR 49 TC 66 Z9 69 U1 0 U2 5 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD SEP PY 2005 VL 386 IS 9 BP 845 EP 855 DI 10.1515/BC.2005.099 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969ZD UT WOS:000232274100003 PM 16164409 ER PT J AU Al Sarraj, J Vinson, C Thiel, G AF Al Sarraj, J Vinson, C Thiel, G TI Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP SO BIOLOGICAL CHEMISTRY LA English DT Article DE amino acid deprivation; asparagine synthetase; ATF4; ATF5; CHOP; CREB2 ID DOMINANT-NEGATIVE INHIBITOR; AMINO-ACID DEPRIVATION; BINDING PROTEIN CREB; ACTIVATING TRANSCRIPTION; EXPRESSION; IDENTIFICATION; INDUCTION; PROMOTER; MEDIATOR; CELLS AB Asparagine synthetase catalyses the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. In human hepatoma cells cultured in medium containing amino acids, the mRNA of asparagine synthetase is not detectable by RNase protection mapping. However, maintaining the cells in amino acid-free Krebs-Ringer bicarbonate buffer strongly upregulated asparagine synthetase biosynthesis. The effect of amino acid deprivation on asparagine synthetase gene transcription is mediated by a genetic element termed the nutrient-sensing response unit. Previous studies revealed that the basic region leucine zipper (bZIP) transcription factor CREB2/ATF4 is involved in the nutrient deprivation-induced upregulation of asparagine synthetase gene transcription. Here we show that overexpression of the bZIP protein ATF5, a transcriptional activator, stimulates asparagine synthetase promoter/reporter gene transcription via the nutrient-sensing response unit. In contrast, ATF5 does not transactivate cAMP response element (CRE)-containing reporter genes. Overexpression of the C/EBP homologous transcription factor CHOP impaired transcriptional activation of the asparagine synthetase promoter following amino acid deprivation or overexpression of ATF5 or CREB2/ATF4. These data indicate that CHOP functions as a shut-off-device for nutrient deprivation-induced gene transcription. C1 Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Thiel, G (reprint author), Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. EM gerald.thiel@uniklinik-saarland.de NR 24 TC 32 Z9 32 U1 0 U2 3 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD SEP PY 2005 VL 386 IS 9 BP 873 EP 879 DI 10.1515/BC.2005.102 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969ZD UT WOS:000232274100006 PM 16164412 ER PT J AU Holt, DJ Bachus, SE Hyde, TM Wittie, M Herman, MM Vangel, M Saper, CB Kleinman, JE AF Holt, DJ Bachus, SE Hyde, TM Wittie, M Herman, MM Vangel, M Saper, CB Kleinman, JE TI Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: An in situ hybridization study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE basal ganglia; cholinergic; in situ hybridization; postmortem; schizophrenia; striatum ID GLUTAMIC-ACID DECARBOXYLASE; MESSENGER-RNA LEVELS; ANTIPSYCHOTIC-DRUGS; ALZHEIMERS-DISEASE; GENE-EXPRESSION; ANTICHOLINERGIC MEDICATION; INSITU HYBRIDIZATION; TYROSINE-HYDROXYLASE; NICOTINIC RECEPTORS; CAUDATE-PUTAMEN AB Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and beta-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and beta-actin mRNA expression levels were measured. Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of beta-actin mRNA expression throughout the striation, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia. C1 Massachusetts Gen Hosp E, Dept Psychiat, Charlestown, MA 02129 USA. NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Brookline, MA USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 149 13th St,Room 2625, Charlestown, MA 02129 USA. EM dholt@partners.org NR 63 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2005 VL 58 IS 5 BP 408 EP 416 DI 10.1016/j.biopsych.2005.04.007 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 959YD UT WOS:000231554600008 PM 16023618 ER PT J AU Rosenberg, PS Alter, BP Socie, G Gluckman, E AF Rosenberg, PS Alter, BP Socie, G Gluckman, E TI Secular trends in outcomes for Fanconi anemia patients who receive transplants: Implications for future studies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Fanconi anemia; stem cell transplant; risk assessment; study design; statistics; numerical data ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; LOW-DOSE CYCLOPHOSPHAMIDE; VERSUS-HOST-DISEASE; APLASTIC-ANEMIA; DONORS; CANCER; BLOOD; RISK; IRRADIATION AB Transplantation protocols for patients with Fanconi anemia are being modified continuously. However, it is unclear how outcomes have changed over time. We determined historical adverse event rates from long-term follow-up of 117 Fanconi anemia patients in the Hopital Saint Louis transplant cohort, who received low-dose cyclophosphamide- and irradiation-based conditioning, in combination with other modalities, between 1976 and October 2002. In high-risk patients with mismatched donors, the peritransplantation mortality rate during 0 to 6 months declined significantly over time (P =.003), from 28%/month (95% confidence interval [CI], 9%-87%/month) during 1985 to 1989 to 3.3%/month (95% CI, 0.8%-13.3%/month) during 2000 to October 2002. The corresponding proportion of patients who developed severe acute graft-versus-host disease also declined significantly over time (P =.003). In low-risk patients with matched sibling donors, the peritransplantation mortality rate was consistently low, 1.4%/month (95% CI, 0.3 %-5.3%/month), during 1990 to October 2002. Sample sizes to detect 2-fold reductions from rates and risks observed since the mid-1990s are larger than recently reported case series. To demonstrate further advances in survival, transplant centers may need to coordinate their protocols and engage in multicenter collaborative studies. (c) 2005 American Society for Blood and Marrow Transplantation. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Hop St Louis, Serv Hematol Greffe Moelle, Paris, France. RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,Execut Blvd,Execut Plaza S,Room, Rockville, MD 20852 USA. EM rosenbep@mail.nih.gov NR 19 TC 17 Z9 17 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2005 VL 11 IS 9 BP 672 EP 679 DI 10.1016/j.bbmt.2005.05.007 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 965GQ UT WOS:000231939000003 PM 16125637 ER PT J AU Li, WJ Tuli, R Huang, XX Laquerriere, P Tuan, RS AF Li, WJ Tuli, R Huang, XX Laquerriere, P Tuan, RS TI Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold SO BIOMATERIALS LA English DT Article DE electrospinning; nanofiber; mesenchymal stem cell; adipogenesis; chondrogenesis; osteogenesis ID IN-VITRO; PROGENITOR CELLS; HUMAN MARROW; CHONDROGENIC DIFFERENTIATION; BONE; TISSUE; CARTILAGE; THERAPY; CULTURE; MUSCLE AB Functional engineering of musculoskeletal tissues generally involves the use of differentiated or progenitor cells seeded with specific growth factors in biomaterial scaffolds. Ideally, the scaffold should be a functional and structural biomimetic of the native extracellular matrix and support multiple tissue morphogenesis. We have previously shown that electrospun, three-dimensional nanofibrous scaffolds that morphologically resemble collagen fibrils are capable of promoting favorable biological responses from seeded cells, indicative of their potential application for tissue engineering. In this study, we tested a three-dimensional nanofibrous scaffold fabricated from poly(e.-caprolactone) (PCL) for its ability to support and maintain multilineage differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in vitro. hMSCs were seeded onto pre-fabricated nanofibrous scaffolds, and were induced to differentiate along adipogenic, chondrogenic, or osteogenic lineages by culturing in specific differentiation media. Histological and scanning electron microscopy observations, gene expression analysis, and immunohistochemical detection of lineage-specific marker molecules confirmed the formation of three-dimensional constructs containing cells differentiated into the specified cell types. These results suggest that the PCL-based nanofibrous scaffold is a promising candidate scaffold for cell-based, multiphasic tissue engineering. Published by Elsevier Ltd. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Res Serv, Dept Hlth & Human Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Cell & Tissue Engn Grad Program, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1503,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov RI Li, Wan-Ju/A-7002-2008; Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 FU NIAMS NIH HHS [Z01 AR 41113] NR 38 TC 406 Z9 430 U1 16 U2 134 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2005 VL 26 IS 25 BP 5158 EP 5166 DI 10.1016/j.biomaterials.2005.01.002 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 920OK UT WOS:000228699800009 PM 15792543 ER PT J AU Huang, L Chen, MH Ibrahim, JG AF Huang, L Chen, MH Ibrahim, JG TI Bayesian analysis for generalized linear models with nonignorably missing covariates SO BIOMETRICS LA English DT Article DE data augmentation; logistic regression; missing data mechanism; nonignorable missing data; Poisson regression; prior distribution; probit regression ID POSTERIOR DISTRIBUTION; REGRESSION-MODELS; PROPRIETY AB We propose Bayesian methods for estimating parameters in generalized linear models (GLMs) with nonignorably missing covariate data. We show that when improper uniform priors are used for the regression coefficients, phi, of the multinomial selection model for the missing data mechanism, the resulting joint posterior will always be improper if (i) all missing covariates are discrete and an intercept is included in the selection model for the missing data mechanism, or (ii) at least one of the covariates is continuous and unbounded. This impropriety will result regardless of whether proper or improper priors are specified for the regression parameters,beta, of the GLM or the parameters, alpha, of the covariate distribution. To overcome this problem, we propose a novel class of proper priors for the regression coefficients, phi, in the selection model for the missing data mechanism. These priors are robust and computationally attractive in the sense that inferences about beta are not sensitive to the choice of the hyperparameters of the prior for phi and they facilitate a Gibbs sampling scheme that leads to accelerated convergence. In addition, we extend the model assessment criterion of Chen, Dey, and Ibrahim (2004a, Biometrika 91, 45-63), called the weighted L measure, to GLMs and missing data problems as well as extend the deviance information criterion (DIC) of Spiegelhalter et al. (2002, Journal of the Royal Statistical Society B 64, 583-639) for assessing whether the missing data mechanism is ignorable or nonignorable. A novel Markov chain Monte Carlo sampling algorithm is also developed for carrying out posterior computation. Several simulations are given to investigate the performance of the proposed Bayesian criteria as well as the sensitivity of the prior specification. Real datasets from a melanoma cancer clinical trial and a liver cancer study are presented to further illustrate the proposed methods. C1 NCI, SRAB, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Chen, MH (reprint author), NCI, SRAB, Div Canc Control & Populat Sci, 6116 Execut Blvd, Rockville, MD 20852 USA. EM mhchen@stat.uconn.edu FU NCI NIH HHS [CA 70101, CA 74015] NR 21 TC 21 Z9 21 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2005 VL 61 IS 3 BP 767 EP 780 DI 10.1111/j.1541-0420.2005.00338.x PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 961VM UT WOS:000231689900013 PM 16135028 ER PT J AU Graubard, BI Fears, TR AF Graubard, BI Fears, TR TI Standard errors for attributable risk for simple and complex sample designs SO BIOMETRICS LA English DT Article DE attributable risk; influence function; population attributable fraction; survey sampling; Taylor deviate ID LOGISTIC-MODELS; INFERENCE; ESTIMATORS AB Adjusted attributable risk (AR) is the proportion of diseased individuals in a population that is due to an exposure. We consider estimates of adjusted AR based on odds ratios from logistic regression to adjust for confounding. Influence function methods used in survey sampling are applied to obtain simple and easily programmable expressions for estimating the variance of AR. These variance estimators can be applied to data from case-control, cross-sectional, and cohort studies with or without frequency or individual matching and for sample designs with subject samples that range from simple random samples to (sample) weighted multistage stratified cluster samples like those used in national household surveys. The variance estimation of AR is illustrated with: (i) a weighted stratified multistage clustered cross-sectional study of childhood asthma from the Third National Health and Examination Survey (NHANES III), and (ii) a frequency-matched case-control study of melanoma skin cancer. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, 6120 Execut Blvd,Room 8024, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov NR 33 TC 40 Z9 40 U1 2 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2005 VL 61 IS 3 BP 847 EP 855 DI 10.1111/j.1541-0420.2005.00355.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 961VM UT WOS:000231689900022 PM 16135037 ER PT J AU Chen, Z Dunson, DB AF Chen, Z Dunson, DB TI Comments about joint modeling of cluster size and binary and continuous subunit-specific outcomes - Reply SO BIOMETRICS LA English DT Editorial Material C1 Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19401 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Chen, Z (reprint author), Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19401 USA. EM dunson1@niehs.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2005 VL 61 IS 3 BP 866 EP 867 DI 10.1111/j.1541-020X.2005.00409_2.x PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 961VM UT WOS:000231689900026 ER PT J AU Albert, PS AF Albert, PS TI Untitled SO BIOMETRICS LA English DT Letter ID CLUSTERED DATA C1 NCI, Div Canc Treatment & Diagnost, Biometr Res Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Div Canc Treatment & Diagnost, Biometr Res Branch, Bethesda, MD 20892 USA. EM Albertp@ctep.nci.nih.gov NR 4 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2005 VL 61 IS 3 BP 879 EP 880 DI 10.1111/j.1541-020X.2005.000415_1.x PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 961VM UT WOS:000231689900030 PM 16135045 ER PT J AU Peddada, SD Dunson, DB Tan, XF AF Peddada, SD Dunson, DB Tan, XF TI Estimation of order-restricted means from correlated data SO BIOMETRIKA LA English DT Article DE correlated data; linked parameters; maximally linked subgraph; Nodal parameter; order restriction; umbrella order ID ISOTONIC REGRESSION; QUADRATIC LOSS; MODELS; INFERENCE; SUBJECT AB In many applications, researchers are interested in estimating the mean of a multivariate normal random vector whose components are subject to order restrictions. Various authors have demonstrated that the likelihood-based methodology may perform poorly under certain conditions for such problems. The problem is much harder when the underlying covariance matrix is nondiagonal. In this paper a simple iterative algorithm is introduced that can be used for estimating the mean of a multivariate normal population when the components are subject to any order restriction. The proposed methodology is illustrated through an application to human reproductive hormone data. C1 NIEHS, Res Triangle Pk, NC 27709 USA. China Life Insurance Co Ltd, Beijing 100020, Peoples R China. RP Peddada, SD (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov; dunson1@niehs.nih.gov; xftan@hotmail.com RI Peddada, Shyamal/D-1278-2012 NR 18 TC 5 Z9 5 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 2005 VL 92 IS 3 BP 703 EP 715 DI 10.1093/biomet/92.3.703 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 959NL UT WOS:000231524600015 ER PT J AU Chahine, NO Chen, FH Hung, CT Ateshian, GA AF Chahine, NO Chen, FH Hung, CT Ateshian, GA TI Direct measurement of osmotic pressure of glycosaminoglycan solutions by membrane osmometry at room temperature SO BIOPHYSICAL JOURNAL LA English DT Article ID ARTICULAR-CARTILAGE; SWELLING PRESSURE; PROTEOGLYCANS; SULFATE; MODULUS; TISSUES; FORCES; MODEL AB Articular cartilage is a hydrated soft tissue composed of negatively charged proteoglycans fixed within a collagen matrix. This charge gradient causes the tissue to imbibe water and swell, creating a net osmotic pressure that enhances the tissue's ability to bear load. In this study we designed and utilized an apparatus for directly measuring the osmotic pressure of chondroitin sulfate, the primary glycosaminoglycan found in articular cartilage, in solution with varying bathing ionic strength ( 0.015 M, 0.15 M, 0.5 M, 1 M, and 2 M NaCl) at room temperature. The osmotic pressure ( p) was found to increase nonlinearly with increasing chondroitin sulfate concentration and decreasing NaCl ionic bath environment. Above 1 M NaCl, pi changes negligibly with further increases in salt concentration, suggesting that Donnan osmotic pressure is negligible above this threshold, and the resulting pressure is attributed to configurational entropy. Results of the current study were also used to estimate the contribution of osmotic pressure to the stiffness of cartilage based on theoretical and experimental considerations. Our findings indicate that the osmotic pressure resulting from configurational entropy is much smaller in cartilage ( based on an earlier study on bovine articular cartilage) than in free solution. The rate of change of osmotic pressure with compressive strain is found to contribute approximately one-third of the compressive modulus (H-A(eff)) of cartilage (Pi similar to H-A(eff)/3), with the balance contributed by the intrinsic structural modulus of the solid matrix ( i.e., H-A similar to 2H(A)(eff)/3). A strong dependence of this intrinsic modulus on salt concentration was found; therefore, it appears that proteoglycans contribute structurally to the magnitude of H-A; in a manner independent of osmotic pressure. C1 Columbia Univ, Dept Mech Engn, Musculoskeletal Biomech Lab, New York, NY 10027 USA. Columbia Univ, Dept Biomed Engn, Cellular Engn Lab, New York, NY 10027 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Ateshian, GA (reprint author), Columbia Univ, Dept Mech Engn, Musculoskeletal Biomech Lab, SW Mudd,500 W 120th St,Mail Code 4703, New York, NY 10027 USA. EM ateshian@columbia.edu RI Chahine, Nadeen/O-5496-2015; OI Chahine, Nadeen/0000-0002-0478-6042 FU NIAMS NIH HHS [AR46532, R01 AR046532-06, R01 AR046532] NR 26 TC 50 Z9 52 U1 4 U2 22 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2005 VL 89 IS 3 BP 1543 EP 1550 DI 10.1529/biophysj.104.057315 PG 8 WC Biophysics SC Biophysics GA 959FL UT WOS:000231502800012 PM 15980166 ER PT J AU Niu, SL Mitchell, DC AF Niu, SL Mitchell, DC TI Effect of packing density on rhodopsin stability and function in polyunsaturated membranes SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-COUPLED RECEPTOR; SEGMENT DISK MEMBRANES; FATTY-ACID DEFICIENCY; HIGHER-ORDER ANALYSIS; SPIN-LABEL; RECOMBINANT MEMBRANES; LATERAL DIFFUSION; METARHODOPSIN-II; BOVINE RHODOPSIN; ANISOTROPY DECAY AB Rod outer segment disk membranes are densely packed with rhodopsin. The recent notion of raft or microdomain structures in disk membranes suggests that the local density of rhodopsin in disk membranes could be much higher than the average density corresponding to the lipid/protein ratio. Little is known about the effect of high packing density of rhodopsin on the structure and function of rhodopsin and lipid membranes. Here we examined the role of rhodopsin packing density on membrane dynamic properties, membrane acyl chain packing, and the structural stability and function of rhodopsin using a combination of biophysical and biochemical techniques. We reconstituted rhodopsin into large unilamellar vesicles consisting of polyunsaturated 18: 0,22: 6n3PC, which approximates the polyunsaturated nature of phospholipids in disk membranes, with rhodopsin/lipid ratios ranging from 1: 422 to 1: 40. Our results showed that increased rhodopsin packing density led to reduced membrane dynamics revealed by the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene, increased phospholipid acyl chain packing, and reduced rhodopsin activation, yet it had minimal impact on the structural stability of rhodopsin. These observations imply that densely packed rhodopsin may impede the diffusion and conformational changes of rhodopsin, which could reduce the speed of visual transduction. C1 NIAAA, Clin Studies Lab, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys,NIH, Bethesda, MD 20892 USA. RP Niu, SL (reprint author), NIAAA, Clin Studies Lab, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys,NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA. EM sniu@niaaa.nih.gov FU NIAAA NIH HHS [Z01 AA000080-12] NR 56 TC 22 Z9 22 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2005 VL 89 IS 3 BP 1833 EP 1840 DI 10.1529/biophysj.105.061812 PG 8 WC Biophysics SC Biophysics GA 959FL UT WOS:000231502800039 PM 15980173 ER PT J AU Yang, J Rau, DC AF Yang, J Rau, DC TI Incomplete ion dissociation underlies the weakened attraction between DNA helices at high spermidine concentrations SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY-DIFFRACTION; HYDRATION FORCES; INTERMOLECULAR FORCES; CONDENSATION; POLYAMINES; DELIVERY; POLYELECTROLYTES; PRECIPITATION; AGGREGATION; MESOPHASES AB We have investigated the salt sensitivity of the hexagonal-to-cholesteric phase transition of spermidine-condensed DNA. This transition precedes the resolubilization of precipitated DNA that occurs at high spermidine concentration. The sensitivity of the critical spermidine concentration at the transition point to the anion species and the NaCl concentration indicates that ion pairing of this trivalent ion underlies this unusual transition. Osmotic pressure measurements of spermidine salt solutions are consistent with this interpretation. Spermidine salts are not fully dissociated at higher concentrations. The competition for DNA binding among the fully charged trivalent ion and the lesser charged complex species at higher concentrations significantly weakens attraction between DNA helices in the condensed state. This is contrary to the suggestion that the binding of spermidine at higher concentrations causes DNA overcharging and consequent electrostatic repulsion. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Vermont, Dept Phys, Burlington, VT 05405 USA. RP Rau, DC (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1E114, Bethesda, MD 20892 USA. EM raud@mail.nih.gov NR 46 TC 41 Z9 42 U1 1 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2005 VL 89 IS 3 BP 1932 EP 1940 DI 10.1529/biophysj.105.065060 PG 9 WC Biophysics SC Biophysics GA 959FL UT WOS:000231502800049 PM 15980178 ER PT J AU Powell, BS Andrews, GP Enama, JT Jendrek, S Bolt, C Worsham, P Pullen, JK Ribot, W Hines, H Smith, L Heath, DG Adamovicz, JJ AF Powell, BS Andrews, GP Enama, JT Jendrek, S Bolt, C Worsham, P Pullen, JK Ribot, W Hines, H Smith, L Heath, DG Adamovicz, JJ TI Design and testing for a nontagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague SO BIOTECHNOLOGY PROGRESS LA English DT Article ID YERSINIA OUTER PROTEINS; COLI INCLUSION-BODIES; V-ANTIGEN; SUBUNIT VACCINE; TRANSFERABLE PLASMID; RECOMBINANT PROTEINS; PESTIS; PURIFICATION; PROTECTION; MICE AB A two-component recombinant fusion protein antigen was re-engineered and tested as a medical counter measure against the possible biological threat of aerosolized Yersinia pestis. The active component of the proposed subunit vaccine combines the F1 capsular protein and V virulence antigen of Y. pestis and improves upon the design of an earlier histidine-tagged fusion protein. In the current study, different production strains were screened for suitable expression and a purification process was optimized to isolate an F1-V fusion protein absent extraneous coding sequences. Soluble F1-V protein was isolated to 99% purity by sequential liquid chromatography including capture and refolding of urea-denatured protein via anion exchange, followed by hydrophobic interaction, concentration, and then transfer into buffered saline for direct use after frozen storage. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing, confirming a purified product of 477 amino acids and removal of the N-terminal methionine. Purity, quality, and higher-order structure were compared between lots using RP-HPLC, intrinsic fluorescence, CD spectroscopy, and multi-angle light scattering spectroscopy, all of which indicated a consistent and properly folded product. As formulated with aluminum hydroxide adjuvant and administered in a single subcutaneous dose, this new F1-V protein also protected mice from wild-type and non-encapsulated Y. pestis challenge strains, modeling prophylaxis against pneumonic and bubonic plague. These findings confirm that the fusion protein architecture provides superior protection over the former licensed product, establish a foundation from which to create a robust production process, and set forth assays for the development of F1-V as the active pharmaceutical ingredient of the next plague vaccine. C1 USA, Med Res Inst Infect Dis, Div Bacteriol, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Toxinol, Ft Detrick, MD 21702 USA. NCI, Biopharmaceut Dev Program, SAIC Frederick, Frederick, MD 21702 USA. NIAID, Vaccine & Prevent Res Program, Div AIDS, NIH,DHHS, Bethesda, MD 20892 USA. Univ Wyoming, Dept Vet Sci, Laramie, WY 82070 USA. RP Powell, BS (reprint author), USA, Med Res Inst Infect Dis, Div Bacteriol, Ft Detrick, MD 21702 USA. EM bradford.powell@amedd.army.mil NR 59 TC 68 Z9 75 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD SEP-OCT PY 2005 VL 21 IS 5 BP 1490 EP 1510 DI 10.1021/bp050098r PG 21 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 972NU UT WOS:000232461300018 PM 16209555 ER PT J AU Mahoney, SF Malcoe, LH AF Mahoney, SF Malcoe, LH TI Cesarean delivery in native American women: Are low rates explained by practices common to the Indian health service? SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article ID MIDWIFERY CARE; MATERNAL AGE; SECTION; RISK; OUTCOMES AB Background: Studying populations with low cesarean delivery rates can identify strategies for reducing unnecessary cesareans in other patient populations. Native American women have among the lowest cesarean delivery rates of all United States populations, yet few studies have focused on Native Americans. The study purpose was to determine the rate and risk factors for cesarean delivery in a Native American population. Methods: We used a case-control design nested within a cohort of Native American live births, >= 35 weeks of gestation (n = 789), occurring at an Indian Health Service hospital during 1996-1999. Data were abstracted from the labor and delivery logbook, the hospital's primary source of birth certificate data. Univariate and multivariate analyses examined demographic, prenatal, obstetric, intrapartum, and fetal factors associated with cesarean versus vaginal delivery. Results: The total cesarean rate was 9.6 percent (95% CI 7.2-12.0). Nulliparity, a medical diagnosis, malpresentation, induction, labor length > 12.1 hours, arrested labor, fetal distress, meconium, and gestations < 37 weeks were each significantly associated with cesarean delivery in unadjusted analyses. The final multivariate model included a significant interaction between induction and arrested labor (p < 0.001); the effect of arrested labor was far greater among induced (OR 161.9) than noninduced (OR 6.0) labors. Other factors significantly associated with cesarean delivery in the final logistic model were an obstetrician labor attendant (OR 2.4; p = 0.02) and presence of meconium (OR 2.3; p = 0.03). Conclusions: Despite a higher prevalence of medical risk factors for cesarean delivery, the rate at this hospital was well below New Mexico (16.4%, all races) and national (21.2%, all races) cesarean rates for 1998. Medical and practice-related factors were the only observed independent correlates of cesarean delivery. Implementation of institutional and practitioner policies common to the Indian Health Service may reduce cesarean deliveries in other populations. C1 Univ New Mexico, Sch Med, Dept Family & Community Med, Albuquerque, NM 87131 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Malcoe, LH (reprint author), Univ New Mexico, Masters Publ Hlth Program, MSC09 5060,1, Albuquerque, NM 87131 USA. NR 35 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD SEP PY 2005 VL 32 IS 3 BP 170 EP 178 DI 10.1111/j.0730-7659.2005.00366.x PG 9 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 963LG UT WOS:000231805200003 PM 16128970 ER PT J AU Pontari, MA McNaughton-Collins, M O'Leary, MP Calhoun, EA Jang, T Kusek, JW Landis, JR Knauss, J Litwin, MS AF Pontari, MA McNaughton-Collins, M O'Leary, MP Calhoun, EA Jang, T Kusek, JW Landis, JR Knauss, J Litwin, MS CA CPCRN Study Grp TI A case-control study of risk factors in men with chronic pelvic pain syndrome SO BJU INTERNATIONAL LA English DT Article DE chronic prostatitis; pelvic pain; urethritis; hypertension ID CHRONIC PROSTATITIS; INTERSTITIAL CYSTITIS; PREVALENCE; COHORT AB Objective To compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome. Patients and Methods Self-administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic age-matched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel-Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods. Results Compared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001). Conclusion A wide range of self-reported medical conditions was associated with CP/CPPS. Further studies are necessary to determine whether they play a role in the pathogenesis of CP/CPPS. C1 Temple Univ, Sch Med, Philadelphia, PA 19140 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Northwestern Univ, Chicago, IL 60611 USA. NIDDKD, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Pontari, MA (reprint author), Temple Univ, Sch Med, 3401 N Broad St,Suite 350 Parkinson Pavil, Philadelphia, PA 19140 USA. EM Pontarm@tuhs.temple.edu RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK53730, U01 DK53572, U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53738, U01 DK53746] NR 19 TC 48 Z9 53 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2005 VL 96 IS 4 BP 559 EP 565 DI 10.1111/j.1464-410X.2005.05684.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 957QK UT WOS:000231387900021 PM 16104910 ER PT J AU Miller, JL AF Miller, JL TI Erythroid Bcl-xL: better late than never SO BLOOD LA English DT Editorial Material AB In this issue of Blood, Rhodes and colleagues propose that the major effect of Bcl-xL deficiency is ineffective erythropoiesis during the late stages of differentiation. C1 NIDDK, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDK, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1515 EP 1516 DI 10.1182/blood-2005-06-2329 PG 2 WC Hematology SC Hematology GA 959CR UT WOS:000231495000008 ER PT J AU Leitman, SF AF Leitman, SF TI Progenitor cell mobilization gets a boost from CXCR4 inhibition SO BLOOD LA English DT Editorial Material ID RECEPTOR; AMD3100 AB Addition of AMD3 100, a selective CXCR4 antagonist, to a standard G-CSF-based progenitor cell mobilization regimen increases the number of CD34(+) cells collected by apheresis, allowing patients with poor hematopoietic reserve to donate a sufficient number of cells for autologous transplantation. C1 NIH, Bethesda, MD 20892 USA. RP Leitman, SF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1516 EP 1517 DI 10.1182/blood-2005-06-2523 PG 2 WC Hematology SC Hematology GA 959CR UT WOS:000231495000009 ER PT J AU Roesler, J Izquierdo, JM Ryser, M Rosen-Wolff, A Gahr, M Valcarcel, J Lenardo, MJ Zheng, LX AF Roesler, J Izquierdo, JM Ryser, M Rosen-Wolff, A Gahr, M Valcarcel, J Lenardo, MJ Zheng, LX TI Haploinsufficiency, rather than the effect of an excessive production of soluble CD95 (CD95 Delta TM), is the basis for ALPS Ia in a family with duplicated 3 ' splice site AG in CD95 intron 5 on one allele SO BLOOD LA English DT Article ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; FAS GENE-MUTATIONS; CHRONIC GRANULOMATOUS-DISEASE; PROGRAMMED CELL-DEATH; LYMPHOCYTE APOPTOSIS; DEFECTIVE LYMPHOCYTE; EXPRESSION; LEUKEMIA; DEFICIENCY; ACTIVATION AB Autoimmune lymphoproliferative syndrome type la (ALPS la) is caused by mutations in the CD95/APO1/\FAS (TNFRSF6) gene, which lead to a defective CD95 ligand (CD95L)-induced apoptosis. Soluble CD95 (sCD95) has been suggested to play an important role in the pathogenesis of diverse autoimmune and malignant diseases by antagonizing CD95L. Here we evaluate a family with 4 of its 5 members harboring an ex-6-3C-->G mutation that affects the splice cis regulatory region (cctacag/ex-6-->cctagag/ ex-6) of the CD95 gene. The mutation causes skipping of exon-6, which encodes the transmembrane region of CD95, and thereby leads to an excessive production of sCD95 in all 4 affected individuals. The mutation is associated with a low penetrance of disease phenotype and caused mild and transient ALPS in one male patient whereas all other family members are completely healthy. In all family members with the mutation we found that the cell surface expression of CD95 was low and the activated T cells were resistant to CD95-induced apoptosis. Unexpectedly, excessive production or addition of sCD95 had no effect on the CD95-induced apoptosis in diverse cells. In contrast, increasing the surface expression of CD95 was able to correct the defect in apoptosis. Thus we conclude that the ALPS in the one male patient was caused by haploinsufficiency of membrane CD95 expression. Our data challenge the hypothesis that sCD95 causes autoimmunity. C1 Univ Clin Carl Gustav Carus, Dept Pediat, D-01307 Dresden, Germany. Ctr Regulacio Genom, Barcelona, Spain. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Roesler, J (reprint author), Univ Clin Carl Gustav Carus, Dept Pediat, Fetscherstr 74, D-01307 Dresden, Germany. EM roeslerj@res.urz.tu-dresden.de NR 43 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1652 EP 1659 DI 10.1182/blood-2004-08-3104 PG 8 WC Hematology SC Hematology GA 959CR UT WOS:000231495000029 PM 15870181 ER PT J AU Mavilio, D Benjamin, J Kim, D Lombardo, G Daucher, M Kinter, A Nies-Kraske, E Marcenaro, E Moretta, A Fauci, AS AF Mavilio, D Benjamin, J Kim, D Lombardo, G Daucher, M Kinter, A Nies-Kraske, E Marcenaro, E Moretta, A Fauci, AS TI Identification of NKG2A and NKp80 as specific natural killer cell markers in rhesus and pigtailed monkeys SO BLOOD LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; IG-LIKE RECEPTORS; NK CELLS; ACTIVATING RECEPTORS; MACACA-FASCICULARIS; DENDRITIC CELLS; MACAQUES; EXPRESSION; INFECTION; MOLECULES AB Investigations of natural killer (NK) cells in simian models of disease have been hampered by a lack of appropriate phenotypic markers and by an inadequate understanding of the regulation of NK cell activities. In the present study, a panel of monoclonal antibodies (mAbs) specific for various human NK receptors was screened for cross-reactivity with NK cells from rhesus macaques and pigtailed macaques. Flow cytometric analyses using anti-human NKG2A and anti-human NKp80 mAbs individually, and particularly in combination with anti-CD16 mAb, allowed for the identification of the entire NK cell population in both species. NK cells in monkeys were generally identified by negative selection of peripheral blood mononuclear cells (PBMCs) for the absence of T-cell, B-cell, and monocyte markers. mAb-mediated ligation of NKp8O induced NK cell cytotoxicity, while in the case of NKG2A it displayed a clear capability to inhibit the lysis of target cells by NK cells from macaques, as well as from humans. This new phenotypic and functional characterization of NKG2A and NKp80 in rhesus and pigtailed macaque NK cells provides a new approach in the analysis of their innate immune system. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20814 USA. Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy. Ctr Eccellenza Ric Biomed, Genoa, Italy. RP Mavilio, D (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6A08A,MSC 1576, Bethesda, MD 20814 USA. EM dmavilio@niaid.nih.gov OI Mavilio, Domenico/0000-0001-6147-0952 NR 41 TC 40 Z9 41 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1718 EP 1725 DI 10.1182/blood-2004-12-4762 PG 8 WC Hematology SC Hematology GA 959CR UT WOS:000231495000037 PM 15899917 ER PT J AU Haining, WN Neuberg, DS Keczkemethy, HL Evans, JW Rivoli, S Gelman, R Rosenblatt, HM Shearer, WT Guenaga, J Douek, DC Silverman, LB Sallan, SE Guinan, EC Nadler, LM AF Haining, WN Neuberg, DS Keczkemethy, HL Evans, JW Rivoli, S Gelman, R Rosenblatt, HM Shearer, WT Guenaga, J Douek, DC Silverman, LB Sallan, SE Guinan, EC Nadler, LM TI Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; KERATINOCYTE GROWTH-FACTOR; INTENSIVE CHEMOTHERAPY; IN-VIVO; VIRUS-INFECTION; RAPID TURNOVER; HIV-INFECTION; RECONSTITUTION; CD8(+); ADULTS AB Despite profound T-cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T-cell numbers, thymopoiesis, and T-cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T-cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in healthy controls. However, the remaining T-cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T-cell memory may, in part, account for the maintenance of protective immunity in lymphopenic Patients treated for ALL. Moreover, because the memory T-cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand preexisting memory T cells. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Texas Childrens Hosp, Houston, TX 77030 USA. NIH, Vaccine Res Ctr, Bethesda, MD USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NCI NIH HHS [P01CA68 484]; NHLBI NIH HHS [K08HL72 750] NR 46 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1749 EP 1754 DI 10.1182/blood-2005-03-1082 PG 6 WC Hematology SC Hematology GA 959CR UT WOS:000231495000041 PM 15920008 ER PT J AU Qiang, YW Walsh, K Yao, L Kedei, N Blumberg, PM Rubin, JS Shaughnessy, J Rudikoff, S AF Qiang, YW Walsh, K Yao, L Kedei, N Blumberg, PM Rubin, JS Shaughnessy, J Rudikoff, S TI Wnts induce migration and invasion of rnyeloma plasma cells SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; MULTIPLE-MYELOMA CELLS; RHO-ASSOCIATED KINASE; VERTEBRATE GASTRULATION; FRIZZLED HOMOLOGS; TUMOR-CELLS; GROWTH; ADHESION; BINDING; CYTOSKELETON AB Multiple myeloma is an incurable form of lymphoid cancer characterized by accumulation of neoplastic plasma cells in the bone marrow cavity. Little is known about the mechanisms regulating myeloma cell movement within the bone marrow and metastasis to secondary sites. Herein, we identify multiple members of the wingless/ int (Wnt) family as promoters of myeloma cell migration/invasion. Wnt-mediated migration was associated with the Wnt/ RhoA pathway and did not necessitate signaling through beta-catenin. Activation of both RhoA and members of the protein kinase C (PKC) family, including PKC alpha, PKC beta, and PKC mu, were required for induction of migration. Activated RhoA and PKC alpha, PKC beta, and PKC mu appear to assemble in macromolecular signaling complexes that are associated with the cell membrane. These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Rudikoff, S (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM rudikoff@helix.nih.gov NR 56 TC 88 Z9 96 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1786 EP 1793 DI 10.1182/blood-2005-01-0049 PG 8 WC Hematology SC Hematology GA 959CR UT WOS:000231495000046 PM 15886323 ER PT J AU Kelly, MH Brillante, B Kushner, H Robey, PG Collins, MT AF Kelly, MH Brillante, B Kushner, H Robey, PG Collins, MT TI Physical function is impaired but quality of life preserved in patients with fibrous dysplasia of bone SO BONE LA English DT Article DE McCune; Albright syndrome; G(s)-alpha; GNAS; outcomes; fibrous dysplasia; quality of life; SF36; CHQ-PF50 ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; DYSFUNCTION; MUTATIONS; GENE; HYPERTHYROIDISM; ABNORMALITIES; PIGMENTATION AB Fibrous dysplasia of bone (FD) is a congenital, non-heritable skeletal disorder that is associated with multiple skeletal complications, including repeated fractures, limb length discrepancy, and bone pain. The disease-specific impact of FD on quality of life outcomes is unknown. We sought to understand the impact of the scope and extent of the skeletal disease on quality of life in adults and children with FD. The health-related quality of life was quantified in a population of adults (n = 56) and children (n = 22) with FD using validated health assessment questionnaires, the Medical Outcomes Study 36 Item Short-Form Health Survey, volume 2 (SF36) (adults) and the Child Health Questionnaire Parent Form 50 (CHQ-PF50) (children). Clinical demographic data and skeletal disease burden scores (SDBS, amount of skeleton involved with FD) were measured, and correlations with health-related quality of life were sought. The SF36 and CHQ-PF50 revealed lower Physical Function Summary scores in FD patients compared to the U.S. population norms (adult 41 vs. 50, Z score < -5.0, pediatric 39 vs. 50, Z score < -5.0). However, the SF36 and CHQ-PF50 Mental/Psychological summary scores were not different from those of U.S. population norms (adult 50 vs. 50, Z score = 0, pediatric 48 vs. 50 Z score = -0.9). The score on the Physical Function Domain of both tools was strongly negatively associated with the SDBS (adult Spearman rho = -0.43, P = 0.009, pediatric Spearman rho = -0.72, P = 0.005). The groups of adult and pediatric patients with SDBS > 30 had decreased Physical Function Domain scores when compared to those with scores < 30 (adult 35 vs. 45, P = 0.002, pediatric 57 vs. 78, P = 0.04, respectively). One of the largest effects was seen in the parents of children with FD, who had significantly lower Parental Emotional scores than those of the parents of healthy nonris (54 vs. 88, Z score < -5.0), suggesting a high degree of emotional morbidity in the parents of children with FD. Despite measurable functional limitations in adults and children, and significant parental emotional impairment, patients with FD achieve a high level of social and emotional function. These data are important for prognosis and parental reassurance. Published by Elsevier Inc. C1 NIDCR, Craniofacial & Skeletal Dis Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. Biomed Comp Res Inst, Philadelphia, PA 19115 USA. RP Collins, MT (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, Dept Hlth & Human Serv, NIH, 30 Convent Dr,MSC-4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 25 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD SEP PY 2005 VL 37 IS 3 BP 388 EP 394 DI 10.1016/j.bone.2005.04.026 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 963CD UT WOS:000231779600011 PM 15963775 ER PT J AU Kruit, MC Launer, LJ Ferrari, MD van Buchem, MA AF Kruit, MC Launer, LJ Ferrari, MD van Buchem, MA TI Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study SO BRAIN LA English DT Article DE migraine; magnetic resonance imaging; brain infarction; posterior circulation; cerebellum ID CEREBRAL-BLOOD-FLOW; FAMILIAL HEMIPLEGIC MIGRAINE; DOMINANT CEREBELLAR-ATAXIA; VON-WILLEBRAND-FACTOR; VIRCHOW-ROBIN SPACES; CLINICAL-FEATURES; ISCHEMIC-STROKE; ARTERIAL TERRITORIES; RISK-FACTORS; HUMAN BRAIN AB In a previous study, migraine cases from the general population were found to be at significantly increased risk of silent infarct-like lesions in the posterior circulation (PC) territory of the brain, notably in the cerebellum. In this study we describe the clinical and neuroimaging characteristics of migraine cases with and without aura and controls with PC lesions. In total, 39 PC infarct-like lesions represented the majority (65%) of all 60 identified brain infarct-like lesions in the study sample (n = 435 subjects with and without migraine). Most lesions (n = 33) were located in the cerebellum, often multiple, and were round or oval-shaped, with a mean size of 7 mm. The majority (88%) of infratentorial infarct-like lesions had a vascular border zone location in the cerebellum. Prevalence of these border zone lesions differed between controls (0.7%), cases with migraine without aura (2.2%) and cases with migraine with aura (7.5%). Besides higher age, cardiovascular risk factors were not more prevalent in cases with migraine with PC lesions. Presence of these lesions was not associated with supratentorial brain changes, such as white matter lesions. The combination of vascular distribution, deep border zone location, shape, size and imaging characteristics on MRI makes it likely that the lesions have an infarct origin. Previous investigators attributed cases of similar 'very small' cerebellar infarcts in non-migraine patients to a number of different infarct mechanisms. The relevance and likelihood of the aetiological options are placed in the context of known migraine pathophysiology. In addition, the specific involvement of the cerebellum in migraine is discussed. The results suggest that a combination of (possibly migraine attack-related) hypoperfusion and embolism is the likeliest mechanism for PC infarction in migraine, and not atherosclerosis or small-vessel disease. C1 Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. Natl Inst Publ Hlth & Environm, Dept Chron Dis & Environm Epidemiol, NL-3720 BA Bilthoven, Netherlands. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Kruit, MC (reprint author), Leiden Univ, Med Ctr, Dept Radiol, POB 9600, NL-2300 RC Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X NR 57 TC 175 Z9 179 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2005 VL 128 BP 2068 EP 2077 DI 10.1093/brain/awh542 PN 9 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961XC UT WOS:000231694100012 PM 16006538 ER PT J AU Neubert, JK Mannes, AJ Keller, J Wexel, M Iadarola, MJ Caudle, RM AF Neubert, JK Mannes, AJ Keller, J Wexel, M Iadarola, MJ Caudle, RM TI Peripheral targeting of the trigeminal ganglion via the infraorbital foramen as a therapeutic strategy SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE trigeminal ganglion; electrical stimulation microinjection; analgesia; rat; infraorbital ID RECEPTOR; NERVE; RAT AB A unique interventional approach for modulating sensory signaling involves targeting neurons in the sensory ganglia through use of pharmacological or gene therapies. This has previously been accomplished in the trigeminal system via stereotactic ganglionic microinjections. However, this procedure can be time consuming and requires expensive stereotactic equipment. The current paper describes a percutaneous approach for injecting the trigeminal ganglion with an electrical-stimulation needle inserted through the infraorbital foramen, infraorbital canal and foramen rotundum. The needle tip was positioned in the ganglion by eliciting a twitch in the ipsilateral masseter following electrical stimulation. The technique was imaged using computerized tomography and methylene blue dye to verify the site of the injection. We validated this technique by reproducing the results from our prior study that involved injection of resiniferatoxin (RTX) into the trigeminal ganglion using the stereotactic approach. Both techniques for intraganglionic injection of RTX produced a specific deletion of C-fiber neurons, as demonstrated by inhibition of neurogenic-induced plasma extravasation and behavioral assays. Thus, we propose a novel and simple technique for studying mechanisms of peripheral sensory modulation of orofacial pain via direct application of drugs, tracers or viral vectors around trigeminal sensory neuronal cell bodies. This technique minimizes trauma to brain structures that may have an impact on pain perception. Published by Elsevier B.V. C1 Univ Florida, Coll Dent, Dept Orthodont, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32610 USA. Univ Florida, Coll Dent, Dept Oral Surg, Gainesville, FL 32610 USA. Univ Florida, Evelyn F & William McKnight Brain Inst, Gainesville, FL 32610 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Neubert, JK (reprint author), Univ Florida, Coll Dent, Dept Orthodont, 1600 SW Archer Rd,POB 100444, Gainesville, FL 32610 USA. EM jneubert@dental.ufl.edu OI Mannes, Andrew/0000-0001-5834-5667 FU NIDCR NIH HHS [1K22DE014865-01A1] NR 9 TC 20 Z9 21 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD SEP PY 2005 VL 15 IS 3 BP 119 EP 126 DI 10.1016/j.brainresprot.2005.05.003 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 972WD UT WOS:000232483000002 PM 16024266 ER PT J AU Montero, A Savani, BN Kurlander, R Read, EJ Leitman, SF Childs, R Solomon, SR Barrett, AJ AF Montero, A Savani, BN Kurlander, R Read, EJ Leitman, SF Childs, R Solomon, SR Barrett, AJ TI Lineage-specific engraftment and outcomes after T-cell-depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE T-cell chimaerism; T-cell depletion; stem cell transplantation; leukaemia ID BONE-MARROW-TRANSPLANTATION; MIXED HEMATOPOIETIC CHIMERISM; CHRONIC MYELOGENOUS LEUKEMIA; HEMATOLOGIC MALIGNANCIES; CYTOGENETIC ANALYSIS; ACUTE GVHD; ADD-BACK; RELAPSE; IMMUNOTHERAPY; PREDICTOR AB Sixty patients with haematological malignancies received a myeloablative regimen of total body irradiation, cyclophosphamide and fludarabine followed by a T-cell-depleted peripheral blood stem cell transplant from a human leucocyte antigen identical sibling. To improve donor immune function, 1 x 10(7) CD3(+) cells/kg were added-back between d 45 and 100. T-cell and myeloid chimaerism were monitored regularly to evaluate the effect of T-cell chimaerism on outcome. The major factor affecting outcome was disease risk, with significantly lower relapse and higher survival in 29 standard risk (SR) patients compared with 31 patients at high risk (HR) for treatment failure (relapse 4.8 +/- 5% vs. 59 +/- 11%, P < 0.0001, and overall survival 93 +/- 5% vs. 39 +/- 10%, P < 0.0001, respectively). Donor myeloid chimaerism reached >= 95% within 14 d of transplant, but in the first several months, donor T-cell chimaerism was frequently mixed. Full T-cell chimaerism was significantly more frequent in HR vs. SR patients. Landmark analysis at days 30 and 90 in HR patients with mixed versus full T-cell chimaerism, showed relapse probabilities of 50.5 +/- 14% vs. 70 +/- 16% (P = 0.62) and 34.4 +/- 20% vs. 58.8 +/- 15% (P = 0.32) respectively. Early full T-cell engraftment correlated with development of severe acute graft-versus-host disease (GVHD). However, mixed T-cell chimaerism was favourable for reducing GVHD, and did not affect relapse in this small series. C1 NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5320,10 Ctr Dr,MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 23 TC 11 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2005 VL 130 IS 5 BP 733 EP 739 DI 10.1111/j.1365-2141.2005.05665.x PG 7 WC Hematology SC Hematology GA 963RW UT WOS:000231824600011 PM 16115130 ER PT J AU Marti, GE Rawstron, AC Ghia, P Hillmen, P Houlston, RS Kay, N Schleinitz, TA Caporaso, N AF Marti, GE Rawstron, AC Ghia, P Hillmen, P Houlston, RS Kay, N Schleinitz, TA Caporaso, N TI MBL and MoBL - Response SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE monoclonal B-cell lymphocytosis; nomenclature ID PLASMID C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20014 USA. Leeds Teaching Hosp, NHS Trust, HMDS, Leeds Gen Infirm, Leeds, W Yorkshire, England. Univ Vita Salute San Raffaele, Milan, Italy. Inst Canc Res, Sect Canc Genet, Surrey, England. Mayo Clin Rochester, Div Hematol, Rochester, MN USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, NIH, Bethesda, MD USA. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20014 USA. EM gemarti@helix.nih.gov RI Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Houlston, Richard/0000-0002-5268-0242 NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2005 VL 130 IS 5 BP 795 EP 796 DI 10.1111/j.1365-2141.2005.05675.x PG 2 WC Hematology SC Hematology GA 963RW UT WOS:000231824600022 ER PT J AU Kato, GJ Martyr, S Blackwelder, WC Nichols, JS Coles, WA Hunter, LA Brennan, ML Hazen, SL Gladwin, MT AF Kato, GJ Martyr, S Blackwelder, WC Nichols, JS Coles, WA Hunter, LA Brennan, ML Hazen, SL Gladwin, MT TI Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE sickle cell disease; endothelial function; vascular biology; liver disease; adhesion molecules ID NITRIC-OXIDE BIOAVAILABILITY; ACUTE CHEST SYNDROME; NF-KAPPA-B; P-SELECTIN; VASCULAR INSTABILITY; VASOOCCLUSIVE CRISIS; HYDROXYUREA THERAPY; PLASMA HEMOGLOBIN; TRANSGENIC MICE; ANEMIA PATIENTS AB Endothelial cell adhesion molecules orchestrate the recruitment and binding of inflammatory cells to vascular endothelium. With endothelial dysfunction and vascular injury, the levels of endothelial bound and soluble adhesion molecules increase. Such expression is modulated by nitric oxide (NO), and in patients with sickle cell disease (SCD), these levels are inversely associated with measures of NO bioavailability. To further evaluate the role of endothelial dysfunction in a population study of SCD, we have measured the levels of soluble endothelium-derived adhesion molecules in the plasma specimens of 160 adult patients with SCD during steady state. Consistent with a link between endothelial dysfunction and end-organ disease, we found that higher levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were associated with markers indicating renal dysfunction and hepatic impairment. Analysis of soluble intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin and sP-selectin levels indicated partially overlapping associations with sVCAM-1, with an additional association with inflammatory stress and triglyceride levels. Importantly, increased soluble adhesion molecule expression correlated with severity of pulmonary hypertension, a clinical manifestation of endothelial dysfunction. Soluble VCAM-1, ICAM-1, and E-selectin were independently associated with the risk of mortality in this cohort. Our data are consistent with steady state levels of soluble adhesion molecules as markers of pulmonary hypertension and risk of death. C1 NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. NIDDK, Mol Med Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA. RP Kato, GJ (reprint author), NIH, Ctr Clin, Dept Nursing, 10 Ctr Dr,MSC 1476,Bldg 10CRC,Room 5-5140, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z01 CL001174-07, Z99 HL999999, ZIA HL006012-01]; NHLBI NIH HHS [P01 HL 076491, P01 HL076491] NR 58 TC 101 Z9 101 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2005 VL 130 IS 6 BP 943 EP 953 DI 10.1111/j.1365-2141.2005.05701.x PG 11 WC Hematology SC Hematology GA 960RS UT WOS:000231611500014 PM 16156864 ER PT J AU Unno, T Matsuyama, H Sakamoto, T Uchiyama, M Izumi, Y Okamoto, H Yamada, M Wess, J Komori, S AF Unno, T Matsuyama, H Sakamoto, T Uchiyama, M Izumi, Y Okamoto, H Yamada, M Wess, J Komori, S TI M-2 and M-3 muscarinic receptor-mediated contractions in longitudinal smooth muscle of the ileum studied with receptor knockout mice SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE M-2 receptors; M-3 receptors; knockout mice; intestinal smooth muscle; carbachol; contractile response; Ca2+ mobilization; pertussis toxin ID GUINEA-PIG ILEUM; NONSELECTIVE CATIONIC CURRENT; ACETYLCHOLINE-RECEPTOR; PROTEIN INVOLVEMENT; SMALL-INTESTINE; PHOSPHOINOSITIDE HYDROLYSIS; INTERNAL CALCIUM; STOMACH FUNDUS; CYCLIC-AMP; CELLS AB 1 Isometric contractile responses to carbachol were studied in ileal longitudinal smooth muscle strips from wild-type mice and mice genetically lacking M-2 or M-3 muscarinic receptors, in order to characterize the mechanisms involved in M-2 and M-3 receptor-mediated contractile responses. 2 Single applications of carbachol (0.1-100 mu M) produced concentration-dependent contractions in preparations from M-2-knockout (KO) and M-3-KO mice, mediated via M-3 and M-2 receptors, respectively, as judged by the sensitivity of contractile responses to blockade by the M-2-preferring antagonist methoctramine (300 nM) or the M-3-preferring antagonist 4-DAMP (30 nM). 3 The M-2-mediated contractions were mimicked in shape by submaximal stimulation with high K+ concentrations (up to 35 mM), almost abolished by voltage-dependent Ca2+ channel (VDCC) antagonists or depolarization with 140 mM K+ medium, and greatly reduced by pertussis toxin (PTX) treatment. 4 The M-3-mediated contractions were only partially inhibited by VDCC antagonists or 140 mM K+-depolarization medium, and remained unaffected by PTX treatment. The contractions observed during high K+ depolarization consisted of different components, either sensitive or insensitive to extracellular Ca2+. 5 The carbachol contractions observed with wild-type preparations consisted of PTX-sensitive and -insensitive components. The PTX-sensitive component was functionally significant only at low carbachol concentrations. 6 The results suggest that the M-2 receptor, through PTX-sensitive mechanisms, induces ileal contractions that depend on voltage-dependent Ca2+ entry, especially associated with action potential discharge, and that the M-3 receptor, through PTX-insensitive mechanisms, induces contractions that depend on voltage-dependent and -independent Ca2+ entry and intracellular Ca2+ release. In intact tissues coexpressing M-2 and M-3 receptors, M-2 receptor activity appears functionally relevant only when fractional receptor occupation is relatively small. C1 Gifu Univ, Fac Appl Biol Sci, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Komori, S (reprint author), Gifu Univ, Fac Appl Biol Sci, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. EM skomori@cc.gifu-u.ac.jp NR 45 TC 40 Z9 46 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2005 VL 146 IS 1 BP 98 EP 108 DI 10.1038/sj.bjp.0706300 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 962HP UT WOS:000231722100012 PM 15965495 ER PT J AU Heineman, EF Ward, MH McComb, RD Weisenburger, DD Zahm, SH AF Heineman, EF Ward, MH McComb, RD Weisenburger, DD Zahm, SH TI Hair dyes and risk of glioma among Nebraska women SO CANCER CAUSES & CONTROL LA English DT Article DE brain cancer; glioma; hair dyes ID BRAIN-TUMORS; UNITED-STATES; CANCER; ADULTS; HAIRDRESSERS; OCCUPATION AB The etiology of brain cancer is not well understood. We conducted a population-based case-control study among 112 white women in Nebraska who were newly diagnosed with glioma between July 1988 and June 1993, and 215 controls, to identify risk factors for this disease. A 1.7-fold increased risk of glioma was observed for women who ever used hair coloring products (95% confidence interval (CI) = 1.0-2.9, 62 cases), and a 2.4-fold risk for those who used permanent hair coloring products (odds ratio (OR) = 2.4, 95% CI = 1.3-4.5, 39 cases). For women with the most aggressive form of glioma, glioblastoma multiforme, risk increased with duration of exposure to 4.9 (95% CI = 1.6-15.7, 10 cases) after 21 or more years of permanent hair coloring use. Higher risks were observed with earlier age at first use, but we did not see an exposure-response pattern with frequency of use of permanent dyes. No association was observed with use of non-permanent (sometimes called temporary or semi-permanent) hair coloring products. These suggestive findings need confirmation in future studies with larger sample sizes, fewer proxy respondents, and the ability to evaluate the effect of changes in formulations over time. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Zahm, SH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 8074, Bethesda, MD 20892 USA. EM zahms@mail.nih.gov RI Zahm, Shelia/B-5025-2015 NR 24 TC 18 Z9 19 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2005 VL 16 IS 7 BP 857 EP 864 DI 10.1007/s10552-005-3204-z PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 955IY UT WOS:000231220800010 PM 16132796 ER PT J AU Wang, H Wang, Z Wang, SY Li, M Nan, L Rhie, JK Covey, JM Zhang, RW Hill, DL AF Wang, H Wang, Z Wang, SY Li, M Nan, L Rhie, JK Covey, JM Zhang, RW Hill, DL TI Preclinical pharmacology of epothilone D, a novel tubulin-stabilizing antitumor agent SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE epothilone D; HPLC; metabolism; protein binding; pharmacokinetics ID DESOXYEPOTHILONE B; CYTOTOXIC ACTIVITY; PACLITAXEL; MECHANISM; CELLS AB Purpose: To determine, for various species, the pharmacological and biochemical properties of epothilone D (EpoD) that are relevant in establishing an appropriate animal model for further evaluation of this promising antitumor agent. Methods: A method involving high-performance liquid chromatography (HPLC) was developed and used to assess the stability and protein binding of EpoD in plasma from various species, its metabolism by various S9 fractions, and its pharmacokinetics in mice. Results: EpoD was stable in dog and human plasma. In plasma from other species, stability decreased in the order: hamster > mouse > guinea pig > rat. EpoD was highly bound to proteins in dog and human plasma. In an evaluation of S9 fractions from mouse, rat, guinea pig, dog, and human, mouse S9 was most efficient in metabolizing EpoD. Following administration to CD2F1 mice, the initial half-lives for plasma elimination of EpoD were < 5 min for an intravenous dose and < 20 min for an intraperitoneal dose. Conclusions: The species differences in EpoD biostability and metabolism may have implications in assessing its antitumor activity and pharmacologic and toxicologic profiles in humans. Relative to humans, the mouse is not a good model for disposition of EpoD; the dog would be more appropriate. C1 Univ Alabama, Ctr Comprehens Canc, Canc Pharmacol Lab,Div Clin Pharmacol, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. NCI, Bethesda, MD 20852 USA. RP Wang, H (reprint author), Univ Alabama, Ctr Comprehens Canc, Canc Pharmacol Lab,Div Clin Pharmacol, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. EM hui.wang@ccc.uab.edu FU NCI NIH HHS [N01-CM-07111] NR 19 TC 14 Z9 15 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2005 VL 56 IS 3 BP 255 EP 260 DI 10.1007/s00280-004-0965-0 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 949AR UT WOS:000230757800004 PM 15868148 ER PT J AU Wang, H Li, M Rhie, JK Hockenbery, DM Covey, JM Zhang, RW Hill, DL AF Wang, H Li, M Rhie, JK Hockenbery, DM Covey, JM Zhang, RW Hill, DL TI Preclinical pharmacology of 2-methoxyantimycin A compounds as novel antitumor agents SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE 2-methoxyantimycin A; HPLC; metabolism; protein binding; pharmacokinetics ID CELL-DEATH; BCL-X; OLIGONUCLEOTIDE PHOSPHOROTHIOATE; ANTIMYCIN-A; PROTEIN; BCL-X(L); PHARMACOKINETICS; DISPOSITION; EXPRESSION; CANCER AB Purpose: The present study was designed to determine pharmacological and biochemical properties of 2-methoxyantimycin A analogs (OMe-A1, OMe-A2, OMe-A3, and OMe-A5), which are novel antitumor compounds, and provide a basis for future pharmaceutical development, preclinical evaluation, and clinical trials. Methods: A high-performance liquid chromatography (HPLC) method was established and employed to assess the biostability of these analogs and to determine their pharmacokinetic properties in mice and rats. Results: In vitro biostability of the 2-methoxyantimycin analogs was esterase-dependent, compound-dependent, and species-dependent. In the absence of esterase inhibitors, all of the analogs were relatively unstable. Stability was greater, however, in human and dog plasma than in rat and mouse plasma. In the presence of esterase inhibitors, OMe-A1 was stable at 37 degrees C for 60 min in mouse and rat plasma, moderately stable in human plasma, and unstable in dog plasma. OMe-A2 was generally stable in all types of plasma. OMe-A3 was stable in dog and rat plasma, but not in human or mouse plasma. OMe-A5 was stable in human and dog plasma, but not in mouse or rat plasma. Each of these analogs was highly bound to plasma proteins. Of S9 fractions from four species, human S9 was least efficient in metabolizing OMe-A3. Following an intravenous dose of OMe-A1 in mice, plasma levels decreased rapidly, with an initial half-life of 2.7 min and a terminal half life of 34 min. Following an intraperitoneal dose in mice, plasma levels decreased less rapidly with a terminal half-life of 215 min. Following an intravenous dose of OMe-A1 or OMe-A3 in rats, plasma levels decreased more rapidly with initial half-lives of about 1.0 min. At an equivalent dose, OMe-A3 had a faster clearance than OMe-A1. Conclusions: For 2-methoxyantimycin A analogs, species differences in biostability, metabolism, and pharmacokinetics may be pertinent in assessing their pharmacological and toxicological profiles and antitumor activity in humans. C1 Univ Alabama, Ctr Comprehens Canc, Dept Pharmacol & Toxicol, Div Clin Pharmacol,Canc Pharmacol Lab, Birmingham, AL 35294 USA. NCI, Bethesda, MD 20852 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Wang, H (reprint author), Univ Alabama, Ctr Comprehens Canc, Dept Pharmacol & Toxicol, Div Clin Pharmacol,Canc Pharmacol Lab, Birmingham, AL 35294 USA. EM hui.wang@ccc.uab.edu FU NCI NIH HHS [N01-CM-07111] NR 15 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2005 VL 56 IS 3 BP 291 EP 298 DI 10.1007/s00280-004-0978-8 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 949AR UT WOS:000230757800009 PM 15883820 ER PT J AU Nouraie, M Pietinen, P Kamangar, F Dawsey, SM Abnet, CC Albanes, D Virtamo, J Taylor, PR AF Nouraie, M Pietinen, P Kamangar, F Dawsey, SM Abnet, CC Albanes, D Virtamo, J Taylor, PR TI Fruits, vegetables, and antioxidants and risk of gastric cancer among male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI; STOMACH-CANCER; BETA-CAROTENE; VITAMIN-E; ALPHA-TOCOPHEROL; SERUM RETINOL; FOLLOW-UP; DIETARY; COHORT; POPULATION AB The effect of consumption of fruits, vegetables, and antioxidants on the incidence of gastric cancer is inconclusive. In this prospective cohort study, we report the association of dietary intake of fruits, vegetables, antioxidants, and baseline serum levels of antioxidants with subsequent incidence of gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Participants of this study were 29,133 male smokers recruited into the (x-Tocopherol, beta-Carotene Cancer Prevention study between 1985 and 1988. At baseline, a self-administered food use questionnaire with 276 food items was used to assess dietary intake. Baseline serum samples were stored at -70 degrees C. During a median follow-up of 12 years, 243 incident gastric adenocarcinomas (64 GCC and 179 GNCC) were diagnosed in this cohort, of whom 220 (57 GCC and 163 GNCC) had complete dietary information. For GCC, high dietary intake of retinol was protective [hazard ratio (HR), 0.46; 95% confidence interval (95% CI), 0.27-0.781, but high intake of alpha-tocopherol (HR, 2.06; 95% Cl, 1.20-3.54) and gamma-tocopherol (HR, 1.94; 95% CI, 1.13-3.34) increased risk. For GNCC, higher intakes of fruits (HR, 0.51; 95% Cl, 0.37-0.71), vitamin C (HR, 0.60; 95% Cl, 0.41-0.86), alpha-tocopherol (HR, 0.78; 95% Cl, 0.55-1.10), gamma-tocopherol (HR, 0.69; 95% Cl, 0.49-0.96), and lycopene (HR, 0.67; 95% CI, 0.47-0.95) were protective. Our results suggest a difference in the effect of some of these exposures on GCC and GNCC. Tocopherols were associated with higher risk of GCC, whereas dietary intake of fruits, vitamin C, tocopherols, and lycopene seemed protective for GNCC. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blve,Suite 320, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU NCI NIH HHS [N01CN45035, N01CN45156] NR 47 TC 66 Z9 69 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2087 EP 2092 DI 10.1158/1055-9965.EPI-05-0038 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400006 PM 16172214 ER PT J AU Koushik, A Hunter, DJ Spiegelman, D Anderson, KE Arslan, AA Beeson, WL van den Brandt, PA Buring, JE Cerhan, JR Colditz, GA Fraser, GE Freudenheim, JL Genkinger, JM Goldbohm, RA Hankinson, SE Koenig, KL Larsson, SC Leitzmann, M McCullough, ML Miller, AB Patel, A Rohan, TE Schatzkin, A Smit, E Willett, WC Wolk, A Zhang, SMM Smith-Warner, SA AF Koushik, A Hunter, DJ Spiegelman, D Anderson, KE Arslan, AA Beeson, WL van den Brandt, PA Buring, JE Cerhan, JR Colditz, GA Fraser, GE Freudenheim, JL Genkinger, JM Goldbohm, RA Hankinson, SE Koenig, KL Larsson, SC Leitzmann, M McCullough, ML Miller, AB Patel, A Rohan, TE Schatzkin, A Smit, E Willett, WC Wolk, A Zhang, SMM Smith-Warner, SA TI Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; BREAST-CANCER; UNITED-STATES; DIETARY QUESTIONNAIRE; WOMENS HEALTH; VITAMIN-C; PREVENTION; EPIDEMIOLOGY; CONSUMPTION; POPULATION AB Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions, increased consumption may reduce the risk of ovarian cancer. Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent. We analyzed and pooled the primary data from 12 prospective studies in North America and Europe. Fruit and vegetable intake was measured at baseline in each study using a validated food frequency questionnaire. To summarize the association between fruit and vegetable intake and ovarian cancer, study-specific relative risks (RR) were estimated using the Cox proportional hazards model, and then combined using a random-effects model. Among 560,441 women, 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies. Total fruit intake was not associated with ovarian cancer risk-the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [95% confidence interval (95% CI), 0.92-1.21; P value, test for trend = 0.73; P value, test for between-studies heterogeneity = 0.741. Similarly, results for total vegetable intake indicated no significant association (pooled multivariate RR, 0.90; 95% Cl, 0.78-1.04, for the highest versus the lowest quartile; P value, test for trend = 0.06; P value, test for between-studies heterogeneity = 0.31). Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk. Associations for total fruits and vegetables were similar for different histologic types. These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NYU, Sch Med, Div Epidemiol, Dept Environm Med, New York, NY USA. NYU, Sch Med, Div Biostat, Dept Environm Med, New York, NY USA. Loma Linda Univ, Sch Med, Ctr Hlth Res, Loma Linda, CA USA. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Coll Med, Rochester, MN 55905 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. TNO, Nutr & Food Res Inst, Dept Epidemiol, Zeist, Netherlands. Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. RI Larsson, Susanna/F-6065-2015; Colditz, Graham/A-3963-2009; OI Larsson, Susanna/0000-0003-0118-0341; Colditz, Graham/0000-0002-7307-0291; Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [CA55075] NR 64 TC 37 Z9 37 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2160 EP 2167 DI 10.1158/1055-9965.EPI-05-0218 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400018 PM 16172226 ER PT J AU Goldstein, AM Landi, MT Tsang, S Fraser, MC Munroe, DJ Tucker, MA AF Goldstein, AM Landi, MT Tsang, S Fraser, MC Munroe, DJ Tucker, MA TI Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MELANOCORTIN-1 RECEPTOR MC1R; HUMAN PIGMENTATION; PHENOTYPE; GENE AB Major risk factors for melanoma include many nevi, especially dysplastic nevi, fair pigmentation, freckling, poor tanning ability, and germ line mutations in the CDKN2A, CDK4, or MC1R genes. We evaluated the relationship between MC1R and melanoma risk in CDKN2A melanoma-prone families with extensive clinical and epidemiologic data. We studied 395 subjects from 16 American CDKN2A families. Major melanoma risk factors were assessed by clinical examination or questionnaire; MC1R was sequenced. Odds ratios were estimated by unconditional and conditional logistic regression models. We examined the distribution of MC1R variants and median ages at melanoma diagnosis in multiple primary melanoma (MPM) and single primary melanoma (SPM) patients. Presence of multiple MC1R variants was significantly associated with melanoma, even after adjustment for major melanoma risk factors. All 40 MPM patients had at least one MC1R variant; 65% of MPM patients versus only 17% of SPM patients had at least two MC1R variants (P < 0.0001). For all 69 melanoma patients combined, as well as the 40 MPM patients, there was a statistically significant decrease in median age at diagnosis as numbers of MCIR variants increased (P = 0.010 and P = 0.008, respectively). In contrast, no significant reduction in age at melanoma diagnosis was observed for SPM patients (P = 0.91). The current study suggests that the presence of multiple MCIR variants is associated with the development of multiple melanoma tumors in patients with CDKN2A mutations. Additional studies are needed to confirm these findings and to explore the mechanisms that may contribute to this relationship. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Lab Mol Technol, Frederick, MD 21701 USA. Sci Applicat Int Corp, Frederick, MD USA. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Execut Plaza S,Room 7004,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. EM goldstea@exchange.nih.gov RI Tucker, Margaret/B-4297-2015 NR 21 TC 65 Z9 66 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2208 EP 2212 DI 10.1158/1055-9965.EPI-05-0321 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400025 PM 16172233 ER PT J AU Parsons, JK Carter, HB Platz, EA Wright, EJ Landis, P Metter, EJ AF Parsons, JK Carter, HB Platz, EA Wright, EJ Landis, P Metter, EJ TI Serum testosterone and the risk of prostate cancer: Potential implications for testosterone therapy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID REPLACEMENT THERAPY; OLDER MEN; HORMONES; RECOMMENDATIONS; FINASTERIDE AB Objective: A potential risk of testosterone replacement therapy is an increase in the incidence of prostate cancer, but it is unclear whether higher levels of serum testosterone are associated with a higher risk of prostate cancer. We prospectively evaluated serum androgen concentrations and prostate cancer risk. Method: Included were 794 members of the Baltimore Longitudinal Study of Aging. We estimated the rate ratio (RR) of prostate cancer by entering serial measures of serum total testosterone, clehydroepiandrosterone sulfate, sex hormone binding globulin, calculated free testosterone, and free testosterone index (FTI) into a Cox proportional hazards regression model with simple updating. Results: Higher calculated free testosterone was associated with an increased age-adjusted risk of prostate cancer {RRs by quartile: 1.00, 1.52 [95% confidence interval (95% CI), 0.93-2.501, 1.16 (95% Cl, 0.61-2.20), 2.59 (95% Cl, 1.285.25); P-trend = 0.031, which persisted after excluding measures in men < 45 years of age [RRs by quartile: 1.00, 1.33 (95% CI, 0.78-2.25), 1.26 (95% CI, 0.68-2.33), 1.89 (95% Cl, 0.99-3.61); Ptrend = 0.031. Compared to men with eugonadal FTI (>= 0.153), men with hypogonadal FTI had a decreased risk of prostate cancer (RR, 0.51; 95% CI, 0.31-0.82). Conclusion: Higher levels of calculated serum free testosterone are associated with an increased risk of prostate cancer. These findings suggest that men receiving testosterone therapy should be regularly monitored for prostate cancer and underscore the need for prospective trials of testosterone therapy incorporating incidence of prostate cancer as a primary safety end point. C1 Harbor Hosp, NIA, Intramural Res Program, Baltimore, MD USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Parsons, JK (reprint author), Johns Hopkins Univ Hosp, Brady Inst Urol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM parsonsk@jhmi.edu NR 25 TC 94 Z9 98 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2257 EP 2260 DI 10.1158/1055-9965.EPI-04-0715 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400032 PM 16172240 ER PT J AU Anderson, KE Kadlubar, FF Kulldorff, M Harnack, L Gross, M Lang, NP Barber, C Rothman, N Sinha, R AF Anderson, KE Kadlubar, FF Kulldorff, M Harnack, L Gross, M Lang, NP Barber, C Rothman, N Sinha, R TI Dietary intake of heterocyclic amines and benzo(a)pyrene: Associations with pancreatic cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PAST MEDICAL HISTORY; RISK-FACTORS; VARYING DEGREES; FOOD; MEAT; PRODUCTS; RATS; CARCINOGEN; MUTAGENS; COOKING AB Objective: Heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons, formed in temperature- and time-dependent manners during the cooking of meat, are mutagens and carcinogens. We sought to assess the association between dietary intake of HCA and benzo(a)pyrene [B(a)PI and exocrine pancreatic cancer in a population-based case-control study. Methods: Subjects (193 cases and 674 controls) provided information on their usual meat intake and preparation method, e.g., stewed, fried, or grilled/barbecued, etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness. We used a meat-derived HCA, B(a)P, and mutagen database with a questionnaire to estimate intake of PhIP, DiMeIQx, MelQx, B(a)P, and mutagenic activity (revertants/g of daily meat intake). Data were analyzed with unconditional logistic regression. Results: In analyses adjusted for age, sex, smoking, education, race, and diabetes, the odds ratio and 95% confidence interval for the highest compared with the lowest quintile were as follows: PhIP, 1.8 (1.0-3.1); DiMeIQx, 2.0 (1.2-3.5); MeIQx, 1.5 (0.9-2.7); 13(a)P, 2.2 (1.2-4.0); and mutagenic activity, 2.4 (1.3-4.3). Conclusions: HCAs and B(a)P from well-done barbecued and pan-fried meats may be associated with increased risk for pancreatic cancer. C1 Univ Minnesota, Div Epidemiol, Sch Publ Hlth, Minneapolis, MN 55454 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Univ Arkansas Med Sci, Dept Surg, Coll Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. NCI, Rockville, MD USA. RP Anderson, KE (reprint author), Univ Minnesota, Div Epidemiol, Sch Publ Hlth, 1300 S 2nd St 300, Minneapolis, MN 55454 USA. EM anderson_k@epi.umn.edu RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kulldorff, Martin/0000-0002-5284-2993 FU NCI NIH HHS [R01-CA-58697] NR 51 TC 55 Z9 59 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2261 EP 2265 DI 10.1158/1055-9965.EPI-04-0514 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400033 PM 16172241 ER PT J AU Lawson, KA Woodson, K Virtamo, J Albanes, D AF Lawson, KA Woodson, K Virtamo, J Albanes, D TI Association of the NAD(P)H : Quinone oxidoreductase (NQ01) 609C -> T polymorphism with lung cancer risk among male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID QUINONE-OXIDOREDUCTASE; GENETIC POLYMORPHISMS; NAD(P)H; NQO1; SMOKING; SUSCEPTIBILITY; POPULATION; GENOTYPE; EXPOSURE; DISEASE C1 NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Lawson, KA (reprint author), Nutr Epidemiol Branch, 6120 Execut Blvd,EPS Suite 320,Room 3032, Rockville, MD 20852 USA. EM lawsonka@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 23 TC 10 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2275 EP 2276 DI 10.1158/1055-9965.EPI-05-0375 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400037 PM 16172245 ER PT J AU Klabunde, C Breen, N Meissner, H AF Klabunde, C Breen, N Meissner, H TI Use of colonoscopy for colorectal cancer screening SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID HEALTH INTERVIEW SURVEY C1 NCI, Bethesda, MD 20892 USA. RP Klabunde, C (reprint author), NCI, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2279 EP 2280 DI 10.1158/1055-9965.EPI-05-0292 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400042 PM 16172249 ER PT J AU Zimonjic, DB Kato, Y Ying, H Popescu, NC Cheng, SY AF Zimonjic, DB Kato, Y Ying, H Popescu, NC Cheng, SY TI Chromosomal aberrations in cell lines derived from thyroid tumors spontaneously developed in TR beta(PV/PV) mice SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HORMONE RECEPTOR-BETA; MOUSE MODEL; MEN1 GENE; CARCINOMA; EXPRESSION; CANCER; MUTATION; CARCINOGENESIS; ABNORMALITIES; RESISTANCE AB The etiology and genetic alterations of follicular thyroid carcinoma are not well understood. By targeting a mutation (PV) into the thyroid hormone receptor beta gene (TR beta PV mouse), we created a knock-in mutant TR beta(PV/PV) mouse that spontaneously develop follicular thyroid carcinoma with progression to metastasis similar to human follicular thyroid carcinoma. This mouse model provides a valuable tool to ascertain the nature and the extent of genomic rearrangements that Occur during carcinogenesis of the thyroid. Spectral karyotyping analysis (SKY) of seven cell lines derived from thyroid tumors developed in TR beta(PV/PV) mice showed that all of them had abnormal karyotypes, with chromosome number ranging from near-diploid (39-42 chromosomes) to hypotetraploid (63-79 chromosomes). These seven cell lines also exhibited a variety of structural chromosomal aberrations, including common recurrent translocations and deletions. This SKY analysis shows that the development and progression of follicular thyroid carcinoma in knock-in TR beta(PV/PV) mutant mice comprise recurrent structural and numerical genomic changes, some of which mimic those described in human thyroid cancer. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. RP Zimonjic, DB (reprint author), NCI, Ctr Canc Res, Expt Carcinogenesis Lab, 37 Convent Dr,MSC 4262,Bldg 37,Room 4128C, Bethesda, MD 20892 USA. EM drazen_zimonjic@nih.gov NR 32 TC 12 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 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 2005 VL 161 IS 2 BP 104 EP 109 DI 10.1016/j.cancergencyto.2005.02.007 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 961VD UT WOS:000231689000002 PM 16102579 ER PT J AU Park, SS Shaffer, AL Kim, JS duBois, W Potter, M Staudt, LM Janz, S AF Park, SS Shaffer, AL Kim, JS duBois, W Potter, M Staudt, LM Janz, S TI Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice SO CANCER RESEARCH LA English DT Article ID PLASMA-CELL DIFFERENTIATION; B-CELL; C-MYC; BALB/C MICE; GENE-EXPRESSION; TRANSGENIC MICE; V-ABL; MURINE PLASMACYTOMAGENESIS; CHROMOSOMAL TRANSLOCATION; RAPID INDUCTION AB Gene-targeted mice that contain a His(6)-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carrying Myc(His), just 5' of the intronic heavy-chain enhancer E mu (strain iMyc(E mu)) provide a specific model of the type of T(12;15) found in a subset (similar to 20%) Of plasmacytomas that develop "spontaneously" in the gut-associated lymphoid tissue (GALT) of interleukin-6 transgenic BALB/c (C) mice. Here we show that the transfer of the iMyc(E mu) transgene from a mixed genetic background of segregating C57BL/6 * 129/SvJ alleles to the background of C increased the incidence of GALT plasmacytomas by a factor of 2.5 in first-generation backcross mice (C.iMYC(E mu) N-1). Third-generation backcross mice (C.iMYC(E mu) N-3, similar to 94% C alleles) were hypersusceptible to inflammation-induced peritoneal plasmacytomas (tumor incidence, 100%; mean tumor onset, 86 +/- 28 days) compared with inbred C mice (tumor incidence, 5% on day 150 after tumor induction). Peritoneal plasmacytomas of C.iMyc(E mu) N3 mice overexpressed Myc(His), produced monoclonal immunoglobulin, and exhibited a unique plasma cell signature upon gene expression profiling on mouse Lymphochip cDNA microarrays. These findings indicated that the iMyc(E mu) transgene accelerates plasmacytoma development by collaborating with tumor susceptibility alleles of strain C and circumventing the requirement for tumor precursors to acquire deregulated Myc by chromosomal translocation. C1 NCI, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Genet Lab, Canc Res Ctr, NIH, Room 3140A,Bldg 37, Bethesda, MD 20892 USA. EM sj4s@nih.gov NR 51 TC 18 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 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7644 EP 7652 DI 10.1158/0008-5472.CAN-05-1222 PG 9 WC Oncology SC Oncology GA 961JX UT WOS:000231659500019 PM 16140930 ER PT J AU Schwartz, SA Weil, RJ Thompson, RC Shyr, Y Moore, JH Toms, SA Johnson, MD Caprioli, RM AF Schwartz, SA Weil, RJ Thompson, RC Shyr, Y Moore, JH Toms, SA Johnson, MD Caprioli, RM TI Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry SO CANCER RESEARCH LA English DT Article ID DIFFERENTIALLY EXPRESSED GENES; PROTEIN EXPRESSION; GLIOMA CLASSIFICATION; S100 PROTEINS; CANCER; MICROARRAY; PROGRESSION; DESORPTION/IONIZATION; IDENTIFICATION; LOCALIZATION AB Clinical diagnosis and treatment decisions for a subset of primary human brain tumors, gliomas, are based almost exclusively on tissue histology. Approaches for glioma diagnosis can be highly subjective due to the heterogeneity and infiltrative nature of these tumors and depend on the skill of the neuropathologist. There is therefore a critical need to develop more precise, nonsubjective, and systematic methods to classify human gliomas. To this end, mass spectrometric analysis has been applied to these tumors to determine glioma-specific protein patterns. Protein profiles have been obtained from human gliomas of various grades through direct analysis of tissue samples using matrix-assisted laser desorption ionization mass spectrometry (MS). Statistical algorithms applied to the MS profiles from tissue sections identified protein patterns that correlated with tumor histology and patient survival. Using a data set of 108 glioma patients, two patient populations, a short-term and a long-term survival group, were identified based on the tissue protein profiles. In addition, a subset of 57 patients diagnosed with high-grade, grade IV, malignant gliomas were analyzed and a novel classification scheme that segregated short-term and long-term survival patients based on the proteomic profiles was developed. The protein patterns described served as an independent indicator of patient survival. These results show that this new molecular approach to monitoring gliomas can provide clinically relevant information on tumor malignancy and is suitable for high-throughput clinical screening. C1 Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Dept Neurosurg, Nashville, TN 37232 USA. Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Dept Biostat, Nashville, TN 37232 USA. Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Dept Pathol, Nashville, TN 37232 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. RP Caprioli, RM (reprint author), Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Dept Biochem, 465 21st Ave S,Room 9160,Med Res Bldg 3, Nashville, TN 37232 USA. EM r.caprioli@vanderbilt.edu FU Intramural NIH HHS; NCI NIH HHS [CA 86243]; NIGMS NIH HHS [GM 58008] NR 40 TC 159 Z9 163 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7674 EP 7681 DI 10.1158/0008-5472.CAN-04-3016 PG 8 WC Oncology SC Oncology GA 961JX UT WOS:000231659500023 PM 16140934 ER PT J AU Vatolin, S Abdullaev, Z Pack, SD Flanagan, PT Custer, M Loukinov, DI Pugacheva, E Hong, JA Morse, H Schrump, DS Risinger, JI Barrett, JC Lobanenkov, VV AF Vatolin, S Abdullaev, Z Pack, SD Flanagan, PT Custer, M Loukinov, DI Pugacheva, E Hong, JA Morse, H Schrump, DS Risinger, JI Barrett, JC Lobanenkov, VV TI Conditional expression of the CTCF-paralogous transcriptional factor BORIS in normal cells results in demethylation and derepression of MAGE-A1 and reactivation of other cancer-testis genes SO CANCER RESEARCH LA English DT Article ID IMPRINTING CONTROL REGION; INSULATOR PROTEIN CTCF; DNA METHYLATION; GERM-LINE; X-INACTIVATION; BINDING-SITES; ANTIGEN GENES; PROMOTER; EPIGENETICS; TUMOR AB Brother of the Regulator of Imprinted Sites (BORIS) is a mammalian CTCF paralog with the same central 11Zn fingers (11ZF) that mediate specific interactions with varying similar to 50-bp target sites. Regulated in vivo occupancy of such sites may yield structurally and functionally distinct CTCF/DNA complexes involved in various aspects of gene regulation, including epigenetic control of gene imprinting and X chromosome inactivation. The latter functions are mediated by meCpG-sensitive 11ZF binding. Because CTCF is normally present in all somatic cells, whereas BORIS is active only in CTCF- and 5-methylcytosine-deficient adult male germ cells, switching DNA occupancy from CTCF to BORIS was suggested to regulate site specificity and timing of epigenetic reprogramming. In addition to 11ZF-binding paternal imprinting control regions, cancer-testis gene promoters also undergo remethylation during CTCF/BORIS switching in germ cells. Only promoters of cancer testis genes are normally silenced in all somatic cells but activated during spermatogenesis when demethylated in BORIS-positive germ cells and are found aberrantly derepressed in various tumors. We show here that BORUS is also expressed in multiple cancers and is thus itself a cancer-testis gene and that conditional expression of BORIS in normal fibroblasts activates cancer-testis genes selectively. We tested if replacement of CTCF by BORIS on regulatory DNA occurs in vivo on activation of a prototype cancer-testis gene, MAGE-A1. Transition from a hypermethylated/silenced to a hypomethylated/activated status induced in normal cells by 5-aza-2'-deoxycytidine (5-azadC) was mimicked by conditional input of BORIS and is associated with complete switching from CTCF to BORIS occupancy at a single 11ZF target. This site manifested a novel type of CTCF/BORIS 11ZF binding insensitive to CpG methylation. Whereas 5-azadC induction of BORIS takes only few hours, derepression of ALIGE-A1 occurred I to 2 days later, suggesting that BORIS mediates cancer-testis gene activation by 5-azadC. Indeed, infection of normal fibroblasts with anti-BORIS short hairpin RNA retroviruses before treatment with 5-azadC blocked reactivation of AMGE-A1. We suggest that BORIS is likely tethering epigenetic machinery to a novel class of CTCF/BORIS 11ZF target sequences that mediate induction of cancer-testis genes. C1 NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD 20852 USA. NCI, NIH, Lab Biosyst & Canc, Bethesda, MD 20892 USA. NCI, NIH, Thorac Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. RP Lobanenkov, VV (reprint author), NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Twinbrook 1,Room 1417,MSC-8152,5640 Fishers Lane, Rockville, MD 20852 USA. EM viobanenkov@niaid.nih.gov RI Pack, Svetlana/C-2020-2014; OI Morse, Herbert/0000-0002-9331-3705 NR 51 TC 122 Z9 126 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7751 EP 7762 DI 10.1158/0008-5472.CAN-05-0858 PG 12 WC Oncology SC Oncology GA 961JX UT WOS:000231659500032 PM 16140943 ER PT J AU Hong, JA Kang, Y Abdullaev, Z Flanagan, PT Pack, SD Fischette, MR Adnani, MT Loukinov, DI Vatolin, S Risinger, JI Custer, M Chen, GA Zhao, M Nguyen, DM Barrett, JC Lobanenkov, VV Schrump, DS AF Hong, JA Kang, Y Abdullaev, Z Flanagan, PT Pack, SD Fischette, MR Adnani, MT Loukinov, DI Vatolin, S Risinger, JI Custer, M Chen, GA Zhao, M Nguyen, DM Barrett, JC Lobanenkov, VV Schrump, DS TI Reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter coincides with derepression of this cancer-testis gene in lung cancer cells SO CANCER RESEARCH LA English DT Article ID H19 GENE; ISCOMATRIX ADJUVANT; DNA METHYLATION; CPG METHYLATION; X-INACTIVATION; T-CELLS; EXPRESSION; EPIGENETICS; INSULATOR; PROTEIN AB Regulatory sequences recognized by the unique pair of paralogous factors, CTCF and BORIS, have been implicated in epigenetic regulation of imprinting and X chromosome inactivation. Lung cancers exhibit genome-wide demethylation associated with derepression of a specific class of genes encoding cancer-testis (CT) antigens such as NY-ESO-1. CT genes are normally expressed in BORIS-positive male germ cells deficient in CTCF and meCpG contents, but are strictly silenced in somatic cells. The present study was undertaken to ascertain if aberrant activation of BORIS contributes to derepression of NY-ESO-1 during pulmonary carcinogenesis. Preliminary experiments indicated that NY-ESO-1 expression coincided with derepression of BORIS in cultured lung cancer cells. Quantitative reverse transcription-PCR analysis revealed robust, coincident induction of BORIS and NY-ESO-1 expression in lung cancer cells, but not normal human bronchial epithelial cells following 5-aza-2'-deoxycytidine (5-azadC), Depsipeptide FK228 (DP), or sequential 5-azadC/DP exposure under clinically relevant conditions. Bisulfite sequencing, methylation-specific PCR, and chromatin immunoprecipitation (ChIP) experiments showed that induction of BORIS coincided with direct modulation of chromatin structure within a CpG island in the 5'-flanking noncoding region of this gene. Cotransfection experiments using promoter-reporter constructs confirmed that BORIS modulates NY-ESO-1 expression in lung cancer cells. Gel shift and ChIP experiments revealed a novel CTCF/BORIS-binding site in the NY-ESO-1 promoter, which unlike such sites in the H19-imprinting control region and X chromosome, is insensitive to CpG methylation in vitro. In vivo occupancy of this site by CTCF was associated with silencing of the NY-ESO-1 promoter, whereas switching from CTCF to BORIS occupancy coincided with derepression of NY-ESO-1. Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas. C1 NCI, Thorac Oncol Sect, Surg Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Canc Res Ctr, Room 4-3942,Bldg 10,10 Ctr Dr MSC 1201, Bethesda, MD 20892 USA. EM david_schrump@nih.gov RI Pack, Svetlana/C-2020-2014 NR 52 TC 113 Z9 115 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7763 EP 7774 DI 10.1158/0008-5472.CAN-05-0823 PG 12 WC Oncology SC Oncology GA 961JX UT WOS:000231659500033 PM 16140944 ER PT J AU Jing, YK Hellinger, N Xia, LJ Monks, A Sausville, EA Zelent, A Waxman, S AF Jing, YK Hellinger, N Xia, LJ Monks, A Sausville, EA Zelent, A Waxman, S TI Benzodithiophenes induce differentiation and apoptosis in human leukemia cells SO CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; PML-RAR-ALPHA; HISTONE DEACETYLASE; ARSENIC TRIOXIDE; HEXAMETHYLENE BISACETAMIDE; TRANSFORMED-CELLS; MYELOID-LEUKEMIA; TARGETED THERAPY; EXPRESSION AB All-trans retinoic acid (ATRA) induces clinical remission in patients with t(15;17) acute promyelocytic leukemia (APL) carrying leukemogenic promyelocytic leukemia-retinoic acid receptor alpha(PML-RAR alpha) fusion protein by overcoming PML-RAR alpha transcriptional repression and inducing myeloid differentiation. To identify more potent chemical differentiation inducers, a screening assay was developed utilizing an ATRA-insensitive NB4 cell line (N-B4-c) in which differentiation could be measured after 48 hours when primed with ATRA followed by other potential inducers. Over 300 cytostatic agents selected from the National Cancer Institute library were screened using this established method. Three compounds, NSC656243, NSC625748, and NSC144168, were identified to amplify ATRA-induced differentiation with acceptable cytotoxicity in NB4-c cells. In the absence of ATRA, these compounds also induced HL-60 and murine erythroleukemia cells to undergo partial differentiation. NSC656243, a benzodithiophene compound, was selected for further studies to examine the underlying mechanism of action. The differentiation effect of NSC656243 was associated with enhanced ATRA-mediated up-regulation of cell cycle regulatory proteins p21(waf1) and p27(kip1) retinoblastoma dephosphorylation, expression of RIG-E and BIG-G, and myelomonocytic differentiation-specific down-regulation of the myeloperoxidase (MPO) gene. Moreover, at 2- to 3-fold higher concentrations than those used to synergize with ATRA, NSC656243 induced apoptosis in NB4-c cells by reactive oxygen species-mediated pathways. The dual effects of benzodithiophenes (i.e., differentiation and apoptosis induction) support further development of these compounds as therapeutic agents for leukemia. C1 Mt Sinai Sch Med, Div Hematol Oncol, Dept Med, New York, NY 10029 USA. SAIC Frederick Inc, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. Inst Canc Res, Hematol Oncol Sect, London SW3 6JB, England. RP Waxman, S (reprint author), Mt Sinai Sch Med, Div Hematol Oncol, Dept Med, Box 1178,1 Gustave L Levy Pl, New York, NY 10029 USA. EM samuel.waxman@mssm.edu RI Zelent, Arthur/B-3532-2009 NR 41 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7847 EP 7855 DI 10.1158/0008-5472.CAN-05-1053 PG 9 WC Oncology SC Oncology GA 961JX UT WOS:000231659500043 PM 16140954 ER PT J AU Sinha, R Peters, U Cross, AJ Kulldorff, M Weissfeld, JL Pinsky, PF Rothman, N Hayes, RB AF Sinha, R Peters, U Cross, AJ Kulldorff, M Weissfeld, JL Pinsky, PF Rothman, N Hayes, RB CA Lung Ovarian Cancer Project Team TI Meat, meat cooking methods and preservation, and risk for colorectal adenoma SO CANCER RESEARCH LA English DT Article ID HETEROCYCLIC AMINE CONTENT; COLON-CANCER; VARYING DEGREES; UNITED-STATES; WELL-DONE; RED MEAT; CONSUMPTION; FOOD; CARCINOGEN; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE AB Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8dimethylimidazo[4,5]quinoxaline and 2-amino-l-methyl-6phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Sinha, R (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 3046, Bethesda, MD 20892 USA. EM sinhar@nih.gov RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kulldorff, Martin/0000-0002-5284-2993; Hayes, Richard/0000-0002-0918-661X NR 29 TC 131 Z9 134 U1 0 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 8034 EP 8041 DI 10.1158/0008-5472.CAN-04-3429 PG 8 WC Oncology SC Oncology GA 961JX UT WOS:000231659500067 PM 16140978 ER PT J AU Dromi, SA Locklin, J Wood, BJ AF Dromi, SA Locklin, J Wood, BJ TI Radiofrequency cauterization: An alternative to reduce post-biopsy hemorrhage SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID RENAL BIOPSY; ABLATION; EMBOLIZATION C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Dromi, SA (reprint author), NIH, Dept Diagnost Radiol, Bldg 10,Room 1C662,10 Ctr Dr, Bethesda, MD 20892 USA. EM dromis@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 6 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD SEP-OCT PY 2005 VL 28 IS 5 BP 681 EP 682 DI 10.1007/s00270-005-0018-z PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 966PU UT WOS:000232033900025 PM 16132383 ER PT J AU Morad, M Soldatov, N AF Morad, M Soldatov, N TI Calcium channel inactivation: Possible role in signal transduction and Ca2+ signaling SO CELL CALCIUM LA English DT Article DE Ca channel inactivation; Ca(v)1.2 channel; Ca signaling; signal transduction; C-terminal of Ca channel ID RAT VENTRICULAR MYOCYTES; ALPHA(1C) SUBUNIT; RYANODINE RECEPTORS; CARDIAC MYOCYTES; CA(V)1.2 CHANNEL; CA2+-DEPENDENT INACTIVATION; MOLECULAR DETERMINANTS; SARCOPLASMIC-RETICULUM; CALMODULIN-BINDING; ACTION-POTENTIALS AB Voltage gated Ca2+ channels are major routes for the entry of intracellular Ca2+ coupled to membrane depolarization that appear to vary greatly with respect to their voltage dependence and kinetics. Such variability maybe in part related to the attached signaling properties of the channel, in addition to the transport of calcium. In the present review we consider the possible role of calcium-dependent inactivation of Ca(v)1.2 in Ca2+ signal transduction and signaling of calcium release from the cardiac sarcoplasmic reticulum. We explore the specific roles of Ca2+-sensing calmodulin-binding domains of the C-terminal tail (LA and K) of the channel in mediating Ca2+-induced Ca2+ release and signal transduction. Our experiments point to an intriguing possibility that the C-terminal tail of Ca-v 1.2 may translocate the Ca2+ signal as a part of inactivation mechanism and the corresponding voltage-gated rearrangement of the C-terminus. We show how a dynamic and transient regulation, in a Ca2+ -dependent manner, defines molecular events including Ca2+ release and signaling of cAMP-responsive element-binding protein (CREB)-dependent transcription. We propose that such Ca2+-dependent C-tail translocation that also initiates the channel inactivation, may have evolved specifically for the Ca-v 1.2 channel. (C) 2005 Elsevier Ltd. All rights reserved. C1 Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20057 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Morad, M (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, 3900 Reservoir Rd NW, Washington, DC 20057 USA. EM moradm@georgetown.edu FU Intramural NIH HHS; PHS HHS [R01 16152] NR 62 TC 30 Z9 30 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD SEP-OCT PY 2005 VL 38 IS 3-4 BP 223 EP 231 DI 10.1016/j.ceca.2005.06.027 PG 9 WC Cell Biology SC Cell Biology GA 969ON UT WOS:000232243700005 PM 16098584 ER PT J AU Arnaoutov, A Dasso, M AF Arnaoutov, A Dasso, M TI Ran-GTP regulates kinetochore attachment in somatic cells SO CELL CYCLE LA English DT Article DE Ran; RanGAP1; crm1; kinetochore; microtubule ID NUCLEAR-PORE COMPLEX; BINDING-SITES; IMPORTIN-BETA; SPINDLE; PROTEIN; MICROTUBULE; MITOSIS; RCC1; NUCLEOPORIN; CHROMOSOME AB The Ran GTPase controls multiple mitotic processes in Xenopus egg extracts, including mitotic checkpoints, spindle assembly and post-mitotic nuclear envelope reassembly. We have analyzed Ran's role in somatic cells. We uncovered a novel mitotic role of Ran-GTP, involving the Crm1 nuclear export receptor. This pathway is an important mode of RanGTP function during mitosis in mammalian somatic cells, which mediates the recruitment of the RanGAP1/RanBP2 complex to kinetochores and maintains the microtubule-based fibers connecting kinetochores to spindle poles (k-fibers). Here we discuss potential implications of these findings for normal k-fiber assembly. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 18,Room 106, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06] NR 34 TC 49 Z9 51 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2005 VL 4 IS 9 BP 1161 EP 1165 PG 5 WC Cell Biology SC Cell Biology GA 959JB UT WOS:000231512900010 PM 16082212 ER PT J AU Mittelstadt, PR Salvador, JSM Fornace, AJ Ashwell, JD AF Mittelstadt, PR Salvador, JSM Fornace, AJ Ashwell, JD TI Activating p38 MAPK - New tricks for an old kinase SO CELL CYCLE LA English DT Article DE p38; ZAP-70; Lck; LAT; TCR; structure; autophosphorylation ID T-CELL ANERGY; PROTEIN-KINASE; DUAL PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; PATHWAY; ERK2; MECHANISM; P38-ALPHA; RECEPTOR AB Mitogen-activated protein kinases (MAPKs) participate in signaling initiated by a wide variety of extracellular stimuli. MAPKs are most commonly activated by a series of phosphorylation events in which one kinase phosphorylates another, the "MAPK cascade". The cascade concludes with the dual phosphorylation of MAPKs on a conserved Thr-X-Tyr motif. In the case of the p38 MAPK, an exception to this paradigm has been found when signaling via the T cell antigen receptor (TCR). Rather than trigger the MAPK cascade, TCR-mediated stimulation activates proximal tyrosine kinases, which results in the phosphorylation of p38 on a noncanonical activating residue, Tyr-323. This phosphorylation activates p38 to phosphorylate third party substrates as well as its own Thr-Gyl-Tyr motif. Here we discuss the structural and functional implications of this alternative p38 activation pathway, which may provide a new target for tissue-specific pharmacologic inhibition. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. Natl Biotechnol Ctr, Dept Immunol & Oncol, Madrid, Spain. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Mittelstadt, PR (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. EM mittelsp@mail.nih.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 32 TC 52 Z9 54 U1 0 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2005 VL 4 IS 9 BP 1189 EP 1192 PG 4 WC Cell Biology SC Cell Biology GA 959JB UT WOS:000231512900016 PM 16103752 ER PT J AU Rogozin, IB Basu, MK Jordan, IK Pavlov, YI Koonin, EV AF Rogozin, IB Basu, MK Jordan, IK Pavlov, YI Koonin, EV TI APOBEC4, a new member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases predicted by computational analysis SO CELL CYCLE LA English DT Article DE cytidine deaminase; DNA/RNA modification; phylogenetic analysis; editing enzyme; innate immunity; APOBEC1 ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; RNA EDITING ENZYME; ESCHERICHIA-COLI; APOLIPOPROTEIN-B; MAXIMUM-LIKELIHOOD; SEQUENCE ALIGNMENT; PROTEIN; EVOLUTION; HYPERMUTATION AB Using iterative database searches, we identified a new subfamily of the AID/APOBEC family of RNA/DNA editing cytidine deaminases. The new subfamily, which is represented by readily identifiable orthologs in mammals, chicken, and frog, but not fishes, was designated APOBEC4. The zinc-coordinating motifs involved in catalysis and the secondary structure of the APOBEC4 deaminase domain are evolutionarily conserved, suggesting that APOBEC4 proteins are active polynucleotide ( deoxy) cytidine deaminases. In reconstructed maximum likelihood phylogenetic trees, APOBEC4 forms a distinct clade with a high statistical support. APOBEC4 and APOBEC1 are joined in a moderately supported cluster clearly separated from AID, APOBEC2 and APOBEC3 subfamilies. In mammals, APOBEC4 is expressed primarily in testis which suggests the possibility that it is an editing enzyme for mRNAs involved in spermatogenesis. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 32 TC 76 Z9 83 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2005 VL 4 IS 9 BP 1281 EP 1285 PG 5 WC Cell Biology SC Cell Biology GA 959JB UT WOS:000231512900029 PM 16082223 ER PT J AU Surgucheva, I Park, BC Yue, BYJT Tomarev, S Surguchov, A AF Surgucheva, I Park, BC Yue, BYJT Tomarev, S Surguchov, A TI Interaction of myocilin with gamma-synuclein affects its secretion and aggregation SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE myocilin; synuclein; glaucoma; ganglion cells ID TRABECULAR MESHWORK CELLS; OPEN-ANGLE GLAUCOMA; CENTRAL-NERVOUS-SYSTEM; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; PROTEASOMAL INHIBITION; GOLGI-APPARATUS; OPTIC-NERVE; GENE; PROTEIN AB Mutations in the gene encoding human myocilin are associated with some cases of juvenile and early-onset glaucoma. Glaucomatous mutations prevent myocilin from being secreted. The analysis of the defects associated with mutations point to the existence of factor(s) in addition to mutations that might be implicated in the development of glaucoma. In the present paper, we found that interaction of myocilin with one of the members of the synuclein family alters its properties, including its ability to be secreted. Results of immunoprecipitation show that myocilin is gamma-synuclein-interacting protein. Further analysis demonstrated that both myocilin and gamma-synuclein are expressed in human TM cells, immortalized rat ganglion (RGC-5) cells, and HT22 hippocampal neurons. According to Western blotting, in addition to monomeric form with molecular weight 17 kDa gamma-synuclein is present as higher molecular weight forms (similar to 35 and 68 KDa), presumably dimer and tetramer. Myocilin and gamma-synuclein have partially overlapping perinuclear localization. Dexamethasone upregulates myocilin expression in RGC-5 cells and HT22 hippocampal neurons. We found alterations of myocilin properties as a result of its interaction with gamma-synuclein. In cultured cells, gamma-synuclein upregulates myocilin expression, inhibits its secretion and prevents the formation of high molecular weight forms of myocilin. Although both alpha-synuclein and gamma-synuclein are expressed in HTM cells, only gamma-synuclein interacts with myocilin and alters its properties. We conclude that myocilin and gamma-synuclein interact and as a result, myocilin's properties are changed. Since myocilin and gamma-synuclein have partially overlapping intracellular localization in cell types that are implicated in glaucoma development, their interaction may play an important role in glaucoma. C1 Vet Adm Med Ctr, Retinal Dis Res Lab, Kansas City, MO 64128 USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. RP Surguchov, A (reprint author), Vet Adm Med Ctr, Retinal Dis Res Lab, 4801 Linwood Blvd, Kansas City, MO 64128 USA. EM asurguchov@kumc.edu FU NEI NIH HHS [EY 13784-03] NR 72 TC 24 Z9 27 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD SEP PY 2005 VL 25 IS 6 BP 1009 EP 1033 DI 10.1007/s10571-005-8471-4 PG 25 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 999RZ UT WOS:000234409500005 PM 16392033 ER PT J AU De Guzman, BB Hisatsune, J Nakayama, M Yahiro, K Wada, A Yamasaki, E Nishi, Y Yamazaki, S Azuma, T Ito, Y Ohtani, M van der Wijk, T den Hertog, J Moss, J Hirayama, T AF De Guzman, BB Hisatsune, J Nakayama, M Yahiro, K Wada, A Yamasaki, E Nishi, Y Yamazaki, S Azuma, T Ito, Y Ohtani, M van der Wijk, T den Hertog, J Moss, J Hirayama, T TI Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTP alpha and RPTP beta, by Helicobacter pylori m2VacA SO CELLULAR MICROBIOLOGY LA English DT Article ID VACUOLATING CYTOTOXIN; VACA; TOXIN; GENE; INDUCTION; CELLS; ASSOCIATION; MOSAICISM; RESISTANT; ACID AB Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian cell lines. Sequence differences in the middle of VacA molecules define two families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine phosphatases, RPTP alpha and RPTP beta suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTP alpha, not RPTP beta, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTP alpha, not RPTP beta, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTP alpha of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTP alpha less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTP alpha from HeLa cells is less than that of the protein from G401 cells, although their extracellular amino acid sequences are virtually identical, with only two amino acid differences noted. Different post-translational modifications of RPTP alpha in HeLa cells may be responsible for the reduced susceptibility to m2VacA. C1 Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan. Chiba Univ, Dept Mol Infectiol, Grad Sch Med, Chiba 2608670, Japan. Univ Fukui, Dept Internal Med, Fac Med Sci, Fukui 9101193, Japan. Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan. EM hirayama@net.nagasaki-u.ac.jp NR 30 TC 19 Z9 21 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD SEP PY 2005 VL 7 IS 9 BP 1285 EP 1293 DI 10.1111/j.1462-5822.2005.00556.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 954IH UT WOS:000231148000008 PM 16098216 ER PT J AU Miyazaki, A Fujisawa, Y Shiotani, K Fujita, Y Li, TY Tsuda, Y Yokoi, T Bryant, SD Lazarus, LH Okada, Y AF Miyazaki, A Fujisawa, Y Shiotani, K Fujita, Y Li, TY Tsuda, Y Yokoi, T Bryant, SD Lazarus, LH Okada, Y TI Studies on the mechanism of 1,2-dihydropyrazin-2-one ring formation from dipeptidyl chloromethyl ketone and its chemical properties: Immediate deamination during catalytic hydrogenation SO CHEMICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE 1,2-dihydropyrazin-2-one; deuterium substitution; cyclization mechanism; catalytic hydrogenation; deamination ID AMINO-ACIDS; FACILE SYNTHESIS; DERIVATIVES; PYRAZINONE; PEPTIDES AB 1,2-Dihydropyrazin-2-one derivatives, which have two aminoalkyl groups at the positions 3 and 6, were found to be efficient tools for the, construction of potent, selective and long-acting opioid mimetics. During the course of preparation, we found that the catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5methyl-1,2-dihydropyrazin-2-one to remove the benzyloxycarbonyl groups resulted in a side reaction. By MS and NMR studies and by preparation of additional 1,2-dihydropyrazin-2-one derivatives, the structure of the byproduct was identified as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. Preparation of additional compounds substituted with deuterium provided us with sufficient information to confirm the structure of the product and to support a cyclization mechanism in its formation. C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Nishi Ku, Kobe, Hyogo 6512180, Japan. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM okada@pharm.kobegakuin.ac.jp NR 20 TC 1 Z9 1 U1 2 U2 8 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0009-2363 J9 CHEM PHARM BULL JI Chem. Pharm. Bull. PD SEP PY 2005 VL 53 IS 9 BP 1152 EP 1158 DI 10.1248/cpb.53.1152 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 962WM UT WOS:000231764000017 PM 16141586 ER PT J AU Cheung, C Ma, XC Krausz, KW Kimura, S Feigenbaum, L Dalton, TP Nebert, DW Idle, JR Gonzalez, FJ AF Cheung, C Ma, XC Krausz, KW Kimura, S Feigenbaum, L Dalton, TP Nebert, DW Idle, JR Gonzalez, FJ TI Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice humanized for CYP1A1 and CYP1A2 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; IN-VITRO; HYDROCARBON RECEPTOR; CYTOCHROME P4501A2; COLORECTAL-CANCER; LIVER-MICROSOMES; ADDUCT FORMATION; TRANSGENIC MICE; GENE; RAT AB The procarcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed during the cooking of foods. Metabolism of PhIP by CYP1A2 differs substantially between humans and rodents, with more N-2-hydroxylation (activation) and less 4 '-hydroxylation (detoxication) in humans. Therefore, the human response to PhIP and other heterocyclic amine exposure may not be accurately reflected in the laboratory rodent. By generating mouse models expressing the human genes, species differences in heterocyclic amine metabolism can be addressed. Two transgenic mouse lines were developed, one expressing the human CYP1A1 - CYP1A2 transgene in a mouse Cyp1a1-null background (hCYP1A1) and another expressing human CYP1A1 - CYP1A2 in a mouse Qypla2-null background (hCYP1A2). Expression of human CYP1A2 protein was detected in the liver and also at considerably lower levels in extrahepatic tissues such as lung, kidney, colon, and heart. In the hCYP1A1 and hCYP1A2 mice, 3-methylcholanthrene (3-MC) induced both human CYP1A1 and CYP1A2 protein in the liver. Differences in the metabolism of the heterocyclic amine PhIP were observed between wild-type and hCYP1A2 mice. PhIP was preferentially metabolized by N-2-hydroxylation in hCYP1A2 mice, whereas in wild-type mice, 4 '-hydroxylation was the predominant pathway. Since the N2-hydroxylation pathway for PhIP metabolism has been reported to be predominant in humans, these results illustrate the potential effectiveness of using these transgenic, humanized mice as models for determining human health risks to PhIP and other heterocyclic amines instead of wild-type mice. C1 NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Lab Anim Sci Program, SAIC, Ft Detrick, MD 21702 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Ctr Environm Genet, Cincinnati, OH 45267 USA. Charles Univ, Fac Med 1, Inst Pharmacol, Prague 12800 2, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Ctr Canc Res, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS; NIEHS NIH HHS [P30-ES06096, R01-ES08147] NR 31 TC 66 Z9 72 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 2005 VL 18 IS 9 BP 1471 EP 1478 DI 10.1021/tx050136g PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 967MP UT WOS:000232095600016 PM 16167840 ER PT J AU Kadiiska, MB AF Kadiiska, MB TI Products of lipid oxidation as measurable indicators of oxidative stress: Validation of biomarkers from rodent CC1(4) and ozone exposure SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Meeting Abstract CT 46th International Conference on the Bioscience of Lipids CY SEP 20-24, 2005 CL Ajaccio, FRANCE SP Agilent Technologies, Alexis Biochem, Avanti Polar Lipids, Caymen, Fondaz Giovanni Lorenzini Med Sci Fdn, GERLI, GlaxoSmithKline, Lesieur, Nutr Fdn Italy, Reg Corsica, Sanofi Aventis, SPI BIO, Takeda, Univ Milan, Waters C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD SEP PY 2005 VL 136 IS 2 BP 136 EP 137 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 971CN UT WOS:000232358800098 ER PT J AU Kong, Y Grembecka, J Edler, MC Hamel, E Mooberry, SL Sabat, M Rieger, J Brown, ML AF Kong, Y Grembecka, J Edler, MC Hamel, E Mooberry, SL Sabat, M Rieger, J Brown, ML TI Structure-based discovery of a boronic acid bioisostere of combretastatin A-4 SO CHEMISTRY & BIOLOGY LA English DT Article ID MOLECULAR-FIELD ANALYSIS; COLCHICINE BINDING-SITE; TUBULIN POLYMERIZATION; PROTEASOME INHIBITOR; ANTIMITOTIC AGENTS; ADVANCED CANCER; SOLID TUMORS; ANALOGS; POTENT; BORTEZOMIB AB Targeting the microtubule system represents an attractive strategy for the development of anticancer agents. In this study, we report a class of combretastatin A-4 (CA-4) analogs derivatized with a boronic acid moiety replacing the hydroxyl group on the C-ring of CA-4. Docking studies of the X-ray structures of our arylboronic analogs onto an X-ray structure of the a, tubulin heterodimer suggested that cis-6 was a potent inhibitor of the colchicine binding. The model indicated that there would be strong hydrogen bonding between the boronic acid moiety and Thr-1 79 and Val-181 of alpha-tubulin. We demonstrate that the cis-6 boronic acid bioisostere of CA-4: (1) inhibits tubulin assembly, (2) competitively displaces colchicine, and (13) is a low-nanomolar inhibitor of human cancer cell lines. We present this isostere as a class of potent analogs of CA-4. C1 Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. Univ Virginia, Charlottesville, VA 22908 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Screening Technol Branch,NIH, Frederick, MD 21702 USA. SW Fdn Biomed Res, Dept Physiol & Med, San Antonio, TX 78245 USA. RP Brown, ML (reprint author), Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. EM mlb2v@virginia.edu NR 27 TC 48 Z9 51 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD SEP PY 2005 VL 12 IS 9 BP 1007 EP 1014 DI 10.1016/j.chembiol.2005.06.016 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 971DH UT WOS:000232361000011 PM 16183025 ER PT J AU Bacon, MC von Wyl, V Alden, C Sharp, G Robison, E Hessol, N Gange, S Barranday, Y Holman, S Weber, K Young, MA AF Bacon, MC von Wyl, V Alden, C Sharp, G Robison, E Hessol, N Gange, S Barranday, Y Holman, S Weber, K Young, MA TI The Women's Interagency HIV Study: an observational cohort brings clinical sciences to the bench SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-PAPILLOMAVIRUS TYPE-16; SEROPOSITIVE WOMEN; INFECTED WOMEN; RISK; HAART; PARTICIPANTS; DEATH; RACE C1 NIAID, DAIDS, BSP, Epidemiol Branch,Div AIDS, Bethesda, MD 20817 USA. Henry M Jackson Fdn Adv Mil Med, Rockville, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. SUNY Hlth Sci Ctr, Brooklyn, NY USA. John H Stroger Hosp Cook Cty, Chicago, IL USA. RP Bacon, MC (reprint author), NIAID, DAIDS, BSP, Epidemiol Branch,Div AIDS, 6700-B Rockledge Dr,Room 4221, Bethesda, MD 20817 USA. EM mbacon@niaid.nih.gov OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [M01-RR-00071, M01 RR000071, M01 RR000079, M01 RR000083, M01-RR-00079, M01-RR-00083]; NIAID NIH HHS [U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI042590, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; OID CDC HHS [U01-CH-32632] NR 25 TC 228 Z9 230 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 2005 VL 12 IS 9 BP 1013 EP 1019 DI 10.1128/CDLI.12.9.1013-1019.2005 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 964QG UT WOS:000231895000001 PM 16148165 ER PT J AU Marques, AR Hornung, RL Dally, L Philipp, MT AF Marques, AR Hornung, RL Dally, L Philipp, MT TI Detection of immune complexes is not independent of detection of antibodies in Lyme disease patients and does not confirm active infection with Borrelia burgdorferi SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SURFACE PROTEIN-A; SERUM; ANTIGEN; OSPA AB The Borrelia burgdorferi-specific immune complex (IC) test, which uses polyethylene glycol (PEG) precipitation to isolate ICs from serum, has been used as a research test in the laboratory diagnosis of early Lyme disease (LD) and has been proposed as a marker of active infection. We examined whether B. burgdorferi-specific antibodies were present within PEG-precipitated ICs (PEG-ICs) in patients with LD, posttreatment Lyme disease syndrome, and controls, including individuals who received the outer surface protein A (OspA) vaccine. Using a B. burgdorferi whole-cell enzyme-linked inummosorbent assay (ELISA), we obtained positive PEG-IC results not only in patients with a history of LD, but also in individuals vaccinated with OspA vaccine. The frequency of positive PEG-IC ELISAs in OspA vaccinees was significantly higher with ELISA-reactive than with ELISA-negative unprocessed serum samples (P = 0.001), demonstrating dependency between the tests. Similar results were found using samples from rhesus macaques infected with B. burgdorferi, uninfected macaques vaccinated with OspA, and controls. Therefore, testing for the presence of antibodies against B. burgdorferi in PEG-IC preparations is not more likely to reflect active infection than testing in unprocessed serum and should not be used in individuals who received the OspA vaccine. C1 NIAID, Clin Studies Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NCI, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EMMES Corp, Rockville, MD USA. Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA USA. RP Marques, AR (reprint author), NIAID, Clin Studies Unit, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N228,10 Ctr Dr MSC 1888, Bethesda, MD 20892 USA. EM amarques@niaid.nih.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 18 TC 13 Z9 13 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 2005 VL 12 IS 9 BP 1036 EP 1040 DI 10.1128/CDLI.12.9.1036-1040.2005 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 964QG UT WOS:000231895000004 PM 16148168 ER PT J AU Philipp, MT Wormser, GP Marques, AR Bittker, S Martin, DS Nowakowski, J Dally, LG AF Philipp, MT Wormser, GP Marques, AR Bittker, S Martin, DS Nowakowski, J Dally, LG TI A decline in C-6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; CONSERVED IMMUNODOMINANT REGION; VLSE IR6 PEPTIDE; ANTIBIOTIC-TREATMENT; INVARIABLE REGION; BURGDORFERI VLSE; DISEASE; SERODIAGNOSIS; RECOMBINANT; ANTIGENS AB C-6, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C-6-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C-6 antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C-6 negative or had a >= 4-fold decrease in C-6 antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C-6 negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C-6 antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis. C1 Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Dept Bacterial & Parasitol, Covington, LA 70433 USA. New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. RP Philipp, MT (reprint author), Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Dept Bacterial & Parasitol, 18703 Three Rivers Rd, Covington, LA 70433 USA. EM Philipp@tpc.tulane.edu FU NCRR NIH HHS [P51 RR000164, RR00164]; NIAID NIH HHS [R01 AI049976, R01-AI49976] NR 34 TC 29 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 2005 VL 12 IS 9 BP 1069 EP 1074 DI 10.1128/CDLI.12.9.1069-1074.2005 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 964QG UT WOS:000231895000009 PM 16148173 ER PT J AU Aletaha, D Smolen, J AF Aletaha, D Smolen, J TI The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): A review of their usefulness and validity in rheumatoid arthritis SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE disease activity score (DAS); rheumatoid arthritis; clinical trials; patient assessment AB Composite indices or pooled indices are useful tools for the evaluation of disease activity in patients with rheumatoid arthritis (RA). They allow the integration of various aspects of the disease into a single numerical value, and may therefore facilitate consistent patient compliance, which both can lead to improved outcomes. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) are two new tools for the evaluation of disease activity in RA. They have been developed to provide physicians and patients with simple and more comprehensible instruments. Moreover, the CDAI is the only composite index that does not incorporate an acute phase response and can therefore be used to conduct a disease activity evaluation essentially anytime and anywhere. These two new tools have not been developed to replace currently available instruments such as the DAS28, but rather to provide options for different environments. The comparative construct, content, and discriminant validity of all three indices-the DAS28, the SDAI, and the CDAI-allow physicians to base their choice of instrument on their infrastructure and their needs, and all of them can also be used in clinical trials. C1 Med Univ Vienna, Dept Rheumatol, A-1090 Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. Lainz Hosp, Dept Med 2, Vienna, Austria. RP Aletaha, D (reprint author), Med Univ Vienna, Dept Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM daniel.aletaha@meduniwien.ac.at NR 52 TC 280 Z9 292 U1 0 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 2005 VL 23 IS 5 SU 39 BP S100 EP S108 PG 9 WC Rheumatology SC Rheumatology GA 980KN UT WOS:000233017500016 PM 16273793 ER PT J AU Bast, RC Lilja, H Urban, N Rimm, DL Fritsche, H Gray, J Veltri, R Klee, G Allen, A Kim, N Gutman, S Rubin, MA Hruszkewycz, A AF Bast, RC Lilja, H Urban, N Rimm, DL Fritsche, H Gray, J Veltri, R Klee, G Allen, A Kim, N Gutman, S Rubin, MA Hruszkewycz, A TI Translational crossroads for biomarkers SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PROSTATE-CANCER; TISSUE MICROARRAYS; QUANTITATIVE-ANALYSIS; BREAST-CANCER; ANTIGEN PSA; EXPRESSION; DISEASE AB A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (cl) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute -supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Yale Univ, Sch Med, New Haven, CT USA. Lawrence Livermore Natl Lab, Livermore, CA USA. diaDexus, San Francisco, CA USA. Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA. US FDA, Rockville, MD 20857 USA. Natl Canc Inst, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. Abbott Labs, Abbott Pk, IL 60064 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bast, RC (reprint author), Univ Texas, MD Anderson Canc Ctr, Box 355,1515 Holcombe Blvd, Houston, TX 77030 USA. EM rbast@mdanderson.org RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Lilja, Hans/0000-0001-5871-7846; Rubin, Mark/0000-0002-8321-9950 NR 16 TC 54 Z9 57 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6103 EP 6108 DI 10.1158/1078-0432.CCR-04-2213 PG 6 WC Oncology SC Oncology GA 962IB UT WOS:000231723600003 PM 16144908 ER PT J AU Yang, SX Simon, RM Tan, AR Nguyen, D Swain, SM AF Yang, SX Simon, RM Tan, AR Nguyen, D Swain, SM TI Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; LUNG-CANCER; PHASE-I; MUTATIONS; GEFITINIB; DOCETAXEL; APOPTOSIS AB Purpose: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. Experimental Design: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. Results: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling, Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor - linked signal transduction (74 genes, P = 0.007). Conclusions: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20889 USA. RP Yang, SX (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM xy32m@nih.gov; swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 NR 22 TC 27 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6226 EP 6232 DI 10.1158/1078-0432.CCR-05-0270 PG 7 WC Oncology SC Oncology GA 962IB UT WOS:000231723600020 PM 16144925 ER PT J AU Gadgeel, SM Wozniak, A Boinpally, RR Wiegand, R Heilbrun, LK Jain, V Parchment, R Colevas, D Cohen, MB LoRusso, PM AF Gadgeel, SM Wozniak, A Boinpally, RR Wiegand, R Heilbrun, LK Jain, V Parchment, R Colevas, D Cohen, MB LoRusso, PM TI Phase I clinical trial of BMS-247550, a derivative of epothilone B, using accelerated titration 213 design SO CLINICAL CANCER RESEARCH LA English DT Article ID MICROTUBULE-STABILIZING AGENTS; DESOXYEPOTHILONE B; PACLITAXEL; ANALOG AB Purpose: BMS-247550 is a semisynthetic derivative of epothilone B with mechanism of action analogous to paclitaxel. It has shown impressive antitumor activity in preclinical studies including in taxane-resistant models. We conducted a phase I trial, based on accelerated titration "2B" design, of BMS-247550 given as a 1-hour infusion every 3 weeks. Experimental Design: Seventeen patients (M:F, 10:7; median age, 54 years; performance status, 0-2) were treated on the trial. Forty-five cycles (1-9 cycles) of BMS-247550 were given at dosages ranging from 7.4 to 56 mg/m(2). All patients received prophylaxis for hypersensitivity reactions, related to Cremophor-EL, with steroids and histamine antagonists. Results: First-course dose-limiting toxicity (DLT) was observed in two of three patients at 56 mg/m(2) (neutropenic sepsis, prolonged grade 4 neutropenia) and in one of six patients at 40 mg/m(2). Nonhematologic grade 3 to 4 toxicities observed were emesis and fatigue and they occurred only at 56 mg/m(2). Grade 1 to 2 peripheral neuropathy was also observed. Other grade 1 to 2 toxicities were myalgias, arthralgias, rash, hand/foot syndrome, and mucositis. AUC and C-max seemed proportional to the dose and the DLT. Development of neutropenia with BMS-247550 is related to the duration of drug exposure above a threshold. Conclusions: The maximum tolerated dose (MTD) of BMS-247550 is 40 mg/m(2) given every 3 weeks. Neutropenia is the DLT. The accelerated titration "2B" design may help in determining MTD with fewer patients enrolled and more being treated closer to the MTD. However, the accelerated titration design did not seem to shorten the study duration. C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP LoRusso, PM (reprint author), Div Hematol Oncol, 4HWCRC,4100 John R, Detroit, MI 48201 USA. EM lorussop@karmanos.org FU NCI NIH HHS [CA-22453, CA-62487] NR 20 TC 59 Z9 60 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6233 EP 6239 DI 10.1158/1078-0432.CCR-05-0127 PG 7 WC Oncology SC Oncology GA 962IB UT WOS:000231723600021 PM 16144926 ER PT J AU Jazaeri, AA Avvtrey, CS Chandramouli, GVR Chuang, YE Khan, J Sotiriou, C Aprelikova, O Yee, CJ Zorn, KK Birrer, MJ Barrett, JC Boyd, J AF Jazaeri, AA Avvtrey, CS Chandramouli, GVR Chuang, YE Khan, J Sotiriou, C Aprelikova, O Yee, CJ Zorn, KK Birrer, MJ Barrett, JC Boyd, J TI Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID CATHEPSIN-D; BREAST-CANCER; EXTRACELLULAR-MATRIX; TUMOR-GROWTH; CELL-GROWTH; RESISTANCE; PROLIFERATION; DNA; CARCINOMA; SPARC AB Purpose: The goal of this study was to determine whether distinct gene expression profiles are associated with intrinsic and/or acquired chemoresistance in epithelial ovarian carcinoma. Experimental Design: Gene expression profiles were generated from 21 primary chemosensitive tumors and 24 primary chemoresistant tumors using cDNA-based microarrays. Gene expression profiles of both groups of primary tumors were then compared with those of 15 ovarian carcinomas obtained following platinum-based chemotherapy ("postchemotherapy" tumors). A theme discovery tool was used to identify functional categories of genes involved in drug resistance. Results: Comparison of primary chemosensitive and chemoresistant tumors revealed differential expression of 85 genes (P < 0.001). Comparison of gene expression profiles of primary chemosensitive tumors and postchemotherapy tumors revealed more robust differences with 760 genes differentiating the two groups (P < 0.001). In contrast, only 230 genes were differentially expressed between primary chemoresistant and postchemotherapy groups (P < 0.001). Common to both gene lists were 178 genes representing transcripts differentially expressed between postchemotherapy tumors and all primary tumors irrespective of intrinsic chemosensitivity. The gene expression profile of postchemotherapy tumors compared with that of primary tumors revealed statistically significant overrepresentation of genes encoding extracellular matrix-related proteins. Conclusions: These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identified that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions. C1 Mem Sloan Kettering Canc Ctr, Gynecol & Breast Res Lab, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. NCI, Pediat Oncol Branch, Bethesda, MD USA. NCI, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD USA. NCI, Lab Biosyst & Canc, Bethesda, MD USA. NCI, Ctr Canc Res, Dept Cell Canc Biol, Rockville, MD USA. RP Boyd, J (reprint author), Mem Sloan Kettering Canc Ctr, Gynecol & Breast Res Lab, Dept Surg, Box 201,1275 York Ave, New York, NY 10021 USA. EM boydj@mskcc.org RI Jazaeri, Amir/A-2400-2008; Khan, Javed/P-9157-2014; Jazaeri, Amir/I-3458-2015 OI Khan, Javed/0000-0002-5858-0488; Jazaeri, Amir/0000-0003-4335-4151 FU NCI NIH HHS [U01 CA88175] NR 47 TC 127 Z9 130 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6300 EP 6310 DI 10.1158/1072-0432.CCR-04-2682 PG 11 WC Oncology SC Oncology GA 962IB UT WOS:000231723600029 PM 16144934 ER PT J AU Yokokawa, J Palena, C Arlen, P Hassan, R Ho, M Pastan, I Schlom, J Tsang, KY AF Yokokawa, J Palena, C Arlen, P Hassan, R Ho, M Pastan, I Schlom, J Tsang, KY TI Identification of novel human CTL Epitopes and their agonist epitopes of mesothelin SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION PROFILES; CYTOTOXIC T-LYMPHOCYTES; MONOCLONAL-ANTIBODY K1; MOLECULAR-CLONING; ANTITUMOR-ACTIVITY; OVARIAN CANCERS; CELL-LINE; IN-VITRO; DENDRITIC CELLS; TUMOR-CELLS AB Purpose: Mesothelin is overexpressed in many pancreatic and ovarian cancers, mesotheliomas, and other tumor types. Clinical trials are ongoing using immunotoxins to target mesothelin, and patients immunized with allogeneic pancreatic tumor cell lines have shown immune responses to previously defined mesothelin epitopes. The purpose of this study was to define novel mesothelin CTL epitopes and, more importantly, agonist epitopes that would more efficiently activate human Tcells to more efficiently lyse human tumors. Experimental Design and Results: Two novel mesothelin HLA-A2 epitopes were defined. T-cell lines generated from one of these epitopes were shown to lyse pancreatic and ovarian tumor cells. Several agonist epitopes were defined and were shown to (a) have higher affinity and avidity for HLA-A2, (b) activate mesothelin-specific T cells from normal individuals or cancer patients to a greater degree than the native epitope in terms of induction of higher levels of IFN-gamma and the chemokine lymphotactin, and (c) lyse several mesothelin-expressing tumor types in a MHC-restricted manner more effectively than Tcells generated using the native peptide. External beam radiation of tumor cells at nontoxic levels was shown to enhance the expression of mesothelin and other accessory molecules, resulting in a modest but statistically significant increase in tumor cell lysis by mesothelin-specific Tcells. Conclusions: The identification of novel CTL agonist epitopes supports and extends observations that mesothelin is a potential target for immunotherapy of pancreatic and ovarian cancers, as well as mesotheliomas. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Ho, Mitchell/F-5059-2015 FU NCI NIH HHS [Z01 BC010427-06, Z01 BC010425-06] NR 48 TC 41 Z9 42 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6342 EP 6351 DI 10.1158/1078-0432.CCR-05-0596 PG 10 WC Oncology SC Oncology GA 962IB UT WOS:000231723600034 PM 16144939 ER PT J AU Hose, C Kaur, G Sausville, EA Monks, A AF Hose, C Kaur, G Sausville, EA Monks, A TI Transcriptional profiling identifies altered intercellular labile iron homeostasis as a contributing factor to the toxicity of adaphostin: Decreased vascular endothelial growth factor secretion is independent of hypoxia-inducible factor-1 regulation SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; CELL-LINES; TYRPHOSTIN AG957; MOLECULAR CONTROL; FERRITIN; METABOLISM; MECHANISMS; EXPRESSION; INDUCTION AB Purpose: Adaphostin was developed as an inhibitor of the p210(bcr-abl) tyrosine kinase, but as its activity is not limited to tumor cell lines containing this translocation, transcriptional profiling was used as a tool to elucidate additional mechanisms responsible for adaphostin cytotoxicity. Experimental design: Profiles of drug-induced transcriptional changes were measured in three hematopoietic cell lines following 1 and 10 mu mol/L adaphostin for 2 to 6 hours and then confirmed with real-time reverse transcription-PCR (2-24 hours). These data indicated altered iron homeostasis, and this was confirmed experimentally. Alteration of vascular endothelial growth factor (VEGF) secretion through hypoxia-inducible factor-1 (HIF-1) regulation was also investigated. Results: Drug-induced genes included heat shock proteins and ubiquitins, but an intriguing response was the induction of ferritins. Measurement of the labile iron pool showed release of chelatable iron immediately after treatment with adaphostin and was quenched with the addition of an iron chelator. Pretreatment of cells with desferrioxamine and N-acetyl-cysteine reduced but did not ablate the sensitivity of the cells to adaphostin, and desferrioxamine was able to modulate adaphostin-induced activation of p38 and inactivation of AKTVEGF secretion was shown to be reduced in cell lines after the addition of adaphostin but was not dependent on HIF-1. Conclusions: Adaphostin-induced cytotoxicity is caused in part by a rapid release of free iron, leading to redox perturbations and cell death. Despite this, reduced VEGF secretion was found to be independent of regulation by the redox responsive transcription factor HIF-1. Thus, aclaphostin remains an interesting agent with the ability to kill tumor cells directly and modulate angiogenesis. C1 NCI, SAIC Frederick Inc, Screening Technol Branch, Lab Funct Genom, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Monks, A (reprint author), NCI, SAIC Frederick Inc, Screening Technol Branch, Lab Funct Genom, POB B, Frederick, MD 21702 USA. EM monks@dtpax2.ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 33 TC 9 Z9 9 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6370 EP 6381 DI 10.1158/1078-0432.CR-05-0291 PG 12 WC Oncology SC Oncology GA 962IB UT WOS:000231723600037 PM 16144942 ER PT J AU Holmes, C Moak, J Eldadah, B Zimmerly, E Sharabi, Y Goldstein, DS AF Holmes, C Moak, J Eldadah, B Zimmerly, E Sharabi, Y Goldstein, DS TI Dopamine contamination of infused tyramine SO CLINICAL CHEMISTRY LA English DT Article ID PLASMA-CATECHOLAMINES; BLOOD-PRESSURE; VASODILATION C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Holmes, C (reprint author), Bldg 10,Room 6N250,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM holmesc@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 13 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2005 VL 51 IS 9 BP 1733 EP 1735 DI 10.1373/clinchem.2005.054361 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 959RF UT WOS:000231535100030 PM 16037411 ER PT J AU Seeff, LB Everhart, JE AF Seeff, LB Everhart, JE TI Is cirrhosis an inevitable consequence of chronic hepatitis C virus infection? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; COMPENSATED CIRRHOSIS; UNITED-STATES; MORTALITY; BLOOD C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 12 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2005 VL 3 IS 9 BP 840 EP 842 DI 10.1053/S1542-3565(05)00535-5 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995NA UT WOS:000234105800005 PM 16234019 ER PT J AU Brooks, BP Kleta, R Stuart, C Tuchman, M Jeong, A Stergiopoulos, SG Bei, T Bjornson, B Russell, L Chanoine, JP Tsagarakis, S Kalsner, LR Stratakis, CA AF Brooks, BP Kleta, R Stuart, C Tuchman, M Jeong, A Stergiopoulos, SG Bei, T Bjornson, B Russell, L Chanoine, JP Tsagarakis, S Kalsner, LR Stratakis, CA TI Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005 SO CLINICAL GENETICS LA English DT Article DE achalasia; adrenal insufficiency; alacrima; autonomic dysfunction; nuclear pore complex; triple A syndrome ID AAAS-GENE MUTATION; FAMILIAL GLUCOCORTICOID DEFICIENCY; NUCLEAR-PORE COMPLEX; WD-REPEAT PROTEIN; ALLGROVE-SYNDROME; ADRENOCORTICAL INSUFFICIENCY; ADRENAL INSUFFICIENCY; NEUROLOGICAL ABNORMALITIES; AUTONOMIC DYSFUNCTION; ACHALASIA AB Triple A syndrome (AAAS, OMIM#231550) is an autosomal recessive condition characterized by adrenal insufficiency, achalasia, alacrima, neurodegeneration and autonomic dysfunction. Mutations in the AAAS gene on chromosome 12q13 have been reported in several subjects with AAAS. Over the last 5 years, we have evaluated six subjects with the clinical diagnosis of AAAS. Three subjects had mutations in the AAAS gene - including one novel mutation (IVS8+1 G > A) - and a broad spectrum of clinical presentations. However, three subjects with classic AAAS did not have mutations in the AAAS gene on both alleles. This finding supports the notion of genetic heterogeneity for this disorder, although other genetic mechanisms cannot be excluded. C1 NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, British Columbia Childrens Hosp, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. Athens Polyclin, Dept Endocrinol, Athens, Greece. Univ Vermont, Coll Med, Dept Neurol, Burlington, VT USA. NICHD, Unit Genet & Endocrinol, Hereditary Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Brooks, BP (reprint author), NEI, Off Sci Director, NIH, 10 Ctr Dr,Bldg 10,Rm 10B16,MSC 1860, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov RI Bjornson, Bruce/A-8616-2010 OI Bjornson, Bruce/0000-0002-1465-6196 NR 33 TC 38 Z9 40 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD SEP PY 2005 VL 68 IS 3 BP 215 EP 221 DI 10.1111/j.1399-0004.2005.00482.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 954IJ UT WOS:000231148300006 PM 16098009 ER PT J AU Sheela, SR Latha, M Liu, P Lem, K Kaler, SG AF Sheela, SR Latha, M Liu, P Lem, K Kaler, SG TI Copper-replacement treatment for symptomatic Menkes disease: ethical considerations SO CLINICAL GENETICS LA English DT Article DE copper histidine; medical ethics; Menkes disease; treatment response ID KINKY HAIR SYNDROME; CANDIDATE GENE; TRICHOPOLIODYSTROPHY; DIAGNOSIS; DISORDER; THERAPY; ENCODES AB We describe a child with classical Menkes disease with a novel ATP7A mutation, intractable seizures, severe hypotonia and developmental delay, hypopigmentation of the skin and hair, and failure to thrive, who was treated with daily subcutaneous copper histidine injections for 21/2 years, beginning at 15 months of age. He became seizure-free and pigmentation of his skin and hair darkened, but he continued to have severe developmental delays. His condition remains stable 8 months after stopping treatment. We review the ethical aspects of offering copper treatment for Menkes disease infants diagnosed after neurological symptoms become manifest. These include (1) the prospect for any benefits, (2) the potential risks and discomforts, (3) the parents' wishes with respect to treatment, (4) the family's understanding of the treatment's potential futility, (5) the family's understanding of the investigational nature of this treatment, (6) the potential for treatment to have an adverse impact on unaffected family members, (7) whether the ultimate decision regarding treatment should rest with health care providers or with the patient's parents, and (8) the duration of treatment. The ethical issues encountered in providing possibly futile treatment in this difficult disorder seem relevant to other pediatric medical conditions as well. C1 NICHHD, Unit Pediat Genet, Lab Clin Genet, NIH, Bethesda, MD 20892 USA. Indira Gandhi Cooperat Hosp, Cochin, Kerala, India. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Lab Clin Genet, NIH, 10 Ctr Dr MSC 1832, Bethesda, MD 20892 USA. EM sgk@box-s.nih.gov NR 22 TC 28 Z9 28 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD SEP PY 2005 VL 68 IS 3 BP 278 EP 283 DI 10.1111/j.1399-0004.2005.00496.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 954IJ UT WOS:000231148300015 PM 16098018 ER PT J AU Biesecker, LG Johnston, J AF Biesecker, LG Johnston, J TI Syndromic and non-syndromic GLI3 phenotypes SO CLINICAL GENETICS LA English DT Letter C1 NHGRI, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD SEP PY 2005 VL 68 IS 3 BP 284 EP 284 DI 10.1111/j.1399-0004.2005.00485.x PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 954IJ UT WOS:000231148300016 PM 16098019 ER PT J AU Oliveira, JB Bidere, N Lenardo, MJ Fleisher, TA AF Oliveira, JB Bidere, N Lenardo, MJ Fleisher, TA TI Up regulation of c-FLIPs in a subgroup of patients with ALPS type III. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NIAID, Dept Lab Med, NIH, Bethesda, MD USA. NIAID, Immunol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD SEP PY 2005 VL 116 IS 3 BP 286 EP 287 PG 2 WC Immunology SC Immunology GA 957NZ UT WOS:000231377900024 ER PT J AU Roden, MM Zaoutis, TE Buchanan, WL Knudsen, TA Sarkisova, TA Schaufele, RL Sein, M Sein, T Chiou, CC Chu, JH Kontoyiannis, DP Walsh, TJ AF Roden, MM Zaoutis, TE Buchanan, WL Knudsen, TA Sarkisova, TA Schaufele, RL Sein, M Sein, T Chiou, CC Chu, JH Kontoyiannis, DP Walsh, TJ TI Epidemiology and outcome of zygomycosis: A review of 929 reported cases SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID LIPOSOMAL AMPHOTERICIN-B; BONE-MARROW-TRANSPLANTATION; OF-THE-LITERATURE; ACUTE LYMPHOBLASTIC-LEUKEMIA; RHINO-ORBITAL MUCORMYCOSIS; PRIMARY CUTANEOUS MUCORMYCOSIS; CUNNINGHAMELLA-BERTHOLLETIAE INFECTION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ACUTE MYELOGENOUS LEUKEMIA; MASSIVE FATAL HEMOPTYSIS AB Background. Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. Methods. We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. Results. The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [ 66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Conclusions. Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy. C1 NCI, Pediat Oncol Branch, CRC, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Yang Ming Univ, Taipei 112, Taiwan. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, CRC, 1W,1-5740,10 Ctr Dr, Bethesda, MD 20892 USA. EM Walsht@mail.nih.gov NR 477 TC 773 Z9 813 U1 5 U2 20 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2005 VL 41 IS 5 BP 634 EP 653 DI 10.1086/432579 PG 20 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952HW UT WOS:000230995600010 PM 16080086 ER PT J AU Lucas, AH Apicella, MA Taylor, CE AF Lucas, AH Apicella, MA Taylor, CE TI Carbohydrate moieties as vaccine candidates SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INFLUENZAE TYPE-B; PNEUMONIAE CAPSULAR POLYSACCHARIDES; PNEUMOCOCCAL CONJUGATE VACCINE; T-CELL HELP; STREPTOCOCCUS-PNEUMONIAE; IMMUNE-RESPONSE; MARGINAL ZONE; PROTECTIVE ANTIBODIES; POSITIVE SELECTION; PEPTIDE MIMOTOPES AB Carbohydrate epitopes or glycotopes are structurally diverse, occur in a variety of chemical contexts, and are present on the surfaces of cells in the body and on the surfaces of pathogens. These various structures and modes of presentation affect how they are perceived and processed by the body and dictate the outcome of the immune response directed against them. This review focuses on mechanisms of carbohydrate immunity, with an emphasis on carbohydrate vaccines that have been or are being developed for protection against encapsulated bacterial pathogens. We discuss the cellular basis of carbohydrate immunity, newly identified glycotope processing pathways and recognition capabilities, and the synthetic and microarray technologies that are being developed that will permit new experimental approaches to carbohydrate vaccine development and the exploration of the interaction of the immune system with self and nonself glycans. C1 NIAID, Bacterial Resp Dis Program, Div Microbiol & Infect Dis, Rockville, MD 20852 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. RP Taylor, CE (reprint author), NIAID, Bacterial Resp Dis Program, Div Microbiol & Infect Dis, 6610 Rockledge Dr,Rm 5045, Rockville, MD 20852 USA. EM ctaylor@niaid.nih.gov NR 77 TC 36 Z9 36 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2005 VL 41 IS 5 BP 705 EP 712 DI 10.1086/432582 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952HW UT WOS:000230995600019 PM 16080094 ER PT J AU Miller, MF Haley, C Koziel, MJ Rowley, CF AF Miller, MF Haley, C Koziel, MJ Rowley, CF TI Impact of hepatitis C virus on immune restoration in HIV-infected patients who start highly active antiretroviral therapy: A meta-analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; COINFECTION; PROGRESSION; RECOVERY; MORBIDITY; MORTALITY; SURVIVAL; BIAS AB Background. There are conflicting data in the medical literature regarding the degree of immune restoration ( as measured by CD4 cell count) in patients who commence highly active antiretroviral therapy (HAART) when coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), compared with those with HIV infection alone. Methods. We performed a meta-analysis that compared CD4 cell count increases after HAART initiation in HCV-negative and HCV-positive patients who were infected with HIV. Published studies in the English-language medical literature that involved cohorts of HCV-negative and HCV-positive patients who were coinfected with HIV were obtained by searching the Medline, Embase Drugs and Pharmacology, and EBM Review-Cochrane Central Register of Controlled Trials databases. Data were extracted independently from relevant studies by 3 investigators and were used in a fixed-effects meta-analysis to determine the mean difference in the expected CD4 count change in the 2 groups. Results. Eight trials involving 6216 patients were analyzed. Patients with HIV-HCV coinfection had a mean increase in the CD4 cell count that was 33.4 cells/mm(3) (95% CI, 23.5-43.3 cells/mm(3)) less than that for HIV-infected patients without HCV infection. The results of the meta-analysis were independent of any one study and were not influenced by the year in which HAART was started. Conclusions. This meta-analysis shows that patients with HIV-HCV coinfection do, in fact, have less immune reconstitution, as determined by CD4 cell count after 48 weeks of HAART, than do patients with HCV infection alone. Future research should examine whether an impaired immunologic response corresponds with meaningful virologic and clinical outcomes. C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. NCI, Div Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Austin Med Educ Programs, Austin, TX USA. RP Rowley, CF (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Lowry Bldg,Ste GB,110 Francis St, Boston, MA 02215 USA. EM crowley1@bidmc.harvard.edu FU NIAID NIH HHS [5T32AI007387-15] NR 20 TC 82 Z9 87 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2005 VL 41 IS 5 BP 713 EP 720 DI 10.1086/432618 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952HW UT WOS:000230995600020 PM 16080095 ER PT J AU Chi-Fishman, G AF Chi-Fishman, G TI Quantitative lingual, pharyngeal and laryngeal ultrasonography in swallowing research: A technical review SO CLINICAL LINGUISTICS & PHONETICS LA English DT Review DE ultrasonography; swallowing; deglutition; tongue; hyoid bone ID REAL-TIME ULTRASOUND; PROGRESSIVE SUPRANUCLEAR PALSY; VOLUMETRIC IMAGING-SYSTEM; TONGUE MOVEMENT; HYOID MOVEMENT; NORMAL ADULTS; NONINVASIVE ASSESSMENT; DIFFERENT AGES; PHYSIOLOGY; DEGLUTITION AB Because of its distinct advantage in radiation-free soft tissue imaging, ultrasonography has been widely used to study lingual, pharyngeal, hyoid, laryngeal, and even esophageal action during swallowing in individuals of all ages. Qualitative ultrasonographic observations have made considerable contributions to our understanding of deglutition. Quantitative ultrasonographic swallowing research has also grown by leaps and bounds over the years with advances in imaging technologies and analytical methodologies. As a technical primer for new investigators, this paper reviews the modem methods for quantitative analysis in ultrasonographic swallowing research. The intended outcome is a basic understanding of the application of ultrasonography with various analysis options to the quantitative study of the deglutitive action of selected upper aerodigestive structures. Though proven useful for swallowing research, ultrasonography has inherent limitations and methodological issues. Future technological advancement and sophisticated image processing and analysis algorithms will resolve some of these issues. C1 Natl Inst Hlth, Oral Pharyngeal Funct & & Ultrasound Imaging Lab, Phys Disabilities Branch, Rehab Med Dept,Clin Ctr, Bethesda, MD 20892 USA. RP Chi-Fishman, G (reprint author), Natl Inst Hlth, Oral Pharyngeal Funct & & Ultrasound Imaging Lab, Phys Disabilities Branch, Rehab Med Dept,Clin Ctr, 10 Ctr Dr, Bethesda, MD 20892 USA. EM gcf@nih.gov NR 72 TC 20 Z9 23 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9206 J9 CLIN LINGUIST PHONET JI Clin. Linguist. Phon. PD SEP-NOV PY 2005 VL 19 IS 6-7 BP 589 EP 604 DI 10.1080/02699200500113996 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 947LV UT WOS:000230647800010 PM 16206486 ER PT J AU DePaulo, JR McMahon, FJ AF DePaulo, JR McMahon, FJ TI Genetic Approaches to Brain Diseases of Psychiatry - Introduction SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Editorial Material C1 Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP DePaulo, JR (reprint author), Johns Hopkins Univ, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-113, Baltimore, MD 21287 USA. EM psychchair@jhmi.edu RI McMahon, Francis/A-7290-2009 NR 0 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD SEP PY 2005 VL 5 IS 1 BP 1 EP 1 DI 10.1016/j.cnr.2005.08.001 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 973SP UT WOS:000232543200001 ER PT J AU McMahon, FJ Schulze, TG AF McMahon, FJ Schulze, TG TI Bipolar disorder as a phenotype in genetic studies SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE phenotype; bipolar disorder; heterogeneous; linkage; nosology ID POPULATION-BASED TWIN; AMINO-ACID OXIDASE; FAMILIAL AGGREGATION; PSYCHOTIC SYMPTOMS; LINKAGE ANALYSIS; PANIC DISORDER; EARLY-ONSET; SCHIZOPHRENIA; AGE; PEDIGREES AB Human genetics has now advanced to the stage that technology is no longer the limiting step in mapping genes that contribute to disease. Instead we now must confront the problems inherent in our diagnostic definitions-what geneticists call phenotypes. This challenge is nowhere clearer than in the field of bipolar affective disorder, where genetic methods have given us a tantalizing glimpse at etiology, but where the imprecision and heterogeneity of the phenotype have slowed progress. It is now time to return to the phenotype as a chief focus of genetic investigation. Published by Elsevier B.V. on behalf of Association for Research in Nervous and Mental Disease. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Heidelberg, Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. RP McMahon, FJ (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, 35 Convent Dr,Room 1A202, Bethesda, MD 20892 USA. EM mcmahonf@intra.nimh.nih.gov RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X NR 65 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD SEP PY 2005 VL 5 IS 1 BP 37 EP 43 DI 10.1016/j.cnr.2005.07.005 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 973SP UT WOS:000232543200006 ER PT J AU Niederehe, G AF Niederehe, G TI Developing psychosocial interventions for depression in dementia: Beginnings and future directions SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE intervention development; psychosocial intervention; depression; dementia; older adults ID DISEASE AB Teri, McKenzie, and LaFazia's (this issue) review of outcome studies suggests that a number of psychosocial interventions have shown positive benefits relative to depression in dementia. However, considerably more research will be required to marshal convincing and practice-relevant evidence for the efficacy of particular intervention techniques in producing clinically significant amelioration of depression in older adults with dementia. This commentary discusses risk-benefit considerations surrounding the use of interventions in vulnerable older adults, as well as suggesting issues to be addressed in intervention development studies on this class of interventions. C1 NIMH, Geriatr Res Branch, Bethesda, MD 20892 USA. RP Niederehe, G (reprint author), NIMH, Geriatr Res Branch, 6001 Execut Blvd,Room 7220,MSC 9634, Bethesda, MD 20892 USA. EM gniedere@mail.nih.gov NR 11 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 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD FAL PY 2005 VL 12 IS 3 BP 317 EP 320 DI 10.1093/clipsy/bpi043 PG 4 WC Psychology, Clinical SC Psychology GA 955KG UT WOS:000231224200013 ER PT J AU Yoshizawa, K Oishi, Y Matsumoto, M Nyska, A AF Yoshizawa, K Oishi, Y Matsumoto, M Nyska, A TI Ischemic brain damage after ketamine and xylazine treatment in a young laboratory monkey (Macaca fascicularis) SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HYPOTENSIVE INFARCTION; PROCEDURAL SEDATION; SPINAL-CORD; MULATTA; PHENCYCLIDINE; NEUROTOXICITY; ANESTHESIA; NECROSIS; NEURONS AB After a 4-year-old female laboratory cynomolgus monkey manifested neurological abnormalities, including tetanic spasm, after intramuscular injection of 20 mg/kg ketamine, we administered 2 mg/kg xylazine in an attempt to control the seizure. However, the animal continued to display opisthotonus, nystagmus, and symptomatic epilepsia. Analysis of blood chemistry revealed a dramatically increased creatine phosphokinase level. Abnormal histopathological findings included acute neuronal necrosis or glial reaction or both in the cerebral cortex, nucleus lentiformis, hippocampus, cerebellar cortex and nucleus, and medulla oblongata; severe myocardial hemorrhagic necrosis; and hepatic subcapsular hematoma. Although the mechanism of this neuronal damage has not been clarified, it may be attributable to an ischemic condition in the brain, probably due to temporal cardiac arrest or hemorrhagic change in the liver and heart, with subsequent decreased blood pressure, after ketamine and/or xylazine treatment. Because both drugs often are used as general anesthetics in veterinary medicine, attention should be paid to this rare case with neural damage. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. Astellas Pharma Inc, Drug Safety Res Labs, Osaka, Japan. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, NIH, MD B3-06, Res Triangle Pk, NC 27709 USA. NR 44 TC 3 Z9 4 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD SEP PY 2005 VL 44 IS 5 BP 19 EP 24 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 965SS UT WOS:000231971200003 PM 16138776 ER PT J AU Yang, H Avila, MY Peterson-Yantorno, K Coca-Prados, M Stone, RA Jacobson, KA Civan, MM AF Yang, H Avila, MY Peterson-Yantorno, K Coca-Prados, M Stone, RA Jacobson, KA Civan, MM TI The cross-species A(3) adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure SO CURRENT EYE RESEARCH LA English DT Article DE A(3) adenosine receptors; aqueous humor inflow; Cl- channels; intraocular pressure; MRS 1292 ID NORMAL-TENSION GLAUCOMA; CL-CHANNELS; A(3) RECEPTOR; ACTIVATION; LIGANDS; DERIVATIVES; SELECTIVITY; MECHANISMS; AGONISTS; RABBITS AB Purpose: Antagonists to A(3) adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A(3)AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. Methods: NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. Results: Adenosine triggered A(3)AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 +/- 11 nM, p < 0.01) and by another A(3)AR antagonist effective in this system, MRS 1191. Topical application of the A3AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 +/- 0.8 mmHg at 25-mu M droplet concentration (n = 10, p < 0.005). Conclusions: MRS 1292 inhibits A(3)AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A(3) antagonist. C1 Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Yale Univ, Dept Ophthalmol & Visual Sci, New Haven, CT USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Civan, MM (reprint author), Univ Penn, Sch Med, Dept Physiol, A303 Richards Bldg,3700 Hamilton Walk, Philadelphia, PA 19104 USA. EM civan@mail.med.upenn.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20]; NEI NIH HHS [EY013624, EY 08343, EY01583, P30 EY001583, R01 EY008343, R01 EY013624] NR 44 TC 46 Z9 47 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 2005 VL 30 IS 9 BP 747 EP 754 DI 10.1080/02713680590953147 PG 8 WC Ophthalmology SC Ophthalmology GA 965VB UT WOS:000231977400004 PM 16146920 ER PT J AU Hansen, A Lipsky, PE Dorner, T AF Hansen, A Lipsky, PE Dorner, T TI Immunopathogenesis of primary Sjogren's syndrome: implications for disease management and therapy SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE animal models; immunopathogenesis; predisposing factors; serology; Sjogren's syndrome; therapy ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYCLIC CITRULLINATED PEPTIDE; B-LYMPHOCYTE STIMULATOR; NONOBESE DIABETIC MOUSE; LABIAL SALIVARY-GLANDS; PILOT CLINICAL-TRIAL; EPSTEIN-BARR-VIRUS; AUTOIMMUNE EXOCRINOPATHY; RHEUMATOID-ARTHRITIS; GENE-TRANSFER AB Purpose of review Recent studies have broadened our understanding of the etiopathogenesis and immunopathology of primary Sjogren's syndrome. This review highlights recent advances in understanding the underlying mechanisms of the disease as well as their implications for clinical handling and therapeutic options. Recent findings It becomes increasingly apparent that certain disturbances of the immune system (i.e. B-cell hyperreactivity and enhanced levels of B-cell-activating factor/B-lymphocyte stimulator) play a central role in this entity. Whether this is a primary abnormality or the result of predisposing factors or infectious, e.g. viral, agents remains uncertain. New insights into the pathogenesis also provide candidates for better diagnosis and classification of disease severity, such as flow cytometric analysis, measurement of soluble cell surface molecules, autoantibodies, cytokines, and ligands (B-cell-activating factor/B-lymphocyte stimulator). Whether B-cell-directed therapies (i.e. blocking B-cell-activating factor/B-lymphocyte stimulator, anti-CD20 therapy) will have an impact on primary Sjogren's syndrome needs to be shown in clinical trials. Alternative therapeutic approaches such as organ-targeted gene transfer are in development but must be carefully evaluated for safety and efficacy in preclinical models that resemble human primary Sjogren's syndrome. Summary The pathogenesis of primary Sjogren's syndrome is complex and the factors initiating and driving autoimmunity in this entity are largely unknown. Recent studies provide new insights into potential pathogenetic mechanisms of the disease and, thereby, the chance for improved strategies in disease management and therapy. C1 Univ Med Berlin, Outpatients Dept, CCM Charite, D-10117 Berlin, Germany. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD USA. RP Hansen, A (reprint author), Univ Med Berlin, Outpatients Dept, CCM Charite, Luisenstr 11-13A, D-10117 Berlin, Germany. EM arne.hansen@charite.de NR 102 TC 69 Z9 71 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD SEP PY 2005 VL 17 IS 5 BP 558 EP 565 DI 10.1097/01.bor.0000172801.56744.c3 PG 8 WC Rheumatology SC Rheumatology GA 957PM UT WOS:000231382800009 PM 16093833 ER PT J AU Stojanov, S Kastner, DL AF Stojanov, S Kastner, DL TI Familial autoinflammatory diseases: genetics, pathogenesis and treatment SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE genetics; hereditary recurrent fevers; inflammasome; systemic autoinflammatory diseases; therapy ID PERIODIC FEVER SYNDROME; MULTISYSTEM INFLAMMATORY DISEASE; MUCKLE-WELLS-SYNDROME; NF-KAPPA-B; INTERLEUKIN-1 RECEPTOR ANTAGONIST; BONE-MARROW-TRANSPLANTATION; ENCODING MEVALONATE KINASE; ACUTE-PHASE RESPONSE; HYPER-IGD SYNDROME; DEATH-DOMAIN-FOLD AB Purpose of review The systemic autoinflammatory diseases are characterised by seemingly unprovoked inflammation, without major involvement of the adaptive immune system. This review focuses mainly on a subset of these illnesses, the hereditary recurrent fevers, which include familial Mediterranean fever, the tumor necrosis factor receptor-associated periodic syndrome, the hyperimmunoglobulinemia D with periodic fever syndrome, and cryoprin-associated periodic syndromes. This review elucidates how recent advances have impacted diagnosis, pathogenesis, and treatment. Recent findings More than 170 mutations have been identified in the four genes underlying the six hereditary recurrent fevers. Genetic testing has broadened the clinical and geographic boundaries of these illnesses, given rise to the concept of the cryopyrin-associated periodic syndromes as a disease spectrum, and permitted diagnosis of compound heterozygotes for mutations in two different hereditary recurrent fever genes. Genetics has also advanced our understanding of amyloidosis, a complication of the hereditary recurrent fevers, and suggested a possible role for common hereditary recurrent fever variants in other inflammatory conditions. Recent advances in molecular pathophysiology include the elucidation of the N-terminal PYRIN domain in protein-protein interactions, the description of the NALP3 (cryopyrin) inflammasome as a macromolecular complex for interleukin-1 beta activation, and the identification of signaling defects other than defective receptor shedding in patients with tumor necrosis factor receptor-associated periodic syndrome. These molecular insights form the conceptual basis for targeted biological therapies. Summary Advances in molecular genetics extend our ability to recognize and treat patients with systemic autoinflammatory diseases and inform our understanding of the regulation of innate immunity in humans. C1 NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. RP Stojanov, S (reprint author), NIAMSD, Genet & Genom Branch, NIH, Bldg 9,Room 1W111,9 Mem Dr, Bethesda, MD 20892 USA. EM stojanos@mail.nih.gov NR 129 TC 203 Z9 211 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD SEP PY 2005 VL 17 IS 5 BP 586 EP 599 DI 10.1097/bor.0000174210.78449.6b PG 14 WC Rheumatology SC Rheumatology GA 957PM UT WOS:000231382800014 PM 16093838 ER PT J AU Ahmad, E Kingma, DW Jaffe, ES Schrager, JA Janik, J Wilson, W Stetler-Stevenson, M AF Ahmad, E Kingma, DW Jaffe, ES Schrager, JA Janik, J Wilson, W Stetler-Stevenson, M TI Flow cytometric immunophenotypic profiles of mature gamma delta T-cell malignancies involving peripheral blood and bone marrow SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE gamma delta T cell; lymphoma; large granular lymphocyte leukemia; flow cytometry ID LYMPHOMA; ENTITY; LOCALIZATION; SKIN AB Background: In this study we compared clinical findings with flow cytometric immunophenotypic results in a series of patients with aggressive and indolent gamma delta T-cell malignancies with peripheral blood and/or bone marrow involvement. Methods: Gamma delta T-cell malignancies were detected based on flow cytometric demonstration of an abnormal T-cell population staining positive with T-cell receptor gamma delta and confirmed by morphologic and clinical reviews. Clinical data were obtained through chart review and discussion with the patients' physicians. Results: Blood or bone marrow involvement was present in all patients. Hepatosplenic and cutaneous gamma delta T-cell lymphomas had an aggressive clinical course, whereas the gamma delta T-cell large granular lymphocyte (LGL) leukemias had an indolent course. Expressions of CD5, CD8, CD16, and CD57 differed in gamma delta T-cell LGL leukemia compared with hepatosplenic and cutaneous gamma delta T-cell lymphomas. Conclusions: Gamma delta T-cell malignancies have a poor prognosis with the exception of gamma delta T-cell LGL leukemia (indolent process). Because CD57 expression is specific for gamma delta T-cell LGL leukemias, expression of this antigen may be associated with a more indolent clinical course. Because cutaneous gamma delta T-cell lymphoma can present with peripheral blood involvement, flow cytometric evaluation of peripheral blood is important in staging these patients. Published 2005 Wiley-Liss, Inc. C1 NCI, NIH, Pathol Lab, CCR, Bethesda, MD 20892 USA. NCI, NIH, Metab Branch, CCR, Bethesda, MD 20892 USA. Good Samaritan Hosp, Dept Pathol, Dayton, OH USA. Carson City Hosp, Dept Pathol, Carson City, MI USA. NCI, NIH, CCR, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, NIH, Pathol Lab, CCR, Bldg 10,Room 2A-33, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov NR 16 TC 28 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2005 VL 67B IS 1 BP 6 EP 12 DI 10.1002/cyto.b.20063 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 962HW UT WOS:000231722900002 PM 15973700 ER PT J AU Mondoro, TH Henslee-Downey, PJ Peterson, CM AF Mondoro, TH Henslee-Downey, PJ Peterson, CM TI NHLBI plans for the promise of cell-based therapies SO CYTOTHERAPY LA English DT Editorial Material DE cell-based therapies; NHLBI; NIH; clinical research AB This article presents the National Heart, Lung and Blood Institute (NHLBI) perspective on the status of cell-based therapies. A summary of current and future NHLBI/National Institutes of Health (NIH) programs is given along with a history of the development of NHLBI/NIH resources to aid the advancement of cell-based therapies. A brief discussion of clinical research programs to utilize cell-based therapies is also included. C1 NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. RP Mondoro, TH (reprint author), NHLBI, Div Blood Dis & Resources, NIH, 6701 Rpckledge Dr,Room 10135, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP PY 2005 VL 7 IS 4 BP 317 EP 327 DI 10.1080/14653240500237741 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 964JK UT WOS:000231876900002 PM 16162453 ER PT J AU Perantoni, AO Timofeeva, O Naillat, F Richman, C Pajni-Underwood, S Wilson, C Vainio, S Dove, LF Lewandoski, M AF Perantoni, AO Timofeeva, O Naillat, F Richman, C Pajni-Underwood, S Wilson, C Vainio, S Dove, LF Lewandoski, M TI Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development SO DEVELOPMENT LA English DT Article DE Cre recombinase; Fgf8; kidney; Lim1; nephron; somitogenesis; T-Cre; Wnt4; mouse ID FIBROBLAST-GROWTH-FACTOR; HOMEOBOX GENE LIM1; METANEPHRIC MESENCHYME; CELL-SURVIVAL; URETERAL BUD; EPITHELIAL TRANSFORMATION; TARGETED DISRUPTION; EXPRESSION PATTERNS; RENAL DEVELOPMENT; VERTEBRATE LIMB AB To bypass the essential gastrulation function of Fgf8 and study its role in lineages of the primitive streak, we have used a new mouse line, T-Cre, to generate mouse embryos with pan-mesodermal loss of Fgf8 expression. Surprisingly, despite previous models in which Fgf8 has been assigned a pivotal role in segmentation/somite differentiation, Fgf8 is not required for these processes. However, mutant neonates display severe renal hypoplasia with deficient nephron formation. In mutant kidneys, aberrant cell death occurs within the metanephric mesenchyme (MM), particularly in the cortical nephrogenic zone, which provides the progenitors for recurring rounds of nephron formation. Prior to mutant morphological changes, Wnt4 and Lim1 expression, which is essential for nephrogenesis, is absent in MM. Furthermore, comparative analysis of Wnt4-null homozygotes reveals concomitant downregulation of Lim1 and diminished tubule formation. Our data support a model whereby FGF8 and WNT4 function in concert to induce the expression of Lim1 for MM survival and tubulogenesis. C1 NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. Univ Oulu, Dept Med Biochem & Mol Biol, FIN-90014 Oulu, Finland. Univ Oulu, Bioctr Oulu, FIN-90014 Oulu, Finland. RP Lewandoski, M (reprint author), NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. EM mlewandoski@mail.ncifcrf.gov RI Naillat, Florence/H-1002-2012 NR 72 TC 181 Z9 185 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 2005 VL 132 IS 17 BP 3859 EP 3871 DI 10.1242/dev.01945 PG 13 WC Developmental Biology SC Developmental Biology GA 972CG UT WOS:000232430900007 PM 16049111 ER PT J AU Zhang, C Gehlbach, P Gongora, C Cano, M Fariss, R Hose, S Nath, A Green, WR Goldberg, MF Zigler, JS Sinha, D AF Zhang, C Gehlbach, P Gongora, C Cano, M Fariss, R Hose, S Nath, A Green, WR Goldberg, MF Zigler, JS Sinha, D TI A potential role for beta- and gamma-crystallins in the vascular remodeling of the eye SO DEVELOPMENTAL DYNAMICS LA English DT Article DE hyaloid and retinal vessels; beta/gamma-crystallins; VEGF; astrocytes; vascular remodeling ID ALPHA-B-CRYSTALLIN; ENDOTHELIAL GROWTH-FACTOR; RAT OPTIC-NERVE; PROGRAMMED CELL-DEATH; RETINAL VASCULATURE; A-CRYSTALLIN; PROTECTIVE ACTIVITY; MAMMALIAN RETINA; VEGF EXPRESSION; CYTOCHROME-C AB We demonstrate that expression of beta- and gamma-crystallins is associated with intraocular vessels during normal vascular development of the eye and also in the Nucl rat, a mutant in which the hyaloid vascular system fails to regress normally. Real-Time RT PCR, Western blot and metabolic labeling studies indicate an increased expression of beta- and gamma-crystallins in Nucl retina. The increased expression of crystallins was localized to the astrocytes surrounding the intraocular vessels. A similar pattern of crystallin expression was also observed in the retinal vessels during normal development. Cultured human astrocytes exposed to 3-nitropropionic acid, an established model of neuronal hypoxia, increased VEGF expression, as expected, but also increased expression of crystallins. Our data suggest that crystallins may function together with VEGF during vascular remodeling. Interestingly, in human PFV (persistent fetal vasculature) disease, where the hyaloid vasculature abnormally persists after birth, we show that astrocytes express both VEGF and crystallins. (c) 2005 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Ophthalmol & Environm Hlth Sci, Sch Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. CNRS, UMR 5160, Fac Pharm, Montpellier, France. NEI, NIH, Bethesda, MD USA. RP Sinha, D (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Ophthalmol & Environm Hlth Sci, Sch Med, Baltimore, MD 21287 USA. EM Debasish@jhmi.edu FU NEI NIH HHS [K08EY13420] NR 66 TC 33 Z9 36 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2005 VL 234 IS 1 BP 36 EP 47 DI 10.1002/dvdy.20494 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 957EY UT WOS:000231353700005 PM 16003775 ER PT J AU Amano, T Fu, LZ Marshak, A Kwak, O Shi, YB AF Amano, T Fu, LZ Marshak, A Kwak, O Shi, YB TI Spatio-temporal regulation and cleavage by matrix metalloproteinase stromelysin-3 implicate a role for laminin receptor in intestinal remodeling during Xenopus laevis metamorphosis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE stromelysin-3; laminin receptor; matrix metalloproteinase; extracellular matrix; Xenopus laevis; cell surface substrate ID THYROID-HORMONE REGULATION; MESSENGER-RNA; BINDING PROTEIN; MOUSE STROMELYSIN-3; EXPRESSION PATTERN; FROG METAMORPHOSIS; BREAST CARCINOMAS; RESPONSE GENES; CELL-SURFACE; CANCER-CELLS AB The 37-kd laminin receptor precursor (LR) was first identified as a 67-kd protein that binds laminin with high affinity. We have recently isolated the Xenopus laevis LR as an in vitro substrate of matrix metalloproteinase stromelysin-3 (ST3), which is highly upregulated during intestinal metamorphosis in Xenopus laevis. Here, we show that LR is expressed in the intestinal epithelium of premetamorphic tadpoles. During intestinal metamorphosis, LR is downregulated in the apoptotic epithelium and concurrently upregulated in the connective tissue but with little expression in the developing adult epithelium. Toward the end of metamorphosis, as adult epithelial cells differentiate, they begin to express LR. Furthermore, LR is cleaved during intestinal remodeling when ST3 is highly expressed or in premetamorphic intestine of transgenic tadpoles overexpressing ST3. These results suggest that LR plays a role in cell fate determination and tissue morphogenesis, in part through its cleavage by ST3. Interestingly, high levels of LR are known to be expressed in tumor cells, which are often surrounded by fibroblasts expressing ST3, suggesting that LR cleavage by ST3 plays a role in both physiological and pathological processes. (c) 2005 Wiley-Liss, Inc. C1 NICHD, LGRD, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHD, LGRD, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM Shi@helix.nih.gov NR 62 TC 14 Z9 15 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2005 VL 234 IS 1 BP 190 EP 200 DI 10.1002/dvdy.20511 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 957EY UT WOS:000231353700020 PM 16059908 ER PT J AU You, SH Jang, SH Kim, YH Kwon, YH Barrow, I Hallett, M AF You, SH Jang, SH Kim, YH Kwon, YH Barrow, I Hallett, M TI Cortical reorganization induced by virtual reality therapy in a child with hemiparetic cerebral palsy SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; INDUCED MOVEMENT THERAPY; FUNCTIONAL MRI; MIRROR MOVEMENTS; STROKE; NEURONS; CORTEX; HAND; FMRI AB Virtual reality (VR) therapy is a new, neurorehabilitation intervention aimed at enhancing motor performance in children with hemiparetic cerebral palsy (CP). This case report investigated the effects of VR therapy on cortical reorganization and associated motor function in an 8-year-old male with hemiparetic CP. Cortical activation and associated motor development were measured before and after VR therapy using functional magnetic resonance imaging (fMRI) and standardized motor tests. Before VR therapy, the bilateral primary sensorimotor cortices (SMCs) and ipsilateral supplementary motor area (SMA) were predominantly activated during affected elbow movement. After VR therapy, the altered activations disappeared and the contralateral SMC was activated. This neuroplastic change was associated with enhanced functional motor skills including reaching, self-feeding, and dressing. These functions were not possible before the intervention. To our knowledge, this is the first fMRI study in the literature that provides evidence for neuroplasticity after VR therapy in a child with hemiparetic CP. C1 Hampton Univ, Phys Therapy Program, Hampton, VA 23668 USA. Yeungnam Univ, Coll Med, Dept Phys Med & Rehabil, Gyongsan, South Korea. Sungkyunkwan Univ, Coll Med, Dept Phys Med & Rehabil, Seoul, South Korea. Yeungnam Univ, Sch Med, Dept Phys Med & Rehabil, Gyongsan, South Korea. NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP You, SH (reprint author), Hampton Univ, Phys Therapy Program, Phoenix Hall 219B, Hampton, VA 23668 USA. EM sung.you@hamptonu.edu RI Kim, Yun Hee/F-4600-2014 NR 29 TC 75 Z9 78 U1 5 U2 24 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD SEP PY 2005 VL 47 IS 9 BP 628 EP 635 DI 10.1017/S0012162205001234 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 958SS UT WOS:000231469100011 PM 16138671 ER PT J AU Tronick, EZ Messinger, DS Weinberg, MK Lester, BA LaGasse, L Seifer, R Bauer, CR Shankaran, S Bada, H Wright, LL Poole, K Liu, J AF Tronick, EZ Messinger, DS Weinberg, MK Lester, BA LaGasse, L Seifer, R Bauer, CR Shankaran, S Bada, H Wright, LL Poole, K Liu, J TI Cocaine exposure is associated with subtle compromises of infants' and mothers' social-emotional behavior and dyadic features of their interaction in the face-to-face still-face paradigm SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE infant; mother; emotion; cocaine exposure; communication ID MATERNAL LIFE-STYLE; DRUG EXPOSURE; ATTACHMENT BEHAVIOR; SUBSTANCE EXPOSURE; GENDER-DIFFERENCES; CHILDREN; PREGNANCY; PSYCHOPATHOLOGY; MECHANISMS; TOXICOLOGY AB Prenatal cocaine and opiate exposure are thought to subtly compromise social and emotional development. The authors observed a large sample of 236 cocaine-exposed and 459 nonexposed infants (49 were opiate exposed and 646 nonexposed) with their mothers in the face-to-face still-face paradigm. Infant and maternal behaviors were microanalytically coded. No opiate-exposure effects were detected. However, mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. Although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Child Dev Unit, Boston, MA 02115 USA. Univ Miami, Dept Psychol, Miami, FL 33152 USA. Univ Miami, Dept Pediat, Miami, FL 33152 USA. Brown Univ, Sch Med, Miller Sch Med, Providence, RI 02912 USA. Brown Univ, Sch Med, Ctr Study Children Risk, Dept Psychiat, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. Brown Univ, Sch Med, Ctr Study Human Dev, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Bradley Hosp, Providence, RI USA. Univ Miami, Miller Sch Med, Dept Pediat, Coral Gables, FL 33124 USA. Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48202 USA. Univ Tennessee, Coll Med, Hlth Sci Ctr, Dept Pediat, Knoxville, TN 37996 USA. Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Messinger, DS (reprint author), Flipse Bldg,POB 249229, Coral Gables, FL 33124 USA. EM dmessinger@miami.edu RI Reis, Aline/G-9573-2012; OI Seifer, Ronald/0000-0003-4879-2839 FU NIDA NIH HHS [U10 DA024119] NR 56 TC 71 Z9 71 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD SEP PY 2005 VL 41 IS 5 BP 711 EP 722 DI 10.1037/0012-1649.41.5.711 PG 12 WC Psychology, Developmental SC Psychology GA 967XT UT WOS:000232125200002 PM 16173869 ER PT J AU Roopnarine, JL Lamb, ME Fouts, HN Lewis-Elligan, TY AF Roopnarine, JL Lamb, ME Fouts, HN Lewis-Elligan, TY TI Mothers' and fathers' behaviors toward their 3-to 4-month-old infants in lower, middle, and upper socioeconomic African American families SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE African Americans; caregiving behaviors; egalitarianism ID TRADITIONAL SWEDISH FAMILIES; CHILD-CARE; LOW-INCOME; DISCIPLINARY PRACTICES; PENNSYLVANIA INFANT; DEVELOPMENT PROJECT; FUNCTIONING STYLE; URBAN FAMILIES; NEW-DELHI; INVOLVEMENT AB African American mothers' and fathers' availability, caregiving, and social behaviors toward their infants in and around their homes were examined. Twenty lower, 21 middle, and 21 upper socioeconomic families and their 3- to 4-month-old infants were observed for 4 3-hr blocks between 8:00 a.m. and 8:00 p.m. on 4 different weekdays. With increasing economic resources, children's exposure to multiple caregivers and nonresident fathers declined. Mothers were more available to infants than fathers were, regardless of socioeconomic status. Mothers fed infants more than fathers did, whereas fathers vocalized more and displayed more affection to infants than mothers did when they were examined in proportion to caregiver presence. Mothers and fathers interacted with male and female infants quite similarly, although, in the upper socioeconomic families, fathers of daughters were more available than fathers of sons. Fathers and mothers in the different socioeconomic groups held, displayed affection to, and soothed their infants differently. C1 Syracuse Univ, Dept Child & Family Studies, Syracuse, NY 13244 USA. NICHHD, Bethesda, MD 20892 USA. Univ Cambridge, Fac Social & Polit Sci, Cambridge, England. Depaul Univ, Dept Sociol, Chicago, IL 60604 USA. RP Roopnarine, JL (reprint author), Syracuse Univ, Dept Child & Family Studies, Syracuse, NY 13244 USA. EM jroopnar@syr.edu NR 74 TC 36 Z9 36 U1 3 U2 13 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD SEP PY 2005 VL 41 IS 5 BP 723 EP 732 DI 10.1037/0012-1649.41.5.723 PG 10 WC Psychology, Developmental SC Psychology GA 967XT UT WOS:000232125200003 PM 16173870 ER PT J AU Veluthakal, R Chvyrkova, I Tannous, M McDonald, P Amin, R Hadden, T Thurmond, DC Quon, MJ Kowluru, A AF Veluthakal, R Chvyrkova, I Tannous, M McDonald, P Amin, R Hadden, T Thurmond, DC Quon, MJ Kowluru, A TI Essential role for membrane lipid rafts in interleukin-1 beta - Induced nitric oxide release from insulin-secreting cells potential regulation by caveolin-1(+) SO DIABETES LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Diabetes-Association CY JUN 04-08, 2004 CL Orlando, FL SP Amer Diabet Assoc ID PANCREATIC BETA-CELL; DEPENDENT DIABETES-MELLITUS; ACTIVATED PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; PLASMA-MEMBRANE; CAPILLARY-PERMEABILITY; SIGNAL-TRANSDUCTION; ACTIN CYTOSKELETON; CAVEOLAE MEMBRANE; HIT-T15 CELLS AB We recently reported that the activation of H-Ras represents one of the signaling steps underlying the interleukin-1 beta (IL-1 beta)-mediated metabolic dysfunction of the islet beta-cell. In the present study, we examined potential contributory roles of membrane-associated, cholesterol-enriched lipid rafts/caveolae and their constituent proteins (e.g., caveolin-1 [Cav-1]) as potential sites for IL-1 beta-induced nitric oxide (NO) release in the isolated beta-cell. Disruption of lipid rafts (e.g., with cyclodextrin) markedly reduced IL-1 beta-induced gene expression of inducible NO synthase (iNOS) and NO release from beta-cells. Immunologic and confocal microscopic evidence also suggested a transient but significant stimulation of tyrosine phosphorylation of Cav-1 in beta-cells briefly (for 15 min) exposed to IL-1 beta that was markedly attenuated by, three structurally distinct inhibitors of protein tyrosine phosphorylation. Overexpression of an inactive mutant of Cav-1 lacking the tyrosine phosphorylation site (Y14F) or an siRNA-mediated Cav-1 knock down also resulted in marked attenuation of IL-1 beta-induced iNOS gene expression and NO release from these cells, thus further implicating Cav-1 in this signaling cascade. IL-1 beta treatment also increased (within 20 min) the translocation of H-Ras into lipid rafts. Here we provide the first evidence to suggest that tyrosine phosphorylation of Cav-1. and subsequent interaction among members of the Ras signaling pathway within the membrane lipid microdomains represent early signaling mechanisms of IL-1 beta in beta-cells. C1 Wayne State Univ, Dept Pharmaceut Sci, Detroit, MI 48201 USA. Wayne State Univ, Dept Internal Med, Detroit, MI 48201 USA. John D Dingell VA Med Ctr, Cell Biochem Res Lab, Detroit, MI USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Ctr Diabet Res, Indianapolis, IN USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Kowluru, A (reprint author), Wayne State Univ, Dept Pharmaceut Sci, 259 Mack Ave, Detroit, MI 48201 USA. EM akowluru@med.wayne.edu RI Quon, Michael/B-1970-2008; Amin, Raj/M-1355-2016; OI Amin, Raj/0000-0001-8741-0018; Quon, Michael/0000-0002-9601-9915 FU NIDDK NIH HHS [DK-56005] NR 51 TC 22 Z9 23 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2005 VL 54 IS 9 BP 2576 EP 2585 DI 10.2337/diabetes.54.9.2576 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959NX UT WOS:000231525900009 PM 16123345 ER PT J AU Kim, WH Lee, JW Suh, YH Hong, SH Choi, JS Lim, JH Song, JH Gao, B Jung, MH AF Kim, WH Lee, JW Suh, YH Hong, SH Choi, JS Lim, JH Song, JH Gao, B Jung, MH TI Exposure to chronic high glucose induces beta-cell apoptosis through decreased interaction of glucokinase with mitochondria - Downregulation of glucokinase in pancreatic beta-cells SO DIABETES LA English DT Article ID CYTOCHROME-C RELEASE; INDUCED INSULIN-SECRETION; FATTY-ACIDS; DEPENDENT MECHANISM; GENE-EXPRESSION; BAX; TOXICITY; ISLETS; GLUT2; OVEREXPRESSION AB Chronic hyperglycemia is toxic to pancreatic beta-cells, impairing cellular functioning as observed in type 2 diabetes; however, the mechanism underlying beta-cell dysfunction and the resulting apoptosis via glucose toxicity are not fully characterized. Here; using MIN6N8 cells, a mouse pancreatic beta-cell line, we show that chronic exposure to high glucose increases cell death mediated by Bax oligomerization, cytochrome C release, and caspase-3 activation. During apoptosis, glucokinase (GCK) expression decreases in high-glucose-treated cells, concomitant with a decrease in cellular ATP production and insulin secretion. Moreover; exposure to a chronically high dose of glucose decreases interactions between GCK and mitochondria with an increase in Bax binding to mitochondria and cytochrome C release. These events are prevented by GCK overexpression, and phosphorylation of proapoptotic Bad proteins in GCK-overexpressing cells is prolonged compared with Neo-transfected cells. Similar results are obtained using primary islet cells. Collectively, these data demonstrate that beta-cell apoptosis from exposure to chronic high glucose occurs in relation to lowered GCK expression and reduced association with mitochondria. Our results show that this may be one mechanism by which glucose is toxic to beta-cells and suggests a novel approach to prevent and treat diabetes by manipulating Bax- and GCK-controlled signaling to promote apoptosis or proliferation. C1 Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, Seoul 122701, South Korea. Korea Res Inst Stand & Sci, Div Opt Metrol, Yuseong, South Korea. NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Jung, MH (reprint author), Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, 5 Nokbun Dong, Seoul 122701, South Korea. EM jung0603@nih.go.kr NR 38 TC 87 Z9 96 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2005 VL 54 IS 9 BP 2602 EP 2611 DI 10.2337/diabetes.54.9.2602 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959NX UT WOS:000231525900012 PM 16123348 ER PT J AU Feng, NP Young, SF Aguilera, G Puricelli, E Adler-Wailes, DC Sebring, NG Yanovski, JA AF Feng, NP Young, SF Aguilera, G Puricelli, E Adler-Wailes, DC Sebring, NG Yanovski, JA TI Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity SO DIABETES LA English DT Article ID RECEPTOR GENE; BODY-COMPOSITION; VARIANTS; IDENTIFICATION; MUTATIONS; MOUSE; PEPTIDES; INSULIN; LINKAGE; SYSTEM AB Both human linkage studies and MC3R knockout mouse models suggest that the MC3R may play an important role in energy homeostasis. Here we show that among 355 overweight and nonoverweight children, 8.2% were double homozygous for a pair of missense MC3R sequence variants (Thr6Lys and Val81Ile). Such children were significantly heavier (BMI and BMI SD score: P < 0.0001), had more body fat (body fat mass and percentage fat mass: P < 0.001), and had greater plasma leptin (P < 0.0001) and insulin concentrations (P < 0.001) and greater insulin resistance (P < 0.008) than wild-type or heterozygous children. Both sequence variants were more common in African-American than Caucasian children. In vitro expression studies found the double mutant MC3R was partially inactive, with significantly fewer receptor binding sites, decreased signal transduction, and less protein expression. We conclude that diminished MC3R expression in this double MC3R variant may be a predisposing factor for excessive body weight gain in children. C1 NIH, Unit Growth & Obes, Bethesda, MD 20892 USA. NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, Rockville, MD USA. Univ Insubria, Dept Pediat, Varese, Italy. NIH, Warren Grant Magnuson Clin Ctr, Dept Nutr, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NIH, Unit Growth & Obes, 10 Ctr Dr,Hatfield CRC,Rm 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [HD-000641, Z01 HD000641] NR 22 TC 71 Z9 74 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2005 VL 54 IS 9 BP 2663 EP 2667 DI 10.2337/diabetes.54.9.2663 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959NX UT WOS:000231525900019 PM 16123355 ER PT J AU Franks, PW Luan, J Barroso, I Brage, S Sanchez, JLG Ekelund, U Rios, MS Schafer, AJ O'Rahilly, S Wareham, NJ AF Franks, PW Luan, J Barroso, I Brage, S Sanchez, JLG Ekelund, U Rios, MS Schafer, AJ O'Rahilly, S Wareham, NJ TI Variation in the eNOS gene modifies the association between total energy expenditure and glucose intolerance SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; TYPE-2 DIABETES-MELLITUS; SKELETAL-MUSCLE; INSULIN-RESISTANCE; BLOOD-PRESSURE; EXERCISE INCREASES; ENDOTHELIAL-CELLS; PHYSICAL-ACTIVITY; LIFE-STYLE; POLYMORPHISMS AB Endothelium-derived nitric oxide (NO) facilitates skeletal muscle glucose uptake. Energy expenditure induces the endothelial NO synthase (eNOS) gene, providing a mechanism for insulin-independent glucose disposal. The object was to test 1) the association of genetic variation in eNOS, as assessed by haplotype-tagging single nucleotide polymorphisms (htSNPs) with type 2 diabetes, and 2) the interaction between eNOS haplotypes and total energy expenditure on glucose intolerance. Using multivariate models, we tested associations between eNOS htSNPs and diabetes (n = 4611 and 474 case and control subjects, respectively) and glucose intolerance (two cohorts of n = 706 and 738 U.K. and Spanish Caucasians, respectively), and we tested eNOS x total energy expenditure interactions on glucose intolerance. An overall association between eNOS haplotype and diabetes was observed (P = 0.004). Relative to the most common haplotype (111), two haplotypes (121 and 212) tended to increase diabetes risk (OR 1.22, 95% CI 0.96-1.55), and one (122) was associated with decreased risk (0.58, 0.39-0.86). In the cohort studies, no association was observed between haplotypes and 2-h glucose (P > 0.10). However, we observed a significant total energy expenditure- haplotype interaction (P = 0.007). Genetic variation at the eNOS locus is associated with diabetes, which may be attributable to an enhanced effect of total energy expenditure on glucose disposal in individuals with specific eNOS haplotypes. Gene-environment interactions such as this may help explain why replication of genetic association frequently fails. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. MRC, Epidemiol Unit, Cambridge, England. Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England. Hosp Univ Clin San Carlos, Dept Med Interna 2, Madrid, Spain. Incyte Genom, Cambridge, England. Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England. Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. 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; njw1004@medschl.cam.ac.uk RI Ekelund, Ulf/A-1046-2008; Brage, Soren/C-6415-2013 OI Brage, Soren/0000-0002-1265-7355 FU Wellcome Trust NR 49 TC 18 Z9 18 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2005 VL 54 IS 9 BP 2795 EP 2801 DI 10.2337/diabetes.54.9.2795 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959NX UT WOS:000231525900035 PM 16123371 ER PT J AU Roglic, G Unwin, N Bennett, PH Mathers, C Tuomilehto, J Nag, S Connolly, V King, H AF Roglic, G Unwin, N Bennett, PH Mathers, C Tuomilehto, J Nag, S Connolly, V King, H TI The burden of mortality attributable to diabetes - Realistic estimates for the year 2000 SO DIABETES CARE LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 05-09, 2004 CL Munich, GERMANY SP European Assoc Study Diabetes ID IMPAIRED GLUCOSE REGULATION; GLOBAL PREVALENCE; FOLLOW-UP; DISEASE; POPULATION; COHORT; RISK; HYPERGLYCEMIA; PROJECTIONS; DEATH AB OBJECTIVE- To estimate the global number of excess deaths due to diabetes in the year 2000. RESEARCH DESIGN AND METHODS- We used a computerized generic formal disease model (DisMod 11), used by the World Health Organization to assess disease burden through modeling the relationships between incidence, prevalence, and disease-specific mortality. Baseline input data included population structure, age- and sex-specific estimates of diabetes prevalence, and available published estimates of relative risk of death for people with diabetes compared with people without diabetes. The results were validated with population-based observations and independent estimates of relative risk of death. RESULTS- The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths. Excess mortality attributable to diabetes accounted for 2-3% of deaths in poorest countries and over 8% in the U.S., Canada, and the Middle East. In people 35-64 years old, 6-27% of deaths were attributable to diabetes. CONCLUSIONS- These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death. C1 WHO, Dept Chron Dis & Hlth Promot, CH-1211 Geneva, Switzerland. NIDDK, NIH, Phoenix, AZ USA. WHO, Measurement & Hlth Informat, Geneva, Switzerland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. S Ostrobot Cent Hosp, Seinajoki, Finland. James Cook Univ Hosp, Diabet Care Ctr, Middlesbrough, Cleveland, England. RP Roglic, G (reprint author), WHO, Dept Chron Dis & Hlth Promot, 20 Ave Appia, CH-1211 Geneva, Switzerland. EM roglicg@who.int NR 28 TC 406 Z9 442 U1 2 U2 27 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2005 VL 28 IS 9 BP 2130 EP 2135 DI 10.2337/diacare.28.9.2130 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959NV UT WOS:000231525700007 PM 16123478 ER PT J AU Lee, YH Nair, S Rousseau, E Allison, DB Page, GP Tataranni, PA Bogardus, C Permana, PA AF Lee, YH Nair, S Rousseau, E Allison, DB Page, GP Tataranni, PA Bogardus, C Permana, PA TI Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes SO DIABETOLOGIA LA English DT Article DE adipocyte; adipose tissue; gene expression; inflammation; microarray; obesity ID TUMOR-NECROSIS-FACTOR; OXYGEN-REGULATED PROTEIN; WHITE ADIPOSE-TISSUE; INSULIN-RESISTANCE; DIABETES-MELLITUS; OVERWEIGHT; CLONING; ORP150; ALPHA; CELLS AB Aims/hypothesis: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. Methods: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25 +/- 3 kg/m(2)) and 19 obese (BMI 55 +/- 8 kg/m(2)) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. Results: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/ immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1 alpha. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22 - q24, a region with linkage to obesity in the Pima Indians. Conclusions/interpretation: This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity. C1 NIDDKD, Obes 7 Diabet clin Res Sect, Phoenix epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. Carl T hayden Vet Affairs Med Ctr, Phoenix, AZ 85012 USA. RP Permana, PA (reprint author), Carl T hayden Vet Affairs Med Ctr, ERS-151,650 E Indian Sch Rd, Phoenix, AZ 85012 USA. EM paska.permana@med.va.gov OI Allison, David/0000-0003-3566-9399 FU NIDDK NIH HHS [Z01 DK069075-08, P30DK056336, P30 DK056336] NR 38 TC 117 Z9 123 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2005 VL 48 IS 9 BP 1776 EP 1783 DI 10.1007/s00125-005-1867-3 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 965GT UT WOS:000231939300012 PM 16059715 ER PT J AU Nair, S Lee, YH Rousseau, E Cam, M Tataranni, PA Baier, LJ Bogardus, C Permana, PA AF Nair, S Lee, YH Rousseau, E Cam, M Tataranni, PA Baier, LJ Bogardus, C Permana, PA TI Increased expression of inflammation-related genes in cultured preadipocytes/stromal vascular cells from obese compared with non-obese Pima Indians SO DIABETOLOGIA LA English DT Article DE adipocyte; adipose tissue; gene expression; inflammation; microarray; obesity; obesity-related inflammation; preadipocyte; stromal vascular cells; tissue remodelling ID ADIPOSE-TISSUE; IN-VITRO; MATRIX; INTERLEUKIN-8; MACROPHAGE; RELEASE AB Aims/hypothesis: The specific contributions made by the various cell types in adipose tissue to obesity, particularly obesity-related inflammation, need to be clarified. The aim of this study was to elucidate the potential role of adipocyte precursor cells (preadipocytes/stromal vascular cells [SVC]). Methods: We performed Affymetrix oligonucleotide microarray expression profiling of cultured abdominal subcutaneous preadipocytes/SVC isolated from the adipose tissue of 14 non-obese ( BMI 25 +/- 4 kg/m(2)) and 14 obese ( 55 +/- 8 kg/m(2)) non-diabetic Pima Indian subjects. Quantitative real-time PCR (RT-PCR) was used to verify the differential expression of several genes in an independent group of subjects. Results: We identified 218 differentially expressed genes with p values less than 0.01. Microarray expression profiling revealed that the expression of inflammation-related genes was significantly upregulated in preadipocytes/SVC of obese individuals. Quantitative RT-PCR confirmed the upregulation of IL8, CTSS, ITGB2, HLA-DRA, CD53, PLA2G7 and MMP9 in preadipocytes/SVC of obese subjects. Conclusions/ interpretation: The upregulation of inflammation-related genes in preadipocytes/SVC of obese subjects may increase the recruitment of immune cells into adipose tissue and may also result in changes in the extracellular matrix ( tissue remodelling) to accommodate adipose tissue expansion in obesity. C1 NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Carl T Hayden Vet Affairs Med Ctr, Phoenix, AZ USA. RP Nair, S (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. EM snair@mail.nih.gov FU NIDDK NIH HHS [Z01 DK069075-08] NR 13 TC 64 Z9 69 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2005 VL 48 IS 9 BP 1784 EP 1788 DI 10.1007/s00125-005-1868-2 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 965GT UT WOS:000231939300013 PM 16034612 ER PT J AU Shieh, JJ Pan, CJ Mansfield, BC Chou, JY AF Shieh, JJ Pan, CJ Mansfield, BC Chou, JY TI In islet-specific glucose-6-phosphatase-related protein, the beta cell antigenic sequence that is targeted in diabetes is not responsible for the loss of phosphohydrolase activity SO DIABETOLOGIA LA English DT Article DE beta cell antigen; diabetes mellitus; glucose-6-phosphatase; mutation analysis; protein stability; structure-function relationship ID STORAGE-DISEASE TYPE-1A; SUBUNIT-RELATED PROTEIN; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; MURINE GLUCOSE-6-PHOSPHATASE; GLUCOSE-HOMEOSTASIS; GENE; IDENTIFICATION; LIVER; RAT; LACTACYSTIN AB Aims/hypothesis: There are three members of the glucose-6-phosphatase (G6Pase) family: ( 1) the liver/ kidney/intestine G6Pase-alpha (encoded by G6PC), which is a key enzyme in glucose homeostasis; ( 2) the ubiquitous G6Pase-beta ( encoded by G6PC3); and ( 3) the islet-specific G6Pase-related protein ( IGRP, encoded by /G6PC2). While G6Pase-alpha and G6Pase-beta are functional glucose-6-phosphate hydrolases, IGRP possesses almost no hydrolase activity. This was unexpected since G6Pase-alpha is more closely related to IGRP than G6Pase-beta. Recently, amino acids 206 - 214 in IGRP were identified as a beta cell antigen targeted by a prevalent population of pathogenic CD8(+) T cells in autoimmune diabetes, suggesting that this peptide confers functional specificity to IGRP. We therefore investigated the molecular events that inactivate IGRP activity and the effects of the beta cell antigen sequence on the stability and enzymatic activity of G6Pase-alpha. Methods: Studies were performed using site-directed mutagenesis and transient expression assays. Protein stability was evaluated by Western blotting, proteasome inhibitor studies and in vitro transcription - translation. Results: We showed that the residues responsible for G6Pase activity are more extensive than previously recognised. Introducing the IGRP antigenic motif into G6Pase-alpha does not completely destroy activity, although it does destabilise the protein. The low hydrolytic activity in IGRP is due to the combination of multiple independent mutations. Conclusions/interpretation: The loss of catalytic activity in IGRP arises from the sum of many sequence differences. G6Pase-alpha mutants containing the beta cell antigen sequence are preferentially degraded in cells, which prevents targeting by pathogenic CD8(+) T cells. It is possible that IGRP levels in beta cells could dictate susceptibilities to diabetes. C1 NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9042,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 NR 33 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2005 VL 48 IS 9 BP 1851 EP 1859 DI 10.1007/s00125-005-1848-6 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 965GT UT WOS:000231939300022 PM 16012821 ER PT J AU Schaefer, A Robbins, KE Nzilambi, EN Louis, MES Quinn, TC Folks, TM Kalish, ML Pieniazek, D AF Schaefer, A Robbins, KE Nzilambi, EN Louis, MES Quinn, TC Folks, TM Kalish, ML Pieniazek, D TI Divergent HIV and simian immunodeficiency virus surveillance, Zaire SO EMERGING INFECTIOUS DISEASES LA English DT Article ID WESTERN-BLOT; BUSHMEAT; TYPE-2; POL AB Recent HIV infection or divergent HIV or simian immunodeficiency virus (SIV) strains may be responsible for Western blot-indeterminate results on 70 serum samples from Zairian hospital employees that were reactive in an enzyme immunoassay. Using universal polymerase chain reaction HIV-1, HIV-2, and SIV primers, we detected 1 (1.4%) HIV-1 sequence. Except for 1 sample, no molecular evidence for unusual HIV- or SIV-like strains in this sampling was found. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Projet Sida, Kinshasa, Congo. Natl Inst Hlth, Bethesda, MD USA. RP Pieniazek, D (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,Mailstop G19, Atlanta, GA USA. EM dxp1@cdc.gov NR 16 TC 2 Z9 2 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2005 VL 11 IS 9 BP 1446 EP 1448 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 960LG UT WOS:000231591400020 PM 16229778 ER PT J AU Toyoshima, Y Gavrilova, O Yakar, S Jou, W Pack, S Asghar, Z Wheeler, MB LeRoith, D AF Toyoshima, Y Gavrilova, O Yakar, S Jou, W Pack, S Asghar, Z Wheeler, MB LeRoith, D TI Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes SO ENDOCRINOLOGY LA English DT Article ID MICE OVEREXPRESSING LEPTIN; ACTIVATED PROTEIN-KINASE; GLUCOSE-METABOLISM; SKELETAL-MUSCLE; PLASMA LEPTIN; OBESE GENE; IN-VIVO; CONGENITAL LIPODYSTROPHY; RECOMBINANT LEPTIN; HEPATIC STEATOSIS AB Leptin has metabolic effects on peripheral tissues including muscle, liver, and pancreas, and it has been successfully used to treat lipodystrophic diabetes, a leptin-deficient state. To study whether leptin therapy can be used for treatment of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes (MKR mice) that show normal leptin levels and are diabetic due to a primary defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we show that leptin administration to the MKR mice resulted in improvement of diabetes, an effect that was independent of the reduced food intake. The main effect of leptin therapy was enhanced hepatic insulin responsiveness possibly through decreasing gluconeogenesis. In addition, the reduction of lipid stores in liver and muscle induced by enhancing fatty acid oxidation and inhibiting lipogenesis led to an improvement of the lipotoxic condition. Our data suggest that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that are not leptin resistant. C1 NIDDKD, Sect Mol & Cellular Physiol, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mouse Metab Core Facil, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. RP LeRoith, D (reprint author), NIDDKD, Sect Mol & Cellular Physiol, Diabet Branch, NIH, Room 8D12,Bldg 10,MSC 1758, Bethesda, MD 20892 USA. EM derek@helix.nih.gov OI Wheeler, Michael/0000-0002-7480-7267; Shyr, Zeenat/0000-0001-8710-9938 NR 65 TC 67 Z9 74 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2005 VL 146 IS 9 BP 4024 EP 4035 DI 10.1210/en.2005-0087 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 955RB UT WOS:000231243600045 PM 15947005 ER PT J AU Benbrahim-Tallaa, L Webber, MM Waalkes, MP AF Benbrahim-Tallaa, L Webber, MM Waalkes, MP TI Acquisition of androgen independence by human prostate epithelial cells during arsenic-induced malignant transformation SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE androgen independent; AR; arsenic; cancer progression; malignant transformation; prostate ID ESTROGEN-RECEPTOR-BETA; CANCER-CELLS; 5-ALPHA-REDUCTASE TYPE-1; PROGRESSION; GENE; LNCAP; ACTIVATION; EXPRESSION; INDUCTION; AROMATASE AB Lethal phenotypes of human prostate cancer are characterized by progression to androgen independence, although the mechanisms behind this progression remain unclear. Arsenic is a potential human prostate carcinogen that may affect tumor progression. In this study, we used a prostate cancer cell model in which an immortalized, nontumorigenic human prostate epithelial cell line (RWPE-1) had been malignantly transformed by chronic low-level arsenic to help determine whether arsenic affects prostate tumor progression. Control and CAsE-PE (chronic-arsenic-exposed human prostate epithelial) cells were continuously maintained in a complete medium [keratinocyte serum-free medium (K-SFM) with bovine pituitary extract and epidermal growth factor] or in a steroid-depleted medium (K-SFM alone). The arsenic-transformed cells showed a more rapid proliferation rate in complete medium than did control cells and also showed sustained proliferation in steroid-reduced medium. Although both control and CAsE-PE cells showed similar levels of androgen receptor (AR), androgens were less effective in stimulating cell proliferation and AR-related gene expression in CAsE-PE cells. For instance, dihydrotestosterone caused a 4.5-fold increase in prostate-specific antigen transcript in control cells but only a 1.5-fold increase in CAsE-PE cells. CAsE-PE cells also showed relatively low levels of growth stimulation by nonandrogen steroids, such as estradiol. Thus, arsenic-induced malignant transformation is associated with acquired androgen independence in human prostate cells. This acquired androgen independence was apparently not due to AR up-regulation, increased activity, or altered ligand specificity. The precise manner in which arsenic altered CAsE-PE growth and progression is undefined but may involve a bypass of AR involving direct stimulation of downstream signaling pathways. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH,Dept Hlth & Human Serv, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov NR 54 TC 19 Z9 20 U1 2 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2005 VL 113 IS 9 BP 1134 EP 1139 DI 10.1289/ehp.7832 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 961QU UT WOS:000231677700029 PM 16140617 ER PT J AU Rajaraman, P Schwartz, BS Rothman, N Yeager, M Fine, HA Shapiro, WR Selker, RG Black, PM Inskip, PD AF Rajaraman, P Schwartz, BS Rothman, N Yeager, M Fine, HA Shapiro, WR Selker, RG Black, PM Inskip, PD TI delta-aminolevulinic acid dehydratase polymorphism and risk of brain tumors in adults SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE AIAD; brain; case-control; meningioma; polymorphism; tumor ID BLOOD LEAD LEVELS; SMELTER WORKERS; GENOTYPE; OCCUPATION; MENINGIOMA; CHILDREN; CANCER; HEME AB The enzyme delta-aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case-control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls). Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6; 95% confidence interval (CI), 1.0-2.6], with the association appearing stronger in males (OR = 3.5; 95% CL 1.3-9.2) than in females (OR = 1.2; 95% Cl, 0.7-2.2). No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma. C1 NCI, REB, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Rajaraman, P (reprint author), NCI, REB, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Room 7085, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov NR 22 TC 15 Z9 16 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2005 VL 113 IS 9 BP 1209 EP 1211 DI 10.1289/ehp.7986 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 961QU UT WOS:000231677700041 PM 16140629 ER PT J AU Schwartz, DA AF Schwartz, DA TI Training the next generation SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM schwartzd@niehs.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2005 VL 113 IS 9 BP A578 EP A578 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 961QU UT WOS:000231677700002 PM 16140602 ER PT J AU Pfeiffer, RM Castle, PE AF Pfeiffer, RM Castle, PE TI With or without a gold standard SO EPIDEMIOLOGY LA English DT Editorial Material ID INFECTION; WOMEN C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 12 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP 595 EP 597 DI 10.1097/01.ede.0000173328.31497.ec PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200001 PM 16135933 ER PT J AU Longnecker, MP Klebanoff, MA Brock, JW Guo, XG AF Longnecker, MP Klebanoff, MA Brock, JW Guo, XG TI Maternal levels of polychlorinated biphenyls in relation to preterm and small-for-gestational-age birth SO EPIDEMIOLOGY LA English DT Article ID HUMAN-MILK; ORGANOCHLORINE PESTICIDES; PRENATAL EXPOSURE; FISHING COMMUNITY; IN-UTERO; WEIGHT; ASSOCIATION; PREGNANCY; CHILDREN; WOMEN AB Background: In developed countries, polychlorinated biphenyls (PCBs) are ubiquitous contaminants of the environment, including foods. Within the range of the resulting low-level exposure, associations of PCBs with lower birth weight have been observed in several studies. Methods: To examine further the association of PCBs with birth outcomes, we measured serum levels in 1034 pregnant women who were enrolled in the U.S. Collaborative Perinatal Project in 1959 to 1965 before PCB manufacturing was banned. Results: The multivariate-adjusted odds ratio for preterm birth among those with PCB levels of >= 4 mu g/L of total PCBs, compared with those with <2 mu g/L, was 1.1 (95% confidence interval = 0.6-2.2); for the same exposure contrast, the odds ratio for delivering an infant who was small-for-gestational-age at birth was 1.6 (0.7-3.7). Birth weight and length of gestation were essentially unrelated to PCB level. Conclusions: In these data, maternal levels of PCBs during pregnancy were essentially unrelated to preterm birth, birth weight, or length of gestation. An association of PCBs with small-for-gestational-age birth was observed, but the results were inconclusive and occurred in the absence of an overall decrease in birth weight. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Constella Grp Inc, Durham, NC USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnecker@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 41 TC 53 Z9 53 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP 641 EP 647 DI 10.1097/01.ede.0000172137.45662.85 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200008 PM 16135940 ER PT J AU Basso, O Frydenberg, M Olsen, SF Olsen, J AF Basso, O Frydenberg, M Olsen, SF Olsen, J TI Two definitions of "small size at birth" as predictors of motor development at six months SO EPIDEMIOLOGY LA English DT Article ID GESTATIONAL-AGE; PERINATAL-MORTALITY; MATERNAL HEIGHT; WEIGHT RATIO; PREGNANCY AB Background: Small babies are known to be at increased risk for a wide range of difficulties. In predicting risk, it may be more informative to estimate smallness in relation to family norm (using the birth weight of an older sibling) rather than to use the standard "small-for-gestational-age" (SGA z-score) measure. Methods: For 10,577 babies born to women enrolled in the Danish National Birth Cohort, we calculated a "birth-weight ratio" (actual birth weight/expected birth weight predicted from older sibling X 100). We identified babies in the lowest decile of the birth-weight ratio (<= 87.7% for boys and <= 87.6% for girls) and compared them with babies in the lowest decile of the sex- and gestational age-specific distribution (SGA z-score). We evaluated how these definitions predicted motor development. We also compared how selected predictors of birth weight influenced the classification of the baby according to the birth-weight ratio and according to the SGA z-score. Results: Birth-weight ratio and SGA identified 1058 and 1059 babies, respectively, with 738 identified by both methods. A low birth-weight ratio predicted delayed motor development slightly better than did SGA. Babies classified as too small solely by the SGA criterion were more often born to small or smoking mothers than those identified solely by the birth-weight ratio. Conclusions: The combined use of the birth-weight ratio and SGA may provide a more sensitive tool for identifying babies at risk. The birth-weight ratio is less likely to classify babies as small based on their mothers' body size, identifying instead babies who were substantially smaller than their sibling. C1 Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, Aarhus, Denmark. Aarhus Univ, Dept Biostat, Aarhus, Denmark. Statens Serum Inst, Danish Epidemiol Sci Ctr, DK-2300 Copenhagen, Denmark. RP Basso, O (reprint author), NIEHS, Epidemiol Branch, NIH, HHS, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 NR 15 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP 657 EP 663 DI 10.1097/01.ede.0000173040.55187.fa PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200010 PM 16135942 ER PT J AU Nguyen, RHN Baird, DD AF Nguyen, RHN Baird, DD TI Accuracy of men's recall of their partner's time to pregnancy SO EPIDEMIOLOGY LA English DT Article ID TO-PREGNANCY; MALE WORKERS; FERTILITY AB Background: Occupational studies of fertility often rely on men's report of time to pregnancy (TTP). We assessed accuracy of men's report of TTP compared with TTP derived from data from their female partners. Methods: Men from the Dieckmann diethylstilbestrol cohort were interviewed to assess fertility. Men were asked TTP for their most recent pregnancies. Their female partner was subsequently interviewed separately; TTP derived from her data was used as the gold standard. Our analysis was based on 202 couples. Results: Men's report was identical to the women's-derived TTP in 32% of couples; 74% differed by no more than 2 cycles. Men tended to underestimate TTP (mean difference = - 1.2 cycles). Weighted kappa was 0.5 overall and varied by the man's education, the number of pregnancies he had fathered, his stated confidence in reporting, his exposure to diethylstilbestrol, pregnancy planning, and whether he was still married to the index partner. Conclusions: Overall accuracy of men's report of TTP was reasonably good, particularly for men who had fathered only one pregnancy. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. RP Nguyen, RHN (reprint author), 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM nguyen5@niehs.nih.gov OI Baird, Donna/0000-0002-5544-2653 FU Intramural NIH HHS NR 13 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP 694 EP 698 DI 10.1097/01.ede.0000173038.93237.b3 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200016 PM 16135949 ER PT J AU Christopher, S AF Christopher, S TI Introduction of session: Capacity development for environmental and occupational health in Southern Africa through Fogarty International Center support. SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 US NIH, Fogarty Int Ctr, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S24 EP S24 DI 10.1097/00001648-200509000-00043 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200042 ER PT J AU De Roos, AJ Hartge, P Lubin, J Colt, JS Davis, S Cerhan, JR Severson, RK Cozen, W Needham, LL Rothman, N AF De Roos, AJ Hartge, P Lubin, J Colt, JS Davis, S Cerhan, JR Severson, RK Cozen, W Needham, LL Rothman, N TI Persistent organochlorines in plasma and risk of non-Hodgkin lymphoma SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. NCI, Dept Hlth & Human Sci, Div Canc Epidemiol & Genet, Rockville, MD USA. Mayo Clin, Rochester, MN USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA. RI Needham, Larry/E-4930-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S52 EP S52 DI 10.1097/00001648-200509000-00122 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200121 ER PT J AU Longnecker, MP AF Longnecker, MP TI Review of human data on effects of DDT, and some new results SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S34 EP S34 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200072 ER PT J AU Longnecker, MP AF Longnecker, MP TI An overview of DDT world policy SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S34 EP S34 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200071 ER PT J AU Lubin, JH Colt, JS Camann, D Davis, S Cerhan, JR Severson, RK Bernstein, L Hartge, P AF Lubin, JH Colt, JS Camann, D Davis, S Cerhan, JR Severson, RK Bernstein, L Hartge, P TI Epidemiologic evaluation of measurement data in the presence of detection limits SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. SW Res Inst, San Antonio, TX USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Mayo Clin, Coll Med, Rochester, MN USA. Wayne State Univ, Dept Family Med, Detroit, MI 48202 USA. Karmanos Canc Inst, Detroit, MI USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch MNed, Dept Prevent Med, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S40 EP S40 DI 10.1097/00001648-200509000-00090 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200089 ER PT J AU Reddy, P Naidoo, R Naidoo, R London, S Robins, T AF Reddy, P Naidoo, R Naidoo, R London, S Robins, T TI Glutathione-S-tranferase gene polymorphisms (GSTM1 and GSTP1) as increased risk factors for asthma SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 Durban Inst Technol, Durban, South Africa. Univ KwaZulu Natal, Durban, South Africa. Natl Inst Environm Hlth, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. RI Naidoo, Rajen/N-4712-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S149 EP S150 DI 10.1097/00001648-200509000-00381 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200380 ER PT J AU Rockett, JC Lynch, CD Buck, GM AF Rockett, JC Lynch, CD Buck, GM TI Home-based collection of biological measurements and specimens from women and children SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 Merck & Co Inc, Rosetta Inpharmat LLC, Preclin Mol Profiling, Seattle, WA 98109 USA. NICHHD, Epidemiol Branch, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S131 EP S131 DI 10.1097/00001648-200509000-00331 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200330 ER PT J AU Rusieck, JA Hou, L Lee, WJ Blair, A Dosemeci, M Lubin, J Bonner, M Samanic, C Hoppin, JA Sandler, DP Alavanja, MCR AF Rusieck, JA Hou, L Lee, WJ Blair, A Dosemeci, M Lubin, J Bonner, M Samanic, C Hoppin, JA Sandler, DP Alavanja, MCR TI Cancer incidence among pesticide applicators exposed to metolachlor in the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 13-16, 2005 CL Johannesburg, SOUTH AFRICA SP Int Soc Environm Epidemiol C1 NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2005 VL 16 IS 5 BP S98 EP S98 DI 10.1097/00001648-200509000-00243 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 963DJ UT WOS:000231783200242 ER PT J AU McNairy, S AF McNairy, S TI Proceedings from Research Centers in Minority Institutions (RCMI) 9th International Symposium on Health Disparities - Foreword SO ETHNICITY & DISEASE LA English DT Editorial Material C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP McNairy, S (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2005 VL 15 IS 4 SU 5 BP S1 EP S2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 988PW UT WOS:000233614100001 ER PT J AU Taylor, HA Wilson, JG Jones, DW Sarpong, DF Srinivasan, A Garrison, RJ Nelson, C Wyatt, SB AF Taylor, HA Wilson, JG Jones, DW Sarpong, DF Srinivasan, A Garrison, RJ Nelson, C Wyatt, SB TI Toward resolution of cardiovascular health disparities in African Americans: Design and methods of the Jackson Heart Study SO ETHNICITY & DISEASE LA English DT Article DE African Americans; cardiovascular disease; Jackson Heart Study; longitudinal study; methods ID HIGH BLOOD-PRESSURE; ATHEROSCLEROSIS RISK; SOCIOECONOMIC-STATUS; DISEASE MORTALITY; SOCIAL SUPPORT; WOMEN; COMMUNITIES; STRESS; RECRUITMENT; RETENTION AB Objective: The design, overall methods, and major phenotypes for the all-African-American Jackson Heart Study (JHS) are detailed. Methods: Participants were enrolled from the three counties that make up the Jackson, Mississippi metropolitan area. Relatives of selected participants were recruited to develop a large, nested family cohort. Participants provided extensive medical and social history, had an array of physical and biochemical measurements and diagnostic procedures, and provided genomic DNA. Results: Data and biologic materials have been collected from 5302 adult African Americans, including 1499 members of 291 families. Participants have a high prevalence of diabetes, hypertension, obesity, and related disorders. Discussion: The JHS dataset and biologic materials (serum, DNA, and cryopreserved cells) offer a valuable resource for the study of diseases that are of particular importance to African Americans. C1 Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Examinat Ctr, Jackson, MS 39216 USA. Jackson State Univ, Sch Publ Hlth, Jackson, MS 39217 USA. Jackson State Univ, Coordinating Ctr, Jackson, MS 39217 USA. Tougaloo Coll, Jackson, MS USA. Jackson Heart Study, Undergrad Training Ctr, Jackson, MS USA. Montgomery Vet Affairs Med Ctr, Jackson, MS USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Taylor, HA (reprint author), Univ Mississippi, Med Ctr, Sch Med, 2500 N State St, Jackson, MS 39216 USA. EM htaylor@medicine.umsmed.edu NR 76 TC 16 Z9 16 U1 2 U2 5 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2005 VL 15 IS 4 SU 6 BP S4 EP S17 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 986HG UT WOS:000233440100002 ER PT J AU Wilson, JG Rotimi, CN Ekunwe, L Royal, CDM Crump, ME Wyatt, SB Steffes, MW Adeyemo, A Zhou, J Taylor, HA Jaquish, C AF Wilson, JG Rotimi, CN Ekunwe, L Royal, CDM Crump, ME Wyatt, SB Steffes, MW Adeyemo, A Zhou, J Taylor, HA Jaquish, C TI Study design for genetic analysis in the Jackson Heart Study SO ETHNICITY & DISEASE LA English DT Article DE African Americans; cardiovascular disease; family study; genetics; Jackson Heart Study; longitudinal study ID WIDE LINKAGE ANALYSIS; BLOOD-PRESSURE; HUMAN GENOME; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; HYPERTENSION; FAMILY; SCAN; CHOLESTEROL; ASSOCIATION AB Objective: This paper describes the preparation of genetic materials and the recruitment and initial characterization of a nested Family Study within the Jackson Heart Study (JHS) cohort. Methods: Genomic DNA was prepared from all consenting JHS participants. In addition, family members of a subset of JHS participants were recruited to the JHS Family Study to allow heritability and linkage analyses and family-based association studies. Family Study participants completed the same questionnaires, measures, and procedures as all other JHS participants and provided blood samples for lymphocyte cryopreservation and transformation. Results: DNA samples were obtained from 4726 JHS participants, including 1499 members of 291 families. In the family cohort, estimated heritabilities of body mass index, selected lipid levels, and blood pressure are highly significant, supporting the validity of the sample. Discussion: The JHS data and genetic materials (DNA and cryopreserved cells) offer valuable opportunities to identify susceptibility alleles for common complex diseases by positional and candidate gene approaches. C1 Montgomery Vet Affairs Med Ctr, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Examinat Ctr, Jackson, MS 39216 USA. Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. RP Wilson, JG (reprint author), Montgomery Vet Affairs Med Ctr, 151,1500 E Woodrow Wilson Dr, Jackson, MS 39216 USA. EM james.wilson1@med.va.gov NR 45 TC 5 Z9 5 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2005 VL 15 IS 4 SU 6 BP S30 EP S37 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 986HG UT WOS:000233440100004 ER PT J AU Pruszczyk, P Kostera-Pruszczyk, A Draminska, A Kaminska, A Szulc, M Goldfarb, LG AF Pruszczyk, P. Kostera-Pruszczyk, A. Draminska, A. Kaminska, A. Szulc, M. Goldfarb, L. G. TI Familial restrictive cardiomyopathy with complete atrioventricular block due to a novel mutation, Glu413Lys, in the desmin gene SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Med Univ Warsaw, Dept Neurol, Warsaw, Poland. Med Univ Warsaw, Dept Neurol, Pol Acad Sci, NU Med Res Cent, Warsaw, Poland. NINDS, NIH, Bethesda, 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 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA 256 BP 16 EP 17 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987100056 ER PT J AU Koh, KK Han, SH Quon, MJ Chung, WJ Shin, EK AF Koh, K. K. Han, S. H. Quon, M. J. Chung, W. -J. Shin, E. K. TI Additive beneficial effects of ramipril combined with simvastatin in the treatment of type II diabetic patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Ghil Hosp, Ctr Heart, Inchon, South Korea. Ghil Hosp, Gachon Med Sch, Inchon, South Korea. NIH, Diabet Unit, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 MA P1839 BP 294 EP 294 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987102082 ER PT J AU Koh, KK Han, SH Quon, MJ Chung, WJ Shin, EK AF Koh, K. K. Han, S. H. Quon, M. J. Chung, W. -J. Shin, E. K. TI Novel anti-inflammatory and metabolic effects of candesartan in hypertensive patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Ghil Hosp, Ctr Heart, Inchon, South Korea. Ghil Hosp, Gachon Med Sch, Inchon, South Korea. NIH, Diabet Unit, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 613 EP 613 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987104324 ER PT J AU Koh, KK Han, SH Quon, MJ Chung, WJ Shin, EK AF Koh, K. K. Han, S. H. Quon, M. J. Chung, W. -J. Shin, E. K. TI Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 Ghil Hosp, Ctr Heart, Inchon, South Korea. Ghil Hosp, Gachon Med Sch, Inchon, South Korea. NIH, Diabet Unit, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 672 EP 672 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987105034 ER PT J AU Scuteri, A Najjar, SS Morrell, CH Lakatta, EG AF Scuteri, A. Najjar, S. S. Morrell, C. H. Lakatta, E. G. TI The metabolic syndrome predicts cardiovascular events in older persons SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol C1 NIA, NIH, Baltimore, MD 21224 USA. INRCA, UO Geriatr, Rome, Italy. 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 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2005 VL 26 SU 1 BP 676 EP 676 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 993WO UT WOS:000233987105049 ER PT J AU Izzotti, A Bagnasco, M Cartiglia, C Longobardi, M Balansky, RM Merello, A Lubet, RA De Flora, S AF Izzotti, A Bagnasco, M Cartiglia, C Longobardi, M Balansky, RM Merello, A Lubet, RA De Flora, S TI Chemoprevention of genome, transcriptome, and proteome alterations induced by cigarette smoke in rat lung SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cancer chemoprevention; N-acetylcysteine; cigarette smoke; DNA adducts; multigene expression; proteome analysis; antibody microarray ID FACTOR-KAPPA-B; BRONCHIAL EPITHELIAL-CELLS; INDUCED C-FOS; N-ACETYLCYSTEINE; GENE-EXPRESSION; KINASE-C; AQUEOUS EXTRACTS; RESPIRATORY-TRACT; OXIDATIVE STRESS; HEME OXYGENASE AB Postgenomic methodologies have provided novel tools for evaluating safety and efficacy of cancer chemopreventive agents. We exposed rats to environmental cigarette smoke (ECS) for 28 days, with or without oral administration of N-acetylcysteine (NAC). As assessed by P-32-postlabelling, ECS caused a 10-fold increase of DNA adduct levels, which were significantly reduced by NAC. Of 518 proteins tested by antibody microarray, ECS stimulated 56 activities involved in stress response, protein removal, cell replication, apoptosis, phagocytosis, and immune response. NAC alone did not change the amounts of any protein, whereas it significantly decreased the amounts of 6 ECS-induced proteins. The intensity of expression of 278 related genes, assessed by cDNA microarray, was significantly correlated with protein amounts. These observed molecular alterations, which can be attenuated by NAC, represent in part adaptive responses and in part reflect mechanisms contributing to the pathogenesis of smoke-related diseases, including lung cancer, asthma, chronic bronchitis, and emphysema. (c) 2005 Elsevier Ltd. C1 Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. Natl Oncol Ctr, Sofia 1756, Bulgaria. NCI, Bethesda, MD 20852 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 NR 62 TC 45 Z9 47 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2005 VL 41 IS 13 BP 1864 EP 1874 DI 10.1016/j.ejca.2005.04.011 PG 11 WC Oncology SC Oncology GA 969TE UT WOS:000232256800005 PM 15953715 ER PT J AU Crowell, JA AF Crowell, JA TI The chemopreventive agent development research program in the division of cancer prevention of the US National Cancer Institute: An overview SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE cancer prevention; chemoprevention; carcinogenesis; drug development ID ESTROGEN-RECEPTOR-BETA; PURIFIED SOY ISOFLAVONES; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; RECURRENT RESPIRATORY PAPILLOMATOSIS; CYCLOOXYGENASE-2 INHIBITOR CELECOXIB; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ORNITHINE DECARBOXYLASE INDUCTION; BRONCHIAL EPITHELIAL-CELLS; HUMAN PROSTATE-CANCER AB Chemoprevention is an innovative area of cancer research that focuses on the development of pharmacological, biological, and nutritional interventions to prevent, reverse, or delay carcinogenesis. Over the past two decades the Division of Cancer Prevention of the US National Cancer Institute has organized a research and development program to provide resources and infrastructure to the research community for the clinical evaluation of potential cancer preventive agents. This program now encompasses preclinical agent and molecular target identification, in vitro and in vivo screening, efficacy and intermediate endpoint testing, pharmacology and toxicology assessments, and finally chemical synthesis and manufacturing leading to Investigational New Drug applications and clinical studies. In this review, examples of agents currently in development, preclinical testing models, and phase 1 and 2 clinical studies are described. Continued commitment to cancer prevention will significantly reduce the economic and medical burden of cancer. Published by Elsevier Ltd. C1 NCI, Div Canc Prevent, DHHS, Bethesda, MD 20892 USA. RP Crowell, JA (reprint author), NCI, Div Canc Prevent, DHHS, Bethesda, MD 20892 USA. NR 239 TC 33 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2005 VL 41 IS 13 BP 1889 EP 1910 DI 10.1016/j.ejca.2005.04.016 PG 22 WC Oncology SC Oncology GA 969TE UT WOS:000232256800007 PM 16005206 ER PT J AU Bredart, A Bottomley, A Blazeby, JM Conroy, T Coens, C D'Haese, S Chie, WC Hammerlid, E Arraras, JI Efficace, F Rodary, C Schraub, S Costantini, M Costantini, A Joly, F Sezer, O Razavi, D Mehlitz, M Bielska-Lasota, M Aaronson, NK AF Bredart, A Bottomley, A Blazeby, JM Conroy, T Coens, C D'Haese, S Chie, WC Hammerlid, E Arraras, JI Efficace, F Rodary, C Schraub, S Costantini, M Costantini, A Joly, F Sezer, O Razavi, D Mehlitz, M Bielska-Lasota, M Aaronson, NK CA European Org Res Treatment Canc Qu TI An international prospective study of the EORTC cancer in-patient satisfaction with care measure (EORTC IN-PATSAT32) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE patient satisfaction; cancer in-patient; psychometrics; quality of care ID PRELIMINARY PSYCHOMETRIC ANALYSIS; QUALITY-OF-LIFE; PATIENT SATISFACTION; COMPREHENSIVE ASSESSMENT; DOCTOR QUESTIONNAIRE; ONCOLOGY; OUTPATIENT; HEALTH AB Little is known about patients' satisfaction with care in oncology hospitals across cultural contexts. Within the EORTC, we developed a 32-item satisfaction with care questionnaire to measure patients' appraisal of hospital doctors and nurses, as well as aspects of care organisation and services. This study assessed the psychometric characteristics of the questionnaire, the EORTC IN-PATSAT32, in a large, international sample of patients with cancer. Patients discharged from a surgery or medical oncology ward in nine countries were invited to complete at home the EORTC IN-PATSAT32 as well as other instruments for psychometric testing. Of 762 eligible patients recruited, 15% failed to return the questionnaire. Of the 647 compliant patients, 63% completed the questionnaires within 15 min and 82% required no help in its completion. Multitrait scaling analysis revealed excellent internal consistency and convergent validity, although some scales within the IN-PATSAT32 were relatively highly correlated. Test-retest data on 113 patients showed high reliability for most scales. Scales of the IN-PATSAT32 and of the QLQ-C30 were not significantly correlated, suggesting that the two questionnaires are assessing quite distinct concepts. The scales of the IN-PATSAT32 were able to discriminate clearly between patients with differing care expectations and differing intentions to recommend their hospital to others. This study supports the acceptability to patients, and the psychometric robustness of the EORTC IN-PATSAT32 questionnaire. Further studies are needed to assess the responsiveness of the questionnaire to changes in the structure and process of care over time. (c) 2005 Elsevier Ltd. All rights reserved. C1 Inst Curie, Psycho Oncol Unit, FR-75005 Paris, France. EORTC, Qual Life Unit, Brussels, Belgium. Univ Bristol, Bristol, Avon, England. Ctr Alexis Vautrin, Nancy, France. EORTC, Data Ctr, Brussels, Belgium. Natl Taiwan Univ, Taipei 10764, Taiwan. Sahlgrenska Univ Hosp, Gothenburg, Sweden. Hosp Navarra, Pamplona, Spain. Inst Gustave Roussy, Villejuif, France. Ctr Paul Strauss, Strasbourg, France. Natl Canc Inst, Genoa, Italy. Sant Andrea Hosp, Rome, Italy. Ctr Francois Baclesse, F-14021 Caen, France. Univ Hosp Charite, Berlin, Germany. Inst Jules Bordet, Brussels, Belgium. Bruederkrankenhaus, Trier, Germany. Marie Curie Sklodowska Canc Ctr, Warsaw, Poland. Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. RP Bredart, A (reprint author), Inst Curie, Psycho Oncol Unit, 26,Rue Ulm, FR-75005 Paris, France. EM anne.bredart@curie.net RI costantini, massimo/G-1443-2012; OI costantini, massimo/0000-0002-5293-7079; Chie, Wei-Chu/0000-0001-5584-6554; Blazeby, Jane/0000-0002-3354-3330 FU NCI NIH HHS [2U10 CA11488-31, 5U10 CA11488-35] NR 26 TC 77 Z9 78 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2005 VL 41 IS 14 BP 2120 EP 2131 DI 10.1016/j.ejca.2005.04.041 PG 12 WC Oncology SC Oncology GA 975GC UT WOS:000232648000019 PM 16182120 ER PT J AU Hardy, J AF Hardy, J. TI Genetic dissection of the etiologies and pathogenesis of neurodegenerative diseases SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 NIH, Neurogenet Lab, NIA, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2005 VL 12 SU 2 BP 3 EP 3 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GW UT WOS:000202992200010 ER PT J AU Santucci, DM Kralik, JD Lebedev, MA Nicolelis, MAL AF Santucci, DM Kralik, JD Lebedev, MA Nicolelis, MAL TI Frontal and parietal cortical ensembles predict single-trial muscle activity during reaching movements in primates SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE brain-machine interface; EMG; motor cortex; multielectrode physiology; posterior parietal cortex; premotor cortex; somatosensory cortex ID PRIMARY MOTOR CORTEX; DORSAL PREMOTOR CORTEX; ARM MOVEMENTS; INTRACORTICAL MICROSTIMULATION; ISOMETRIC CONTRACTIONS; BEHAVING ANIMALS; MACAQUE MONKEYS; JOINT POSITION; INTERNAL-MODEL; NEURONS AB Previously we have shown that the kinematic parameters of reaching movements can be extracted from the activity of cortical ensembles. Here we used cortical ensemble activity to predict electromyographic (EMG) signals of four arm muscles in New World monkeys. The overall shape of the EMG envelope was predicted, as well as trial-to-trial variations in the amplitude and timing of bursts of muscle activity. Predictions of EMG patterns exhibited during reaching movements could be obtained not only from primary motor cortex, but also from dorsal premotor, primary somatosensory and posterior parietal cortices. These results suggest that these areas represent signals correlated to EMGs of arm muscles in a distributed manner, and that the larger the population sampled, the more reliable the predictions. We propose that, in the future, recordings from multiple cortical areas and the extraction of muscle patterns from these recordings will help to restore limb mobility in paralysed patients. C1 Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. Duke Univ, Ctr Neuroengn, Durham, NC USA. Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. Duke Univ, Dept Psychol & Brain Sci, Durham, NC 27706 USA. RP Nicolelis, MAL (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Box 3209,101 Res Dr,Room 327E Bryan Res Bldg, Durham, NC 27710 USA. EM nicoleli@neuro.duke.edu RI Lebedev, Mikhail/H-5066-2016 OI Lebedev, Mikhail/0000-0003-0355-8723 NR 77 TC 39 Z9 40 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2005 VL 22 IS 6 BP 1529 EP 1540 DI 10.1111/j.1460-9568.2005.04320.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 968DL UT WOS:000232142000025 PM 16190906 ER PT J AU Finnema, SJ Seneca, N Farde, L Gulyas, B Bang-Andersen, B Wikstrom, HV Innis, RB Halldin, C AF Finnema, S. J. Seneca, N. Farde, L. Gulyas, B. Bang-Andersen, B. Wikstrom, H. V. Innis, R. B. Halldin, C. TI Scatchard Analysis of the D2 Receptor Agonist [C-11]MNPA in the Monkey Brain Using PET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Finnema, S. J.; Seneca, N.; Farde, L.; Gulyas, B.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. [Bang-Andersen, B.] Lundbeck AS, Dept Med Chem, Valby, Denmark. [Wikstrom, H. V.] Univ Groningen, Dept Med Chem, Groningen, Netherlands. [Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S82 EP S82 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100299 ER PT J AU Lu, SY Liow, JS Zoghbi, SS Brown, AK Musachio, JL Vermeulen, ES Wikstrom, HV Innis, RB Pike, VW AF Lu, S. Y. Liow, J. S. Zoghbi, S. S. Brown, A. K. Musachio, J. L. Vermeulen, E. S. Wikstrom, H. V. Innis, R. B. Pike, V. W. TI Synthesis and preliminary evaluation of [F-18] S14506 as a novel PET radioligand for brain 5-HT1A receptors in rat SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Lu, S. Y.; Liow, J. S.; Zoghbi, S. S.; Brown, A. K.; Musachio, J. L.; Innis, R. B.; Pike, V. W.] NIMH, Bethesda, MD 20892 USA. [Vermeulen, E. S.; Wikstrom, H. V.] Univ Groningen, Groningen, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S52 EP S52 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100159 ER PT J AU Schou, M Pike, VW Sovago, J Gulyas, B Farde, L Halldin, C AF Schou, M. Pike, V. W. Sovago, J. Gulyas, B. Farde, L. Halldin, C. TI Synthesis and PET Evaluation of (R)-[C-11] OHDMI - A Candidate Radioligand for the Brain Norepinephrine Transporter SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Schou, M.; Sovago, J.; Gulyas, B.; Farde, L.; Halldin, C.] Karolinska Inst, Stockholm, Sweden. [Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S53 EP S53 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100162 ER PT J AU Schou, M Airaksinen, A Truong, P Pike, VW Halldin, C AF Schou, M. Airaksinen, A. Truong, P. Pike, V. W. Halldin, C. TI Synthesis and first in vivo results of [18F]-2-Fluoromethyl-L-Phenylalanine, a new potential tracer for in vivo diagnosis in humans with PET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Schou, M.; Airaksinen, A.; Truong, P.; Halldin, C.] Karolinska Inst, Stockholm, Sweden. [Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RI Airaksinen, Anu/N-9070-2014 OI Airaksinen, Anu/0000-0002-5943-3105 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S52 EP S53 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100160 ER PT J AU Schou, M Halldin, C Pike, VW Mozley, P Dobson, D Innis, RB Farde, L Hall, H AF Schou, M. Halldin, C. Pike, V. W. Mozley, P. Dobson, D. Innis, R. B. Farde, L. Hall, H. TI (S,S)-[F-18]FMeNER-D-2 is Superior to (S,S)-[C-11]MeNER as a Positron-Emitting Radioligand for Imaging Norepinephrine Transporters in the Post Mortem Human Brain SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Schou, M.; Halldin, C.; Farde, L.; Hall, H.] Karolinska Inst, Stockholm, Sweden. [Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Mozley, P.; Dobson, D.] Eli Lilly Co, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S44 EP S44 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100122 ER PT J AU Seneca, N Finnema, S Ichise, M Gulyas, B Wikstrom, H Innis, R Farde, L Halldin, C AF Seneca, N. Finnema, S. Ichise, M. Gulyas, B. Wikstrom, H. Innis, R. Farde, L. Halldin, C. TI A comparison of amphetamine induced changes in agonist and antagonist radioligand binding potential on the dopamine D2 receptor in primate brain SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Seneca, N.; Finnema, S.; Gulyas, B.; Farde, L.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. [Ichise, M.; Innis, R.] NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Wikstrom, H.] Univ Groningen, Dept Med Chem, Groningen, Netherlands. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S82 EP S82 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100298 ER PT J AU Seneca, N Andree, B Sjoholm, N Schou, M Pauli, S Mozley, P Stubbs, J Liow, J Sovago, J Gulyas, B Innis, R Halldin, C AF Seneca, N. Andree, B. Sjoholm, N. Schou, M. Pauli, S. Mozley, P. Stubbs, J. Liow, J. Sovago, J. Gulyas, B. Innis, R. Halldin, C. TI Whole-body biodistribution and radiation dosimetry estimates for the PET norepinephrine transporter probe (S,S)-[F-18] FMeNER-D-2 in non-human primates SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 [Seneca, N.; Andree, B.; Sjoholm, N.; Schou, M.; Pauli, S.; Sovago, J.; Gulyas, B.; Halldin, C.] Karolinska Inst, Stockholm, Sweden. [Mozley, P.] Eli Lily Co, Indianapolis, IN USA. [Stubbs, J.] Radiat Dosimetry Syst Inc, Alpharetta, GA USA. [Liow, J.; Innis, R.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2005 VL 32 SU 1 BP S81 EP S81 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V29JQ UT WOS:000208745100294 ER PT J AU Chang, CH Reeve, BB AF Chang, CH Reeve, BB TI Item response theory and its applications to patient-reported outcomes measurement SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE item response theory; health; outcomes; assessment; computerized adaptive testing ID CATEGORIES; ABILITY; MODEL AB This article provides an overview of item response theory (IRT) models and how they, can be appropriately applied to patient-reported outcomes (PROs) measurement. Specifically, the following topics are discussed: (a) basics of IRT, (b) types of IRT models, (c) how IRT models have been applied to date, and (d) new directions in applying IRT to PRO measurements. C1 Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. NCI, Bethesda, MD 20892 USA. RP Chang, CH (reprint author), Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. NR 45 TC 56 Z9 57 U1 6 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2005 VL 28 IS 3 BP 264 EP 282 DI 10.1177/0163278705278275 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 954IR UT WOS:000231149300002 PM 16123257 ER PT J AU Puleo, E Zapka, JG Goins, KV Yood, MU Mouchawar, J Manos, M Taplin, S AF Puleo, E Zapka, JG Goins, KV Yood, MU Mouchawar, J Manos, M Taplin, S TI Recommendations for care related to follow-up of abnormal cancer screening tests - Accuracy of patient report SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE congruence; validity; screening follow-up; provider/patient communication; patient surveys; doctor-patient interaction; delivery of health care; survey research ID SELF-REPORT; BREAST; MAMMOGRAPHY; WOMEN; PAP; COMMUNICATION; EVENTS; RECALL; SMEARS AB When using patient self-report of processes of care as part of measuring quality performance, validity and reliability are important considerations. In this study, the congruence of patient report of recommendations of screening follow-up care was compared with record audit data. Survey data were collected from a random sample of patients with abnormal breast (n = 230) or cervical (n = 219) cancer screening tests from four health centers. With patient consent, record audits were conducted to validate self-report. Measures of congruence for recommendations for follow-up were calculated along with sensitivity and specificity for procedure-specific recommendations. Overall congruence was higher in the mammography sample (81%) as compared to the Pap sample (61%). Predictors of overall congruence for the abnormal Pap test sample included health plan, self-reported health status, and test result. There were no significant predictors of congruence for the abnormal mammogram test sample from the potential variables collected. Raw agreement rates support using patient self-report in assessing abnormal test follow-up recommendations. C1 Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NCI, Bethesda, MD 20892 USA. RP Puleo, E (reprint author), Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. OI Ulcickas Yood, Marianne/0000-0003-4204-0871 FU NCI NIH HHS [U19CA79689] NR 23 TC 7 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2005 VL 28 IS 3 BP 310 EP 327 DI 10.1177/0163278705278273 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 954IR UT WOS:000231149300005 PM 16123260 ER PT J AU Illei, GG Pavletic, SZ AF Illei, GG Pavletic, SZ TI Blood stem cells as therapy for severe lupus SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE stem cell transplantation; systemic lupus; treatment-resistant ID BONE-MARROW-TRANSPLANTATION; SEVERE RHEUMATOID-ARTHRITIS; HIGH-DOSE CYCLOPHOSPHAMIDE; REFRACTORY SYSTEMIC-LUPUS; TERM-FOLLOW-UP; AUTOIMMUNE-DISEASES; IMMUNOSUPPRESSIVE THERAPY; PERIPHERAL-BLOOD; INTRAVENOUS CYCLOPHOSPHAMIDE; MYCOPHENOLATE-MOFETIL AB High-dose immunosuppression followed by autologous haematopoietic stem cell therapy has the promise of long-term response in systemic lupus erythematosus (SLE), but is associated with an increased risk of serious short-term complications. Haematopoietic stem cell transplantation induced major clinical responses in similar to 65% of patients with SLE who failed standard therapies. In some of these patients such responses are durable for at least several years, but the curative potential of this procedure in severe SLE is still unknown. Procedure-related mortality in earlier studies was up to 12%, but is < 5% in more recent experiences from larger single-centre studies. Allogeneic haematopoietic stem cell therapy from HLA-matched donors holds a strong promise for cure, and newer, much safer transplantation regimens are now available. To accomplish the best therapeutic and scientific results, it is necessary to treat all patients in carefully planned innovative protocols conducted by specialised teams of lupus specialists and transplanters. All immunoablative protocols should incorporate studies of immune reconstitution to understand the mechanisms of cure or failure. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Autoimmun Branch, 9000 Rockville Pike,CRC Room 3-3330, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov; pavletis@mail.nih.gov FU Intramural NIH HHS NR 77 TC 2 Z9 3 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2005 VL 5 IS 9 BP 1153 EP 1164 DI 10.1517/14712598.5.9.1153 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 960TY UT WOS:000231617300003 PM 16120046 ER PT J AU Segarra, M Vilardell, C Matsumoto, K Esparza, J Lozano, E Serra-Pages, C Urbano-Marquez, A Yamada, KM Cid, MC AF Segarra, M Vilardell, C Matsumoto, K Esparza, J Lozano, E Serra-Pages, C Urbano-Marquez, A Yamada, KM Cid, MC TI Dual function of focal adhesion kinase in regulating integrin-induced MMP-2 and MMP-9 release by human T lymphoid cells SO FASEB JOURNAL LA English DT Article DE matrix metalloproteinases; lymphocytes; fibronectin ID PROTEIN-TYROSINE KINASE; SRC FAMILY KINASES; GTPASE-ACTIVATING PROTEIN; JNK SIGNALING PATHWAY; GELATINASE-A MMP-2; N-TERMINAL KINASE; MATRIX METALLOPROTEINASES; TRANSENDOTHELIAL MIGRATION; TUMOR PROGRESSION; IN-VIVO AB Integrin engagement induces matrix metalloproteinase (MMP) production by lymphocytes, allowing their progression into tissues. Focal adhesion kinase (FAK) is a key component of integrin-mediated signaling pathways regulating cell migration. We explored the role of FAK in integrin-induced gelatinase production by Jurkat T cells. Elevation of FAK expression by transient transfection increased cell invasiveness and gelatinase production and release driven by fibronectin. FAK point mutants revealed that gelatinase release was not dependent on FAK kinase activity but did require Y397, a binding site for Src-type tyrosine kinases. Requirement of Src kinases was further demonstrated by transfection with Src kinase-deficient mutants and treatment with a Src inhibitor. Transfection of truncated forms demonstrated dual functional elements in the FAK molecule. The FRNK fragment decreased gelatinase release, whereas the FAT subfragment enhanced it. FRNK inhibitory signals were transduced through Src-dependent pCAS phosphorylation and subsequent ERK1/2 activation. In contrast, FAT stimulated gelatinase secretion, which was also dependent on Src-kinase activity, was associated with a decreased ERK1/2 phosphorylation. This dual function of FAK in gelatinase secretion is then associated with changes in ERK1/2 activation status, a pathway coordinating cycles of adhesion/ release required for cell migration and defines a novel regulatory step in the complex control of MMP function. C1 Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Dept Internal Med, E-08036 Barcelona, Spain. Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Dept Immunol, E-08036 Barcelona, Spain. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Cid, MC (reprint author), Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Dept Internal Med, Villarroel 170, E-08036 Barcelona, Spain. EM mccid@clinic.ub.es OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938; Yamada, Kenneth/0000-0003-1512-6805 NR 71 TC 42 Z9 45 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2005 VL 19 IS 11 BP 1875 EP + DI 10.1096/fj.05-3574fje PG 25 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700009 PM 16260653 ER PT J AU Keiper, T Al-Fakhri, N Chavakis, E Athanasopoulos, AN Isermann, B Herzog, S Saffrich, R Hersemeyer, K Bohle, RM Haendeler, J Preissner, KT Santoso, S Chavakis, T AF Keiper, T Al-Fakhri, N Chavakis, E Athanasopoulos, AN Isermann, B Herzog, S Saffrich, R Hersemeyer, K Bohle, RM Haendeler, J Preissner, KT Santoso, S Chavakis, T TI The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment SO FASEB JOURNAL LA English DT Article DE atherosclerosis; endothelial cells; inflammation; vascular smooth muscle cells ID ENDOTHELIAL-CELL MIGRATION; LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROTIC LESIONS; TRANSENDOTHELIAL MIGRATION; IN-VIVO; IMMUNOGLOBULIN SUPERFAMILY; LIPID HYDROPEROXIDE; APOLIPOPROTEIN-E; XYLENOL ORANGE; DEFICIENT MICE AB The junctional adhesion molecule-C (JAM-C) was recently shown to be a counter receptor for the leukocyte beta 2-integrin Mac-1 (CD11b/CD18), thereby mediating interactions between vascular cells, particularly in inflammatory cell recruitment. Here, we investigated the role of JAM-C in oxidized low-density lipoprotein (LDL)-mediated leukocyte recruitment. As compared with normal arteries, immunostaining of atherosclerotic vessels revealed a high expression of JAM-C in association with neointimal smooth muscle cells and the endothelium. Moreover, JAM-C was strongly up-regulated in the spontaneous early lesions in ApoE -/- mice. In vitro, cultured human arterial smooth muscle cells (HASMC) were found to express JAM-C, and oxLDL, as well as enzymatically modified LDL (eLDL) significantly up-regulated JAM-C on both HASMC and endothelial cells in a time-and dose-dependent manner. Although under quiescent conditions, JAM-C predominantly localized to interendothelial cell-cell contacts in close proximity to zonula occludens-1 (ZO-1), oxLDL treatment induced a disorganization of JAM-C localization that was no more restricted to the interendothelial junctions. JAM-C thereby mediated both leukocyte adhesion and leukocyte transendothelial migration upon oxLDL treatment of endothelial cells, whereas JAM-C on quiescent endothelial cells only mediates leukocyte transmigration. Thus, upon oxLDL stimulation endothelial JAM-C functions as both an adhesion, as well as a transmigration receptor for leukocytes. Taken together, JAM-C is upregulated by oxLDL and may thereby contribute to increased inflammatory cell recruitment during atherosclerosis. JAM-C may therefore provide a novel molecular target for antagonizing interactions between vascular cells in atherosclerosis. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Internal Med 1, Heidelberg, Germany. Univ Giessen, Inst Clin Chem & Pathobiochem, Giessen, Germany. Univ Frankfurt, Dept Internal Med 3, D-6000 Frankfurt, Germany. Univ Heidelberg, Dept Internal Med 5, Heidelberg, Germany. Univ Giessen, Inst Biochem, Giessen, Germany. Univ Giessen, Inst Pathol, Giessen, Germany. Univ Giessen, Inst Clin Immunol & Transfus Med, Giessen, Germany. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Rm 4B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov OI Saffrich, Rainer/0000-0002-0547-4550 FU Intramural NIH HHS NR 49 TC 56 Z9 56 U1 0 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2005 VL 19 IS 11 BP 2078 EP + DI 10.1096/fj.05-4196fje PG 24 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700001 PM 16195363 ER PT J AU Muller, R Hulsmeier, AJ Altmann, F Ten Hagen, K Tiemeyer, M Hennet, T AF Muller, R Hulsmeier, AJ Altmann, F Ten Hagen, K Tiemeyer, M Hennet, T TI Characterization of mucin-type core-1 beta 1-3 galactosyltransferase homologous enzymes in Drosophila melanogaster SO FEBS JOURNAL LA English DT Article DE Drosophila; galactosyltransferase; glycolipid; glycosylation; mucin ID INDUCIBLE ANTIBACTERIAL PEPTIDE; MURINE UDP-GALACTOSE; O-GLYCANS; EXPRESSION; FAMILY; BETA-1,3-GALACTOSYLTRANSFERASE; CLONING; GLYCOSYLATION; PURIFICATION; EUKARYOTES AB Mucin type O-glycosylation is a widespread modification of eukaryotic proteins. The transfer of N-acetylgalactosamine to selected serine or threonine residues is catalyzed by a family of polypeptide N-acetylgalactosaminyltransferases localized in the Golgi apparatus. The most abundant elongation of O-glycans is the addition of a beta 1-3 linked galactose by the core-1 beta 1-3 galactosyltransferase (core-1 beta 3GalT), thereby building the T-antigen or core-1 structure Gal(beta 1-3)GalNAc(alpha 1-O). We have isolated four Drosophila melanogaster cDNAs encoding proteins structurally similar to the human core-1 beta 3GalT enzyme and expressed them as FLAG-tagged proteins in Sf9 insect cells. The identity of these D. melanogaster beta 3GalT enzymes with a core-1 beta 3GalT activity was confirmed by utilization of MUC5AC mucin derived O-glycopeptide acceptors. In addition to the core-1 beta 3GalT activity toward O-glycoprotein substrates, one member of this enzyme family showed a strong activity towards glycolipid acceptors, thereby building the core-1 terminated Nz6 glycosphingolipid. Transcripts of the embryonically expressed core-1 beta 3GalTs were found in the maternally deposited mRNA, in salivary glands and in the amnioserosa. The presence of multiple core-1 beta 3GalT genes in D. melanogaster suggests an increased complexity of core-1 O-glycan expression, which is possibly related to multiple developmental and physiological functions attributable to this class of glycans. C1 Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. Agr Univ Vienna, Inst Chem, A-1180 Vienna, Austria. Natl Inst Dent & Craniofacial Res, Dev Glycobiol Unit, NIH, Bethesda, MD USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. RP Hennet, T (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM thennet@access.unizh.ch NR 34 TC 34 Z9 37 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD SEP PY 2005 VL 272 IS 17 BP 4295 EP 4305 DI 10.1111/j.1742-4658.2005.04838.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959GS UT WOS:000231506800001 PM 16128800 ER PT J AU Christiansen, M Thorslund, T Jochimsen, B Bohr, VA Stevnsner, T AF Christiansen, M Thorslund, T Jochimsen, B Bohr, VA Stevnsner, T TI The Cockayne syndrome group B protein is a functional dimer SO FEBS JOURNAL LA English DT Article DE Cockayne syndrome group B protein; DNA-dependent ATPase; homodimer; SWI2/SNF2; transcription coupled repair ID COUPLING FACTOR CSB/ERCC6; RNA-POLYMERASE-II; DNA-DAMAGE; ATPASE DOMAIN; ACIDIC REGION; GENE-PRODUCT; CSB PROTEIN; REPAIR; HELICASE; MUTATIONS AB Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by developmental abnormalities, UV sensitivity, and premature aging. The CS group B (CSB) protein belongs to the SNF2-family of DNA-dependent ATPases and is implicated in transcription elongation, transcription coupled repair, and base excision repair. It is a DNA stimulated ATPase and remodels chromatin in vitro. We demonstrate for the first time that full-length CSB positively cooperates in ATP hydrolysis as a function of protein concentration. We have investigated the quaternary structure of CSB using a combination of protein-protein complex trapping experiments and gel filtration, and found that CSB forms a dimer in solution. Chromatography studies revealed that enzymatically active CSB has an apparent molecular mass of approximately 360 kDa, consistent with dimerization of CSB. Importantly, in vivo protein cross-linking showed the presence of the CSB dimer in the nucleus of HeLa cells. We further show that dimerization occurs through the central ATPase domain of the protein. These results have implications for the mechanism of action of CSB, and suggest that other SNF2-family members might also function as dimers. C1 Aarhus Univ, Danish Ctr Mol Gerontol, Dept Biol Mol, DK-8000 Aarhus, Denmark. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Stevnsner, T (reprint author), Aarhus Univ, Danish Ctr Mol Gerontol, Dept Biol Mol, Bldg 130, DK-8000 Aarhus, Denmark. EM tvs@mb.au.dk OI Thorslund, Tina/0000-0001-9207-0070 NR 29 TC 10 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD SEP PY 2005 VL 272 IS 17 BP 4306 EP 4314 DI 10.1111/j.1742-4658.2005.04844.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959GS UT WOS:000231506800002 PM 16128801 ER PT J AU Wu, CP Calcagno, AM Hladky, SB Ambudkar, SV Barrand, MA AF Wu, CP Calcagno, AM Hladky, SB Ambudkar, SV Barrand, MA TI Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5) SO FEBS JOURNAL LA English DT Article DE ABC transporters; drug resistance; multidrug-resistant proteins 1; 4 and 5; plant polyphenols; red blood cells ID HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE PROTEIN-4; ATP HYDROLYSIS; HUMAN ERYTHROCYTES; CATALYTIC CYCLE; DIETARY FLAVONOIDS; TUMOR-CELLS; TRANSPORT; CANCER; MRP4 AB Plant flavonoids are polyphenolic compounds, commonly found in vegetables, fruits and many food sources that form a significant portion of our diet. These compounds have been shown to interact with several ATP-binding cassette transporters that are linked with anticancer and antiviral drug resistance and, as such, may be beneficial in modulating drug resistance. This study investigates the interactions of six common polyphenols; quercetin, silymarin, resveratrol, naringenin, daidzein and hesperetin with the multidrug-resistance-associated proteins, MRP1, MRP4 and MRP5. At nontoxic concentrations, several of the polyphenols were able to modulate MRP1-, MRP4- and MRP5-mediated drug resistance, though to varying extents. The polyphenols also reversed resistance to NSC251820, a compound that appears to be a good substrate for MRP4, as predicted by data-mining studies. Furthermore, most of the polyphenols showed direct inhibition of MRP1-mediated [H-3]dinitrophenyl S-glutathione and MRP4-mediated [H-3]cGMP transport in inside-out vesicles prepared from human erythrocytes. Also, both quercetin and silymarin were found to inhibit MRP1-, MRP4- and MRP5-mediated transport from intact cells with high affinity. They also had significant effects on the ATPase activity of MRP1 and MRP4 without having any effect on [P-32]8-azidoATP[alpha P] binding to these proteins. This suggests that these flavonoids most likely interact at the transporter's substrate-binding sites. Collectively, these results suggest that dietary flavonoids such as quercetin and silymarin can modulate transport activities of MRP1, -4 and -5. Such interactions could influence bioavailability of anticancer and antiviral drugs in vivo and thus, should be considered for increasing efficacy in drug therapies. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Pharmacol, Cambridge CB2 1TN, England. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2120,37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Ambudkar, Suresh/B-5964-2008; Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010030-10] NR 41 TC 94 Z9 97 U1 0 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD SEP PY 2005 VL 272 IS 18 BP 4725 EP 4740 DI 10.1111/j.1742-4658.2005.04888.x PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 962MQ UT WOS:000231737300016 PM 16156793 ER PT J AU Barad, DH Stefanick, ML Cochrane, B Barnabei, V Brunner, R Rossouw, J AF Barad, DH Stefanick, ML Cochrane, B Barnabei, V Brunner, R Rossouw, J TI Baseline vasomotor symptoms and cardiovascular events among postmenopausal women using conjugated equine estrogens (CEE) or CEE plus medroxyprogesterone (MPA) in the Women's Health Initiative (WHI) clinical trials. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Stanford Univ, Stanford, CA 94305 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. NHLBI, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S119 EP S119 DI 10.1016/j.fertnstert.2005.07.288 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600289 ER PT J AU Chu, L Maduro, MR Murthy, L Lipshultz, LI Lamb, DJ AF Chu, L Maduro, MR Murthy, L Lipshultz, LI Lamb, DJ TI Functional evidence of mismatch repair deficiency in non-obstructive azoospermia. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Baylor Coll Med, NIH, Humagen Fertil Diagnost Council Advisors, Houston, TX 77030 USA. Yale Univ, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S5 EP S6 DI 10.1016/j.fertnstert.2005.07.012 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600013 ER PT J AU Covington, SN Fitzgerald, OR Calis, KA Koziol, DE Vanderhoff, VH Nelson, LM AF Covington, SN Fitzgerald, OR Calis, KA Koziol, DE Vanderhoff, VH Nelson, LM TI Spiritual well-being is significantly associated with functional well-being in women with spontaneous premature ovarian failure. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Dev Endocrinol Branch, Sect Womens Hlth Res, Bethesda, MD 20892 USA. NIH, Mark O Hatfield Clin Res Ctr, Spiritual Minist Dept, Bethesda, MD 20892 USA. NIH, Mark O Hatfield Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA. Mark O Hatfield Clin Res Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S232 EP S232 DI 10.1016/j.fertnstert.2005.07.598 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600592 ER PT J AU Edwards, S Barnhart, K Zhang, J Frederick, M Huang, X Tureck, R AF Edwards, S Barnhart, K Zhang, J Frederick, M Huang, X Tureck, R TI Comparison of manual vacuum aspiration with electric vacuum aspiration for the management of first trimester pregnancy loss. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Univ Penn, Philadelphia, PA 19104 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Clin Trials & Survey Corp, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S32 EP S32 DI 10.1016/j.fertnstert.2005.07.076 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600077 ER PT J AU Feinberg, EC Larsen, FW Catherino, WH Armstrong, AY AF Feinberg, EC Larsen, FW Catherino, WH Armstrong, AY TI Increased access to care results in increased utilization of ART services by African American women. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Bethesda, MD USA. NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S238 EP S238 DI 10.1016/j.fertnstert.2005.07.615 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600608 ER PT J AU Feinberg, EC Larsen, FW Catherino, WH Segars, JH Armstrong, AY AF Feinberg, EC Larsen, FW Catherino, WH Segars, JH Armstrong, AY TI Leiomyoma may explain racial differences in ART outcome between African American and Caucasian women. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Bethesda, MD USA. NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S141 EP S141 DI 10.1016/j.fertnstert.2005.07.344 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600345 ER PT J AU Gustofson, RL Wada, K Defagot, M Hu, L Krsmanovic, LZ Catt, KJ AF Gustofson, RL Wada, K Defagot, M Hu, L Krsmanovic, LZ Catt, KJ TI Expression and intracellular signaling of estrogen alpha- and beta-receptor subtypes in native and immortalized GnRH neurons. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S380 EP S381 DI 10.1016/j.fertnstert.2005.07.996 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601370 ER PT J AU Gustofson, RL Tong, Z Larsen, FW Nelson, LM AF Gustofson, RL Tong, Z Larsen, FW Nelson, LM TI Women who meet the clinical characteristics of a maternal effect gene defect have a higher incidence of unexplained infertility. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. Combined Fed Fellowship Reprod Endocrinol & Infer, Washington, DC 20307 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S140 EP S140 DI 10.1016/j.fertnstert.2005.07.342 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600343 ER PT J AU Gustofson, RL Browne, P Van Nest, RL Richter, KS Larsen, FW AF Gustofson, RL Browne, P Van Nest, RL Richter, KS Larsen, FW TI Aggressive outpatient management of severe ovarian hyperstimulation syndrome avoids complications and prolonged disease course. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Shady GRove Fertil Ctr, Rockville, MD USA. Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. Combined Fellowship REI, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S95 EP S95 DI 10.1016/j.fertnstert.2005.07.229 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600230 ER PT J AU Gustofson, RL Segars, JH Larsen, FW AF Gustofson, RL Segars, JH Larsen, FW TI GnRH antagonist salvage protocol avoids cycle cancellation and coasting in women at risk for ovarian hyperstimulation syndrome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Walter Reed Army Med Ctr ART Program, Combined Fed Fellowship REI & Reprod Biol & Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S39 EP S39 DI 10.1016/j.fertnstert.2005.07.093 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600095 ER PT J AU Levens, E Gustofson, RL Segars, JH Armstrong, AY AF Levens, E Gustofson, RL Segars, JH Armstrong, AY TI Mayer-Rokitansky-Kuster-Hauser syndrome and premature ovarian failure: A rare combination. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NICHHD, Combined Fed Fellowship Reprod Endocrinol, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S425 EP S426 DI 10.1016/j.fertnstert.2005.07.1112 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601486 ER PT J AU Levens, E Payson, M AF Levens, E Payson, M TI Persistent unexplained low level hCG: Quiescent gestational trophoblastic disease. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S166 EP S166 DI 10.1016/j.fertnstert.2005.07.409 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600409 ER PT J AU McKeeby, JL Richter, KS Neithardt, AB Levy, MJ AF McKeeby, JL Richter, KS Neithardt, AB Levy, MJ TI Spontaneous abortion (SAB) of clinical intrauterine pregnancy (IUP) following in vitro fertilization (IVF) is not correlated with follicle stimulating hormone (FSH). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S423 EP S423 DI 10.1016/j.fertnstert.2005.07.1106 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601480 ER PT J AU Nelson, LM Troendle, JF Vanderhoof, VH Grabill, KM Calis, KA AF Nelson, LM Troendle, JF Vanderhoof, VH Grabill, KM Calis, KA TI Effects of transdermal estradiol therapy (100 micrograms per day) on gonadotropin levels in young women with 46,XX spontaneous premature ovarian failure. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Dev Endocrinol Branch, Sect Womens Hlth Res, Bethesda, MD 20892 USA. NICHHD, NIH, Div Epidemiol, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. NIH, Mark O Hatfield Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S436 EP S436 DI 10.1016/j.fertnstert.2005.07.1141 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601515 ER PT J AU Orshan, SA Vander-hoof, VH Grabill, KM Troendle, JF Covington, SN Nelson, LM AF Orshan, SA Vander-hoof, VH Grabill, KM Troendle, JF Covington, SN Nelson, LM TI Women with spontaneous premature ovarian failure have reduced self-esteem and perceived social support. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Dev Endocrinol Branch, Sect Womens Hlth Res, Bethesda, MD 20892 USA. NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S22 EP S22 DI 10.1016/j.fertnstert.2005.07.051 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600052 ER PT J AU Parker, JD Segars, JH Catherino, WH AF Parker, JD Segars, JH Catherino, WH TI Human leiomyoma express a second form of gonadotropin-releasing hormone (GnRH 2) and receptor (GnRHR 2). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Combined Fed Program Fellowship REI, NIH, NICHD,RBMB,NNMC,WRAMC, Bethesda, MD 20814 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S419 EP S419 DI 10.1016/j.fertnstert.2005.07.1095 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601469 ER PT J AU Payson, M Mayers, C Catherino, W AF Payson, M Mayers, C Catherino, W TI Confirmation of multiple glycolysis alterations in hereditary leiomyomatosis and renal cell cancer. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S414 EP S414 DI 10.1016/j.fertnstert.2005.07.1081 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601455 ER PT J AU Payson, M Segars, J Catherino, W AF Payson, M Segars, J Catherino, W TI Level of activating transcription factor 3 correlates with racial prevalence of leiomyoma. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S409 EP S410 DI 10.1016/j.fertnstert.2005.07.1071 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601445 ER PT J AU Robinson, N Gustofson, RL Larsen, FW AF Robinson, N Gustofson, RL Larsen, FW TI Regular use of ibuprofen does not affect semen analysis parameters, need for ICSI, or ART clinical pregnancy rate. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NIH, NICHHD, Walter Reed Army Med Ctr ART Program, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S14 EP S14 DI 10.1016/j.fertnstert.2005.07.034 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600035 ER PT J AU Rogers, R Leppert, P Catherino, W Payson, M Segars, J AF Rogers, R Leppert, P Catherino, W Payson, M Segars, J TI Brx expression and mechanotransduction in uterine leiomyomas. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, DHHS, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S145 EP S146 DI 10.1016/j.fertnstert.2005.07.355 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600356 ER PT J AU Stegmann, BJ Sinaii, N Liu, S Segars, J Nieman, LK Stratton, P AF Stegmann, BJ Sinaii, N Liu, S Segars, J Nieman, LK Stratton, P TI A follow up on the use of location, color, size, and depth of lesions resected at the time of surgery to predict endometriosis. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S123 EP S124 DI 10.1016/j.fertnstert.2005.07.300 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114600301 ER PT J AU Wittenberger, MD Gustofson, RL Armstrong, A Segars, JH AF Wittenberger, MD Gustofson, RL Armstrong, A Segars, JH TI A cost comparison of "ganirelix salvage" protocol versus "coasting" strategy for patients at risk for ovarian hyperstimulation syndrome (OHSS). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Conjoint Annual Meeting of the American-Society-for-Reproductive-Medicine/Canadian-Fertility-and-Androl ogy-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc C1 NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2005 VL 84 SU 1 BP S318 EP S318 DI 10.1016/j.fertnstert.2005.07.832 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 967TR UT WOS:000232114601205 ER PT J AU Eblan, MJ Goker-Alpan, O Sidransky, E AF Eblan, MJ Goker-Alpan, O Sidransky, E TI Perinatal lethal Gaucher disease: A distinct phenotype along the neuronopathic continuum SO FETAL AND PEDIATRIC PATHOLOGY LA English DT Article DE glucocerebrosidase; lysosomal storage disorder; hydrops fetalis; congenital ichthyosis; recombinant allele ID NONIMMUNE HYDROPS-FETALIS; PLASMA CHITOTRIOSIDASE ACTIVITY; HUMAN GLUCOCEREBROSIDASE GENE; LYSOSOMAL STORAGE DISEASES; GLUCOSYLSPHINGOSINE ACCUMULATION; TARGETED DISRUPTION; PRENATAL-DIAGNOSIS; MOUSE MODEL; TYPE-2; MUTATION AB Gaucher disease, the inherited deficiency of glucocerebrosidase, is characterized by significant genetic and phenotypic heterogeneity. At the extreme end of the phenotypic continuum is the perinatal lethal variant, typically presenting in utero or during the neonatal period as hydrops and/or congenital ichthyosis, with severe and progressive neurological involvement. Insights from the null-allele Gaucher mouse model contributed to the identification of this distinct phenotype, which has unique epidermal involvement. While multiple mutations are encountered, many affected infants are homozygous for recombinant alleles. The diagnosis is often missed due to the early lethality and the failure to recognize the association between lysosomal disorders and hydrops fetalis. The incidence of severe perinatal Gaucher disease may prove more common than currently appreciated with greater physician awareness of the disorder. C1 NIMH, Sect Mol Neurogenet, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. RP Sidransky, E (reprint author), NIMH, Sect Mol Neurogenet, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov NR 58 TC 21 Z9 24 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1551-3815 J9 FETAL PEDIATR PATHOL JI Fetal Pediatr. Pathol. PD SEP-OCT PY 2005 VL 24 IS 4-5 BP 205 EP 222 DI 10.1080/15227950500405296 PG 18 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 999LS UT WOS:000234391400001 PM 16396828 ER PT J AU Flynn, KM Delclos, KB Newbold, RR Ferguson, SA AF Flynn, KM Delclos, KB Newbold, RR Ferguson, SA TI Long term dietary methoxychlor exposure in rats increases sodium solution consumption but has few effects on other sexually dimorphic behaviors SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE xenoestrogen; sodium preference; endocrine disrupter; developmental; sexually dimorphic; methoxychlor ID MAMMARY-GLAND DEVELOPMENT; REPRODUCTIVE-SYSTEM; SEX-DIFFERENCES; ENDOCRINE DISRUPTORS; GENISTEIN EXPOSURE; OFFSPRING TOXICITY; RESEARCH NEEDS; BISPHENOL-A; SALT INTAKE; ESTROGEN AB Methoxychlor is an insecticide with estrogen-like activity, thus exposure during development might cause sexually dimorphic behavioral alterations. To evaluate this, pregnant rats consumed diets containing 0, 10, 100 or 1000 ppm methoxychlor from gestational day 7, and offspring continued on these diets until postnatal day (PND) 77. Assessments of sexually dimorphic behaviors in offspring indicated that intake of a 3.0% sodium chloride solution was significantly increased (41%) in males and females of the 1000 ppm group. No treatment group differed from controls in open field nor running wheel activity, play behavior, nor 0.3% saccharin solution intake. Offspring of the 1000 ppm. group showed significantly decreased body weight, reaching 17% less than controls at PND 77, but not clearly related to their salt solution intake. During pregnancy, 1000 ppm dams consumed 23% less food and weighed 10% less than controls, but this did not affect litter outcomes. These results indicate that in rodents, developmental and chronic exposure to dietary methoxychlor alters the sexually dimorphic behavior of salt-solution intake in young adults of both sexes. Similar behavioral alterations with other xenoestrogens, and the potential for interactions among xenoestrogens, suggest that this report may minimize the true effects of dietary methoxychlor exposure. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Flynn, KM (reprint author), Adelphi Univ, Dept Biol, 1 S Ave, Garden City, NY 11530 USA. EM flynn@adelphi.edu NR 41 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 2005 VL 43 IS 9 BP 1345 EP 1354 DI 10.1016/j.fct.2005.03.009 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 960IH UT WOS:000231583300004 PM 15989973 ER PT J AU Singh, M Jeang, KT Smith, SM AF Singh, M Jeang, KT Smith, SM TI HIV vaccine development SO FRONTIERS IN BIOSCIENCE LA English DT Review DE HIV-1; HIV-2; SIV; SIVmne; SIVmac; SHIV; macaque; human vaccine trials; prime-boost; inactivated whole virus; live-attenuated; passive immunization; mechanism of protection; review ID SIMIAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTE RESPONSES; HUMAN MONOCLONAL-ANTIBODIES; REGIMEN INDUCES BROAD; LONG-TERM CONTROL; RHESUS MACAQUES; AIDS VACCINE; IMMUNE-RESPONSES; PASSIVE-IMMUNIZATION; DISEASE PROGRESSION AB For the past two decades, scientists have aggressively pursued the development of a vaccine against human immunodeficiency virus (HIV). The magnitude of this effort is unprecedented in the history of infectious diseases. However, difficulties in finding promising candidate vaccines have limited the number of clinical efficacy trials. The macaque model is well suited for the evaluation of potential vaccines, but comparison of results among studies is often complicated by the use of different macaque species and/or challenge viruses. This review discusses current results obtained in the macaque model and human vaccine trials. C1 St Michaels Hosp, Newark, NJ 07102 USA. NIAID, Mol Virol Sect, Mol Med Lab, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Smith, SM (reprint author), St Michaels Hosp, Newark, NJ 07102 USA. EM ssmith1824@aol.com RI Jeang, Kuan-Teh/A-2424-2008 NR 138 TC 4 Z9 6 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2005 VL 10 SU S BP 2064 EP 2081 DI 10.2741/1682 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OU UT WOS:000232320300009 PM 15970479 ER PT J AU Bagrov, AY Fedorova, OV AF Bagrov, AY Fedorova, OV TI Cardenolide and bufadienolide ligands of the sodium pump. How they work together in NaCl sensitive hypertension SO FRONTIERS IN BIOSCIENCE LA English DT Article DE Na+; K+; exchange ATPase; antagonists; inhibitors; ouabain; bufadienolides; marinobufagenin; renin; angiotensin; aldosterone system; sodium; diet; hypertension; review ID RENIN-ANGIOTENSIN SYSTEM; DIGITALIS-LIKE FACTORS; OUABAIN-LIKE COMPOUND; VOLUME-EXPANDED DOGS; DAHL-S RATS; ENDOGENOUS DIGITALIS; MARINOBUFAGENIN-LIKE; BRAIN SODIUM; BUFO-MARINUS; PLASMA AB For the past 50 years biomedical scientists have been in quest of an unidentified factor (hormone) that elevates blood pressure and regulates renal sodium transport, i.e., natriuretic hormone. Recent discoveries have led to the identification of such factors which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other regulatory systems. In experimental NaCl sensitive hypertension brain endogenous ouabain, via activation of renin-angiotensin system and of sympathetic nervous system, stimulates adrenocortical production of marinobufagenin, a natriuretic and a vasoconstrictor. The combined effects of these endogenous factors may account for the classical properties attributed by Dahl, deWardener and others to the hypothetical "natriuretic hormone". C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. IM Sechenov Evolutionary Physiol & Biochem Inst, Pharmacol Lab, St Petersburg 194223, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@grc.nia.nih.gov NR 59 TC 25 Z9 26 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2005 VL 10 SU S BP 2250 EP 2256 DI 10.2741/1694 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OU UT WOS:000232320300021 PM 15970491 ER PT J AU Bagrov, YY Manusova, NB Egorova, IA Fedorova, OV Bagrov, AY AF Bagrov, YY Manusova, NB Egorova, IA Fedorova, OV Bagrov, AY TI Endogenous digitalis-like ligands and Na/K-atpase inhibition in experimental diabetes mellitus SO FRONTIERS IN BIOSCIENCE LA English DT Article DE Na+; K+ exchanging ATPase; antagonists; inhibitors; diabetes mellitus; bufadienolides; marinobufagenin; review ID INSULIN-RESISTANCE; SODIUM-PUMP; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; NA+/K+-ATPASE; SALT INTAKE; RAT; NA+,K+-ATPASE; OUABAIN; ALPHA AB Dysregulation of the Na/K-ATPase (NKA) in the kidney, cardiovascular system, and peripheral nervous system is believed to contribute to pathogenesis of diabetes mellitus (DM) and its complications. Recently we demonstrated that, in addition to endogenous ouabain ( EO), mammalian tissues contain another NKA inhibitor, a bufadienolide marinobufagenin (MBG). In vitro MBG, a natriuretic and a vasoconstrictor, acts as a selective inhibitor of alpha-1 NKA, the main isoform of the sodium pump in renal tubules and vascular smooth muscle. To determine whether digitalis-like NKA inhibitors are linked to NKA dysregulation in DM, we studied changes in renal excretion and plasma levels of MBG and EO and the activity of erythrocyte NKA in male Wistar rats with type 1 DM and type 2 DM. Rats with type 1 DM were studied four weeks following a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ)( n = 12), and rats with type 2 DM were studied 10 weeks after intraperitoneal injection of STZ during the neonatal period (n = 12). Renal excretion and plasma levels of EO did not change in rats with both types of DM as compared to that in the control groups. Renal excretion (57.5 +/- 9.4 pmol/kg/ 3 hours vs. 12.6 +/- 2.1 pmol/kg/3 hours; P < 0.01) and plasma levels (2.23 +/- 0.82 nmol/L vs. 0.29 +/- 0.07 nmol/L; P < 0.01) of MBG increased, and NKA activity in erythrocytes was inhibited by 50% in rats with type 1 DM as compared to controls. In rats with type 2 DM, plasma levels (1.48 +/- 0.09 nmol/L vs. 0.46 +/- 0.02 nmol/ L; P < 0.01) and renal excretion (21.3 +/- 3.2 pmol/kg/3 hours vs. 13.1 +/- 2.1 pmol/kg/3 hours) of MBG also became elevated, but less than in the animals with type 1 DM. Accordingly, activity of NKA in erythrocytes from rats with type 2 DM was inhibited by 35%. In vitro treatment of erythrocytes from rats with type 1 and type 2 DM with anti-MBG antibody reversed the DM induced inhibition of the NKA. These results suggest that digitalis-like factors are involved in the pathogenesis of DM, and that MBG, rather than EO, is responsible for DM-induced NKA inhibition. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Russian Acad Sci, IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 196140, Russia. RP Bagrov, YY (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@grc.nia.nih.gov FU Intramural NIH HHS NR 40 TC 23 Z9 24 U1 1 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2005 VL 10 SU S BP 2257 EP 2262 DI 10.2741/1695 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OU UT WOS:000232320300022 PM 15970492 ER PT J AU Limburg, PJ Wei, WQ Ahnen, DJ Qiao, YL Hawk, ET Wang, GQ Giffen, CA Wang, GQ Roth, MJ Lu, N Korn, EL Ma, YR Caldwell, KL Dong, ZW Taylor, PR Dawsey, SM AF Limburg, PJ Wei, WQ Ahnen, DJ Qiao, YL Hawk, ET Wang, GQ Giffen, CA Wang, GQ Roth, MJ Lu, N Korn, EL Ma, YR Caldwell, KL Dong, ZW Taylor, PR Dawsey, SM TI Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib SO GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; VITAMIN MINERAL SUPPLEMENTATION; NUTRITION INTERVENTION TRIALS; PREVENT COLORECTAL ADENOMAS; DISEASE-SPECIFIC MORTALITY; SERUM SELENIUM LEVELS; GENERAL-POPULATION; UNITED-STATES; UP-REGULATION; ASPIRIN USE AB Background & Aims: Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide. Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. Methods: We conducted a randomized, controlled trial of selenomethionine 200 mu g daily and/or celecoxib 200 mg twice daily (2 x 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). Results: Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs -19%) compared with no selenomethionine (P =.08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among :115 subjects with mild esophageal squamous dysplasia at baseline (P =.02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P =.78) or by baseline histology subgroup. Conclusions: After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect. Although it is based on unplanned stratified analyses, this finding is the first report of a possible beneficial effect for any candidate esophageal squamous cell carcinoma chemopreventive agent in a randomized controlled trial. C1 Mayo Clin, Coll Med, Rochester, MN 55905 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100037, Peoples R China. Univ Colorado, Denver, CO 80202 USA. NCI, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Dalian Med Coll, Dalian, Peoples R China. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Limburg, PJ (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM limburg.paul@mayo.edu RI Caldwell, Kathleen/B-1595-2009; Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 FU CCR NIH HHS [N01-RC-91019]; NCI NIH HHS [K07-CA-92216] NR 45 TC 60 Z9 64 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2005 VL 129 IS 3 BP 863 EP 873 DI 10.1053/j.gastro.2005.06.024 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 963PO UT WOS:000231816500014 PM 16143126 ER PT J AU Anderson, SK Dewar, K Goulet, ML Leveque, G Makrigiannis, AP AF Anderson, SK Dewar, K Goulet, ML Leveque, G Makrigiannis, AP TI Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype SO GENES AND IMMUNITY LA English DT Article DE Ly49; natural killer cell; haplotype; comparative genomics; BALB/c ID LY49 GENE-CLUSTER; NK CELLS; MURINE CYTOMEGALOVIRUS; ACTIVATION RECEPTOR; SEQUENCE-ANALYSIS; BONE-MARROW; GENOMIC DNA; MICE; IDENTIFICATION; ORGANIZATION AB The BALB/c inbred mouse is widely used in models of infectious disease, transplantation, and cancer. The differences in the immune responses of BALB/c compared to C57BL/6 mice are especially valuable for the identification of immune regulation genes. One striking immune variance between these mice is in the function of natural killer (NK) cells, and there is strong evidence implicating differential expression of Ly49 genes. In this study, the complete BALB/c Ly49 gene cluster has been sequenced and found to contain six functional genes and two pseudogenes. Compared to C57BL/6 mice, there is a 200 kb region absent in the BALB/c cluster including a complete lack of Ly49h-related genes, which explains the increased susceptibility of BALB/c to cytomegalovirus infection. In addition, there is no BALB/c Ly49d allele, explaining the inability of BALB/c NK cells to kill certain tumor cells. The Ly49 region has now been sequenced in three different inbred mouse strains, and comparisons indicate that the evolution of each haplotype is not straightforward and has involved large-scale deletions/insertions, gene recombination, and unequal crossing over between divergent haplotypes. This study confirms that relatively small murine class I MHC receptor haplotypes exist, analogous to observations made of human killer cell Ig-like receptor gene haplotypes. C1 NCI, SAIC Frederick, Basic Res Program, Frederick, MD USA. McGill Univ, Ctr Human Genet, Montreal, PQ, Canada. Genome Quebec Innovat Ctr, Montreal, PQ, Canada. IRCM, Lab Mol Immunol, Montreal, PQ, Canada. Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Med, Div Expt Med, Montreal, PQ, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. RP Makrigiannis, AP (reprint author), Inst Rech Clin Montreal, Lab Mol Immunol, Rm 1340,110 Ave Pins Ouest, Montreal, PQ H2W 1R7, Canada. EM makriga@ircm.qc.ca RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01CO12400] NR 43 TC 29 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD SEP PY 2005 VL 6 IS 6 BP 481 EP 492 DI 10.1038/sj.gene.6364232 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 960EI UT WOS:000231572600005 PM 15931229 ER PT J AU Knutsen, T Gobu, V Knaus, R Padilla-Nash, H Augustus, M Strausberg, RL Kirsch, IR Sirotkin, K Ried, T AF Knutsen, T Gobu, V Knaus, R Padilla-Nash, H Augustus, M Strausberg, RL Kirsch, IR Sirotkin, K Ried, T TI The interactive online SKY/M-FISH & CGH database and the Entrez cancer chromosomes search database: Linkage of chromosomal aberrations with the genome sequence SO GENES CHROMOSOMES & CANCER LA English DT Article ID UPDATE AB To catalog data on chromosomal aberrations in cancer derived from emerging molecular cytogenetic techniques and to integrate these data with genome maps, we have established two resources, the NCI and NCBI SKY/M-FISH & CGH Database and the Cancer Chromosomes database. The goal of the former is to allow investigators to submit and analyze clinical and research cytogenetic data. It contains a karyotype parser tool, which automatically converts the ISCN short-form karyotype into an internal representation displayed in detailed form and as a colored ideogram with band overlay, and also has a tool to compare CGH profiles from multiple cases. The Cancer Chromosomes database integrates the SKY/M-FISH & CGH Database with the Mitelman Database of Chromosome Aberrations in Cancer and the Recurrent Chromosome Aberrations in Cancer database. These three datasets can now be searched seamlessly by use of the Entrez search and retrieval system for chromosome aberrations, clinical data, and reference citations. Common diagnoses, anatomic sites, chromosome breakpoints, junctions, numerical and structural abnormalities, and bands gained and lost among selected cases can be compared by use of the "similarity" report. Because the model used for CGH data is a subset of the karyotype data, it is now possible to examine the similarities between CGH results and karyotypes directly. All chromosomal bands are directly linked to the Entrez Map Viewer database, providing integration of cytogenetic data with the sequence assembly. These resources, developed as a part of the Cancer Chromosome Aberration Project (CCAP) initiative, aid the search for new cancer-associated genes and foster insights into the causes and consequences of genetic alterations in cancer. Published 2005 Wiley-Liss, Inc. C1 NCI, Sect Canc Genom, Genet Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. TAJ Technol Inc, Mendota Hts, MN USA. Management Syst Designers Inc, Fairfax, VA USA. Avalon Pharmaceut, Germantown, MD USA. J Craig Venter Inst, Rockville, MD USA. RP Knutsen, T (reprint author), NCI, Sect Canc Genom, Genet Branch, Canc Res Ctr,NIH, 50 South Dr,Room 1408, Bethesda, MD 20892 USA. EM knutsent@mail.nih.gov FU NCI NIH HHS [Z01 SC010298-07] NR 18 TC 55 Z9 57 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 2005 VL 44 IS 1 BP 52 EP 64 DI 10.1002/gcc.20224 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 949JJ UT WOS:000230781000006 PM 15934046 ER PT J AU Triplett, AA Sakamoto, K Matulka, LA Shen, L Smith, GH Wagner, KU AF Triplett, AA Sakamoto, K Matulka, LA Shen, L Smith, GH Wagner, KU TI Expression of the whey acidic protein (Wap) is necessary for adequate nourishment of the offspring but not functional differentiation of mammary epithelial cells SO GENESIS LA English DT Article DE whey acidic protein (WAP); mammary gland; differentiation; gene targeting ID GENE-EXPRESSION; TRANSGENIC MICE; GLAND DEVELOPMENT; MOUSE; PREGNANCY; TISSUE; STAT5; PROLIFERATION; ACTIVATION; KNOCKOUT AB Whey acidic protein (WAP) is the principal whey protein found in rodent milk, which contains a cysteine-rich motif identified in some protease inhibitors and proteins involved in tissue modeling. The expression of the Wap gene, which is principally restricted to the mammary gland, increases more than 1,000-fold around mid-pregnancy. To determine whether the expression of this major milk protein gene is a prerequisite for functional differentiation of mammary epithelial cells, we generated conventional knockout mice lacking two alleles of the Wap gene. Wap-deficient females gave birth to normal litter sizes and, initially, produced enough milk to sustain the offspring. The histological analysis of postpartum mammary glands from knockout dams does not reveal striking phenotypic abnormalities. This suggests that the expression of the Wap gene is not required for alveolar specification and functional differentiation. In addition, we found that Wap is dispensable as a protease inhibitor to maintain the stability of secretory proteins in the milk. Nevertheless, a significant number of litters thrived poorly on Wap-deficient dams, in particular during the second half of lactation. This observation suggests that Wap may be essential for the adequate nourishment of the growing young, which triple in size within the first 10 days of lactation. Important implications of these findings for the use of Wap as a marker for advanced differentiation of mammary epithelial cells and the biology of pluripotent progenitors are discussed in the final section. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mammary Biol & Tumorigenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Wagner, KU (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Nebraska Med Ctr,Rm 8009, Omaha, NE 68198 USA. EM ktiwagner@unmc.edu RI Wagner, Kay-Uwe/B-6044-2009 FU NCI NIH HHS [CA93797] NR 37 TC 29 Z9 29 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD SEP PY 2005 VL 43 IS 1 BP 1 EP 11 DI 10.1002/gene.20149 PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 965TL UT WOS:000231973100001 PM 16106354 ER PT J AU Spinka, C Carroll, RJ Chatterjee, N AF Spinka, C Carroll, RJ Chatterjee, N TI Analysis of case-control studies of genetic and environmental factors with missing genetic information and haplotype-phase ambiguity SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-control studies; gene-environment interactions; EM algorithm; haplotype; semiparametric methods ID MAXIMUM-LIKELIHOOD-ESTIMATION; GENOTYPE DATA; ASSOCIATIONS; INFERENCE AB Case-control studies of unrelated subjects are now widely used to study the role of genetic susceptibility and gene-environment interactions in the etiology of complex diseases. Exploiting an assumption of gene-environment independence, and treating the distribution of environmental exposures as completely nonparametric, Chatterjee and Carroll [2005] (Biometrika 92:399-418) recently developed an efficient retrospective maximum-likelihood method for analysis of case-control studies. In this article, we develop an extension of the retrospective maximum-likelihood approach to studies where genetic information may be missing on some study subjects. In particular, special emphasis is given to haplotype-based studies where missing data arise due to linkage-phase ambiguity of genotype data. We use a profile likelihood technique and an appropriate expectation-maximization (EM) algorithm to derive a relatively simple procedure for parameter estimation, with or without a rare disease assumption, and possibly incorporating information on the marginal probability of the disease for the underlying population. We also describe two alternative robust approaches that are less sensitive to the underlying gene-environment independence and Hardy-Weinberg-equilibrium assumptions. The performance of the proposed methods is studied using simulation studies in the context of haplotype-based studies of gene-environment interactions. An application of the proposed method is illustrated using a case-control study of ovarian cancer designed to investigate the interaction between BRCA1/2 mutations and reproductive risk factors in the etiology of ovarian cancer. C1 NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. Univ Missouri, Dept Stat, Columbia, MO 65211 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Execut Blvd,EPS 8038, Rockville, MD 20852 USA. EM chattern@mail.nih.gov FU NCI NIH HHS [R01 CA057030, CA-57030, R25 CA090301, U01 CA057030, R37 CA057030, R25 CA090301-08, CA-90302]; NIEHS NIH HHS [P30 ES009106, P30-ES09306] NR 14 TC 45 Z9 46 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2005 VL 29 IS 2 BP 108 EP 127 DI 10.1002/gepi.20085 PG 20 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 959PY UT WOS:000231531400002 PM 16080203 ER PT J AU Kistner, EO Weinberg, CR AF Kistner, EO Weinberg, CR TI A method for identifying genes related to a quantitative trait, incorporating multiple siblings and missing parents SO GENETIC EPIDEMIOLOGY LA English DT Article DE multiple siblings; linkage disequilibrium; association; missing parents; population admixture ID ASSOCIATION; TESTS; DISEQUILIBRIUM; LINKAGE AB When studying either qualitative or quantitative traits, tests of association in the presence of linkage are necessary for fine-mapping. In a previous report (Kistner and Weinberg [2004] Genet Epidemiol 27:33-42), we suggested a polytomous logistic approach to testing linkage and association between a di-allelic marker and a quantitative trait locus, using genotyped triads, consisting of an individual whose quantitative trait has been measured and his or her two parents. Here we extend that approach to incorporate marker information from entire nuclear families. By computing a weighted score function instead of a maximum likelihood test, we allow for both an unspecified correlation structure between siblings and "informative" family size (Williamson et al. [2003] Biometrics 59:36-42). Both this approach and our original approach allow for population admixture by conditioning on parental genotypes. The proposed method allows for missing parental genotype data through a multiple imputation procedure. We use simulations based on a population with admixture to compare our method to a popular non-parametric family-based association test (FBAT), testing the null of no association in the presence of linkage. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM weinberg@niehs.nih.gov NR 16 TC 13 Z9 13 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2005 VL 29 IS 2 BP 155 EP 165 DI 10.1002/gepi.20084 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 959PY UT WOS:000231531400005 PM 16025442 ER PT J AU Barton, JC Acton, RT Dawkins, FW Adams, PC Lovato, L Leiendecker-Foster, C McLaren, CE Reboussin, DM Speechley, MR Gordeuk, VR McLaren, GD Sholinsky, P Harris, EL AF Barton, JC Acton, RT Dawkins, FW Adams, PC Lovato, L Leiendecker-Foster, C McLaren, CE Reboussin, DM Speechley, MR Gordeuk, VR McLaren, GD Sholinsky, P Harris, EL CA Hemochromatosis Iron Overload Scr TI Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in whites and blacks in the hemochromatosis and iron overload screening study SO GENETIC TESTING LA English DT Article ID AFRICAN-AMERICANS; HEREDITARY HEMOCHROMATOSIS; UNITED-STATES; HEPATITIS-C; GENE POLYMORPHISMS; MUTATION ANALYSIS; PREVALENCE; POPULATION; STORES; DISEASE AB We compared initial screening data of 44,082 white and 27,124 black Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. Each underwent serum transferrin saturation (TfSat) and ferritin (SF) measurements without regard to fasting, and HFE C282Y and H63D genotyping. Elevated measurements were defined as: TfSat more than 50% (men), more than 45% (women); and SF more than 300 ng/ml (men), more than 200 ng/ml (women). Mean TfSat and percentages of participants with elevated TfSat were significantly greater in whites than in blacks. Mean SIT and percentages of participants with elevated SF were significantly greater in blacks than in whites. TfSat and SF varied by gender and age in whites and blacks. Prevalences of genotypes that included either C282Y or H63D were significantly greater in whites than in blacks. The prevalence of elevated TfSat and SF plus genotypes C282Y/C282Y, C282Y/H63D, or H63D/H63D was 0.006 in whites and 0.0003 in blacks. Among whites with HFE C282Y homozygosity, 76.8% of men and 46.9% of women had elevated TfSat and SF values. Three black participants had HFE C282Y homozygosity; one had elevated TfSat and SF values. Possible explanations for differences in TfSat and SF in whites and blacks and pertinence to the detection of hemochromatosis, iron overload, and other disorders with similar phenotypes are discussed. C1 So Iron Disorders Ctr, Birmingham, AL 35209 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Int Hlth, Birmingham, AL 35294 USA. Howard Univ, Div Hematol Oncol, Washington, DC 20059 USA. Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. London Hlth Sci Ctr, Dept Med, Div Gastroenterol, London, ON, Canada. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27103 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. Univ Western Ontario, Dept Biostat & Epidemiol, London, ON, Canada. VA Long Beach Healthcare Syst, Long Beach, CA USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Kaiser Permanente NW, Dept Genet, Portland, OR USA. RP Barton, JC (reprint author), So Iron Disorders Ctr, G105,2022 Brookwood Med Ctr Dr, Birmingham, AL 35209 USA. EM ironmd@dnamail.com FU NCI NIH HHS [N01-CM-07003-74]; NCRR NIH HHS [M01-RR10284, M01-RR00827, M01-RR00032]; NHLBI NIH HHS [N01-HC05186, N01-HC05191, N01-HC05188, N01-HC05190, UH1-HL03679-05, N01-HC05185]; PHS HHS [N01-C05189, N01-C05192] NR 81 TC 34 Z9 34 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2005 VL 9 IS 3 BP 231 EP 241 DI 10.1089/gte.2005.9.231 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 977EG UT WOS:000232784600008 PM 16225403 ER PT J AU Pentz, RD Peterson, SK Watts, B Vernon, SW Lynch, PM Koehly, LM Gritz, ER AF Pentz, RD Peterson, SK Watts, B Vernon, SW Lynch, PM Koehly, LM Gritz, ER TI Hereditary nonpolyposis colorectal cancer family members' perceptions about the duty to inform and health professionals' role in disseminating genetic information SO GENETIC TESTING LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Clinical-Oncology CY 2003 CL Chicago, IL SP Amer Soc Clin Oncol ID OVARIAN-CANCER; MUTATION CARRIERS; COLON-CANCER; RISK; COMMUNICATION; DISCLOSURE; SUSCEPTIBILITY; INDIVIDUALS; ATTITUDES; BREAST AB This study's aim was to ascertain hereditary nonpolyposis colorectal cancer (HNPCC) families' views on the duty to inform with particular focus on the role of health professionals in disseminating familial genetic information. Eighty members of 16 families with a clinical or molecular diagnosis of HNPCC completed qualitative interviews regarding views on family members' right to know and who should disseminate familial genetic information. Most indicated that everyone in the family should know about the presence of a mutation in the family, with family members themselves being the preferable informant, supported by health professionals who were seen as helpful in overcoming barriers. All but one respondent indicated that if a parent did not test and presumably did not inform his/her child about the family mutation, the child should be informed by other family members or by a health professional. Many were attuned to confidentiality concerns, but judged them to be outweighed by the importance of family members knowing about the mutation and undertaking proper surveillance. Respondents were more private about the disclosure of individual results to other family members, clearly distinguishing personal results from familial genetic information. These families with a hereditary colon cancer syndrome favor open sharing of genetic information within the family, and desire the supportive involvement of health care professionals in disseminating genetic information. C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Houston Sch Publ Hlth, Houston, TX USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Pentz, RD (reprint author), Emory Univ, Winship Canc Inst, 1365 C Clifton Rd NE,Room C 3008, Atlanta, GA 30322 USA. EM Rebecca.Pentz@emoryhealthcare.org FU NHGRI NIH HHS [2R01HG1200-6, R01 HG001200, R01 HG001200-06] NR 50 TC 25 Z9 25 U1 1 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2005 VL 9 IS 3 BP 261 EP 268 DI 10.1089/gte.2005.9.261 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 977EG UT WOS:000232784600011 PM 16225406 ER PT J AU Lee, MP Howcroft, K Kotekar, A Yang, HH Buetow, KH Singer, DS AF Lee, MP Howcroft, K Kotekar, A Yang, HH Buetow, KH Singer, DS TI ATG deserts define a novel core promoter subclass SO GENOME RESEARCH LA English DT Article ID RNA-POLYMERASE-II; CPG-ISLANDS; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; TATA BOX; DIFFERENTIAL UTILIZATION; START SITES; DNA-BINDING; ELEMENT; COMPLEX AB The MHC class I gene, PDI, has neither functional TATAA nor Initiator (Inr) elements in its core promoter and initiates transcription at multiple, dispersed sites over an extended region in vitro. Here, we define a novel core promoter feature that supports regulated transcription through selective transcription start site (TSS) usage. We demonstrate that TSS selection is actively regulated and context dependent. Basal and activated transcriptions initiate from largely nonoverlapping TSS regions. Transcripts derived from multiple TSS encode a single protein, due to the absence of any ATG triplets within similar to 430 bp upstream of the major transcription start site. Thus, the PDI core promoter is embedded within an "ATG desert." Remarkably, extending this analysis genome-wide, we find that ATG deserts define a novel promoter subclass. They occur nonrandomly, are significantly associated with non-TATAA promoters that use multiple TSS, independent of the presence of CpG islands (CGI). We speculate that ATG deserts may provide a core promoter platform upon which complex upstream regulatory signals can be integrated, targeting multiple TSS whose products encode a single protein. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM dinah.singer@nih.gov NR 60 TC 15 Z9 16 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2005 VL 15 IS 9 BP 1189 EP 1197 DI 10.1101/gr.3873705 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 962HB UT WOS:000231720500002 PM 16109972 ER PT J AU Portnoy, ME McDermott, KJ Antonellis, A Margulies, EH Prasad, AB Kingsley, DM Green, ED Mortlock, DP AF Portnoy, ME McDermott, KJ Antonellis, A Margulies, EH Prasad, AB Kingsley, DM Green, ED Mortlock, DP CA NISC Comparative Sequencing Prog TI Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer SO GENOMICS LA English DT Article DE Gdf6; enhancer elements; bacterial artificial chromosome; transgenes; sequence analysis ID TGF-BETA-SUPERFAMILY; GENOMIC DNA-SEQUENCES; GENE; EXPRESSION; MEMBER; INSIGHTS; DEFECTS; MICE; DIFFERENTIATION; MORPHOGENESIS AB The identification of noncoding functional elements within vertebrate genomes, such as those that regulate gene expression, is a major challenge. Comparisons of orthologous sequences from multiple species are effective at detecting highly conserved regions and can reveal potential regulatory sequences. The GDF6 gene controls developmental patterning of skeletal joints and is associated with numerous, distant cis-acting regulatory elements. Using sequence data from 14 vertebrate species, we performed novel multispecies comparative analyses to detect highly conserved sequences flanking GDF6. The complementary tools WebMCS and ExactPlus identified a series of multispecies conserved sequences (MCSs). Of particular interest are MCSs within noncoding regions previously shown to contain GDF6 regulatory elements. A previously reported conserved sequence at -64 kb was also detected by both WebMCS and ExactPlus. Analysis of LacZ-reporter transgenic mice revealed that a 440-bp segment from this region contains an enhancer for Gdf6 expression in developing proximal limb joints. Several other MCSs represent candidate GDF6 regulatory elements; many of these are not conserved in fish or frog, but are strongly conserved in mammals. (c) 2005 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NISC, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA. RP Mortlock, DP (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. EM mortlock@chgr.mc.vanderbilt.edu RI Prasad, Arjun/C-6736-2008; Mortlock, Douglas/C-9981-2010; Morlock, Doug/C-3482-2012 FU NIAMS NIH HHS [5R37AR042236-12]; NICHD NIH HHS [1R01HD47880-01]; NIGMS NIH HHS [1T32GM62758-03] NR 44 TC 10 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2005 VL 86 IS 3 BP 295 EP 305 DI 10.1016/ygeno.2005.05.003 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 957DR UT WOS:000231350300005 PM 15979840 ER PT J AU Takanohashi, A Yabe, T Schwartz, JP AF Takanohashi, A Yabe, T Schwartz, JP TI Pigment epithelium-derived factor induces the production of chemokines by rat microglia SO GLIA LA English DT Article DE pigment epithelium-derived factor; NF kappa B; activation markers; chemokines; macrophage inflammatory protein-1 alpha ID CENTRAL-NERVOUS-SYSTEM; MACROPHAGE INFLAMMATORY PROTEIN-2; MEDIATED GENE-TRANSFER; KAPPA-B ACTIVATION; IN-VITRO; NEUROTROPHIC FACTOR; MOTOR-NEURONS; FACTOR PEDF; CELL-LINE; RESTING MICROGLIA AB Many studies have shown that pigment epithelium-derived factor (PEDF) has neurotrophic effects on retinal cells and hippocampal, spinal cord, and cerebellar granule cell neurons, but much less work has examined the effects of PEDF on glia. In this study, we show that PEDF changes microglial morphology within 1 h of exposure, to a more deactivated form, while having no effect on the expression of such activation markers as OX-42 and ED-1. In contrast, urea activates acid phosphatase, and PEDF blocks that activation. PEDF also activates NF kappa B, accompanied by the induction of mRNAs and proteins for the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha, MIP-2, and MIP-3 alpha. All the chemokines stimulate acid phosphatase activity, and high doses of MIP-2 and MIP-3 alpha), alter the morphology of the microglia at 1 h after treatment. These results suggest that the use of PEDF for clinical treatments, such as for retinal neovascularization, brain injury, or ischemia, should be undertaken with caution because of the possibility of induction of inflammation caused by microglial or other immune cell migration in response to the chemokines induced by PEDF. (C) 2005 Wiley-Liss, Inc. C1 NINDS, Neurotroph Factors Sect, NIH, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NIH, Off Intramural Res, Off Director, Bldg 1,Room 135, Bethesda, MD 20892 USA. EM jps@helix.nih.gov OI Takanohashi, Asako/0000-0003-3292-1595 NR 68 TC 14 Z9 15 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2005 VL 51 IS 4 BP 266 EP 278 DI 10.1002/glia.20203 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 956DC UT WOS:000231278100003 PM 15816038 ER PT J AU Goedert, JJ AF Goedert, JJ CA Second Multictr Hemophilia Cohort TI Prevalence of conditions associated with human immunodeficiency and hepatitis virus infections among persons with haemophilia, 2001-2003 SO HAEMOPHILIA LA English DT Article DE acquired immunodeficiency syndrome; alcoholism; cancer; cohort study; haemophilia; hepatitis B; hepatitis C ID LIVER-DISEASE; VIRAL-HEPATITIS; NATURAL-HISTORY; UNITED-STATES; C INFECTION; COHORT; HIV; MULTICENTER; POPULATION; MORTALITY AB Before the mid-1980s, haemophilia often was unknowingly treated with contaminated plasma products, resulting in high rates of human immunodeficiency virus (HIV-1), hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To estimate the impact of these infections, a new cohort was established. All HCV-seropositive patients, age 13-88 years, at 52 comprehensive haemophilia treatment centres were eligible. Cross-sectional data collected during April 2001 to January 2004 (median June 2002) were analysed. Plasma HIV-1 and HCV RNA were quantified by polymerase chain reaction. Highly active antiretroviral therapy (HAART) was defined as use of at least three recommended medications. Among 2069 participants, 620 (30%) had HIV-1. Of 1955 with known HBV status, 814 (42%) had resolved HBV and 90 (4.6%) were HBV carriers. Although 80% of the HIV-1-positive participants had >= 200 CD4(+) cells mu L-1, only 59% were on HAART. HIV-1 RNA was undetectable in 23% of those not taking antiretroviral medications. Most (72%) participants had received no anti-HCV therapy. HCV RNA was detected less frequently (59%) among participants treated with standard interferon plus ribavirin (P = 0.0001) and more frequently among HIV-1-positive than HIV-1-negative participants (85% vs. 70%, P < 0.0001). HIV-1-positive participants were more likely to have pancytopenia and subclinical hepatic abnormalities, as well as persistent jaundice, hepatomegaly, splenomegaly and ascites. HAART recipients did not differ from HIV-negative participants in the prevalence of ascites. The clinical abnormalities were more prevalent with older age but were not confounded by HBV status or self-reported alcohol consumption. Eleven participants presented with or previously had hepatocellular carcinoma or non-Hodgkin lymphoma. Although prospective analysis is needed, our data reveal the scale of hepatic and haematological disease that is likely to manifest in the adult haemophilic population during the coming years unless most of them are successfully treated for HIV-1, HCV or both. C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, 6120 Execut Blvd,Room 8012, Bethesda, MD 20892 USA. EM goedertj@mail.nih.gov FU NCI NIH HHS [N01-CP-01004, N01-CO-12400] NR 24 TC 25 Z9 26 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2005 VL 11 IS 5 BP 516 EP 528 DI 10.1111/j.1365-2516.2005.01138.x PG 13 WC Hematology SC Hematology GA 959GY UT WOS:000231507400014 PM 16128897 ER PT J AU Hawkins, JS Emanuel, EJ AF Hawkins, JS Emanuel, EJ TI Clarifying confusions about coercion SO HASTINGS CENTER REPORT LA English DT Article ID INFORMED-CONSENT C1 Univ Toronto, Toronto, ON, Canada. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Hawkins, JS (reprint author), Univ Toronto, Toronto, ON, Canada. NR 15 TC 34 Z9 35 U1 1 U2 1 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 SEP-OCT PY 2005 VL 35 IS 5 BP 16 EP 19 DI 10.1353/hcr.2005.0075 PG 4 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 967WQ UT WOS:000232122300013 PM 16295260 ER PT J AU Wendler, D AF Wendler, D TI Protecting subjects who cannot give consent SO HASTINGS CENTER REPORT LA English DT Article ID MINIMAL RISK; CHILDREN; STANDARD; ADULTS C1 NIH, Unit Vulnerable Populat, Dept Clin Bioeth, Bethesda, MD 20892 USA. Natl Inst Drug Abuse, IRB, Bethesda, MD 20892 USA. NIH, Bioeth Consultat Serv, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Unit Vulnerable Populat, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 23 TC 25 Z9 26 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 SEP-OCT PY 2005 VL 35 IS 5 BP 37 EP 43 DI 10.1353/hcr.2005.0087 PG 7 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 967WQ UT WOS:000232122300016 PM 16295263 ER PT J AU Druzgal, CH Chen, Z Yeh, NT Thomas, GR Ondrey, FG Duffey, DC Vilela, RJ Ende, K McCullagh, L Rudy, SF Muir, C Herscher, LL Morris, JC Albert, PS Van Waes, C AF Druzgal, CH Chen, Z Yeh, NT Thomas, GR Ondrey, FG Duffey, DC Vilela, RJ Ende, K McCullagh, L Rudy, SF Muir, C Herscher, LL Morris, JC Albert, PS Van Waes, C TI A pilot study of longitudinal serum cytokine and angiogenesis factor levels as markers of therapeutic response and survival in patients with head and neck squamous cell carcinoma SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE squamous cell carcinoma; cytokines; interleukin-6; interleukin-8; vascular endothelial growth factor; growth regulated oncogene 1 ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-KAPPA-B; LUNG-CANCER; PROANGIOGENIC CYTOKINES; CLINICAL-SIGNIFICANCE; BREAST-CANCER; FACTOR VEGF; EXPRESSION; INTERLEUKIN-6; DISEASE AB Background. Head and neck squamous cell carcinomas (HNSCCs) were previously shown to express a repertoire of cytokines and angiogenesis factors that contribute to malignant pathogenesis and are detectable in serum. Pretreatment and posttreatment serum levels of cytokines and angioaenesis factors were evaluated as markers for outcome in patients with HNSCC. Methods, Baseline cytokine and factor levels of 29 patients with HNSCC were compared with those of 15 age-matched and sex-matched controls, and pretreatment and posttreatment levels of 22 of the patients eligible for treatment and followed for a median of 37 months were compared. Results. Mean serum concentrations of interleukin (IL)-6, IL-8, hepatocyte growth factor (HGF), vascular enclothelial growth factor (VEGF), and growth regulated oncogene 1 (GRO-1) were increased in patients with HNSCC, but elevation of these factors was not associated with clinical outcome. However, changes in first posttreatment serum cytokine levels were observed for many of the patients consistent with response, progression, and survival. Later increases in IL-6 or HGF were observed in patients who had a relapse and inflammatory or infectious complications. A relationship between the change in the pretreatment and first posttreatment cytokine measurement with survival was detected for HGF, IL-8, IL-6, and VEGF using a Cox-proportional hazards model (p =.004, p =.06, p =. 10, and p =.11). The association between longitudinal decreases in IL-6, L-8, VEGF, and HGF throughout the follow-up with survival was detected with a time-dependent Cox model (p =.01, .07, .08, and .05, respectively). Conclusions. Longitudinal changes in serum HGF, IL-6, IL-8, and VEGF were detected with treatment response, relapse, or complications in individual patients and were associated with survival, with HGF showing the strongest relationship with survival. HGF, IL-6, IL-8, and VEGF merit investigation as markers of response, survival, and recurrence in larger prospective studies. (c) 2005 Wiley Periodicals, Inc. C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. NIH, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NIH, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bldg 10 CRC,Rm 4-2732,10 Ctr Dr, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [DC-00016] NR 38 TC 57 Z9 58 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD SEP PY 2005 VL 27 IS 9 BP 771 EP 784 DI 10.1002/hed.20246 PG 14 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 959QI UT WOS:000231532600005 PM 15920746 ER PT J AU Kerner, J Rimer, B Emmons, K AF Kerner, J Rimer, B Emmons, K TI Introduction to the Special Section on Dissemination - Dissemination research and research dissemination: How can we close the gap? SO HEALTH PSYCHOLOGY LA English DT Editorial Material DE dissemination research; knowledge translation AB One of the greatest challenges facing health promotion and disease prevention is translating research findings into evidence-based public health and clinical practices that are actively disseminated and widely adopted. Despite the tremendous strides made in developing effective disease prevention and control programs, there has been little study of effective dissemination of evidence-based programs to and adoption by community, public health, and clinical practice settings. This special section provides a venue in which to highlight exemplary dissemination research efforts while also identifying limitations in research to date and framing important future research questions. This issue establishes a resource for investigators interested in dissemination research, with relevance to health psychology. In this sense, it can serve as a benchmark by which to examine subsequent progress. The 6 articles reflect the state of the science in dissemination research for the promotion and adoption of health behavior change interventions. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Dana Farber Canc Inst, Dept Med Oncol Populat Sci, Boston, MA 02115 USA. RP Kerner, J (reprint author), NCI, Div Canc Control & Populat Sci, NIH, EPN 6144,6130 Execut Blvd, Bethesda, MD 20892 USA. EM kemerj@mail.nih.gov OI Kerner, Jon/0000-0002-8792-3830 NR 17 TC 156 Z9 157 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2005 VL 24 IS 5 BP 443 EP 446 DI 10.1037/0278-6133.24.5.443 PG 4 WC Psychology, Clinical; Psychology SC Psychology GA 962RN UT WOS:000231750000001 PM 16162037 ER PT J AU Nettles, RE Kieffer, TL Cofrancesco, J Gallant, JE Quinn, T Jackson, B Flexner, C Carson, KA Wu, AW Siliciano, RF AF Nettles, RE Kieffer, TL Cofrancesco, J Gallant, JE Quinn, T Jackson, B Flexner, C Carson, KA Wu, AW Siliciano, RF TI Psychological distress and physical pain appear to have no short-term adverse impact on plasma HIV-1 RNA levels in patients on successful HAART SO HIV CLINICAL TRIALS LA English DT Article DE HIV; pain; viral load ID AUTONOMIC NERVOUS-SYSTEM; DEPRESSIVE SYMPTOMS; INFECTED MEN; LYMPHOCYTE SUBSETS; PROTEASE INHIBITOR; SOCIAL SUPPORT; HEALTH SURVEY; VIRAL LOAD; STRESS; PERFORMANCE AB Purpose: Previous studies have linked depression and stressful life events in HIV disease with a more rapid decline in CD4 count and progression to AIDS. However, the short-term effect of psychological and physical distress on HIV-1 RNA levels in patients on successful HAART has not been well studied. Method: Ten asymptomatic HIV-infected adults with suppression of viremia to < 50 copies/mL on a stable HAART regimen for >= 6 months were studied. Participants donated blood every 2-3 days over a 3-4 month period for duplicate independent viral load measurements and drug level monitoring. At each time point, psychological distress was measured using the Mental Health Inventory-5 (MHI-5) and an 11-point numeric rating scale for emotional stress. Physical pain was assessed using an 11-point numeric rating scale. Results: All patients maintained successful viral suppression throughout the study. Twenty-six of 713 (3.6%) viral load measurements were > 50 copies/mL. Psychological distress and physical pain were not associated with episodes of detectable viremia. Conclusion: Using frequent monitoring of HIV-1 RNA levels and patient ratings of mood, stress, and pain, we found that psychological distress and physical pain had no short-term adverse impact on HIV-1 RNA levels in highly adherent patients with stable suppression of viremia on HAART. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Howard Hughes Med Inst, Baltimore, MD USA. RP Nettles, RE (reprint author), Bristol Myers Squibb Co, MS E12-16,POB 4000, Princeton, NJ 08543 USA. EM Richard.Nettles@BMS.com FU NCRR NIH HHS [M01-RR00052]; NIAID NIH HHS [AI43222, AI51178, F32 AI056696, K08 AI060367, U01 AI38858] NR 27 TC 2 Z9 2 U1 1 U2 2 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 SEP-OCT PY 2005 VL 6 IS 5 BP 262 EP 271 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 996HS UT WOS:000234165600004 PM 16425464 ER PT J AU Morgan, RA Walker, R Carter, CS Natarajan, V Tavel, JA Bechtel, C Herpin, B Muul, L Zheng, ZL Jagannatha, S Bunnell, BA Fellowes, V Metcalf, JA Stevens, R Baseler, M Leitman, SF Read, EJ Blaese, RM Lane, HC AF Morgan, RA Walker, R Carter, CS Natarajan, V Tavel, JA Bechtel, C Herpin, B Muul, L Zheng, ZL Jagannatha, S Bunnell, BA Fellowes, V Metcalf, JA Stevens, R Baseler, M Leitman, SF Read, EJ Blaese, RM Lane, HC TI Preferential survival of CD4(+) T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals SO HUMAN GENE THERAPY LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; PERIPHERAL-BLOOD LYMPHOCYTES; RETROVIRAL VECTORS; ADOPTIVE TRANSFER; REV FUNCTION; CELLS; EXPRESSION; REPLICATION; PROTEIN; PERSISTENCE AB The present study examined the safety and relative in vivo survival of genetically engineered CD4(+) T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. Ten pairs of identical twins discordant for HIV infection were recruited, with the uninfected twin serving as the lymphocyte donor. Ten subjects were treated with a total of 19 separate infusions of retroviral vector-transduced CD4+ enriched T cells. Control (neo gene) or anti-HIV gene (antisense trans-activation response [TAR] element and/or trans-dominant Rev)-engineered lymphocytes were monitored in peripheral blood for 3 years, using a vector-specific PCR assay. Data from 9 of the 10 patients (15 of the 19 infusions) demonstrated preferential survival of CD4(+) lymphocytes containing the anti-HIV gene(s) in the immediate weeks after infusion. In six of six patients studied long term (> 100 weeks), only T cells containing the anti-HIV genes were consistently detected. In addition, a marked survival advantage of anti-HIV gene-containing T cells was observed in a patient treated during a period of high viral load. Thus, these data strongly support the hypothesis that anti-HIV genes afford a survival advantage to T cells and potential benefit to HIV-1(+) individuals. C1 NIAID, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. SAIC Frederick, Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Tavel, JA (reprint author), NIAID, NIH, Bldg 10,Room 11C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM jtavel@mail.nih.gov FU NCI NIH HHS [N01-CO-56000] NR 31 TC 43 Z9 47 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2005 VL 16 IS 9 BP 1065 EP 1074 DI 10.1089/hum.2005.16.1065 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 965MR UT WOS:000231955100007 PM 16149905 ER PT J AU Kimchi-Sarfaty, C Brittain, S Garfield, S Caplen, NJ Tang, QQ Gottesman, MM AF Kimchi-Sarfaty, C Brittain, S Garfield, S Caplen, NJ Tang, QQ Gottesman, MM TI Efficient delivery of RNA interference effectors via in vitro-packaged SV40 pseudovirions SO HUMAN GENE THERAPY LA English DT Article ID GENE-THERAPY; VECTORS; EXPRESSION; SIRNAS; CELLS AB Previously we have shown that in vitro-packaged simian virus 40 (SV40) pseudovirions (IVPs) are an efficient delivery system for supercoiled DNA plasmids of up to 17.7 kb, with or without SV40 sequences. RNA interference (RNAi) is a naturally occurring gene-silencing mechanism mediated by small double-stranded RNA molecules (small interfering RNAs, siRNAs). This study demonstrates the first use of SV40 pseudovirions to deliver into human cells both principal types of RNAi effector molecules: plasmid-expressed short hairpin RNAs (shRNAs) and synthetic siRNAs. We first established the ability of human lymphoblastoid cells to support RNAi, using sequential transduction of .45 cells with packaged plasmid DNA expressing the green fluorescent protein (IVP-GFP), and an shRNA corresponding to the GFP (IVP-shGFP). SV40 mediates DNA transfer of nucleic acid to the cytoplasm, where RNAi-associated cleavage of mRNA principally occurs. Using SV40 pseudovirions, siRNA-mediated RNAi was observed in both .45 cells, after sequential transduction of IVP-GFP and IVP-packaged siRNAs corresponding to GFP (IVP-siGFP), and in HeLa cells stably expressing a GFP transduced with IVP-siGFP. Our findings indicate that SV40 pseudovirions may be a useful addition to the delivery systems currently being used for the transfer of RNAi effector molecules. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Gene Silencing Sect, Off Sci & Technol Partnerships, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Genomics & Drug Discovery, Rockville, MD 20852 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS NR 16 TC 19 Z9 23 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2005 VL 16 IS 9 BP 1110 EP 1115 DI 10.1089/hum.2005.16.1110 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 965MR UT WOS:000231955100011 PM 16149909 ER PT J AU Gallagher, PG Nilson, DG Wong, C Weisbein, JL Garrett-Beal, LJ Eber, SW Bodine, DM AF Gallagher, PG Nilson, DG Wong, C Weisbein, JL Garrett-Beal, LJ Eber, SW Bodine, DM TI A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis SO HUMAN MOLECULAR GENETICS LA English DT Article ID RNA-POLYMERASE-II; GAMMA-GLOBIN GENE; CORE PROMOTER; TATA-BOX; BINDING-PROTEINS; TRANSGENIC MICE; LESS PROMOTER; MUTATIONS; ELEMENT; SPECTRIN AB Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In some HS patients, mutations in the ankyrin promoter have been hypothesized to lead to decreased ankyrin mRNA synthesis. The ankyrin erythroid promoter is a member of the most common class of mammalian promoters which lack conserved TATA, initiator or other promoter cis elements and have high G+C content, functional Sp1 binding sites and multiple transcription initiation sites. We identified a novel ankyrin gene promoter mutation, a TG deletion adjacent to a transcription initiation site, in a patient with ankyrin-linked HS and analyzed its effects on ankyrin expression. In vitro, the mutant promoter directed decreased levels of gene expression, altered transcription initiation site utilization and exhibited defective binding of TATA-binding protein (TBP) and TFIID complex formation. In a transgenic mouse model, the mutant ankyrin promoter led to abnormalities in gene expression, including decreased expression of a reporter gene and altered transcription initiation site utilization. These data indicate that the mutation alters ankyrin gene transcription and contributes to the HS phenotype by decreasing ankyrin gene synthesis via disruption of TFIID complex interactions with the ankyrin core promoter. These studies support the model that in promoters that lack conserved cis elements, the TFIID complex directs preinitiation complex formation at specific sites in core promoter DNA and provide the first evidence that disruption of TBP binding and TFIID complex formation in this type of promoter leads to alterations in start site utilization, decreased gene expression and a disease phenotype in vivo. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Kinderklin Zurich, CH-8032 Zurich, Switzerland. RP Gallagher, PG (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. EM patrick.gallagher@yale.edu FU NIDDK NIH HHS [DK062039] NR 47 TC 11 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2005 VL 14 IS 17 BP 2501 EP 2509 DI 10.1093/hmg/ddi254 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 958UI UT WOS:000231473300005 PM 16037067 ER PT J AU Kim, U Wooding, S Ricci, D Jorde, LB Drayna, D AF Kim, U Wooding, S Ricci, D Jorde, LB Drayna, D TI Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci SO HUMAN MUTATION LA English DT Article DE bitter taste; TAS2R; cSNP; haplotypes; natural selection ID NATURAL-SELECTION; LINKAGE DISEQUILIBRIUM; POPULATION DIFFERENCES; HUMAN GENOME; EVOLUTION; NUCLEOTIDE; SIGNATURES; GENES; RECONSTRUCTION; MAP AB Bitter taste perception in humans is mediated by receptors encoded by 25 genes that together comprise the TAS2R (or T2R) gene family. The ability to identify the ligand(s) for each of these receptors is dependent on understanding allelic variation in TAS2R genes, which may have a significant effect on ligand recognition. To investigate the extent of coding variation among TAS2R alleles, we performed a comprehensive evaluation of sequence and haplotype variation in the human bitter taste receptor gene repertoire. We found that these genes exhibit substantial coding sequence diversity. In a worldwide population sample of 55 individuals, we found an average of 4.2 variant amino acid positions per gene. In aggregate, the 24 genes analyzed here, along with the phenylthiocarbamide (PTC) receptor gene analyzed previously, specify 151 different protein coding haplotypes. Analyses of the ratio of synonymous and nonsynonymous nucleotide substitutions using the K-a/K-s ratio revealed an excess of amino acid substitutions relative to most other genes examined to date (K-a/K-s = 0.94). In addition, comparisons with more than 1,500 other genes revealed that levels of diversity in the TAS2R genes were significantly greater than expected (pi=0.11%; P < 0.01), as were levels of differentiation among continental populations (F-ST = 0.22; p < 0.05). These diversity patterns indicate that unusually high levels of allelic variation are found within TAS2R loci and that human populations differ appreciably with respect to TAS2R allele frequencies. Diversity in the TAS2R genes may be accounted for by natural selection, which may have favored alleles responsive to toxic, bitter compounds found in plants. These findings are consistent with the view that different alleles of the TAS2R genes encode receptors that recognize different ligands, and suggest that the haplotypes we have identified will be important in studies of receptor-ligand recognition. C1 NIDCD, NIH, Rockville, MD 20850 USA. Kyungpook Natl Univ, Dept Biol, Taegu, South Korea. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. RP Drayna, D (reprint author), NIDCD, NIH, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU NHLBI NIH HHS [HL070048]; NIDCD NIH HHS [Z01-DC000046-04]; NIEHS NIH HHS [ES12125] NR 33 TC 114 Z9 115 U1 6 U2 30 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2005 VL 26 IS 3 BP 199 EP 204 DI 10.1002/humu.20203 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 960ZH UT WOS:000231631200005 PM 16086309 ER PT J AU Bergen, AW Haque, KA Qi, Y Beerman, MB Garcia-Closas, M Rothman, N Chanock, SJ AF Bergen, AW Haque, KA Qi, Y Beerman, MB Garcia-Closas, M Rothman, N Chanock, SJ TI Comparison of yield and genotyping performance of multiple displacement OmniPlex (TM) whole genome amplified DNA generated from multiple DNA sources SO HUMAN MUTATION LA English DT Article DE whole genome amplification; multiple displacement amplification; GenomiPhi (TM); REPLI-g (TM) 2500S; OmniPlex (TM); AmpFlSTR (R) identifiler (R) assay; TaqMan (TM) assay ID SINGLE NUCLEOTIDE POLYMORPHISM; GENETIC-ANALYSIS; AMPLIFICATION; POLYMERASE; CELLS; PRIMER; PCR; HYBRIDIZATION; VALIDATION; SAMPLES AB The promise of whole genome amplification (WGA) is that genomic DNA (gDNA) quantity will not limit molecular genetic analyses. Multiple displacement amplification (MDA) and the OmniPlex (TM) PCR,based WGA protocols were evaluated using 4 and 5 ng of input gDNA from 60 gDNA samples from three tissue sources (mouthwash, buffy coat, and lymphoblast). WGA DNA (wgaDNA) yield and genotyping performance were evaluated using genotypes determined from gDNA and wgaDNA using the AmpFlSTR (R) Identifiler (R) assay and N = 49 TaqMan (R) SNP assays. Short tandem repeat (STR) and SNP genotyping completion and concordance rates were significantly reduced with wgaDNA from all WGA methods compared with gDNA. OmniPlex wgaDNA exhibited a greater reduction in genotyping performance than MDA wgaDNA. Reduced wgaDNA genotyping performance was due to allelic (all protocols) and locus (OmniPlex) amplification bias leading to heterozygote and locus dropout, respectively, and %GC sequence content (%GC) was significantly correlated with TaqMan assay performance. Lymphoblast wgaDNA exhibited higher yield (OmniPlex), huffy coat wgaDNA exhibited higher STR genotyping completion (MDA), whereas mouthwash wgaDNA exhibited higher SNP genotyping discordance (MDA). Genotyping of wgaDNA generated from <= 5 ng gDNA, e.g., from archaeological, forensic, prenatal diagnostic, or pathology samples, may require additional genotyping validation with gDNA and/or more sophisticated analysis of genotypes incorporating observed reductions in genotyping performance. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, NIH, Gaithersburg, MD USA. NCI FCRDC, SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. RP Bergen, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Executive Blvd, Bethesda, MD 20892 USA. EM bergena@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Bergen, Andrew/0000-0002-1237-7644 FU NCI NIH HHS [N01-CO-12400] NR 33 TC 56 Z9 61 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2005 VL 26 IS 3 BP 262 EP 270 DI 10.1002/humu.20213 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 960ZH UT WOS:000231631200012 PM 16086324 ER PT J AU Kowarz, L Goker-Alpan, O Banerjee-Basu, S LaMarca, ME Kinlaw, L Schiffmann, R Baxevanis, AD Sidransky, E AF Kowarz, L Goker-Alpan, O Banerjee-Basu, S LaMarca, ME Kinlaw, L Schiffmann, R Baxevanis, AD Sidransky, E TI Gaucher mutation N188S is associated with myoclonic epilepsy SO HUMAN MUTATION LA English DT Letter ID DISEASE AB The recent article by Montfort et al. [2004] reported a functional analysis of 13 glucocerebrosidase alleles, including mutation N188S, which they considered to be a "very mild mutations' or "modifier variant." Our clinical experience with patients carrying this mutation and preliminary protein modeling data lead us to dispute this conclusion. C1 Natl Inst Mental Hlth, Sect Mol Neurogenet, Clin Neurosci Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, Computat Genom Program, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Bethesda, MD USA. RP Sidransky, E (reprint author), Natl Inst Mental Hlth, Sect Mol Neurogenet, Clin Neurosci Branch, 35 Convet Dr,Bldg 35,Room 1A213, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 8 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2005 VL 26 IS 3 BP 271 EP 273 DI 10.1002/humu.20217 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 960ZH UT WOS:000231631200013 PM 16086325 ER PT J AU Aisner, DL Maker, A Rosenberg, SA Berman, DM AF Aisner, DL Maker, A Rosenberg, SA Berman, DM TI Loss of S100 antigenicity in metastatic melanoma SO HUMAN PATHOLOGY LA English DT Article DE S100; melanoma; antigenicity; diagnosis ID MALIGNANT-MELANOMA; LOSS VARIANTS; LYMPH-NODE; EXPRESSION; CANCER; IMMUNOTHERAPY; IDENTIFICATION; PREDICTORS; TYROSINASE; SURVIVAL AB Melanoma is a highly malignant disease that may initially present as a poorly differentiated metastatic tumor. Therefore, the SIN immunostain, immunoreactive in 96% to 99% of melanoma, is used to evaluate poorly differentiated malignant tumors. To develop criteria for correctly diagnosing S100-negative melanomas, we studied the immunohistochemical profile of 1553 patients enrolled in ongoing National Cancer Institute clinical trials for melanoma. Seventeen patients (1%) had metastatic melanoma specimens that were negative for S100. Of the 17 S100-negative lesions, 10 (59%) were immunoreactive for both GP100 and MART-1. Of the 17 S100-negative cases, 13 had a documented primary melanoma. Twenty-four percent of the S100-negative cases had an ocular primary, whereas only 6% of all melanomas had an ocular origin. In 11 of the 17 cases with previous surgical specimens, a prior documented S100-immunoreactive specimen was identified in 9 cases (82%). The time interval for loss of SIN immunoreactivity ranged from 3 weeks to 3 years (average, 13.5 months). There was no association between S100-negative status and histological appearance or site of metastasis. We conclude that all S100-negative melanomas could be correctly identified by negative workup for carcinoma, lymphoma, and sarcoma plus (1) GP100/MART-1 immunoreactivity and/or (2) prior documentation of melanoma. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Berman, DM (reprint author), NCI, Pathol Lab, Bethesda, MD 20892 USA. EM david.berman@bms.com FU Intramural NIH HHS [Z01 SC003811-33] NR 23 TC 21 Z9 22 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2005 VL 36 IS 9 BP 1016 EP 1019 DI 10.1016/j.humpath.2005.07.010 PG 4 WC Pathology SC Pathology GA 966ZH UT WOS:000232060800012 PM 16153466 ER PT J AU Najjar, SS Scuteri, A Lakatta, EG AF Najjar, SS Scuteri, A Lakatta, EG TI Arterial aging - Is it an immutable cardiovascular risk factor? SO HYPERTENSION LA English DT Review DE aging; arteries; arteriosclerosis; risk factors; angiotensin II; cardiovascular diseases ID SMOOTH-MUSCLE-CELLS; PULSE-WAVE VELOCITY; ISOLATED SYSTOLIC HYPERTENSION; LIFE-STYLE MODIFICATION; ENDOTHELIAL DYSFUNCTION; TELOMERE LENGTH; CAROTID ATHEROSCLEROSIS; INSULIN-RESISTANCE; NITRIC-OXIDE; MATRIX METALLOPROTEINASE-2 AB Age is the dominant risk factor for cardiovascular diseases. However, until recently, convincing mechanistic or molecular explanations for the increased cardiovascular risks conferred by aging have been elusive. Aging is associated with alterations in a number of structural and functional properties of large arteries, including diameter, wall thickness, wall stiffness, and endothelial function. Emerging evidence indicates that these age- associated changes are also accelerated in the presence of cardiovascular diseases, and that these changes are themselves risk factors for the appearance or progression of these diseases. In this review, the evidence demonstrating that arterial aging is accelerated in cardiovascular diseases and that accelerated arterial aging is a risk factor for adverse cardiovascular outcomes is briefly reviewed, and selected advances in vascular biology that provide insights into the mechanisms that may underlie the increased risks conferred by arterial aging are summarized. Remarkably, a host of biochemical, enzymatic, and cellular alterations that are operative in accelerated arterial aging have also been implicated in the pathogenesis and progression of arterial diseases. These vascular alterations are thus putative candidates that could be targeted by interventions aimed at attenuating arterial aging, similar to the lifestyle and pharmacological interventions that have already been proven effective. Therefore, the notion that aging is a chronological process and that its risky components cannot be modulated is no longer tenable. It is our hope that a greater appreciation of the links between arterial aging and cardiovascular diseases will stimulate further investigation into strategies aimed at preventing or retarding arterial aging. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. INRCA, UO Geriatria, Rome, Italy. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@mail.nih.gov NR 85 TC 326 Z9 355 U1 0 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2005 VL 46 IS 3 BP 454 EP 462 DI 10.1161/01.HYP.0000177474.06749.98 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 958MO UT WOS:000231452600002 PM 16103272 ER PT J AU Bartesaghi, A Sapiro, G Subramaniam, S AF Bartesaghi, A Sapiro, G Subramaniam, S TI An energy-based three-dimensional segmentation approach for the quantitative interpretation of electron tomograms SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE distance functions; electron tomography; energy-based segmentation; geodesics; high resolution; HIV; minimal surfaces; volume segmentation ID ACTIVE CONTOUR MODELS; ALGORITHMS; FRONTS; 3D AB Electron tomography allows for the determination of the three-dimensional structures of cells and tissues at resolutions significantly higher than that which is possible with optical microscopy. Electron tomograms contain, in principle, vast amounts of information on the locations and architectures of large numbers of subcellular assemblies and organelles. The development of reliable quantitative approaches for the analysis of features in tomograms is an important problem, and a challenging prospect due to the low signal-to-noise ratios that are inherent to biological electron microscopic images. This is, in part, a consequence of the tremendous complexity of biological specimens. We report on a new method for the automated segmentation of HIV particles and selected cellular compartments in electron tomograms recorded from fixed, plastic-embedded sections derived from HIV-infected human macrophages. Individual features in the tomogram are segmented using a novel robust algorithm that finds their boundaries as global minimal surfaces in a metric space defined by image features. The optimization is carried out in a transformed spherical domain with the center an interior point of the particle of interest, providing a proper setting for the fast and accurate minimization of the segmentation energy. This method provides tools for the semi-automated detection and statistical evaluation of HIV particles at different stages of assembly in the cells and presents opportunities for correlation with biochemical markers of HIV infection. The segmentation algorithm developed here forms the basis of the automated analysis of electron tomograms and will be especially useful given the rapid increases in the rate of data acquisition. It could also enable studies of much larger data sets, such as those which might be obtained from the tomographic analysis of HIV-infected cells from studies of large populations. C1 Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN 55455 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Bartesaghi, A (reprint author), Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN 55455 USA. EM abarte@umn.edu; guille@umn.edu; subramas@mail.nih.gov NR 29 TC 27 Z9 29 U1 1 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD SEP PY 2005 VL 14 IS 9 BP 1314 EP 1323 DI 10.1109/TIP.2005.852467 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 956SF UT WOS:000231319400009 PM 16190467 ER PT J AU Bornstein, MH AF Bornstein, MH TI Parenting matters SO INFANT AND CHILD DEVELOPMENT LA English DT Article C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Natl Inst Child Hlth & Human Dev, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM marc_h_bornstein@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1522-7227 J9 INFANT CHILD DEV JI Infant Child Dev. PD SEP PY 2005 VL 14 IS 3 BP 311 EP 314 DI 10.1002/icd.394 PG 4 WC Psychology, Developmental SC Psychology GA 970CA UT WOS:000232281600006 ER PT J AU Iborra, S Carrion, J Anderson, C Alonso, C Sacks, D Soto, M AF Iborra, S Carrion, J Anderson, C Alonso, C Sacks, D Soto, M TI Vaccination with the Leishmania infantum acidic, ribosomal P0 protein plus CpG oligodeoxynucleotides induces protection against cutaneous leishmaniasis in C57BL/6 mice but does not prevent progressive disease BALB/c mice SO INFECTION AND IMMUNITY LA English DT Article ID VISCERAL LEISHMANIASIS; INDEPENDENT MECHANISM; MURINE LEISHMANIASIS; INTERFERON-GAMMA; DENDRITIC CELLS; T-CELLS; DNA; ACTIVATION; IMMUNITY; INFECTION AB We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on the Leishmania infantum acidic ribosomal protein PO (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L. major parasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces the L. major infection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or LiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-gamma) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-gamma in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced by L. major infection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates. C1 Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Soto, M (reprint author), Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. EM msoto@cbm.uam.es RI Iborra, Salvador /J-2863-2015; OI Iborra, Salvador /0000-0002-1607-1749; Soto Alvarez, Manuel/0000-0001-6825-841X NR 35 TC 41 Z9 44 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 SEP PY 2005 VL 73 IS 9 BP 5842 EP 5852 DI 10.1128/IAI.73.9.5842-5852.2005 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000060 PM 16113303 ER PT J AU Henderson, DK AF Henderson, DK TI Healthcare behaviors and risky business: First, do no harm SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID HIV-1 INFECTION C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), Bldg 10,Room 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA. EM dkh@nih.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2005 VL 26 IS 9 BP 739 EP 742 DI 10.1086/502611 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 970VE UT WOS:000232338900001 PM 16209379 ER PT J AU Vermeulen, R Jonsson, BAG Lindh, CH Kromhout, H AF Vermeulen, R Jonsson, BAG Lindh, CH Kromhout, H TI Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE rubber industry; carbon disulphide; phthalates; biomonitoring ID MANUFACTURING-INDUSTRY; POPULATION; CHROMATOGRAPHY; METABOLITES; URINE AB Objectives: We studied the range in urinary levels of 2-thiothiazolidine-4-carboxyl acid (TTCA), a metabolite of CS, and phthalic acid (PA), a common metabolite of phthalates, across factories and departments in the contemporary rubber manufacturing industry. Methods: Spot urine samples from 101 rubber workers employed in nine different factories were collected on Sunday and during the workweek on Tuesday, Wednesday and Thursday at similar to 4 pm. In total, 386 urine samples were successfully analyzed. Results: Levels of both biomarkers increased significantly by a factor 2 (paired t-test P-value < 0.05) during the working week as compared to the Sunday biomarker levels with absolute increases of approximately 70 mu g/l and 5 mu mol/mol creatinine for PA and TTCA, respectively. Levels in both biomarkers did not differ markedly between working days. Increases seemed to be restricted to specific factories and/or departments (e.g. molding and curing). Conclusions: The results of this study demonstrate that rubber workers in the contemporary rubber industry are exposed to phthalates and low levels Of CS2 (similar to 0.05 ppm) as measured by PA and TTCA, respectively. Exposures to both compounds are largely driven by specific circumstances in Factories. Therefore, when estimating exposures to phthalates and CS2 detailed information should be collected on the type and amount of phthalate containing ester plasticizers, dithlocarbamates and thiurams used. Preferably, personal exposure data should be collected. In this case, biological monitoring seems a reasonable approach. However, in the case of PA attention should be given to individual background levels as this could lead to a substantial overestimation of the Occupational contribution to total phthalate exposure. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, Rockville, MD 20852 USA. Univ Utrecht, Inst Risk Assessment Sci, Div Environm & Occupat Hlth, Utrecht, Netherlands. Univ Lund Hosp, Dept Occupat & Environm Med, S-22185 Lund, Sweden. RP Vermeulen, R (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, 6120 Execut Blvd, Rockville, MD 20852 USA. EM vermeulr@mail.nih.gov RI Kromhout, Hans/A-9159-2008; Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Jonsson, Bo/0000-0002-8767-0589; Lindh, Christian/0000-0001-7435-9890 NR 22 TC 13 Z9 13 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-0131 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD SEP PY 2005 VL 78 IS 8 BP 663 EP 669 DI 10.1007/s00420-005-0017-z PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977CE UT WOS:000232779200008 PM 16041606 ER PT J AU Yang, XH Beerman, M Bergen, AW Parry, DM Sheridan, E Liebsch, NJ Kelley, MJ Chanock, S Goldstein, AM AF Yang, XH Beerman, M Bergen, AW Parry, DM Sheridan, E Liebsch, NJ Kelley, MJ Chanock, S Goldstein, AM TI Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE chordoma; linkage; single nucleotide polymorphism (SNP); genetic heterogeneity ID LINKAGE ANALYSIS; MICROSATELLITES; GENOME; MAPS; PROGRAM; MARKERS; TUMOR AB Chordoma, a rare bone tumor originating from notochordal remnants, has a genetic predisposition in some families. Previously, we performed linkage analysis using microsatellite (STR) markers on 3 unrelated chordoma kindreds (16 patients with chordoma) and reported significant evidence for linkage to chromosome 7q33 (Z(max) = 4.78) with a minimal disease gene region of 11 cM. In our present study, we performed linkage analysis in these 3 families using chromosome 7 single nucleotide polymorphisms (SNPs). Parametric and nonparametric multipoint analyses showed significant linkage to 7q markers with p < 0.001 and Z(max) = 2.77, respectively. The minimal disease gene region was not reduced by combined SNP and STIR haplotype analysis compared to the previous STR haplotype analysis alone. We genotyped members of a fourth chordoma family with SNP and STR markers for chromosome 7q and for 1p36, the location of a previously reported chordoma locus. Affected members of this family did not share a common haplotype on 7q, and the family did not show evidence of linkage to 1p36. Thus, we corroborated a chordoma locus on chromosome 7q in the 3 original families and demonstrated evidence for genetic heterogeneity in the fourth family. Our study also provided insights into some limitations and analytical complexities associated with using a dense SNP marker set in linkage analysis of complex pedigrees. (C) 2005 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Duke Univ, Dept Med, Durham, NC USA. RP Yang, XH (reprint author), NCI, Genet Epidemiol Branch, DCEG, 6120 Execut Blvd,Rm 7014, Rockville, MD 20852 USA. EM royang@mail.nih.gov OI Kelley, Michael/0000-0001-9523-6080; Bergen, Andrew/0000-0002-1237-7644 NR 28 TC 18 Z9 18 U1 0 U2 0 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 SEP 1 PY 2005 VL 116 IS 3 BP 487 EP 491 DI 10.1002/ijc.21006 PG 5 WC Oncology SC Oncology GA 944YC UT WOS:000230466100022 ER PT J AU Tanofsky-Kraff, M Faden, D Yanovski, SZ Wilfley, DE Yanovski, JA AF Tanofsky-Kraff, M Faden, D Yanovski, SZ Wilfley, DE Yanovski, JA TI The perceived onset of dieting and loss of control eating behaviors in overweight children SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article; Proceedings Paper CT International Conference on Eating Disorders CY MAY 29-JUN 01, 2003 CL Denver, CO DE middle childhood; overweight; dieting; lossofcontrol; binge eating ID RISK-FACTORS; ADOLESCENT GIRLS; DISORDERED BEHAVIORS; FEMALE ADOLESCENTS; PUBERTAL CHANGES; WEIGHT CONCERNS; PSYCHOPATHOLOGY; PREVALENCE; PREDICTORS; THERAPY AB Objective: The current study investigated the self-reported temporal relationships of dieting, binge eating, and overweight in childhood. Method: One hundred five non-treatment-seeking overweight children ages 6-13 years were interviewed with the children's Eating Disorder Examination (ChEDE) and queried regarding dieting, loss of control (LOC) eating, and overweight history. Questionnaires of depressive symptoms, trait anxiety, and parent-reported problems were completed. Results: Sixty percent of the children reported having attempted at least one diet. These children had higher ChEDE scores (global, p < .001), greater body mass index (BMI) and body fat mass (p <= .001), and a trend towards an earlier reported age of overweight onset (p = .06) compared with children who had never clieted. The 29.5% of children who reported LOC eating had significantly higher ChEDE scores (global, p < .001), ineffectiveness, negative self-esteem, and externalizing scores (all ps < .05) compared with those who had never experienced LOC eating. Most children reported becoming overweight before either dieting (79.4%) or experiencing LOC eating (63.6%). Among the 25.7% reporting both dieting and LOC eating, two thirds reported LOC eating before dieting. Participants who reported dieting before overweight had higher negative mood scores (p < .01). Children reporting dieting before LOC eating had higher ChEDE Weight Concern (p < .01) and global (p < .05) scores. Discussion: For overweight, non-treatment-seeking children, both dieting and LOC eating are common. Dieting precedes the development of LOC eating only one third of the time, but is associated with greater disordered eating cognitions. The relationship between childhood-onset dieting and LOC eating in overweight children requires further investigation to determine the causal pathways for the subsequent development of eating disorders. (c) 2005 by Wiley Periodicals, Inc. C1 NICHHD, Unit Growth & Obes, Dev Exdocrimol Branch, NIH,CRC,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Tanofsky-Kraff, M (reprint author), NICHHD, Unit Growth & Obes, Dev Exdocrimol Branch, NIH,CRC,Dept Hlth & Human Serv, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM tanofskm@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01-HD-04-00641] NR 53 TC 79 Z9 79 U1 2 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2005 VL 38 IS 2 BP 112 EP 122 DI 10.1002/eat.20158 PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 961DQ UT WOS:000231642500003 PM 16134103 ER PT J AU Zamboni, M Mazzali, G Zoico, E Harris, TB Meigs, JB Di Francesco, V Fantin, F Bissoli, L Bosello, O AF Zamboni, M Mazzali, G Zoico, E Harris, TB Meigs, JB Di Francesco, V Fantin, F Bissoli, L Bosello, O TI Health consequences of obesity in the elderly: a review of four unresolved questions SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Review DE aging; BMI; fat distribution; disability; sarcopenic obesity ID BODY-MASS INDEX; ALL-CAUSE MORTALITY; FAT-FREE MASS; OBSTRUCTIVE SLEEP-APNEA; SIMPLE ANTHROPOMETRIC INDEXES; ABDOMINAL SAGITTAL DIAMETER; CARDIOVASCULAR RISK-FACTORS; VISCERAL ADIPOSE-TISSUE; CORONARY-HEART-DISEASE; SKELETAL-MUSCLE MASS AB Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity. C1 Univ Verona, Div Geriatr Med, I-37126 Verona, Italy. NIA, Off Geriatr Epidemiol, Epidemiol & Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Zamboni, M (reprint author), Univ Verona, Osped Maggiore, Piazzale Stefani 1, I-37126 Verona, Italy. EM mauro.zamboni@univr.it OI ZOICO, Elena/0000-0002-5235-1545; ZAMBONI, Mauro/0000-0001-6961-9483 NR 141 TC 286 Z9 291 U1 5 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2005 VL 29 IS 9 BP 1011 EP 1029 DI 10.1038/sj.ijo.0803005 PG 19 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 954CC UT WOS:000231130700001 PM 15925957 ER PT J AU Kawakami, K Kawakami, M Liu, Q Puri, RK AF Kawakami, K Kawakami, M Liu, Q Puri, RK TI Combined effects of radiation and interleukin-13 receptor-targeted cytotoxin on glioblastoma cell lines SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE glioblastoma; interleukin-13 receptor; cytotoxin; radiation ID CONVECTION-ENHANCED DELIVERY; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; MALIGNANT GLIOMA; CARCINOMA-CELLS; IL-13 RECEPTOR; DECOY RECEPTOR; CANCER-CELLS; ALPHA CHAIN; PROTEIN AB Purpose: Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly cytotoxic to human glioblastoma (GBM) cells. Although this molecule is being tested in a multicenter Phase III clinical trial (PRECISE Study) in patients with recurrent disease, the activity of IL13-PE38 when combined with radiation therapy has not been investigated. Methods and Materials: Cytotoxicity of IL13-PE38 to GBM cell lines was assessed by protein synthesis inhibition and clonogenic assays, and the growth of GBM cells receiving radiation was assessed by thymidine uptake assays. Expression of IL-13 receptor alpha 2 (IL-13R alpha 2) messenger ribonucleic acid (mRNA) in GBM cells exposed to radiation was assessed by quantitative reverse transcriptase/polymerase chain reaction (RT-PCR) and IL-13R density by radiolabeled IL-13 binding assays. Results: Prior irradiation of GBM cell lines followed by IL13-PE38 treatment did not enhance cytotoxicity; however, concomitant 5 Gy irradiation and IL13-PE38 treatment was highly cytotoxic to T98G, M059K, A172, and LN-229 cell lines as determined by cell viability assays. There was a statistically significant decrease in number of viable cells in IL13-PE38 and irradiated cells compared with irradiated cells alone (p < 0.05) or IL13-PE38 treated cells alone (p < 0.05). In contrast, U251, SN19, and U87MG cell lines did not show any combined effect. These results were confirmed by clonogenic assays. Although three GBM cell lines-U251, SN19, and A172-showed 2.8- to 13.9-fold upregulation of IL-13R alpha 2 mRNA expression at 6-24 h after exposure to 5 Gy radiation, specific binding of radiolabeled IL-13 to these cell lines did not improve. Conclusions: Our results suggest that concomitant radiation therapy and IL13-PE38 treatment may be beneficial for the treatment of patients with GBM. This strategy may be worth exploring in animal models of human glioma. (c) 2005 Elsevier Inc. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 32 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2005 VL 63 IS 1 BP 230 EP 237 DI 10.1016/j.ijrobp.2005.05.017 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 956TK UT WOS:000231322500029 PM 16111594 ER PT J AU Li, G Xie, HC Ning, H Capala, J Arora, BC Coleman, CN Camphausen, K Miller, RW AF Li, G Xie, HC Ning, H Capala, J Arora, BC Coleman, CN Camphausen, K Miller, RW TI A novel 3D volumetric voxel registration technique for volume-view-guided image registration of multiple imaging modalities SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE multimodality image registration; 3D voxel image registration; volume-view-guided image registration; accelerated image registration with improved accuracy; radiation treatment planning ID FREE-FORM DEFORMATIONS; MUTUAL-INFORMATION; MEDICAL IMAGES; MR-IMAGES; PET; CT; BRAIN; FUSION; SPECT; IMRT AB Purpose: To provide more clinically useful image registration with improved accuracy and reduced time, a novel technique of three-dimensional (3D) volumetric voxel registration of multimodality images is developed. Methods and Materials: This technique can register up to four concurrent images from multimodalities with volume view guidance. Various visualization effects can be applied, facilitating global and internal voxel registration. Fourteen computed tomography/magnetic resonance (CT/MR) image sets and two computed tomography/positron emission tomography (CT/PET) image sets are used. For comparison, an automatic registration technique using maximization of mutual information (MMI) and a three-orthogonal-planar (3P) registration technique are used. Results: Visually sensitive registration criteria for CT/MR and CT/PET have been established, including the homogeneity of color distribution. Based on the registration results of 14 CT/MR images, the 3D voxel technique is in excellent agreement with the automatic MMI technique and is indicatory of a global positioning error (defined as the means and standard deviations of the error distribution) using the 3P pixel technique: 1.8 degrees +/- 1.2 degrees in rotation and 2.0 +/- 1.3 (voxel unit) in translation. To the best of our knowledge, this is the first time that such positioning error has been addressed. Conclusion: This novel 3D voxel technique establishes volume-view-guided image registration of up to four modalities. It improves registration accuracy with reduced time, compared with the 3P pixel technique. This article suggests that any interactive and automatic registration should be safeguarded using the 3D voxel technique. (c) 2005 Elsevier Inc. C1 NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA. RP Li, G (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, Bldg 10,Rm B2-3561,MSC-1682,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ligeorge@mail.nih.gov OI Li, Guang/0000-0002-9022-2883 NR 26 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2005 VL 63 IS 1 BP 261 EP 273 DI 10.1016/j.ijrobp.2005.05.008 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 956TK UT WOS:000231322500033 PM 16024179 ER PT J AU Macrae, J Friedman, AL Friedman, EA Eggers, P AF Macrae, Jeanne Friedman, Amy L. Friedman, Eli A. Eggers, Paul TI Live and deceased donor kidney transplantation in patients aged 75 years and older in the United States SO INTERNATIONAL UROLOGY AND NEPHROLOGY LA English DT Article DE deceased donor; ESRD; geriatric patients; kidney transplantation; live donor; prognosis; USRDS AB Objective: To examine the outcomes of geriatric ESRD patients selected for kidney transplantation. Design: Data were extracted from the USRDS Standard Analysis Files (SAF). All persons ages 75 and over who received a kidney transplant from 1994 to 2000 were compared with those remaining on dialysis or on a transplant waiting list. Data on mortality or removal from the waiting list were obtained from the United Network for Organ Sharing (UNOS). The main outcome measure was patient and kidney transplant survival. Results: Superior five year survival after kidney transplantation was attained by the geriatric cohort given a live donor transplant (59.9%), compared with recipients of deceased donor kidneys (40.3%), dialysis patients waiting for transplant (29.7%), and those who were not selected for kidney transplantation and remained on dialysis (12.5%). The likelihood of being removed from the waiting list for any reason was higher in this group (over 75) (30.3%) than in the 66-75 age group (26.8%). Their average annual mortality rate on the waiting list was 7.9%, compared to 6.6% for those 66-75. Conclusion: Even after the age of 75 years, kidney transplantation provides substantial life prolongation and excellent graft survival. C1 Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Macrae, J (reprint author), Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. EM Jeanne.Macrae@Downstate.edu RI gholamnezhad, reza/D-5731-2015 OI gholamnezhad, reza/0000-0003-0326-7061 NR 15 TC 27 Z9 27 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-1623 J9 INT UROL NEPHROL JI Int. Urol. Nephrol. PD SEP PY 2005 VL 37 IS 3 BP 641 EP 648 DI 10.1007/s11255-004-0010-6 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA V43OF UT WOS:000202943700042 PM 16307355 ER PT J AU Yuksel, D Optican, LM Lefevre, P AF Yuksel, D Optican, LM Lefevre, P TI Properties of saccades in Duane retraction syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN EYE-MOVEMENTS; SYNDROME TYPE-1; MUSCLE; ABNORMALITIES AB PURPOSE. To improve understanding of the binocular control of saccades by making high-resolution eye movement recordings in patients with unilateral Duane retraction syndrome (DRS) type I ( marked by congenital absence of the sixth cranial nerve). METHODS. Binocular eye movements were recorded in four patients in binocular viewing conditions during a saccade task. RESULTS. Affected-side gaze showed normal saccades of the sound eye and undershooting saccades of the affected eye evidence of intact interneurons, but deficient motoneurons, in the sixth-nerve nucleus on the affected side. Postsaccadic smooth onward drift followed undershooting saccades of the affected eye. Sound-side gaze, in the centripetal direction, showed relatively accurate saccades despite large offsets in initial position between the two eyes. In the centrifugal direction, there was a consistent undershoot of the affected eye. The sound eye showed unexpected overshoot. Postsaccadic drifts in opposite directions in the two eyes brought both eyes onto the target in an optimal time course. CONCLUSIONS. Studying the characteristics of the saccadic system in this oculomotor disorder gives new insight into binocular control of saccades and adaptation. In these patients, the oculomotor system was not capable of adapting the pulse command to the two eyes separately, even though DRS offers clear advantages of independent control. In contrast, independent adaptation of the saccadic step command was sent to the two eyes. This supports the idea that the rapid part of the saccadic command is common to both eyes. C1 Univ Catholique Louvain, CESAME, B-1348 Louvain, Belgium. Univ Catholique Louvain, Neurophysiol Lab, B-1348 Louvain, Belgium. Clin Univ St Luc, Dept Ophthalmol, B-1200 Brussels, Belgium. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Lefevre, P (reprint author), Univ Catholique Louvain, CESAME, Ave Georges Lemaitre 4, B-1348 Louvain, Belgium. EM lefevre@csam.ucl.ac.be NR 29 TC 4 Z9 5 U1 1 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 SEP PY 2005 VL 46 IS 9 BP 3144 EP 3151 DI 10.1167/iovs.05-0060 PG 8 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800019 PM 16123413 ER PT J AU Sergeev, YV Soustov, LV Chelnokov, EV Bityurin, NM Backlund, PS Wingfield, PT Ostrovsky, MA Hejtmancik, JF AF Sergeev, YV Soustov, LV Chelnokov, EV Bityurin, NM Backlund, PS Wingfield, PT Ostrovsky, MA Hejtmancik, JF TI Increased sensitivity of amino-arm truncated beta A3-crystallin to UV-light-induced photoaggregation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ALPHA-B-CRYSTALLIN; AUTOSOMAL-DOMINANT CATARACT; CONGENITAL NUCLEAR CATARACT; DESMIN-RELATED MYOPATHY; LENS PROTEIN SOLUTIONS; X-RAY-ANALYSIS; EYE-LENS; GAMMA-CRYSTALLIN; MOLECULAR CHAPERONE; NONSENSE MUTATION AB PURPOSE. Exposure to UV- B light ( wavelength, 290 - 320 nm) is a well- documented risk factor for age- related cataracts. As the lens ages, beta- crystallins tend to undergo proteolytic cleavage of their terminal extensions. To delineate the effects of loss of terminal arms on beta- crystallin function, the sensitivity of purified recombinant wild- type ( r beta A3) to UV- irradiation induced aggregation was compared with that of beta A3- crystallin missing the N- terminal extension ( r beta A3tr). METHODS. Proteins were expressed in baculovirus- infected Sf9 cells and purified by chromatography. Purified protein solutions ( pH 7.4) were reduced by using Tris ( 2- carboxyethyl) phosphine HCl and irradiated with a 308- nm excimer laser at physiologically relevant UV doses and wavelengths ( 308 nm), and light- scattering ( 633 nm) was measured. Irradiated crystallins were analyzed by matrix- assisted desorption ionization ( MALDI) and tandem liquid chromatography/ mass spectrometry ( LC- MS/ MS). RESULTS. UV- irradiation of both r beta A3 and r beta A3tr resulted in major loss of soluble protein, as shown by absorption at 280 nm, size- exclusion chromatography ( SEC) and SDS- PAGE, with concomitant formation of insoluble aggregates producing light-scattering. Compared with wild- type r beta A3, r beta A3tr showed a significant tendency to begin scattering light at lower UV dose and had a higher aggregation rate with increasing UV exposure. Changes in irradiated crystallins include aggregation and cross- linking, photolysis, and oxidation of methionine and tryptophan residues. CONCLUSIONS. Loss of beta- crystallin terminal arms appears to increase their tendency to aggregate in response to UV irradiation, suggesting that this loss in the maturing lens may increase susceptibility to age- related cataract. C1 NEI, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Appl Phys, Nizhnii Novgorod 603600, Russia. Inst Biochem Phys, Moscow, Russia. RP NEI, NIH, 10-10B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM sergeev@helix.nih.gov NR 63 TC 12 Z9 15 U1 1 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2005 VL 46 IS 9 BP 3263 EP 3273 DI 10.1167/iovs.05-0112 PG 11 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800034 PM 16123428 ER PT J AU Marin-Castano, ME Csaky, KG Cousins, SW AF Marin-Castano, ME Csaky, KG Cousins, SW TI Nonlethal oxidant injury to human retinal pigment epithelium cells causes cell membrane blebbing but decreased MMP-2 activity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID HUMAN ENDOTHELIAL-CELLS; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX; OXIDATIVE STRESS; TISSUE INHIBITOR; GENE-EXPRESSION; MESANGIAL CELLS; IN-VITRO; AGE; ACTIVATION AB PURPOSE. This study was undertaken to determine whether transient or sustained nonlethal oxidant injury can induce RPE cell membrane blebbing and alter RPE expression of matrix metalloproteinase ( MMP)- 2 and type IV collagen, two molecules that are necessary for regulation of the turnover of the RPE basal lamina. METHODS. The ARPE- 19 cell line stably expressing green fluorescent protein ( GFP) targeted to the cell membrane was bleb injured by exposure to myeloperoxidase ( MPO; 10 microunits) and H2O2 ( 100 mu M). Sustained ( > 6 hours) or transient ( up to 6 hours) exposure to MPO/ H2O2 was evaluated. An MTS assay conversion and cell counts were used to detect cell viability. Supernatants and the cell homogenates were collected from cultured ARPE- 19 to assess fluorescent GFP- derived blebs, MMP- 2 protein by Western blot, MMP- 2 activity by zymography, and type IV collagen accumulation by ELISA. Expression of MMP- 2 was examined by real- time RT- PCR with total RNA. RESULTS. Both sustained and transient exposure of RPE cells to nonlethal oxidant injury upregulated blebbing and increased pro- MMP2 protein, but downregulated the MMP- 2 activity released into the supernatant in a time- dependent manner. Only sustained oxidant injury for 24 hours induced an increase in collagen type IV. After removal of transient oxidant exposure, blebbing resolved and RPE MMP- 2 activity and protein recovered to normal levels within 48 hours. CONCLUSIONS. Sustained or transient oxidant injury causes increased cell membrane blebbing but decreased activation of MMP- 2. The findings lead to the hypothesis that blebs released in the absence of active MMP- 2 may become trapped between the RPE and its basal lamina as sub- RPE deposits, possibly contributing to drusen formation in age- related macular degeneration. Also, the results lead to the postulation that oxidant injury disrupts the cell- specific surface proteases necessary to cleave and activate pro- MMP- 2. C1 Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Marin-Castano, ME (reprint author), Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 USA. EM mcastano@med.miami.edu FU NEI NIH HHS [1R01 EY 014477, 1R01 EY 015249, 1R01 EY 13318] NR 58 TC 44 Z9 45 U1 1 U2 2 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 SEP PY 2005 VL 46 IS 9 BP 3331 EP 3340 DI 10.1167/iovs.04-1224 PG 10 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800043 PM 16123437 ER PT J AU Mandal, MNA Heckenlively, JR Burch, T Chen, LC Vasireddy, V Koenekoop, RK Sieving, PA Ayyagari, R AF Mandal, MNA Heckenlively, JR Burch, T Chen, LC Vasireddy, V Koenekoop, RK Sieving, PA Ayyagari, R TI Sequencing arrays for screening multiple genes associated with early-onset human retinal degenerations on a high-throughput platform SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RECESSIVE RETINITIS-PIGMENTOSA; DENSITY OLIGONUCLEOTIDE ARRAYS; CONE-ROD DYSTROPHY; HETEROZYGOUS MUTATIONS; CGMP PHOSPHODIESTERASE; MACULAR DEGENERATION; ALPHA-SUBUNIT; ABCR ABCA4; RDS GENE; MICROARRAY AB PURPOSE. To develop and apply microarray-based resequencing technology to detect sequence alterations in multiple autosomal recessive retinal disease genes on a single high-throughput platform. METHODS. Oligonucleotides corresponding to both strands of the target exons and the flanking intron sequences of 29,214 bp from 11 genes associated with autosomal recessive retinitis pigmentosa (arRP) were tiled on 20 x 25-mu m microarrays (arRP-I arrays). A total of 155 exons were amplified from 35 arRP patient DNA samples, with each sample being sequenced on an arRP-I chip by hybridization. RESULTS. With the arRP-I arrays, 97.6% of the tiled sequence were determined with more than 99% accuracy and reproducibility. Of the 2.4% unread sequence, 89.5% involved stretches of G or C. In analyzing the 903,140-bp sequence from the 35 patient samples, 506 sequence changes have been detected in which 386 are previously reported alterations, and 120 are novel. In addition to four known causative mutations, six novel sequence changes that are potentially pathogenic were observed. Additional analysis is needed to determine whether these changes are responsible for arRP in these patients. CONCLUSIONS. The use of microarray for sequencing is a novel approach, and the arRP-I chip is the first successful application of this technology for determining sequence alteration in multiple disease-related genes. These arrays can be used for high-throughput genotyping of patients with relevant retinal conditions. In addition, these arrays offer a unique opportunity to interrogate complex patterns of inheritance due to the involvement of more one gene by screening multiple genes on a single platform. C1 Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. McGill Univ, Ctr Hlth, MTL Childrens Hosp, McGill Ocular Genet Lab, Montreal, PQ, Canada. NEI, NIH, Bethesda, MD 20892 USA. RP Ayyagari, R (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, 1000 Wall St,Room 325, Ann Arbor, MI 48105 USA. EM ayyagari@umich.edu FU NEI NIH HHS [EY 07060, EY 07003, EY 13198] NR 39 TC 43 Z9 44 U1 1 U2 2 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 SEP PY 2005 VL 46 IS 9 BP 3355 EP 3362 DI 10.1167/iovs.05-0007 PG 8 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800046 PM 16123440 ER PT J AU Ayyagari, R Mandal, MNA Karoukis, AJ Chen, LC McLaren, NC Lichter, M Wong, DT Hitchcock, PF Caruso, RC Moroi, SE Maumenee, IH Sieving, PA AF Ayyagari, R Mandal, MNA Karoukis, AJ Chen, LC McLaren, NC Lichter, M Wong, DT Hitchcock, PF Caruso, RC Moroi, SE Maumenee, IH Sieving, PA TI Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SORSBY FUNDUS DYSTROPHY; OPEN-ANGLE GLAUCOMA; HONEYCOMB RETINAL DYSTROPHY; PIGMENT DISPERSION SYNDROME; MALATTIA LEVENTINESE; DARK-ADAPTATION; MARFAN-SYNDROME; LARGE FAMILY; TIMP3 GENE; MAPS AB PURPOSE. To identify the gene responsible for a complex ocular phenotype of late-onset macular degeneration, long anterior zonules (LAZ), and elevated intraocular pressure (IOP) and to study its expression. METHODS. Ocular examination, visual field, fluorescein angiography, and electrophysiology testing were performed. One affected individual was treated with vitamin A. DNA from 55 family members (UM: H389) was used for linkage, mapping, and mutation analysis. Linkage analysis of macular degeneration and LAZ phenotypes was performed independently. Mutations in candidate genes were screened by sequencing. mRNA expression of CTRP5 and MFRP, which are bicistronic genes, was studied by semiquantitative RT-PCR (qRT-PCR) in various human tissues. CTRP5 expression was also evaluated by in situ hybridization. RESULTS. Affected members had LAZ detectable by the third decade and/or macular degeneration by the fourth to fifth decade. A six-month treatment with vitamin A shortened dark adaptation considerably in one affected member. Both conditions mapped independently with zero recombination to 11q23, with maximum lod scores of 3.31 for macular degeneration and 5.41 for LAZ. The same CTRP5 missense mutation was identified in all affected individuals. Retinal pigment epithelium (RPE) and ciliary epithelium (CE) showed highest CTRP5 transcript expression, which was also true for MFRP. CTRP5 tissue expression was confirmed by in situ hybridization. CONCLUSIONS. A single locus at 11q23 is implicated in a complex ocular phenotype involving RPE and CE, tissues of neuroectodermal origin. All individuals with either LAZ and/or macular degeneration carry the same CTRP5 S163R mutation, which is transmitted in autosomal dominant manner. C1 Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA. NEI, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD 20892 USA. RP Ayyagari, R (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, 1000 Wall St,Room 325, Ann Arbor, MI 48105 USA. EM ayyagari@umich.edu OI Hitchcock, Peter/0000-0001-9454-2684 FU NEI NIH HHS [EY 07003, EY 07060, EY 13198] NR 59 TC 64 Z9 66 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 SEP PY 2005 VL 46 IS 9 BP 3363 EP 3371 DI 10.1167/iovs.05-0159 PG 9 WC Ophthalmology SC Ophthalmology GA 959AH UT WOS:000231488800047 PM 16123441 ER PT J AU Hashimoto, K Durbin, JE Zhou, WS Collins, RD Ho, SB Kolls, JK Dubin, PJ Sheller, JR Goleniewska, K O'Neal, JF Olson, SJ Mitchell, D Graham, BS Peebles, RS AF Hashimoto, K Durbin, JE Zhou, WS Collins, RD Ho, SB Kolls, JK Dubin, PJ Sheller, JR Goleniewska, K O'Neal, JF Olson, SJ Mitchell, D Graham, BS Peebles, RS TI Respiratory syncytial virus infection in the absence of STAT1 results in airway dysfunction, airway mucus, and augmented IL-17 levels SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE viral; inflammation; rodent; cytokines; mucus; IL-17; IL-23 ID TYPE-2 CYTOKINE PRODUCTION; MUCIN GENE-EXPRESSION; SENSITIZED MICE; ALLERGIC-ASTHMA; GOBLET CELLS; ACUTE BRONCHIOLITIS; VIRAL DISEASE; CUTTING EDGE; BALB/C MICE; HYPERRESPONSIVENESS AB Background: Respiratory syncytial virus (RSV) is the leading infectious cause of respiratory failure and wheezing in infants and young children. Prematurity is the greatest risk factor for severe RSV-induced disease, and recent studies suggest that premature children have lower levels of the type I IFNs (alpha/beta), for which signal transducer and activator of transcription (STAT) 1 is a critical intracellular signaling molecule. Objective: We hypothesized that RSV infection in STAT-1 knockout (STAT1 KO) mice would result in both increased airway resistance and airway hyperresponsiveness. Methods: Wild-type (WT) and STAT1 KO mice on a BALB/c background were either RSV or mock infected. Phenotypic response to infection was assessed by means of plethysmography, immunohistochemistry, and lung cytokine measurement. Results: We found that STAT1 KO mice infected with RSV (STAT1 KO-RSV) had greater baseline lung resistance (P = .05) and airway responsiveness (P < .001) than mock-infected STAT1 KO (STAT1 KO-MOCK), RSV-infected wild type (WT-RSV), and mock-infected wild type (WT-MOCK) mice. In addition, the STAT1 KO-RSV mice showed induction of mucus production and expression of gob-5 and Muc5ac, conditions not present in any of the other 3 groups. IL-17, a cytokine that regulates Muc5ac expression, was expressed in the lungs of the STAT1 KO-RSV mice, whereas lung levels of IL-17 were undetectable in the remaining groups. Expression of the IL-23-specific p19 subunit was also increased in the STAT1 KO-RSV mice but not in the WT-RSV mice. Conclusion: These results show that STAT1 has an important regulatory role in RSV-induced alteration of airway function. C1 Vanderbilt Univ, Sch Med, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Fukushima Med Univ, Dept Microbiol, Fukushima, Japan. Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. Univ Minnesota, Vet Affairs Med Ctr, Dept Med, Minneapolis, MN USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Peebles, RS (reprint author), Vanderbilt Univ, Sch Med, Med Ctr, Dept Med, T-1217 MCN,221 Kirkland Hall, Nashville, TN 37232 USA. EM stokes.peebles@vanderbilt.edu FU NHLBI NIH HHS [HL 69949]; NIAID NIH HHS [AI 45512, AI 54660] NR 49 TC 71 Z9 73 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2005 VL 116 IS 3 BP 550 EP 557 DI 10.1016/j.jaci.2005.03.051 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 017IE UT WOS:000235686500013 PM 16159623 ER PT J AU Salo, PM Yin, M Arbes, SJ Cohn, RD Sever, M Muilenberg, M Burge, HA London, SJ Zeldin, DC AF Salo, PM Yin, M Arbes, SJ Cohn, RD Sever, M Muilenberg, M Burge, HA London, SJ Zeldin, DC TI Dustborne Alternaria alternata antigens in US homes: Results from the National Survey of Lead and Allergens in Housing SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Alternaria alternata; allergen; antigen; indoor; exposure; asthma; allergy ID AIRBORNE FUNGAL SPORES; RESPIRATORY HEALTH; ASTHMA; EXPOSURE; CHILDREN; OUTDOOR; INDOOR; SENSITIZATION; SYMPTOMS; DUST AB Background: Alternaria alternata is one of the most common fungi associated with allergic disease. However, Alternaria exposure in indoor environments is not well characterized. Objective: The primary goals of this study were to examine the prevalence of Alternaria exposure and identify independent predictors of Alternaria antigen concentrations in US homes. Methods: Data for this cross-sectional study were obtained from the National Survey of Lead and Allergens in Housing. A nationally representative sample of 831 housing units in 75 different locations throughout the United States completed the survey. Information on housing and household characteristics was obtained by questionnaire and environmental assessments. Concentrations of A alternata antigens in dust collected from various indoor sites were assessed with a polyclonal anti-Alternaria antibody assay. Results: Alternaria antigens were detected in most (95% to 99%) of the dust samples. The geometric mean concentration, reflecting the average Alternaria concentration in homes, was 4.88 mu g/g (SEM, 0.13 mu g/g). In the multivariable linear regression analysis, the age of the housing unit, geographic region, urbanization, poverty, family race, observed mold and moisture problems, use of dehumidifier, and presence of cats and dogs were independent predictors of Alternaria antigen concentrations. Less frequent cleaning and smoking indoors also contributed to higher Alternaria antigen levels in homes. Conclusion: Exposure to A alternata antigens in US homes is common. Antigen levels in homes are influenced not only by regional factors but also by residential characteristics. Preventing mold and moisture problems, avoiding smoking indoors, and regular household cleaning may help reduce exposure to Alternaria antigens indoors. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Constella Grp Inc, Durham, England. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. EMLab Inc, San Bruno, CA USA. RP Zeldin, DC (reprint author), NIEHS, NIH, 111 Alexander Dr Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Sever, Michelle/0000-0002-2435-1214; London, Stephanie/0000-0003-4911-5290 NR 48 TC 47 Z9 47 U1 1 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2005 VL 116 IS 3 BP 623 EP 629 DI 10.1016/j.jaci.2005.05.030 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 017IE UT WOS:000235686500024 PM 16159634 ER PT J AU Gleeson, T Petersen, K Mascola, J AF Gleeson, T Petersen, K Mascola, J TI Successful treatment of Acinetobacter meningitis with meropenem and rifampicin SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter DE nosocomial meningitis; post-neurosurgical meningitis; ventriculostomy ID BETA-LACTAMS; BAUMANNII; IMIPENEM; OUTBREAK; MODEL C1 USN, Med Ctr, Dept Infect Dis, Bethesda, MD 20889 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gleeson, T (reprint author), USN, Med Ctr, Dept Infect Dis, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 6 TC 17 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD SEP PY 2005 VL 56 IS 3 BP 602 EP 603 DI 10.1093/jac/dki274 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 961WL UT WOS:000231692400031 PM 16046467 ER PT J AU Loucks, TMJ Poletto, CJ Saxon, KG Ludlow, CL AF Loucks, TMJ Poletto, CJ Saxon, KG Ludlow, CL TI Laryngeal muscle responses to mechanical displacement of the thyroid cartilage in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE somatosensory; sternothyroid; thyroarytenoid; stretch reflex ID HUMAN THYROARYTENOID MUSCLE; INTRINSIC MUSCLES; STRETCH REFLEXES; SPINDLES; FEEDBACK; CAT; VOCALIZATION; AFFERENTS; RECEPTORS; PRESSURE AB Speakers may use laryngeal sensory feedback to adjust vocal fold tension and length before initiating voice. The mechanism for accurately initiating voice at an intended pitch is unknown, given the absence of laryngeal muscle spindles in animals and conflicting findings regarding their existence in humans. Previous reports of rapid changes in voice fundamental frequency following thyroid cartilage displacement suggest that changes in vocal fold length modulate laryngeal muscle contraction in humans. We tested the hypothesis that voice changes resulting from mechanical perturbation are due to rapid responses in the intrinsic laryngeal muscles. Hooked wire electrodes were used to record from the thyroarytenoid, cricothyroid, and sternothyroid muscles along with surface electrodes on the skin overlying the thyroid cartilage in 10 normal adults. Servomotor displacements produced consistent changes in the subjects' vocal fundamental frequency at 70-80 ms, demonstrating changes in vocal fold length and tension. No simultaneous electromyographic responses occurred in the thyroarytenoid or cricothyroid muscles in any subjects. Instead, short-latency responses at 25-40 ms following stimulus onset occurred in the sternothyroid muscles, simultaneous with responses in the surface recordings. The sternothyroid responses may modulate long-latency changes in voice fundamental frequency (similar to 150 ms). The absence of intrinsic laryngeal muscle responses is consistent with a lack of spindles in these muscles. Our results suggest that other sensory receptors, such as mucosal mechanoreceptors, provide feedback for voice control. C1 NINDS, Laryngeal & Speech Sect, Clin Neurosci Program, Bethesda, MD 20892 USA. RP Loucks, TMJ (reprint author), NINDS, Laryngeal & Speech Sect, Clin Neurosci Program, Bldg 10,Rm 5D 38,10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA. EM louckst@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 NR 30 TC 16 Z9 17 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2005 VL 99 IS 3 BP 922 EP 930 DI 10.1152/japplphysiol.00402.2004 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 959RW UT WOS:000231538000020 PM 15932961 ER PT J AU Dabrazhynetskaya, A Sergueev, K Austin, S AF Dabrazhynetskaya, A Sergueev, K Austin, S TI Species and incompatibility determination within the P1par family of plasmid partition elements SO JOURNAL OF BACTERIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; P1 PLASMID; ESCHERICHIA-COLI; VIRULENCE PLASMID; YERSINIA-PESTIS; PARB PROTEIN; DNA-SEQUENCE; SYSTEM; CENTROMERE; SPECIFICITY AB The P1par family of active plasmid partition systems consists of at least six members, broadly distributed in a variety of plasmid types and bacterial genera. Each encodes two Par proteins and contains a cis-acting parS site. Individual par systems can show distinct species specificities; the proteins from one type cannot function with the parS site of another. P1par-versus-P7par specificity resides within two hexamer BoxB repeats encoded by parS that contact the ParB protein near the carboxy terminus. Here, we examine the species specificity differences between Yersinia pestis pMT1parS and Escherichia coli PI and P7parS. pMT1parS site specificity could be altered to that of either P1 or P7 by point mutation changes in the BoxB repeats. Just one base change in a single BoxB repeat sometimes sufficed. The BoxB sequence appears to be able to adopt a number of forms that define exclusive interactions with different ParB species. The looped parS structure may facilitate this repertoire of interaction specificities. Different P1par family members have different partition-mediated incompatibility specificities. This property defines whether two related plasmids can coexist in the same cell and is important in promoting the evolution of new plasmid species. BoxB sequence changes that switch species specificity between P1, P7, and pMT1 species switched partition-mediated plasmid incompatibility in concert. Thus, there is a direct mechanistic link between species specificity and partition-mediated incompatibility, and the BoxB-ParB interaction can be regarded as a special mechanism for facilitating plasmid evolution. C1 NCI, CCR, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, CCR, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. EM austin@ncifcrf.gov NR 32 TC 9 Z9 9 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 SEP PY 2005 VL 187 IS 17 BP 5977 EP 5983 DI 10.1128/JB.187.17.5977-5983.2005 PG 7 WC Microbiology SC Microbiology GA 957XF UT WOS:000231406000014 PM 16109939 ER PT J AU Fields, KA Fischer, ER Mead, DJ Hackstadt, T AF Fields, KA Fischer, ER Mead, DJ Hackstadt, T TI Analysis of putative Chlamydia trachomatis chaperones Scc2 and Scc3 and their use in the identification of type III secretion substrates SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; YERSINIA-PSEUDOTUBERCULOSIS; ESCHERICHIA-COLI; MACROPHAGE APOPTOSIS; SHIGELLA-FLEXNERI; V-ANTIGEN; YOPD; LCRH; PNEUMONIAE; CASPASE-1 AB The obligate intracellular pathogen Chlamydia trachomatis expresses a type III secretion system (T3SS) which has the potential to contribute significantly to pathogenesis. Based on a demonstrated role of type III secretion (T3S)-specific chaperones in the secretion of antihost proteins by gram-negative pathogens, we initiated a study of selected putative Chlamydia T3S chaperones in an effort to gain mechanistic insight into the Chlamydia T3SS and to potentially identify Chlamydia-specific secreted products. C. trachvinatis Scc2 and Scc3 are homologous to SycD of Yersinia spp. Functional studies of the heterologous Yersinia T3SS indicated that although neither Scc2 nor Scc3 was able to fully complement a sycD null mutant, both have SycD-like characteristics. Both were able to associate with the translocator protein YopD, and Sec3 expression restored limited secretion of YopD in in vitro studies of T3S. CopB (CT578) and CopB2 (CT861) are encoded adjacent to scc2 and scc3, respectively, and have structural similarities with the YopB family of T3S translocators. Either Scc2 or Scc3 coprecipitates with CopB from C. trachomatis extracts. Expression of CopB or CopB2 in Yersinia resulted in their type III-dependent secretion, and localization studies with C. trachomatis-infected cells indicated that both were secreted by Chlamydia. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. NIAID, Microscopy Branch, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. EM Ted_Hackstadt@NIH.GOV NR 52 TC 52 Z9 54 U1 0 U2 2 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 SEP PY 2005 VL 187 IS 18 BP 6466 EP 6478 DI 10.1128/JB.187.6466-6478.2005 PG 13 WC Microbiology SC Microbiology GA 965PR UT WOS:000231963200026 PM 16159780 ER PT J AU Li, WJ Mauck, RL Tuan, RS AF Li, Wan-Ju Mauck, Robert L. Tuan, Rocky S. TI Electrospun Nanofibrous Scaffolds: Production, Characterization, and Applications for Tissue Engineering and Drug Delivery SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY LA English DT Review DE Tissue Engineering; Drug Delivery; Electrospinning; Nanofiber; Scaffold AB Tissue engineering is a promising solution for the problem of organ or tissue shortage. A key requirement is the use of biologically functional scaffolds to deliver cells to the implant site and/or provide a structure for cell attachment to replace lost or damaged extracellular matrix. While a large number of polymers have been used to fabricate microscale woven and non-woven scaffolds for tissue regeneration, the natural extracellular matrix is nanoscale, a characteristic that should be incorporated into scaffold design for tissue engineering applications. A nanofibrous scaffold, such as those produced by the electrospinning process, has several unique advantages over microscale fibrous meshes, including high surface area to volume ratio, improved mechanical properties, and morphological similarities to natural extracellular matrix. Over the past five years, many polymers, including natural and synthetic, biodegradable and non-biodegradable, have been successfully electrospun into nanofibers, characterized, and evaluated for their potential applications for various tissue engineering and drug delivery applications. In this review, we survey these polymers and electrospun nanofibrous scaffolds and discuss the critical parameters for successful tissue engineering applications in the future. C1 [Li, Wan-Ju; Mauck, Robert L.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 137 TC 56 Z9 56 U1 9 U2 33 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1550-7033 J9 J BIOMED NANOTECHNOL JI J. Biomed. Nanotechnol. PD SEP PY 2005 VL 1 IS 3 BP 259 EP 275 DI 10.1166/jbn.2005.032 PG 17 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA V85AS UT WOS:000205747800002 ER PT J AU Sviridov, AP Chernomordik, V Hassan, M Boccara, AC Russo, A Smith, P Gandjbakhche, A AF Sviridov, AP Chernomordik, V Hassan, M Boccara, AC Russo, A Smith, P Gandjbakhche, A TI Enhancement of hidden structures of early skin fibrosis using polarization degree patterns and Pearson correlation analysis SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT 4th Inter Workshop on Optical Imaging from Bench to Bedside CY SEP, 2004 CL NIH, Bethesda, MD HO NIH DE x-ray irradiation; fibrosis; polarized light; pattern recognition; Pearson correlation analysis ID IONIZING-RADIATION; FIBROTIC DISEASES; SCATTERING MEDIA; LIGHT; TISSUES; PROPAGATION; IMAGES; MICE AB The skin of athymic nude mice is irradiated with a single dose of x-ray irradiation that initiated fibrosis. Digital photographs of the irradiated mice are taken by illuminating the mouse skin with linearly polarized probe light of 650 nm. The specific pattern of the surface distribution of the degree of polarization enables the detection of initial skin fibrosis structures that were not visually apparent. Data processing of the raw spatial distributions of the degree of polarization based on Fourier filtering of the high-frequency noise improves subjective perception of the revealed structure in the images. In addition, Pearson correlation analysis provides information about skin structural size and directionality. (c) 2005 Society of Photo-Optical Instrumentation Engineers. C1 NICHD, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Laser & Informat Technol, Troitsk 142190, Moscow Reg, Russia. Ecole Super Phys & Chim Ind Ville Paris, F-75005 Paris, France. RP Chernomordik, V (reprint author), NICHD, NIH, Bldg 9 ,Rm B1E11, Bethesda, MD 20892 USA. EM vchern@helix.nih.gov NR 23 TC 8 Z9 8 U1 0 U2 5 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2005 VL 10 IS 5 AR 051706 DI 10.1117/1.2073727 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 989YY UT WOS:000233711300023 PM 16292958 ER PT J AU Wax, A Pyhtila, JW Graf, RN Nines, R Boone, CW Dasari, RR Feld, MS Steele, VE Stoner, GD AF Wax, A Pyhtila, JW Graf, RN Nines, R Boone, CW Dasari, RR Feld, MS Steele, VE Stoner, GD TI Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT 4th Inter Workshop on Optical Imaging from Bench to Bedside CY SEP, 2004 CL NIH, Bethesda, MD HO NIH DE light scattering; low-coherence interferometry; cell diagnostics ID LIGHT; DISTRIBUTIONS; TOMOGRAPHY AB Angle-resolved low-coherence interferometry (a/LCI) is used to obtain quantitative, depth-resolved nuclear morphology measurements. We compare the average diameter and texture of cell nuclei in rat esophagus epithelial tissue to grading criteria established in a previous a/LCI study to prospectively grade neoplastic progression. We exploit the depth resolution of a/LCI to exclusively examine the basal layer of the epithelium, approximately 50 to 100 mu m beneath the tissue surface, without the need for exogenous contrast agents, tissue sectioning, or fixation. The results of two studies are presented that compare the performance of two a/LCI modalities. Overall, the combined studies show 91% sensitivity and 97% specificity for detecting dysplasia, using histopathology as the standard. In addition, the studies enable the effects of dietary chemopreventive agents, difluoromethylornithine (DFMO) and curcumin, to be assessed by observing modulation in the incidence of neoplastic change. We demonstrate that a/LCI is highly effective for monitoring neoplastic change and can be applied to assessing the efficacy of chemopreventive agents in the rat esophagus. (c) 2005 Society of Photo-optical Instrumentation Engineers. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. MIT, GR Harrison Spect Lab, Cambridge, MA 02139 USA. RP Wax, A (reprint author), Duke Univ, Dept Biomed Engn, Box 90281, Durham, NC 27708 USA. EM a.wax@duke.edu RI Wax, Adam/A-4760-2008; OI Wax, Adam/0000-0002-1827-5112 FU NCI NIH HHS [CN15011-72]; NCRR NIH HHS [P41-RR02594]; NIBIB NIH HHS [T32 EB001040] NR 16 TC 35 Z9 35 U1 1 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2005 VL 10 IS 5 AR 051604 DI 10.1117/1.2102767 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 989YY UT WOS:000233711300017 PM 16292952 ER PT J AU Barsony, J Prufer, K AF Barsony, J Prufer, K TI Regulation of vitamin D receptor subcellular trafficking. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Natl Inst Hlth, Bethesda, MD USA. Georgetown Univ, Bethesda, MD USA. Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S31 EP S31 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800119 ER PT J AU Beck, GR Camalier, CE Conrads, KA Simpson, KA Lucas, DA Veenstra, TD Conrads, TP AF Beck, GR Camalier, CE Conrads, KA Simpson, KA Lucas, DA Veenstra, TD Conrads, TP TI Large-scale proteomic and microarray analysis of inorganic phosphate treated MC3T3-E1 cells reveals Ddynamic changes in protein regulation and gene expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NCI, Ctr Canc Res, Frederick, MD 21701 USA. NCI, SAIC, Lab Proteom & Analyt Technol, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S357 EP S358 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503804251 ER PT J AU Boyce, AT Tuan, RS AF Boyce, AT Tuan, RS TI The effects of Growth/Differentiation Factors-5, 6, and 7 on mesenchymal cell condensation and chondrogenesis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S322 EP S322 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503804101 ER PT J AU Collins, MT Lindsay, JR Jain, A Kelly, MH Cutler, CM Weinstein, LS Jie, L Fedarko, NS Winer, KK AF Collins, MT Lindsay, JR Jain, A Kelly, MH Cutler, CM Weinstein, LS Jie, L Fedarko, NS Winer, KK TI Fibroblast growth factor-23 is regulated by 1,25-dihydroxyvitamin D. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIDCR, CSDB, NIH, Bethesda, MD USA. NICHD, PREB, NIH, Bethesda, MD USA. Johns Hopkins Univ, GCRC, Baltimore, MD USA. NIH, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. NIDDK, MDB, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Med, Div Geriatr Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S178 EP S178 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802126 ER PT J AU Day, TF Guo, X Garrett-Beal, L Yang, Y AF Day, TF Guo, X Garrett-Beal, L Yang, Y TI Canonical Wnt signaling controls osteoblast or chondrocyte differentiation from mesenchymal progenitor cells during skeletogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S17 EP S18 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800065 ER PT J AU Geller, JL Cutler, C Kelly, MH Adams, JS Collins, MT AF Geller, JL Cutler, C Kelly, MH Adams, JS Collins, MT TI Cinacalcet is associated with decreased serum FGF-23 and improved phosphorous homeostasis in patients with tumor-induced osteomalacia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Div Endocrinol,Burns & Allen Res Inst, Los Angeles, CA USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S177 EP S177 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802124 ER PT J AU Guo, X Day, TF Jiang, X Garrett-Beal, L Topol, L Yang, Y AF Guo, X Day, TF Jiang, X Garrett-Beal, L Topol, L Yang, Y TI Wnt/beta-catenin signaling play pivotal roles in synovial joint induction and chondrocyte maturation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S62 EP S62 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800246 ER PT J AU Inkson, CA Wadhwa, S Robey, PG Young, MF AF Inkson, CA Wadhwa, S Robey, PG Young, MF TI Wnt induced secreted protein 1 (WISP-1) splice variants and possible relationship with BMP signalling. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIDCR, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S207 EP S208 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802253 ER PT J AU Kamiya, N Ye, L Kobayashi, T Kronenberg, HM Feng, J Mishina, Y AF Kamiya, N Ye, L Kobayashi, T Kronenberg, HM Feng, J Mishina, Y TI Tamoxifen induced bone morphological protein receptor 1A (Bmpr1a) conditional knockout mice display an age-dependent phenotype in long bones different from calvariae SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Univ Missouri, Sch Dent, Kansas City, MO 64110 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S10 EP S10 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800037 ER PT J AU Kammerer, CM Shaffer, JR Reich, D Ziv, E Bauer, DC Li, J Newman, AB Cauley, JA Harris, TB Tylavsky, F Zmuda, JM AF Kammerer, CM Shaffer, JR Reich, D Ziv, E Bauer, DC Li, J Newman, AB Cauley, JA Harris, TB Tylavsky, F Zmuda, JM TI Genetic markers for ancestry are correlated with bone density and size in African Americans. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 1 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S338 EP S338 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503804168 ER PT J AU Kelly, MH Brillante, BA Cineceros, X Guirguis, S Collins, MT AF Kelly, MH Brillante, BA Cineceros, X Guirguis, S Collins, MT TI Fibrous dysplasia: Pain prevalence increases with age but is not due to an increase in bone disease. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIH, Nursing & Patient Care Serv, Bethesda, MD USA. Henry M Jackson Fdn Advancement Mil Med, Rockville, MD USA. Wooten High Sch, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S417 EP S417 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503805201 ER PT J AU Kuznetsov, SA Mankani, MH Leet, A Robey, PG AF Kuznetsov, SA Mankani, MH Leet, A Robey, PG TI Circulating chondrogenic precursors. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Natl Inst Dent & Craniofacial Res, Craniofacila & Skeletal Dis Branch, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S196 EP S196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802203 ER PT J AU Maeda, Y Nguyen, M Mackem, S Lanske, B AF Maeda, Y Nguyen, M Mackem, S Lanske, B TI Chondrocyte-specific deletion of Indian hedgehog (Ihh) in postnatal life. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S61 EP S61 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800242 ER PT J AU Mak, K Garrett-Beal, L Yang, Y AF Mak, K Garrett-Beal, L Yang, Y TI Hedgehog signaling interacts with Wnt/b-catenin signaling in controlling endochondral bone formation and synovial joint development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S2 EP S2 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800004 ER PT J AU Perry, S Tylavsky, FA Ryder, KA Cauley, J Lee, J Pope, S Harris, T Sebastian, A Sellmeyer, DE AF Perry, S Tylavsky, FA Ryder, KA Cauley, J Lee, J Pope, S Harris, T Sebastian, A Sellmeyer, DE TI The net acid-producing American diet adversely affects whole body and hip bone density assessed cross-sectionally in older individuals. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ N Carolina, Chapel Hill, NC USA. Univ Arkansas, Little Rock, AR 72204 USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S86 EP S86 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801054 ER PT J AU Rao, H Palacios, VG Sheppard, D Anderson, J Patrene, K Choi, SJ Blair, HC Roodman, GD AF Rao, H Palacios, VG Sheppard, D Anderson, J Patrene, K Choi, SJ Blair, HC Roodman, GD TI alpha(9)beta(1) integrin signaling is required for normal osteoclast activity. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Natl Inst Dent & Craaniofacial Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S143 EP S144 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801285 ER PT J AU Schwartz, AV Vittinghoff, E Sellmeyer, DE De Rekeneire, N Feingold, KR Nevitt, MC Strotmeyer, ES Resnick, HE Shorr, RI Cauley, JA Faulkner, KA Cummings, SR Harris, TB AF Schwartz, AV Vittinghoff, E Sellmeyer, DE De Rekeneire, N Feingold, KR Nevitt, MC Strotmeyer, ES Resnick, HE Shorr, RI Cauley, JA Faulkner, KA Cummings, SR Harris, TB TI Risk factors for falls in older adults with diabetes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Medstar Res Inst, Hyattsville, MD USA. Univ Tennessee, Memphis, TN USA. Calif Pacific Med Ctr, San Francisco, CA USA. RI Strotmeyer, Elsa/F-3015-2014; Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S89 EP S89 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801069 ER PT J AU Siggeirsdottir, K Aspelund, T Eiriksdottir, G Mogensen, B Chang, M Launer, L Harris, T Sigurdsson, G Jonsson, BY Gudnason, V AF Siggeirsdottir, K Aspelund, T Eiriksdottir, G Mogensen, B Chang, M Launer, L Harris, T Sigurdsson, G Jonsson, BY Gudnason, V TI The accuracy of self-report of fractures in older people; A comparison of questionnaire and fracture registry in the AGES Reykjavik study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Iceland Heart Assoc, Kopavogur, Iceland. Landspitalinn Univ Hosp, Dept Emergency Med, Reykjavik, Iceland. Landspitalinn Univ Hosp, Dept Endocrinol, Reykjavik, Iceland. NIA, Bethesda, MD 20892 USA. Malmo Univ Hosp, Dept Orthopaed, Malmo, Sweden. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S266 EP S266 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503803201 ER PT J AU Taylor, ED Tanofsky-Kraff, M Adler-Wailes, D Calis, K Ghorbani, S Mirch, M Theim, K Brady, S Yanovski, JA AF Taylor, ED Tanofsky-Kraff, M Adler-Wailes, D Calis, K Ghorbani, S Mirch, M Theim, K Brady, S Yanovski, JA TI Prevalence of orthopedic complications in overweight children and adolescents: A multi-dimensional cross-sectional analysis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NICHHD, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S101 EP S101 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503801114 ER PT J AU Torigoe, K Ishijima, M Nakamura, T Haruyama, N Kulkarni, AB Karlsson, S Yamada, Y AF Torigoe, K Ishijima, M Nakamura, T Haruyama, N Kulkarni, AB Karlsson, S Yamada, Y TI Abnormal axial skeleton in TGF-beta type I receptor-deficient mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIH, CDBRB, Mol Biol Sect, Bethesda, MD 20892 USA. NIDCR, CDBRB, Funct Genom Sect, NIH, Bethesda, MD 20892 USA. Lund Univ, Lund, Sweden. RI Haruyama, Naoto/D-1993-2011 OI Haruyama, Naoto/0000-0001-6225-5816 NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S49 EP S49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800193 ER PT J AU Yakar, S LeRoith, D Rosen, C Bouxsein, M AF Yakar, S LeRoith, D Rosen, C Bouxsein, M TI Temporal deletion of the hepatic IGF-I gene at 4 weeks of age has a dramatic effect on acquisition of cortical and trabecular bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 NIDDK, Bethesda, MD USA. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S49 EP S49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800194 ER PT J AU Yin, J Chock, M Oberst, M Ward, Y Kelly, K AF Yin, J Chock, M Oberst, M Ward, Y Kelly, K TI Ral activation promotes prostate cancer metastasis to bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Natl Canc Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S32 EP S32 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800123 ER PT J AU Zemel, B Kalkwarf, H Leonard, M Shepherd, J Mahboubi, S Frederick, M Winer, K AF Zemel, B Kalkwarf, H Leonard, M Shepherd, J Mahboubi, S Frederick, M Winer, K TI Effects of skeletal and sexual maturation on trabecular and cortical density of the peripheral skeleton. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Cincinatti Childrens Med Ctr, Cincinnati, OH USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Clin Trials & Survey Corp, Baltimore, MD USA. NICHHD, Rockville, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 2 Z9 2 U1 0 U2 0 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 SEP PY 2005 VL 20 IS 9 SU 1 BP S59 EP S59 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503800231 ER PT J AU Wagner, JA Abesser, M Karcher, J Laser, M Kunos, G AF Wagner, JA Abesser, M Karcher, J Laser, M Kunos, G TI Coronary vasodilator effects of endogenous cannabinoids in vasopressin-preconstricted unpaced rat isolated hearts SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE anandamide; cannabinoid; Langendorff heart; coronary vasodilation; CB1 receptor ID ANANDAMIDE-INDUCED VASORELAXATION; SENSORY NERVES MEDIATE; MESENTERIC VASODILATION; VANILLOID RECEPTORS; INDUCED HYPOTENSION; CB1 RECEPTORS; ENDOTHELIUM; RELAXATION; ARTERIES; LIPOPOLYSACCHARIDE AB The mechanisms by which cannabinoids alter coronary vascular tone and cardiac performance are controversial. We investigated the effects of various cannabinoids in spontaneously beating Langendorff-perfused rat hearts. Bolus injections of anandamide (0.1-1 mu mol) caused no change in coronary flow (CF) or left ventricular systolic pressure (LVSP). In hearts preperfused with vasopressin to induce vasoconstrictor tone, anandamide or the selective CB1 receptor agonist ACEA (1-100 nmol) dose-dependently increased CF by up to 267% and LVSP by 20 turn Hg. The metabolically stable endocannabinoid derivatives, R-methanandamide and noladin ether, displayed similar effects. In contrast, Delta(9)-THC (10-100 nmol), the major psychoactive ingredient of cannabis, strongly decreased CF and LVSP. The CB2 receptor agonist JWH-133 (10-100 nmol) elicited vasodilator and positive inotropic effects only at higher doses. The CB1 antagonists SR141716A and AM-251 as well as the potassium channel inhibitors tetraethylammonium and iberiotoxin blocked the anandamide-induced increases in CF and LVSP, whereas the CB2 antagonist SR144528 and the putative "CB3 antagonist" O-1918 did not have an inhibitory effect. Immunohistochemistry revealed the presence of cardiac CB1 but no CB2 receptors. Anandamide and 2-arachidonoylglycerol were detected in heart tissue. However, combined application of fatty acid amidohydrolase inhibitors and the transport inhibitor AM-404 to augment tissue levels of endocannabinoids was without effect on CF or LVSP. We conclude that in the rat isolated heart with reestablished vasoconstrictor tone, cannabinoids including anandamide elicit coronary vasodilation and a secondary increase in contractility via CB1 receptors and potassium channels. C1 Univ Wurzburg, Dept Internal Med 1, Ctr Cardiovasc Med, D-97080 Wurzburg, Germany. NIAAA, NIH, Bethesda, MD USA. RP Wagner, JA (reprint author), Univ Wurzburg, Dept Med, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM wagner_j@klinik.uni-wuerzburg.de NR 39 TC 30 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD SEP PY 2005 VL 46 IS 3 BP 348 EP 355 DI 10.1097/01.fjc.0000175437.87283.f2 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 009EI UT WOS:000235093700016 PM 16116341 ER PT J AU Floel, A Jansen, A Deppe, M Kanowski, M Konrad, C Sommer, J Knecht, S AF Floel, A Jansen, A Deppe, M Kanowski, M Konrad, C Sommer, J Knecht, S TI Atypical hemispheric dominance for attention: functional MRI topography SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE functional magnetic resonance imaging; hemispheric lateralization; language; spatial attention ID LINE BISECTION JUDGMENTS; TRANSCRANIAL DOPPLER SONOGRAPHY; LANGUAGE DOMINANCE; CROSSED APHASIA; CORTICAL ORGANIZATION; SPATIAL ATTENTION; RIGHT-HANDERS; NEGLECT; FMRI; LATERALIZATION AB The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention. C1 NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Munster, Dept Neurol, D-4400 Munster, Germany. Univ Magdeburg, Dept Neurol 2, D-39106 Magdeburg, Germany. Univ Munster, Dept Psychiat, D-4400 Munster, Germany. RP Floel, A (reprint author), NINDS, Human Cortical Physiol Sect, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM floela@ninds.nih.gov RI Floel, Agnes/A-9426-2017; Deppe, Michael/C-5780-2017; OI Deppe, Michael/0000-0002-8372-9678; Knecht, Stefan/0000-0003-1056-9228 NR 52 TC 10 Z9 11 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2005 VL 25 IS 9 BP 1197 EP 1208 DI 10.1038/sj.jcbfm.9600114 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 960FR UT WOS:000231576100010 PM 15815582 ER PT J AU Budhani, S Blair, RJR AF Budhani, S Blair, RJR TI Response reversal and children with psychopathic tendencies: success is a function of salience of contingency change SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE ADHD; aggression; antisocial behavior; orbitofrontal cortex; psychopathy; response reversal ID ORBITOFRONTAL CORTEX DYSFUNCTION; DEFICIT HYPERACTIVITY DISORDER; CONDUCT PROBLEMS; PREFRONTAL CORTEX; ATTENTION-DEFICIT; PASSIVE-AVOIDANCE; ADHD SYMPTOMS; OFFENDERS; ANXIETY; DAMAGE AB Background: Previous work has inconsistently reported difficulties with response reversal/extinction in children with psychopathic tendencies. Method: We tested the hypothesis that the degree of impairment seen in children with psychopathic tendencies is a function of the salience of contingency change. We investigated the performance of children with psychopathic tendencies on a novel probabilistic response reversal task involving four conditions with gradated reward-punishment contingencies (100-0, 90-10, 80-20 and 70-30; i.e., for the 100-0 contingency, responding to one object is always rewarded while responding to the other is always punished). results: In line with predictions, the impairment seen in the children with psychopathic tendencies was an inverse function of the salience of the contingency change. Conclusions: We suggest that this data is consistent with suggestions of subtle orbital frontal cortex impairment in children with psychopathic tendencies. C1 NIMH, Mood & Anxiety Disorders Program, Unit Affect Cognit Neurosci, NIH,Dept HHS, Bethesda, MD 20892 USA. UCL, Dept Psychol, London WC1E 6BT, England. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Disorders Program, Unit Affect Cognit Neurosci, NIH,Dept HHS, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 62 TC 74 Z9 74 U1 4 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2005 VL 46 IS 9 BP 972 EP 981 DI 10.1111/j.1469-7610.2004.00398.x PG 10 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 955XG UT WOS:000231262000007 PM 16109000 ER PT J AU Fletcher, JM Francis, DJ Morris, RD Lyon, GR AF Fletcher, JM Francis, DJ Morris, RD Lyon, GR TI Evidence-based assessment of learning disabilities in children and adolescents SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID GENERAL READING BACKWARDNESS; DISCREPANCY DEFINITIONS; PHONOLOGICAL-CORE; IQ; DYSLEXIA; RETARDATION; PREVALENCE; CLASSIFICATION; IDENTIFICATION; INTERVENTION AB The reliability and validity of 4 approaches to the assessment of children and adolescents with learning disabilities (LD) are reviewed, including models based on (a) aptitude-achievement discrepancies, (b) low achievement, (c) intra-individual differences, and (d) response to intervention (RTI). We identify serious psychometric problems that affect the reliability of models based on aptitude-achievement discrepancies and low achievement. There are also significant validity problems for models based on aptitude-achievement discrepancies and intra-individual differences. Models that incorporate RTI have considerable potential for addressing both the reliability and validity issues but cannot represent the sole criterion for LD identification. We suggest that models incorporating both low achievement and RTI concepts have the strongest evidence base and the most direct relation to treatment. The assessment Of children for LD must reflect a stronger underlying classification that takes into account relations with other childhood disorders as well as the reliability and validity of the underlying classification and resultant assessment and identification system. The implications of this type of model for clinical assessments of children for whom LD is a concern are discussed. C1 Univ Texas, Hlth Sci Ctr, Dept Pediat, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Ctr Acad & Reading Skills, Houston, TX 77030 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. Univ Houston, Texas Inst Measurement Evaluat & Stat, Houston, TX 77004 USA. Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. NICHHD, Child Dev & Behav Branch, Bethesda, MD 20892 USA. RP Fletcher, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pediat, 700 Fannin St,UCT 2479, Houston, TX 77030 USA. EM Jack.Fletcher@uth.tmc.edu OI Francis, David/0000-0003-3944-3274 FU NICHD NIH HHS [P50 HD052117, R01 HD028172]; PHS HHS [P50 21888] NR 84 TC 53 Z9 54 U1 2 U2 16 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1537-4416 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PD SEP PY 2005 VL 34 IS 3 BP 506 EP 522 DI 10.1207/s15374424jccp3403_7 PG 17 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 948GG UT WOS:000230703500007 PM 16083392 ER PT J AU Kravariti, M Naka, KK Kalantaridou, SN Kazakos, N Katsouras, CS Makrigiannakis, A Paraskevaidis, EA Chrousos, GP Tsatsoulis, A Michalis, LK AF Kravariti, M Naka, KK Kalantaridou, SN Kazakos, N Katsouras, CS Makrigiannakis, A Paraskevaidis, EA Chrousos, GP Tsatsoulis, A Michalis, LK TI Predictors of endothelial dysfunction in young women with polycystic ovary syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 12th International Congress of Endocrinology CY AUG 31-SEP 04, 2004 CL Lisbon, PORTUGAL ID CORONARY-HEART-DISEASE; TERM-FOLLOW-UP; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; MEDIATED DILATATION; NITRIC-OXIDE; RISK; ARTERY; ATHEROSCLEROSIS; ASSOCIATION AB Context: Women with polycystic ovary syndrome ( PCOS) may be at increased risk for cardiovascular disease. Endothelial dysfunction is an early marker of atherosclerosis. Objectives: The objectives of this study were to 1) compare endothelial function in young women with PCOS and regularly menstruating control women, and 2) to identify the determinants of endothelial function and investigate its relationship with body mass index in women with PCOS. Design: This was a cross-sectional study. Setting: This study was conducted at a tertiary cardiovascular research center. Patients: Sixty-two young women with PCOS( mean age, 22.7 yr) and 17 control women, matched as a group for age and body mass index, were studied. Twenty-three women with PCOS were lean, 21 were overweight, and 18 were obese. Main Outcome Measures: Endothelium-dependent and -independent diameter change during hand hyperemia and after sublingual glyceryl trinitrate administration, respectively). Results: FMD and nitrate-mediated dilation were significantly lower in PCOS than in control women ( reduced by approximately 50 and 25%, respectively; both P < 0.0005). Insulin resistance, total testosterone, and total cholesterol were independent predictors of FMD, accounting for 21, 10, and 9% of the variance, respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to overweight and obese PCOS women was observed, but differences among groups were not statistically significant. Conclusions: Women with PCOS have significant endothelial dysfunction at an early age (i.e. early 20s), and largely independent of obesity. This suggests that women with PCOS are at increased risk for early onset cardiovascular disease and may gain particular benefit from measures to improve endothelial function. C1 Univ Ioannina, Dept Endocrinol, Michaelid Cardiac Ctr, GR-45110 Ioannina, Greece. Univ Hosp, Dept Endocrinol, Ioannina 45110, Greece. Univ Hosp, Div Reprod Endocrinol, Dept Obstet & Gynecol, Ioannina 45110, Greece. Univ Crete, Dept Obstet & Gynecol, Iraklion 71110, Greece. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Tsatsoulis, A (reprint author), Univ Ioannina, Dept Endocrinol, Michaelid Cardiac Ctr, Panepistimiou Ave, GR-45110 Ioannina, Greece. EM atsatsou@cc.uoi.gr NR 41 TC 105 Z9 110 U1 0 U2 1 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 SEP PY 2005 VL 90 IS 9 BP 5088 EP 5095 DI 10.1210/jc.2005-0151 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962DM UT WOS:000231711200014 PM 15985492 ER PT J AU Batista, D Courkoutsakis, NA Oldfield, EH Griffin, KJ Keil, M Patronas, NJ Stratakis, CA AF Batista, D Courkoutsakis, NA Oldfield, EH Griffin, KJ Keil, M Patronas, NJ Stratakis, CA TI Detection of adrenocorticotropin-secreting pituitary adenomas by magnetic resonance imaging in children and adolescents with Cushing disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SPIN-ECHO TECHNIQUE; TRANSSPHENOIDAL SURGERY; GADOLINIUM-DTPA; MR; MICROADENOMAS; DIAGNOSIS; TUMORS; EXPERIENCE; CHILDHOOD; HORMONE AB Context: We recently showed that pre- and postcontrast spoiled gradient-recalled acquisition in the steady-state (SPGR) was superior to conventional pre- and postcontrast T-1 weighted spin echo ( SE) acquisition magnetic resonance imaging (MRI) for the diagnostic evaluation of pituitary tumors in adult patients. Objective: The present investigation assessed the use of SPGR vs. SE-MRI in the diagnostic evaluation of ACTH-secreting tumors in children and adolescents with Cushing disease. Design: Data were analyzed retrospectively from a series of patients seen over 7 yr (1997-2004). Setting: The setting for this study was a tertiary care referral center. Patients: Thirty children with Cushing disease (13 females and 17 males with a mean age of 12 +/- 3 yr) were studied. Interventions and Outcome Measures: Imaging results were compared with surgical and pathological findings and the clinical outcome. Results: Twenty-eight patients had microadenomas, and two had macroadenomas; the latter were identified by both MRI techniques. Precontrast SE and SPGR-MRI identified four and six of the microadenomas, respectively. Postcontrast SPGR-MRI identified the location of the tumor in 18 of 28 patients, whereas postcontrast SEMRI identified the location and accurately estimated the size of the tumor in only five patients (P < 0.001). Conclusions: We conclude that conventional MRI, even with contrast enhancement, mostly failed to identify ACTH-secreting microadenomas in children and adolescents with Cushing disease. Postcontrast SPGR-MRI was superior to SE-MRI and should be used in addition to conventional SE-MRI in the pituitary evaluation of children and adolescents with suspected Cushing disease. C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 32 TC 46 Z9 49 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 SEP PY 2005 VL 90 IS 9 BP 5134 EP 5140 DI 10.1210/jc.2005-1778 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962DM UT WOS:000231711200021 PM 15941871 ER PT J AU Stathatos, N Bourdeau, I Espinosa, AV Saji, M Vasko, VV Burman, KD Stratakis, CA Ringel, MD AF Stathatos, N Bourdeau, I Espinosa, AV Saji, M Vasko, VV Burman, KD Stratakis, CA Ringel, MD TI KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases myocyte-enriched calcineurin interacting protein 1 expression and chronically inhibits calcineurin activity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOWN-SYNDROME; THYROID-CANCER; PAPILLARY CARCINOMA; CELL PROLIFERATION; GENE-EXPRESSION; MIGRATION; GPR54; ANGIOGENESIS; MALIGNANCIES; PROGRESSION AB Objective: Tumor metastasis is a critical determinant of death from cancer. Metastin, a product of the KiSS-1 gene, is an endogenously expressed metastasis suppressor that is the ligand for G protein-coupled receptor 54 (GPR54), a Gq/11-coupled receptor. In the present study, our goal was to define the basis of GPR54 action using thyroid cancer cells as a model. Design and Results: We used GPR54-null thyroid cancer cells to create a stable GPR54 overexpression model. Cell growth and cell migration of the GPR54-expressing lines were inhibited by recombinant metastin, and metastin stimulated the protein kinase C, ERK, and phosphatidylinositol-3-kinase pathways. To identify metastin-regulated genes, we performed microarray analyses using RNA isolated from GPR54 stable transfectants before and after 1 and 24 h of metastin stimulation. Consistent increases in expression of the gene encoding myocyte-enriched calcineurin interacting protein 1 (MCIP-1), an inhibitor of calcineurin, were identified and confirmed using real-time RT-PCR and Western blot. Functionally, metastin treatment of GPR54-expressing cells initially increased calcineurin activity, followed by a prolonged reduction in calcineurin activity for 24 and 48 h, consistent with the pattern of MCIP-1 expression. In addition, treatment with cyclosporin A, a calcineurin inhibitor, blocked cell migration. Lymph node metastasis in papillary thyroid cancers demonstrated loss of MCIP-1 expression in comparison with primary tumors. Conclusions: These data suggest a role for MCIP-1 and calcineurin inhibition in GPR54-mediated metastasis suppression in human cancers. C1 Ohio State Univ, Columbus, OH 43210 USA. Arthur G James Comprehens Canc Ctr, Columbus, OH 43210 USA. Washington Hosp Ctr, MedStar Res Inst, Washington, DC 20010 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHD, Sect Endocrinol & Genet, DEB, NIH, Bethesda, MD 20892 USA. RP Ringel, MD (reprint author), Ohio State Univ, 445D McCampbell Hall,1581 Dodd Dr, Columbus, OH 43210 USA. EM ringel.11@osu.edu RI Levesque, Isabelle/A-1899-2012; Saji, Motoyasu/E-4007-2011 FU NCI NIH HHS [IR21CA111461] NR 36 TC 47 Z9 51 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 SEP PY 2005 VL 90 IS 9 BP 5432 EP 5440 DI 10.1210/jc.2005-0963 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962DM UT WOS:000231711200069 PM 15998767 ER PT J AU Du Val, G Gensler, G Danis, M AF Du Val, G Gensler, G Danis, M TI Ethical dilemmas encountered by clinical researchers SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID CONSULTATION SERVICE C1 Univ Toronto, Fac Law, Toronto, ON M5S 1A1, Canada. EMMES Corp, Rockville, MD USA. NIH, Sect Eth & Hlth Policy, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Du Val, G (reprint author), Univ Toronto, Fac Law, 100 Coll St, Toronto, ON M5S 1A1, Canada. EM gordon.duval@utoronto.ca NR 22 TC 3 Z9 3 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2005 VL 16 IS 3 BP 267 EP 276 PG 10 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 006OT UT WOS:000234907500014 PM 16302553 ER PT J AU Williams, K Westmoreland, S Greco, J Ratai, E Lentz, M Kim, WK Fuller, RA Kim, JP Autissier, P Sehgal, PK Schinazi, RF Bischofberger, N Piatak, M Lifson, JD Masliah, E Gonzalez, RG AF Williams, K Westmoreland, S Greco, J Ratai, E Lentz, M Kim, WK Fuller, RA Kim, JP Autissier, P Sehgal, PK Schinazi, RF Bischofberger, N Piatak, M Lifson, JD Masliah, E Gonzalez, RG TI Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; CD8(+) T-CELLS; PROTON MR SPECTROSCOPY; HIV-POSITIVE PATIENTS; CEREBROSPINAL-FLUID; ANTIRETROVIRAL THERAPY; BLOOD MONOCYTES; RHESUS MACAQUES AB Difficulties in understanding the mechanisms of HIV neuropathogenesis include the inability to study dynamic processes of infection, cumulative effects of the virus, and contributing host immune responses. We used H-1 magnetic resonance spectroscopy and studied monocyte activation and progression of CNS neuronal injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus macaque monkeys. We found early, consistent neuronal injury coincident with viremia and SIV infection/activation of monocyte subsets and sought to define the role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral therapy with essentially non-CNS-penetrating agents resulted in slightly decreased levels of plasma virus, a significant reduction in the number of activated and infected monocytes, and rapid, near-complete reversal of neuronal injury. Robust macrophage accumulation and productive virus replication were found in brains of infected and CD8 lymphocyte-depleted animals, but no detectable virus and few scattered infiltrating macrophages were observed in CD8 lymphocyte-depleted animals compared with animals not receiving antiretroviruses that were sacrificed at the same time after infection. These results underscore the role of activated monocytes and monocyte infection outside of the brain in driving CNS disease. C1 Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Emory Univ, Sch Med, Vet Affairs Med Ctr, Lab Biochem Pharmacol,Dept Pediat, Atlanta, GA 30322 USA. Gilead Sci, Foster City, CA 94404 USA. Sci Applicat Int Corp Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD USA. UCSD, Dept Neurosci, La Jolla, CA USA. RP Williams, K (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, RE113,330 Brookline Ave, Boston, MA 02215 USA. EM rggonzalez@partners.org RI Schinazi, Raymond/B-6777-2017 FU NCRR NIH HHS [RR00168, K01 RR000150, K26 RR000168, P41 RR014075, P51 RR000168, R24 RR016001, RR000150, RR13214, RR14075, RR16001]; NIAID NIH HHS [2P30-AI-50409, P30 AI050409]; NIMH NIH HHS [P50 MH045294]; NINDS NIH HHS [NS0050041, NS34626, NS40237, R01 NS034626, R01 NS040237, R01 NS050041] NR 90 TC 86 Z9 88 U1 0 U2 0 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 SEP PY 2005 VL 115 IS 9 BP 2534 EP 2545 DI 10.1172/JCI22953 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 962CL UT WOS:000231708500031 PM 16110325 ER PT J AU Fedorko, DP Preuss, JC Fahle, GA Li, L Fischer, SH Hohman, P Cohen, JI AF Fedorko, DP Preuss, JC Fahle, GA Li, L Fischer, SH Hohman, P Cohen, JI TI Comparison of methods for detection of vaccinia virus in patient specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REAL-TIME PCR; SMALLPOX VACCINATION; ACCIDENTAL INFECTION; LABORATORY WORKER; DNA; COMPLICATIONS; LIGHTCYCLER; DIAGNOSIS; VIREMIA; ASSAY AB We analyzed a shell vial culture assay (SVA), real-time PCR, and a direct fluorescent antibody assay (DFA) for rapid detection of vaccinia virus from vaccination sites of Dryvax vaccine recipients. Of 47 samples assayed, 100% were positive by PCR, 89% were positive by SVA, and 40% were positive by DFA. DFA was limited by the need for adequate numbers of cells, with 32% of samples inadequate for interpretation. DFA performed better with specimens from patients who had not previously received the vaccine. PCR was positive for longer times postvaccination than was SVA. Infectious virus could be recovered after 45 min of acetone fixation of shell vial coverslips. Commercially available polyclonal antibodies cross-reacted with other orthopoxviruses and herpes simplex 1, but commercially available monoclonal antibodies were specific for vaccinia virus. In summary, PCR was the most sensitive test for detecting vaccinia virus in clinical specimens, while the DFA was the most rapid but the least sensitive test. C1 NIAID, Microbiol Serv, DLM, Clin Ctr,NIH,Warren G Magnuson Clin Ctr,US Dept H, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fedorko, DP (reprint author), NIAID, Microbiol Serv, DLM, Clin Ctr,NIH,Warren G Magnuson Clin Ctr,US Dept H, Bldg 10,Room 2C385,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM dfedorko@nih.gov NR 27 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 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2005 VL 43 IS 9 BP 4602 EP 4606 DI 10.1128/JCM.43.9.4602-4606.2005 PG 5 WC Microbiology SC Microbiology GA 966LD UT WOS:000232020400044 PM 16145113 ER PT J AU Stanton, AL Ganz, PA Kwan, L Meyerowitz, BE Bower, JE Krupnick, JL Rowland, JH Leedham, B Belin, TR AF Stanton, AL Ganz, PA Kwan, L Meyerowitz, BE Bower, JE Krupnick, JL Rowland, JH Leedham, B Belin, TR TI Outcomes from the moving beyond cancer psychoeducational, randomized, controlled trial with breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 112th Annual Convention of the American-Psychological-Association CY JUL 28-AUG 01, 2004 CL Honolulu, HI SP Amer Psychol Assoc ID QUALITY-OF-LIFE; POSTTRAUMATIC GROWTH; LONG-TERM; PSYCHOLOGICAL INTERVENTIONS; ADJUVANT CHEMOTHERAPY; COPING STRATEGIES; INFORMATION NEEDS; COMMUNITY SAMPLE; WOMEN; ADJUSTMENT AB Purpose Evidence suggests that the re-entry phase (ie, early period after medical treatment completion) presents distinct challenges for cancer patients. To facilitate the transition to recovery, we conducted the Moving Beyond Cancer (MBC) trial, a multisite, randomized, controlled trial of psychoeducational interventions for breast cancer patients. Methods Breast cancer patients were registered within 6 weeks after surgery. After medical treatment, they completed baseline measures and were randomly assigned to standard National Cancer Institute print material (CTL); standard print material and peer-modeling videotape (VID); or standard print material, videotape, two sessions with a trained cancer educator, and informational workbook (EDU). Two primary end points were examined: energy/fatigue and cancer-specific distress. Secondary end points were depressive symptoms and post-traumatic growth. Perceived preparedness for re-entry was analyzed as a moderator of effects. Results Of 558 women randomly assigned to treatment, 418 completed the 6-month assessment and 399 completed the 12-month assessment. In analyses controlling for study site and baseline depressive symptoms, VID produced significant improvement in energy/fatigue at 6 months relative to CTL, particularly among women who felt less prepared for re-entry at baseline. No significant main effect of the interventions emerged on cancer-specific distress, but EDU prompted greater reduction in this outcome relative to CTL at 6 months for patients who felt more prepared for re-entry. Between-group differences in the primary outcomes were not significant at 12 months, and no significant effects emerged on the secondary end points. Conclusion A peer-modeling videotape can accelerate the recovery of energy during the re-entry phase in women treated for breast cancer, particularly among those who feel less prepared for re-entry. C1 Univ Calif Los Angeles, Dept Psychol, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. Univ So Calif, Dept Psychol, Sch Med, Los Angeles, CA USA. Univ So Calif, Dept Psychol, Sch Publ Hlth, Los Angeles, CA USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC USA. Natl Canc Inst, Off Canc Survivorship, Bethesda, MD USA. RP Stanton, AL (reprint author), Univ Calif Los Angeles, Dept Psychol, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM astanton@ucla.edu FU NCI NIH HHS [R01-CA63028] NR 71 TC 116 Z9 118 U1 0 U2 13 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 SEP 1 PY 2005 VL 23 IS 25 BP 6009 EP 6018 DI 10.1200/JC0.2005.09.101 PG 10 WC Oncology SC Oncology GA 960PT UT WOS:000231606300025 PM 16135469 ER PT J AU Attia, P Phan, GQ Maker, AV Robinson, MR Quezado, MM Yang, JC Sherry, RM Topalian, SL Kammula, US Royal, RE Restifo, NP Haworth, LR Levy, C Mavroukakis, SA Nichol, G Yellin, MJ Rosenberg, SA AF Attia, P Phan, GQ Maker, AV Robinson, MR Quezado, MM Yang, JC Sherry, RM Topalian, SL Kammula, US Royal, RE Restifo, NP Haworth, LR Levy, C Mavroukakis, SA Nichol, G Yellin, MJ Rosenberg, SA TI Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CELL-CYCLE PROGRESSION; REGULATORY CELLS; CTLA-4-MEDIATED INHIBITION; CTLA-4 BLOCKADE; ACTIVATION; CD28; TOLERANCE; IMMUNOTHERAPY; PROLIFERATION AB Purpose Previously, we reported our experience treating 14 patients with metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) in conjunction with peptide vaccination. We have now treated 56 patients to evaluate two different dose schedules of anti-CTLA-4 and to explore the relationship between autoimmunity and tumor regression. Patients and Methods A total of 56 patients with progressive stage IV melanoma were enrolled onto the study. All had Karnofsky performance status >= 60% with no prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti-CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received concomitant vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). Results Two patients achieved a complete response (ongoing at 30 and 31 months, respectively) and five patients achieved a partial response (durations of 4, 6, 25+, 26+, and 34+ months, respectively), for an overall objective response rate of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%) experienced a clinical response compared with only two responses in the 42 patients (5%) with no autoimmune toxicity (P = .008). There were no significant differences in response rate or toxicity between the two dose schedules. Conclusion Administration of anti-CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma. C1 NCI, Surg Branch, NIH, CRC, Bethesda, MD 20892 USA. Medarex Inc, Princeton, NJ USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC, Room 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 42 TC 558 Z9 573 U1 1 U2 8 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 SEP 1 PY 2005 VL 23 IS 25 BP 6043 EP 6053 DI 10.1200/JCO.2005.06.205 PG 11 WC Oncology SC Oncology GA 960PT UT WOS:000231606300029 PM 16087944 ER PT J AU Hamilton, AL Eder, JP Pavlick, AC Clark, JW Liebes, L Garcia-Carbonero, R Chachoua, A Ryan, DP Soma, V Farrell, K Kinchla, N Boyden, J Yee, H Zeleniuch-Jacquotte, A Wright, J Elliott, P Adams, J Muggia, FM AF Hamilton, AL Eder, JP Pavlick, AC Clark, JW Liebes, L Garcia-Carbonero, R Chachoua, A Ryan, DP Soma, V Farrell, K Kinchla, N Boyden, J Yee, H Zeleniuch-Jacquotte, A Wright, J Elliott, P Adams, J Muggia, FM TI Proteasome inhibition with bortezomib (PS-341): A phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER-THERAPY; P53 FUNCTION; MALIGNANCIES; APOPTOSIS; TRIAL; PHOSPHORYLATION; ASSOCIATION; DEGRADATION; ARREST; AGENTS AB Purpose We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. Patients and Methods Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m(2) on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. Results On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m(2) dose levels, most commonly in patients receiving individual total doses >= 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m(2); 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. Conclusion Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m(2)), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea. C1 NYU, Med Ctr, Sch Med, New York, NY 10016 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Muggia, FM (reprint author), NYU, Med Ctr, Sch Med, 550 1St Ave, New York, NY 10016 USA. EM muggif01@gcrc.med.nyu.edu OI Muggia, Franco/0000-0003-0703-9146; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [P30 CA16087, U01 CA76642]; NCRR NIH HHS [M01 RR00096]; PHS HHS [U01 62490] NR 30 TC 69 Z9 69 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 SEP 1 PY 2005 VL 23 IS 25 BP 6107 EP 6116 DI 10.1200/JCO.2005.01.136 PG 10 WC Oncology SC Oncology GA 960PT UT WOS:000231606300035 PM 16135477 ER PT J AU Daw, NC Furman, WL Stewart, CF Iacono, LC Krailo, M Bernstein, ML Dancey, JE Speights, RA Blaney, SM Croop, JM Reaman, GH Adamson, PC AF Daw, NC Furman, WL Stewart, CF Iacono, LC Krailo, M Bernstein, ML Dancey, JE Speights, RA Blaney, SM Croop, JM Reaman, GH Adamson, PC TI Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: A children's oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; HUMAN RHABDOMYOSARCOMA CELLS; FACTOR RECEPTOR; COLORECTAL-CANCER; ZD1839 IRESSA; TRIAL; EGFR; EXPRESSION AB Purpose Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. Patients and Methods Gefitinib (150, 300, 400, or 500 mg/m(2)) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). Results Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m(2) and elevated ALT and AST in one patient treated with 400 mg/m(2). The maximum-tolerated dose was 400 mg/m(2)/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to >= 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m(2), the median peak gefitinib plasma concentration was 2.2 mu g/mL (range, 1.2 to 3.6 mu g/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m(2) (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. Conclusion Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued. C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Daw, NC (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM najat.daw@stjude.org FU NCI NIH HHS [CA 97452] NR 57 TC 67 Z9 67 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2005 VL 23 IS 25 BP 6172 EP 6180 DI 10.1200/JCO.2005.11.429 PG 9 WC Oncology SC Oncology GA 960PT UT WOS:000231606300043 PM 16135484 ER PT J AU Mondick, JT Barrett, JS Widemann, B Cole, D Auton, T Adamson, PC AF Mondick, JT Barrett, JS Widemann, B Cole, D Auton, T Adamson, PC TI A population pharmacokinetic model to describe carboxypeptidase-G2 intervention in patients exhibiting high-dose methotrexate-induced nephrotoxicity. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 11-13, 2005 CL Rockville, MD SP Amer Coll Clin Pharmacol C1 Childrens Hosp Philadelphia, Div Clin Pharmacol, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Prother PLC, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2005 VL 45 IS 9 MA 84 BP 1087 EP 1087 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 956OO UT WOS:000231309900088 ER PT J AU Siluk, D Markuszewski, MJ Baczek, T Wiczling, P Marszall, M Frackowiak, T Radwanska, A Damasiewicz, B Kaliszan, R Sobiczewski, W Rynkiewicz, A AF Siluk, D Markuszewski, MJ Baczek, T Wiczling, P Marszall, M Frackowiak, T Radwanska, A Damasiewicz, B Kaliszan, R Sobiczewski, W Rynkiewicz, A TI Application of an HPLC method to the determination of celiprolol bioequivalence after single oral dose SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 11-13, 2005 CL Rockville, MD SP Amer Coll Clin Pharmacol C1 Med Univ Gdansk, Dept Biopharmaceut & Pharmacodynam, Gdansk, Poland. NIA, NIH, Gerontol Res Ctr, Bethesda, MD 20892 USA. Med Univ Gdansk, Dept Cardiol, Gdansk, Poland. RI Kaliszan, Roman/E-4784-2011; Markuszewski, Michal/E-4768-2011; Marszall, Michal/G-8936-2014 OI Markuszewski, Michal/0000-0003-1166-4817; NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2005 VL 45 IS 9 MA 92 BP 1089 EP 1089 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 956OO UT WOS:000231309900096 ER PT J AU Shaw, P Bramham, J Lawrence, EJ Morris, R Baron-Cohen, S David, AS AF Shaw, P Bramham, J Lawrence, EJ Morris, R Baron-Cohen, S David, AS TI Differential effects of lesions of the amygdala and prefrontal cortex on recognizing facial expressions of complex emotions SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HIGH-FUNCTIONING AUTISM; TEMPORAL-LOBE EPILEPSY; ASPERGER-SYNDROME; CEREBRAL ASYMMETRY; MIND IMPAIRMENTS; DECISION-MAKING; NORMAL ADULTS; DAMAGE; RECOGNITION; BRAIN AB Humans can detect facial expressions of both simple, basic emotions and expressions reflecting more complex states of mind. The latter includes emotional expressions that regulate social interactions ("social expressions" such as looking hostile or friendly) and expressions that reflect the inner thought state of others ("cognitive expressions" such as looking pensive). To explore the neural substrate of this skill, we examined performance on a test of detection of such complex expressions in patients with lesions of the temporal lobe (n = 54) or frontal lobe (n = 31). Of the temporal group, 18 had unilateral focal lesions of the amygdala and of the frontal group, 14 patients had unilateral lesions of the ventromedial prefrontal cortex-two regions held to be pivotal in mediating social cognitive skills. Damage to either the left or right amygdala was associated with impairment in the recognition of both social and cognitive expressions, despite an intact ability to extract information relating to invariant physical attributes. Lesions to all of the right prefrontal cortex-not just the ventromedial portions-led to a specific deficit in recognizing complex social expressions with a negative valence. The deficit in the group with right prefrontal cortical damage may contribute to the disturbances in social behavior associated with such lesions. The results also suggest that the amygdala has a role in processing a wide range of emotional expressions. C1 NIH, NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Inst Psychiat, London, England. Univ Cambridge, Cambridge, England. RP Shaw, P (reprint author), NIH, NIMH, Child Psychiat Branch, Bldg 10,Rm 3N202, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov RI Shaw, Philip/A-1129-2008; Frank, David/E-8213-2012; David, Anthony/C-1315-2011; OI David, Anthony/0000-0003-0967-774X; Bramham, Jessica/0000-0002-6696-7500 NR 43 TC 57 Z9 57 U1 5 U2 11 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2005 VL 17 IS 9 BP 1410 EP 1419 DI 10.1162/0898929054985491 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 962TR UT WOS:000231756000007 PM 16197694 ER PT J AU Beeler, AB Acquilano, DE Su, QB Yan, F Roth, BL Panek, JS Porco, JA AF Beeler, AB Acquilano, DE Su, QB Yan, F Roth, BL Panek, JS Porco, JA TI Synthesis of a library of complex macrodiolides employing cyclodimerization of hydroxy esters SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Article ID DIVERSITY-ORIENTED SYNTHESIS; SOLID-PHASE SYNTHESIS; NATURAL-PRODUCT; ORGANIC-SYNTHESIS; PARALLEL SYNTHESIS; STEREOCHEMICAL DIVERSITY; COMBINATORIAL LIBRARIES; CONFORMATIONAL-ANALYSIS; DISTANNOXANE CATALYSTS; MACROCYCLIC DILACTONES AB The synthesis of complex macrodiolides involving microwave-accelerated transesterification of chiral, nonracemic, hydroxy esters is described. Methodology development studies indicate that both microwave power and reaction temperature play an important role in the efficiency of cyclodimerizations. Hydroxy ester monomer pairs were evaluated using an analytical rehearsal leading to the preparation of a 127-member library of highly diverse and stereochemically well-defined macrodiolides. Preliminary assays identified a novel macrodiolide antagonist of the kappa opioid receptor. C1 Boston Univ, Dept Chem, Boston, MA 02115 USA. Boston Univ, Ctr Chem Methodol & Library Dev, Boston, MA 02115 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. RP Porco, JA (reprint author), Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02115 USA. EM porco@chem.bu.edu RI Roth, Bryan/F-3928-2010 NR 88 TC 30 Z9 30 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD SEP-OCT PY 2005 VL 7 IS 5 BP 673 EP 681 DI 10.1021/cc050064b PG 9 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 964HZ UT WOS:000231871600007 PM 16153061 ER PT J AU Maggio, M Ceda, GP De Cicco, G Cattadori, E Visioli, S Ablondi, F Beghi, C Gherli, T Basaria, S Ceresini, G Valenti, G Ferrucci, L AF Maggio, M Ceda, GP De Cicco, G Cattadori, E Visioli, S Ablondi, F Beghi, C Gherli, T Basaria, S Ceresini, G Valenti, G Ferrucci, L TI Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE elderly; CABG; cardiopulmonary bypass; hormones; testosterone; IGF-I ID IGF-BINDING PROTEIN-1; TUMOR-NECROSIS-FACTOR; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; CARDIAC-SURGERY; STRESS-RESPONSE; GROWTH-HORMONE; HEART-FAILURE; PLASMA-LEVELS; MEN AB Objectives: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) causes an acute stress response characterized by changes in the levels of several hormones, which might play a role in the high complication rate experienced by older patients after CABG. Thus, the aim of the study was to investigate changes in the circulating levels of anabolic and catabolic hormones in old people undergoing CABG with CPB. Design: Intervention case study. Methods: 19 patients (112 males, 7 females) aged 70.1 +/- 6.1 yr (age range 62-80) with coronary artery disease and an ejection fraction < 40% who underwent cardiac surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E-2), total testosterone (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and 1, 2, 3, 4, and 30 days after CABG. Results: After surgery, serum IGF-I levels decreased (p < 0.001), while levels of Cort, DHEAS and E-2 significantly increased in both men and women. Alterations in Te levels differed between the two sexes with a significant decline in men and a significant increment in women. Conclusion: CABG with CPB resulted in a dramatic drop in Te levels in old men and a significant decline in IGF-I in both sexes. Serum Cort levels also significantly increased in both sexes. These hormonal changes may, at least partially, explain why the elderly need prolonged rehabilitation after CABG. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Endocrinol, Dept Med,Bayview Med Ctr, Baltimore, MD USA. Civil Hosp, Cardiac Surg Unit, Brescia, Italy. Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. Univ Parma, Dept Cardiac Surg & Cardiol, I-43100 Parma, Italy. RP Ferrucci, L (reprint author), NIA, NIH, Harbor Hosp, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Ceda, Gian Paolo/0000-0002-9648-8295 NR 46 TC 29 Z9 31 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD SEP PY 2005 VL 28 IS 8 BP 711 EP 719 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 977OY UT WOS:000232814300006 PM 16277167 ER PT J AU Menotti-Raymond, MA David, VA Wachter, LL Butler, JM O'Brien, SJ AF Menotti-Raymond, MA David, VA Wachter, LL Butler, JM O'Brien, SJ TI An STIR forensic typing system for genetic individualization of domestic cat (Felis catus) samples SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; domestic cat; STR; forensic typing system; multiplex amplification; cat breeds ID CHROMOSOME-BANDING PATTERNS; POLYMERASE-CHAIN-REACTION; LINKAGE MAP; CANINE MICROSATELLITES; GENOME; MARKERS; IDENTIFICATION; VALIDATION; DOG; INTERRELATIONSHIPS AB A forensic genotyping panel of 11 tetranucleotide STR loci from the domestic cat was characterized and evaluated for genetic individualization of cat tissues. We first examined 49 candidate STR loci and their frequency assessment in domestic cat populations. The STR loci (3-4 base pair repeat motifs), mapped in the cat genome relative to 579 coding loci and 255 STR loci, are well distributed across the 18 feline autosomes. All loci exhibit Mendelian inheritance in a multi-generation pedigree. Eleven loci that were unlinked and were highly heterozygous in cat breeds were selected for a forensic panel. Heterozygosity values obtained for the independent loci, ranged from 0.60-0.82, while the average cat breed heterozygosity obtained for the 11 locus panel was 0.71 (range of 0.57-0.83). A small sample set of outbred domestic cats displayed a heterozygosity of 0.86 for the 11 locus panel. The power of discrimination of the panel is moderate to high in the cat breeds examined, with an average P-m of 3.7E-06. The panel shows good potential for genetic individualization within outbred domestic cats with a Pm of 5.31E-08. A multiplex protocol, designed for the co-amplification of the 11 loci and a gender-identifying locus, is species specific and robust, generating a product profile with as little as 0.125 nanograms of genomic DNA. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. RP Menotti-Raymond, MA (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 11-38, Frederick, MD 21702 USA. RI Butler, John/C-7812-2011 FU NCI NIH HHS [N01-CO-12400] NR 44 TC 66 Z9 67 U1 1 U2 8 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 2005 VL 50 IS 5 BP 1061 EP 1070 PG 10 WC Medicine, Legal SC Legal Medicine GA 961KE UT WOS:000231660300008 PM 16225210 ER PT J AU Khorana, AA Hu, YC Ryan, CK Komorowski, RA Hostetter, G Ahrendt, SA AF Khorana, AA Hu, YC Ryan, CK Komorowski, RA Hostetter, G Ahrendt, SA TI Vascular endothelial growth factor and DPC4 predict adjuvant therapy outcomes in resected pancreatic cancer SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 5th Biennial Meeting of the American-Hepato-Pancreato-Biliary-Association CY APR 14-17, 2005 CL Ft Lauderdale, FL SP Amer Hepato Pancreato Biliary Assoc DE pancreatic cancer; VEGF; DPC4; microvessel density ID DUCTAL ADENOCARCINOMA; CURATIVE RESECTION; POOR-PROGNOSIS; THYMIDINE PHOSPHORYLASE; TUMOR ANGIOGENESIS; HIGH EXPRESSION; CARCINOMA; CHEMOTHERAPY; SURVIVAL; PANCREATICODUODENECTOMY AB Angiogenesis is important for pancreatic cancer progression, but its role in predicting response to therapy is not known. We investigated the association of various angiogenic factors and intratumoral microvessel density (IMD) with adjuvant therapy and survival in resected pancreatic cancer. Tissue cores from a multi-institutional retrospective series of resected patients were used to build a pancreatic cancer tissue microarray. Vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), CD31 (for IMD), and DPC4 expression were determined using immunohistochemistry. Expression of VEGF and PD-ECGF, both proangiogenic factors, was observed in 70 (56%) and 75 (59%) of 124 tumors, respectively. Expression of DPC4, an angiogenesis inhibitor, was observed in 59 of 124 (48%) tumors. VEGF expression correlated significantly with increased IMD (P = .03), as did loss of antiangiogenic DPC4 (P = .05). PD-ECGF expression did not correlate with IMD. Use of adjuvant therapy was associated with increased survival in patients with VEGF-positive tumors (18.8 [treated] versus 11.2 [untreated] months; hazard ratio [HR] = 0.38, 95% confidence interval [CI], 0.19-0.76; P = .005), but not in patients with VEGF-negative tumors. Similarly, improved survival was observed in patients with high IMD (16.3 [treated] versus 11.2 [untreated] months; HR = 0.44, 95% CI, 0.23-0.87; P = .02) and in patients with loss of DPC4 (20.3 [treated] versus 11.2 [untreated] months; HR = 0.31, 95 % CI, 0.14-0.67; P = .002), but not in those with low IMD or normal DPC4 expression. VEGF (stimulator) and DPC4 (inhibitor) are important regulators of pancreatic tumor angiogenesis and predictive of benefit from adjuvant therapy. Adjuvant therapy may have both antiangiogenic and cytotoxic effects. Addition of anti-VEGF agents to adjuvant regimens may further improve outcomes. C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Univ Rochester, Dept Med, Rochester, NY USA. Univ Rochester, Dept Surg, Rochester, NY USA. Univ Rochester, Sch Med, Dept Pathol & Lab Med, Rochester, NY USA. Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Translat Gen Res Inst, Phoenix, AZ USA. RP Khorana, AA (reprint author), 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM alok_khorana@URMC.rochester.edu NR 33 TC 24 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP-OCT PY 2005 VL 9 IS 7 BP 903 EP 911 DI 10.1016/j.gassur.2005.06.021 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 972LK UT WOS:000232455100006 PM 16137582 ER PT J AU Di Bisceglie, AM Sterling, RK Chung, RT Everhart, JE Dienstag, JL Bonkovsky, HL Wright, EC Everson, GT Lindsay, KL Lok, ASF Lee, WM Morgan, TR Ghany, MG Gretch, DR AF Di Bisceglie, AM Sterling, RK Chung, RT Everhart, JE Dienstag, JL Bonkovsky, HL Wright, EC Everson, GT Lindsay, KL Lok, ASF Lee, WM Morgan, TR Ghany, MG Gretch, DR CA HALT C Trial Grp TI Serum alpha-fetoprotein levels in patients with advanced hepatitis C: Results from the HALT-C Trial SO JOURNAL OF HEPATOLOGY LA English DT Article DE cirrhosis; hepatitis C; antiviral therapy; alpha-fetoprotein ID CHRONIC LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; DIAGNOSIS; CIRRHOSIS; INTERFERON; NECROSIS; UTILITY; ADULTS; ASSAYS; WOMEN AB Background/Aims: Alpha-fetoprotein (AFP) has been useful in the diagnosis of hepatocellular carcinoma (HCC) but lacks specificity. We assessed serum AFP among patients with chronic hepatitis C and advanced fibrosis to establish predictors of AFP elevations and changes with antiviral therapy. Methods: Serum AFP was measured at baseline and on therapy in patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C). AFP levels were correlated with patient demographic and clinical features. Results: Baseline AFP was >= 20 ng/mL in 191 of 1145 patients (16.6 %). Mean AFP values were significantly higher in patients with cirrhosis than in those with bridging fibrosis (22.5 vs. 11.4 ng/mL, P < 0.0001). Factors independently associated with raised serum AFP in patients with cirrhosis were female gender, black race, decreased platelet count, increased serum AST/ALT ratio, serum ferritin, and Mallory bodies in liver biopsies. Serum AFP levels decreased significantly during therapy with pegylated interferon alpha-2a and ribavirin. HCC was identified in six subjects, only three of whom had AFP > 20 ng/mL. Conclusions: Among patients with advanced chronic hepatitis C, serum AFP values are frequently elevated, even in the absence of HCC. Factors associated with raised AFP include severity of liver disease, female gender and black race. Serum AFP levels decline during antiviral therapy. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Dept Med, St Louis, MO 63110 USA. Virginia Commonwealth Univ, Hepatol Sect, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. Harvard Univ, Med Sch, Massachusetts Gen Hosp, Gastrointest Unit,Med Serv, Boston, MA USA. Harvard Univ, Med Sch, Dept Med, Boston, MA USA. NIH, Natl Inst Diabet & Digest & Kidney Dis, Dept Hlth & Human Serv, Div Digest Dis & Nutr, Bethesda, MD USA. Univ Connecticut, Hlth Ctr, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Connecticut, Hlth Ctr, Gen Clin Res Ctr, Farmington, CT USA. New England Res Inst, Watertown, MA USA. Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO USA. Univ So Calif, Div Gastroenterol & Liver Dis, Los Angeles, CA USA. Univ Michigan, Ctr Med, Div Gastroenterol, Ann Arbor, MI USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. NIDDKD, Dept Hlth & Human Serv, Liver Dis Sect, Div Digest Dis & Nutr,NIH, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Di Bisceglie, AM (reprint author), St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Dept Med, 3635 Vista Ave, St Louis, MO 63110 USA. EM dibiscam@slu.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01--DK-9-2326, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2327, N01-DK-9-2328] NR 35 TC 117 Z9 120 U1 1 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 SEP PY 2005 VL 43 IS 3 BP 434 EP 441 DI 10.1016/j.jhep.2005.03.019 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 958XJ UT WOS:000231481200010 PM 16136646 ER PT J AU Brissova, M Fowler, MJ Nicholson, WE Chu, A Hirshberg, B Harlan, DM Powers, AC AF Brissova, M Fowler, MJ Nicholson, WE Chu, A Hirshberg, B Harlan, DM Powers, AC TI Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE pancreatic islets; confocal microscopy; architecture; composition ID TYPE-1 DIABETES-MELLITUS; CELL-TYPE SEGREGATION; MOLECULE N-CAM; TRANSPLANTATION; EXPRESSION; IMMUNOSUPPRESSION; AGGREGATION; POLYPEPTIDE; LANGERHANS; RECEPTOR AB The recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from six separate isolations provided by three different islet isolation centers were compared with isolated mouse and non-human primate islets. As expected from histological sections of murine pancreas, in isolated murine islets a and 6 cells resided at the periphery of the p-cell core. However, human islets were markedly different in that alpha, beta, and delta cells were dispersed throughout the islet. This pattern of cell distribution was present in all human islet preparations and islets of various sizes and was also seen in histological sections of human pancreas. The architecture of isolated non-human primate islets was very similar to that of human islets. Using an image analysis program, we calculated the volume of (alpha, beta, and delta cells. In contrast to murine islets, we found that populations of islet cell types varied considerably in human islets. The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets. C1 Vanderbilt Univ, Div Diabet Endocrinol & Metab, Sch Med, Nashville, TN 37232 USA. NIDDKD, Islet & Autoimmun Branch, Bethesda, MD 20892 USA. VA Tennessee Valley Healthcare Syst, Nashville, TN USA. RP Powers, AC (reprint author), Vanderbilt Univ, Div Diabet Endocrinol & Metab, Sch Med, 715 PRB, Nashville, TN 37232 USA. EM Al.Powers@Vanderbilt.edu FU NIDDK NIH HHS [DK-55233, DK-62641, DK-63439, DK20593] NR 28 TC 291 Z9 296 U1 4 U2 20 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 2005 VL 53 IS 9 BP 1087 EP 1097 DI 10.1369/jhc.5C6684.2005 PG 11 WC Cell Biology SC Cell Biology GA 960HD UT WOS:000231580300004 PM 15923354 ER PT J AU Barrington, RA Zhang, M Zhong, XM Jonsson, H Holodick, N Cherukuri, A Pierce, SK Rothstein, TL Carroll, MC AF Barrington, RA Zhang, M Zhong, XM Jonsson, H Holodick, N Cherukuri, A Pierce, SK Rothstein, TL Carroll, MC TI CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FAS-MEDIATED APOPTOSIS; DOMAIN-CONTAINING PROTEIN; FLICE-INHIBITORY PROTEIN; ANTIGEN RECEPTOR; TRANSGENIC MICE; C-FLIP; MOLECULAR ADJUVANT; LYMPHOCYTES-B; CUTTING EDGE; DEATH DOMAIN AB The adaptive immune response is tightly regulated to limit responding cells in an Ag-specific manner. On B cells, coreceptors CD21/CD19 modulate the strength of BCR signals, potentially influencing cell fate. The importance of the CD95 pathway was examined in response of B cells to moderate affinity Ag using an adoptive transfer model of lysozyme-specific Ig transgenic (HEL immunoglobulin transgene (MD4) strain) B cells. Although adoptively transferred Cr2(+/+) MD4 B cells are activated and persist within splenic follicles of duck egg lysozyme-immunized mice, Cr2(-/-) MD4 B cells do not. In contrast, Cr2(-/-) MD4 lpr B cells persist after transfer, suggesting that lack of CD21/CD35 signaling results in CD95-mediated elimination. Cr2 deficiency did not affect CD95 levels, but cellular FLIP (c-FLIP) protein and mRNA levels were reduced 2-fold compared with levels in Cr2(+/+) MD4 B cells. In vitro culture with Cr2(+/+) MD4 B cells demonstrated that equimolar amounts of rHEL-C3d(3) were more effective than hen egg lysozyme alone in up-regulating c-FLIP levels and for protection against CD95-mediated apoptosis. Collectively, this study implies a mechanism for regulating B cell survival in vivo whereby the strength of BCR signaling (including coreceptor) determines c-FLIP levels and protection from CD95-induced death. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Boston, MA 02115 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Boston Univ, Med Ctr, Dept Immunobiol, Boston, MA 02118 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu FU NIAID NIH HHS [AI40181, AI39246] NR 71 TC 29 Z9 32 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2005 VL 175 IS 5 BP 2859 EP 2867 PG 9 WC Immunology SC Immunology GA 966HL UT WOS:000232010600014 PM 16116172 ER PT J AU la Sala, A Gadina, M Kelsall, BL AF la Sala, A Gadina, M Kelsall, BL TI G(i)-protein-dependent inhibition of IL-12 production is mediated by activation of the phosphatidylinositol 3-kinase-protein 3 kinase B/Akt pathway and JNK SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA-PRODUCTION; INTERLEUKIN-12 PRODUCTION; PROTEIN-KINASE; DIFFERENTIAL REGULATION; SELECTIVE SUPPRESSION; GLUTATHIONE REDOX; GENE-EXPRESSION; HUMAN MONOCYTES; MEASLES-VIRUS; MAP KINASE AB Ligands for certain G(i)-protein-coupled receptors (GiPCRs) potently inhibit the production of IL-12 by human monocytes. We addressed the intracellular signaling mechanisms by which this occurs using primary human cells. Stimulation with the GiPCR ligands C5a and 1-deoxy-1-[6-[(3-iodophenyl)methyl]amino]-9H-purine-9-yl]-N-methyl-beta-D-ribofuranuronamide (IB-MECA) blocked the production of IL-12 p70 by human monocytes stimulated with LPS and IFN-gamma. In addition, C5a reduced the expression of mRNA for IL-12 p35, p40, IL-23 p19, and IL-27 p28. This effect was due neither to a down-regulation of TLR4 or IFN-gamma receptor on the cell surface nor to interference with IFN-gamma signaling, because IFN-gamma-induced up-regulation of HLA-DR and CD40 were unaffected. C5a or IB-MECA activated the PI3K/Akt signaling pathway and induced the phosphorylation of the MAPK p38, ERK, and JNK. Inhibition of the PI3K/Akt signaling pathway with wortmannin or an inhibitor of Akt activity, and inhibition of JNK but not ERK prevented IL-12 and IL-23 suppression by C5a. These data extend observations on IL-12 suppression by C5a to IL-23 and IL-27, and are the first to demonstrate the intracellular signaling events leading to IL-12 and IL-23 inhibition after GiPCR activation. C1 NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Queens Univ Belfast, Dept Microbiol & Immunol, Belfast BT7 1NN, Antrim, North Ireland. RP Kelsall, BL (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 10 Ctr Dr,11-N228, Bethesda, MD 20892 USA. EM kelsall@nih.gov RI la Sala, Andrea/A-3228-2009 OI la Sala, Andrea/0000-0003-1268-6516 NR 30 TC 67 Z9 68 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 SEP 1 PY 2005 VL 175 IS 5 BP 2994 EP 2999 PG 6 WC Immunology SC Immunology GA 966HL UT WOS:000232010600028 PM 16116186 ER PT J AU Youn, HS Lee, JY Fitzgerald, KA Young, HA Akira, S Hwang, DH AF Youn, HS Lee, JY Fitzgerald, KA Young, HA Akira, S Hwang, DH TI Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: Molecular targets are TBK1 and RIP1 in TRIF complex SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; DOMAIN-CONTAINING ADAPTER; TOLL-LIKE RECEPTOR-4; MITOGEN-INDUCIBLE CYCLOOXYGENASE; CANCER CHEMOPREVENTIVE ACTIVITY; TRANSCRIPTION FACTORS; GENE-EXPRESSION; CUTTING EDGE; FATTY-ACIDS; ACTIVATION AB TLRs can activate two distinct branches of downstream signaling pathways. MyD88 and Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF) pathways lead, to the expression of proinflammatory cytokines and type I IFN genes, respectively. Numerous reports have demonstrated that resveratrol, a phytoalexin with anti-inflammatory effects, inhibits NF-kappa B activation and other downstream signaling pathways leading to the suppression of target gene expression. However, the direct targets of resveratrol have not been identified. In this study, we attempted to identify the molecular target for resveratrol in TLR-mediated signaling pathways. Resveratrol suppressed NF-kappa B activation and cyclooxygenase-2 expression in RAW264.7 cells following TLR3 and TLR4 stimulation, but not TLR2 or TLR9. Further, resveratrol inhibited NF-kappa B activation induced by TRIF, but not by MyD88. The activation of IFN regulatory factor 3 and the expression of IFN-beta induced by LPS, poly(I:C), or TRIF were also suppressed by resveratrol. The suppressive effect of resveratrol on LPS-induced NF-kappa B activation was abolished in TRIF-deficient mouse embryonic fibroblasts, whereas LPS-induced degradation of I kappa B alpha and expression of cyclooxygenase-2 and inducible NO synthase were still inhibited in MyD88-deficient macrophages. Furthermore, resveratrol inhibited the kinase activity of TANK-binding kinase 1 and the NF-kappa B activation induced by RIP1 in RAW264.7 cells. Together, these results demonstrate that resveratrol specifically inhibits TRIF signaling in the TLR3 and TLR4 pathway by targeting TANK-binding kinase 1 and RIP1 in TRIF complex. The results raise the possibility that certain dietary phytochemicals can modulate TLR-derived signaling and inflammatory target gene expression and can alter susceptibility to microbial infection and chronic inflammatory diseases. C1 Univ Calif Davis, Western Human Nutr Res Ctr, USDA ARS, Davis, CA 95616 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Osaka, Japan. RP Hwang, DH (reprint author), Univ Calif Davis, Western Human Nutr Res Ctr, USDA ARS, Meyer Hall,1Shields Ave, Davis, CA 95616 USA. EM Dhwang@whnrc.usda.gov RI Akira, Shizuo/C-3134-2009 FU NCI NIH HHS [CA75613]; NIDDK NIH HHS [DK41868, DK064007] NR 61 TC 152 Z9 166 U1 4 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2005 VL 175 IS 5 BP 3339 EP 3346 PG 8 WC Immunology SC Immunology GA 966HL UT WOS:000232010600068 PM 16116226 ER PT J AU Green, NM Zhang, SZ Porcella, SF Nagiec, MJ Barbian, KD Beres, SB LeFebvre, RB Musser, JM AF Green, NM Zhang, SZ Porcella, SF Nagiec, MJ Barbian, KD Beres, SB LeFebvre, RB Musser, JM TI Genome sequence of a serotype m28 strain of group A Streptococcus: Potential new insights into puerperal sepsis and bacterial disease specificity SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FIBRONECTIN-BINDING PROTEIN; ACUTE RHEUMATIC-FEVER; SERUM OPACITY FACTOR; M3 STRAIN; SURFACE-PROTEINS; UNITED-STATES; PYOGENES; INFECTIONS; GENE; VIRULENCE AB Puerperal sepsis, a major cause of death of young women in Europe in the 1800s, was due predominantly to the gram-positive pathogen group A Streptococcus. Studies conducted during past decades have shown that serotype M28 strains are the major group A Streptococcus organisms responsible for many of these infections. To begin to increase our understanding of their enrichment in puerperal sepsis, we sequenced the genome of a genetically representative strain. This strain has genes encoding a novel array of prophage virulence factors, cell-surface proteins, and other molecules likely to contribute to host-pathogen interactions. Importantly, genes for 7 inferred extracellular proteins are encoded by a 37.4-kb foreign DNA element that is shared with group B Streptococcus and is present in all serotype M28 strains. Proteins encoded by the 37.4-kb element were expressed extracellularly and in human infections. Acquisition of foreign genes has helped create a disease-specialist clone of this pathogen. C1 Baylor Coll Med, Ctr Human Bacterial Pathogenesis Res, Dept Pathol, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Musser, JM (reprint author), Baylor Coll Med, Ctr Human Bacterial Pathogenesis Res, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM musser@bcm.tmc.edu FU PHS HHS [U01-60595] NR 73 TC 149 Z9 461 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2005 VL 192 IS 5 BP 760 EP 770 DI 10.1086/430618 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952QC UT WOS:000231019600007 PM 16088825 ER PT J AU Sumby, P Porcella, SF Madrigal, AG Barbian, KD Virtaneva, K Ricklefs, SM Sturdevant, DE Graham, MR Vuopio-Varkila, J Hoe, NP Musser, JM AF Sumby, P Porcella, SF Madrigal, AG Barbian, KD Virtaneva, K Ricklefs, SM Sturdevant, DE Graham, MR Vuopio-Varkila, J Hoe, NP Musser, JM TI Evolutionary origin and emergence of a highly successful clone of serotype M1 group A Streptococcus involved multiple horizontal gene transfer events SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOXIC-SHOCK-SYNDROME; COMPLETE GENOME SEQUENCE; DIPHOSPHOPYRIDINE NUCLEOTIDASE; PYROGENIC EXOTOXIN; HEMOLYTIC STREPTOCOCCI; RHEUMATIC-FEVER; STREPTOLYSIN-O; PYOGENES; EXPRESSION; DISEASE AB To better understand the molecular events involved in the origin of new pathogenic bacteria, we studied the evolution of a highly virulent clone of serotype M1 group A Streptococcus (GAS). Genomic, DNA-DNA microarray, and single-nucleotide polymorphism analyses indicated that this clone evolved through a series of horizontal gene transfer events that involved (1) the acquisition of prophages encoding streptococcal pyrogenic exotoxin A and extracellular DNases and (2) the reciprocal recombination of a 36-kb chromosomal region encoding the extracellular toxins NAD(+)-glycohydrolase (NADase) and streptolysin O (SLO). These gene transfer events were associated with significantly increased production of SLO and NADase. Virtual identity in the 36-kb region present in contemporary serotype M1 and M12 isolates suggests that a serotype M12 strain served as the donor of this region. Multiple horizontal gene transfer events were a crucial factor in the evolutionary origin and emergence of a very abundant contemporary clone of serotype M1 GAS. C1 Baylor Coll Med, Ctr Human Bacterial Pathogenesis Res, Dept Pathol, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. Natl Publ Hlth Inst, Helsinki, Finland. RP Musser, JM (reprint author), Baylor Coll Med, Ctr Human Bacterial Pathogenesis Res, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM musser@bcm.tmc.edu FU PHS HHS [U01-060595] NR 50 TC 199 Z9 627 U1 1 U2 12 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 SEP 1 PY 2005 VL 192 IS 5 BP 771 EP 782 DI 10.1086/432514 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952QC UT WOS:000231019600008 PM 16088826 ER PT J AU Emerson, SU Arankalle, VA Purcell, RH AF Emerson, SU Arankalle, VA Purcell, RH TI Thermal stability of hepatitis E virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd European Workshop on Software Architecture CY JUN 13-14, 2005 CL Pisa, ITALY SP ArchWare European R&D Project ID WILD BOAR; SWINE; INFECTION; SEQUENCE; LIVER; DEER AB The thermal stability of virulent hepatitis E virus (HEV) and hepatitis A virus (HAV) was compared. Fecal suspensions of virus were heated to temperatures between 45 degrees C and 70 degrees C, and residual infectivity was determined in a cell culture system that was permissive for both viruses. Although HEV was less stable than was HAV, some HEV would most likely survive the internal temperatures of rare-cooked meat. C1 NIAID, LID, Mol Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Virol, Hepatitis Div, Pune, Maharashtra, India. RP Emerson, SU (reprint author), NIAID, LID, Mol Hepatitis Viruses Sect, NIH, Bldg 50,Room 6537,50 South Dr,MSC 8009, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov FU Intramural NIH HHS NR 12 TC 111 Z9 119 U1 0 U2 10 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 SEP 1 PY 2005 VL 192 IS 5 BP 930 EP 933 DI 10.1086/432488 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952QC UT WOS:000231019600026 PM 16088844 ER PT J AU Kapikian, AZ Simonsen, L Vesikari, T Hoshino, Y Morens, DM Chanock, RM La Montagne, JR Murphy, BR AF Kapikian, AZ Simonsen, L Vesikari, T Hoshino, Y Morens, DM Chanock, RM La Montagne, JR Murphy, BR TI A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed for use in developing countries and delivered in a schedule with the potential to eliminate the risk of intussusception SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID YOUNG-CHILDREN; INFANTS; INFECTION; EFFICACY; SAFETY; TRIAL; IMMUNOGENICITY; ASSOCIATION; CANDIDATES; PREVENTION AB There is an urgent need for a rotavirus vaccine, because up to 592,000 infants and young children < 5 years old die each year from rotavirus diarrhea, predominantly in the developing countries. We have developed a tetravalent human-bovine rotavirus (UK) reassortant vaccine with VP7 (G) specificity for serotypes 1, 2, 3, and 4, which has been shown to be safe, immunogenic, and effective in preventing severe rotavirus diarrhea. However, because of the emergence of VP7 (G) serotype 9 as an epidemiologically important serotype and the importance of VP7 (G) serotype 8 in focal areas, we are planning to add human-bovine (UK) reassortants with G8 and G9 specificity to the tetravalent vaccine, thereby formulating a "designed" hexavalent vaccine for universal use. In addition, we propose that the vaccine be administered orally in a 2-dose schedule, with the first dose given at 0-4 weeks of age and the second dose given at 4-8 weeks of age, when infants are relatively refractory to developing intussusception, thereby avoiding the age period when naturally occurring intussusception is most prevalent (i.e., ages 3-4 months through age 9 months). In this way, there may be the potential to eliminate or at least significantly decrease the risk of intussusception associated with rotavirus vaccination. C1 NIAID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. RP Kapikian, AZ (reprint author), NIAID, NIH, Dept Hlth & Human Serv, Bldg 50,Rm 6306,50 S Dr,MSC 8026, Bethesda, MD 20892 USA. EM akapikian@niaid.nih.gov NR 53 TC 37 Z9 39 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2005 VL 192 SU 1 BP S22 EP S29 DI 10.1086/431510 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 953WX UT WOS:000231113500004 PM 16088801 ER PT J AU Simonsen, L Viboud, C Elixhauser, A Taylor, RJ Kapikian, AZ AF Simonsen, L Viboud, C Elixhauser, A Taylor, RJ Kapikian, AZ TI More on RotaShield and intussusception: The role of age at the time of vaccination SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th International Rotavirus Symposium CY JUL 07-09, 2004 CL Mexico City, MEXICO ID NATIONAL IMMUNIZATION SURVEY; ORAL ROTAVIRUS VACCINE; YOUNG-CHILDREN; INFECTION; ASSOCIATION; INFANTS; PROGRAM AB Background. RotaShield, a vaccine intended to prevent severe rotavirus diarrhea, was withdrawn in July 1999, 9 months after it became available in the United States, because of a temporal association with intussusception events that occurred in vaccinated infants. We explore here the effect of age on the risk of intussusception. Methods. We reanalyzed a case-control database of the Centers for Disease Control and Prevention by use of a 21-day window, to define vaccine-associated events. We obtained data on vaccine use from the National Immunization Survey and estimated the age-stratified background incidence of intussusception by use of Healthcare Cost and Utilization Project data. We combined these data to estimate how absolute risk varies with age and to model the projected population-attributable risk associated with 3 different vaccination schedules. Results. We found that the incidence of intussusception associated with the first dose of vaccine increased with age. Infants >= 90 days old accounted for 80% of cases of intussusception associated with a first dose but had received only 38% of first doses. Modeling of the recommended schedule of vaccination at ages 2, 4, and 6 months projected 1 intussusception event/11,000-16,000 vaccine recipients; modeling of a 2-dose schedule beginning in the neonatal period projected 1 intussusception event/38,000-59,000 vaccine recipients. Conclusions. The practice of initiating immunization after age 90 days, which we call "catch-up" vaccination, contributed disproportionately to the occurrence of intussusception associated with the use of RotaShield. A fully implemented 2-dose vaccination schedule begun during the neonatal period would lead to, at most, a 7% increase in the incidence of intussusception above the annual background incidence. C1 NIAID, Off Global Affairs, NIH, Bethesda, MD 20892 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Agcy Hlth Care Res & Qual, Bethesda, MD 20892 USA. RP Simonsen, L (reprint author), NIAID, Off Global Affairs, NIH, 6610 Rockledge Dr,Rm 2033, Bethesda, MD 20892 USA. EM Lsimonsen@niaid.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 26 TC 92 Z9 100 U1 0 U2 2 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 SEP 1 PY 2005 VL 192 SU 1 BP S36 EP S43 DI 10.1086/431512 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 953WX UT WOS:000231113500006 PM 16088803 ER PT J AU He, YY Huang, JL Block, ML Hong, JS Chignell, CF AF He, YY Huang, JL Block, ML Hong, JS Chignell, CF TI Role of phagocyte oxidase in UVA-induced oxidative stress and apoptosis in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE apoptosis; gp91; keratinocytes; NADPH oxidase; reactive oxygen species; UVA ID HUMAN SKIN CELLS; SUPEROXIDE-GENERATING-SYSTEM; CULTURED HUMAN-FIBROBLASTS; REACTIVE OXYGEN; NADPH OXIDASE; EPIDERMAL-KERATINOCYTES; PHOTOOXIDATIVE STRESS; LIPID-PEROXIDATION; ACTIVATION; GP91PHOX AB Chronic exposure to ultraviolet radiation including ultraviolet A (315-400 nm) (UVA) may cause photocarcinogenesis and photoaging. The UVA-induced production of reactive oxygen species (ROS) and the resultant oxidative stress exposure play an important role in these biological processes. Here we have investigated the role of phagocyte oxidase (PHOX, gp91phox) in the production of ROS, redox status change, and apoptosis after UVA exposure by using gp91phox-deficient (gp91(phox-/-)) primary keratinocytes. UVA radiation resulted in increased ROS production and oxidation of reduced glutathione (GSH) to its oxidized form (GSSG). The presence of diphenylene iodonium (DPI) inhibited ROS production by UVA. In comparison with wild-type cells, gp91(phox-/-) cells produced slightly less ROS and GSH oxidation. UVA radiation induced apoptosis in wild-type keratinocytes as detected by phosphatidylserine (PS) translocation, caspase activation, and DNA fragmentation. As compared with wild-type cells, UVA induced less PS translocation in gp91phox-deficient cells. No difference, however, was observed in caspase activation and DNA fragmentation after UVA exposure in wild-type and gp91(phox-/-) cells. These findings suggest that gp91phox plays a limited role in the UVA-induced ROS production, oxidative stress, and therefore the PS translocation, but has no effect on UVA-induced caspase activation and DNA fragmentation during apoptosis. C1 Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP He, YY (reprint author), Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. EM he3@niehs.nih.gov NR 40 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 BP 560 EP 566 DI 10.1111/j.0022-202X.2005.23851.x PG 7 WC Dermatology SC Dermatology GA 963RR UT WOS:000231824100022 PM 16117799 ER PT J AU Takeuchi, S Takeuchi, F Masutaka, F Katz, SI AF Takeuchi, S Takeuchi, F Masutaka, F Katz, SI TI Collared mice: A model to assess the effects of scratching SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 4th Georg Rajka International Symposium on Atopic Dermatitis CY SEP 15-17, 2005 CL Arcachon, FRANCE C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Kyushu Univ, Fac Med, Dept Dermatol, Fukuoka 812, Japan. EM takeuchs@dermatol.med.kyushu-u.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 BP 603 EP 603 PG 1 WC Dermatology SC Dermatology GA 963RR UT WOS:000231824100082 ER PT J AU Buchau, AS Lewrenz, V Wolf, R Ruzicka, T Walz, M AF Buchau, AS Lewrenz, V Wolf, R Ruzicka, T Walz, M TI The psoriasis-associated S100A15 is regulated by cytokines, UVB radiation, and bacterial microbes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Univ Dusseldorf, D-4000 Dusseldorf, Germany. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 405 BP A69 EP A69 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600400 ER PT J AU Kim, AL Tang, X Russo, J Kopelovich, L Athar, M Bickers, DR AF Kim, AL Tang, X Russo, J Kopelovich, L Athar, M Bickers, DR TI A novel mouse model for spontaneous and ultraviolet B (UVB)-induced basal cell carcinomas (BCCs): Ptch1 heterozygosity bred into a tumor-susceptible SKH-1 hairless genetic background SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Columbia Univ, Med Ctr, New York, NY 10027 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 357 BP A61 EP A61 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600353 ER PT J AU Moelle, K Butsch, F Tada, Y Lopez, S Shibagaki, N Knop, J Udey, MC Von Stebut, E AF Moelle, K Butsch, F Tada, Y Lopez, S Shibagaki, N Knop, J Udey, MC Von Stebut, E TI Vaccination with TAT-LACK fusion proteins protects mice against progressive infection with Leishmania major SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 478 BP A81 EP A81 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600474 ER PT J AU Tang, X Kim, AL Zhu, Y Kopelovich, L Bickers, DR Athar, M AF Tang, X Kim, AL Zhu, Y Kopelovich, L Bickers, DR Athar, M TI CP-31398 a mutant p53-rescuing chemical agent, suppresses ultraviolet B (UVB)-induced skin photocarcinogenesis in SKH-1 hairless mice (SKH) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Columbia Univ, Dept Dermatol, New York, NY 10027 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 343 BP A59 EP A59 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600340 ER PT J AU Weber, HO Ludwig, RL Morrison, D Kotlyarov, A Gaestel, M Vousden, KH AF Weber, HO Ludwig, RL Morrison, D Kotlyarov, A Gaestel, M Vousden, KH TI Regulation of HDM2 activity by MK2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 22-24, 2005 CL Tubingen, GERMANY SP European Soc Dermatol Res, Centocor Schering Plough, Galderma, Novartis, Chanel, Hermal Germany, Nat Publ Grp, Fujisawa, Intendis, Serono C1 Univ Tubingen, D-72074 Tubingen, Germany. Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. NCI, Bethesda, MD 20892 USA. Hannover Med Sch, D-3000 Hannover, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2005 VL 125 IS 3 SU S MA 031 BP A6 EP A6 PG 1 WC Dermatology SC Dermatology GA 964EW UT WOS:000231862600032 ER PT J AU Wagner, S Law, MP Riemann, B Pike, VW Breyholz, HJ Holtke, C Faust, A Schober, O Schafers, M Kopka, K AF Wagner, S Law, MP Riemann, B Pike, VW Breyholz, HJ Holtke, C Faust, A Schober, O Schafers, M Kopka, K TI Synthesis of (R)- and (S)-[O-methyl-C-11]N-[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethy l]-N '-(4-methoxy-phenyl)-urea as candidate high affinity beta(1)-adrenoceptor PET radioligands SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE 3-aryloxy-2-propanolamine; ICI 89,406; beta(1)-adrenoceptor selective ligand; PET radioligand ID SELECTIVE BETA-1-ADRENOCEPTOR LIGAND; BETA-ADRENOCEPTOR; HEART-FAILURE; ICI-89,406; CARDIOMYOPATHY; ANTAGONIST; CGP-12177; SUBTYPES; DISEASE; BINDING AB Molecular imaging and quantification of myocardial beta(1)-adrenoceptor (AR) rather than total beta-AR density is of great clinical interest since cardiac biopsy studies suggest that myocardial beta(1)-AR density is reduced in patients with chronic heart failure whereas cardiac beta(2)-AR density may vary. Positron emission tomography (PET), with appropriate radioligands, offers the possibility to assess beta-AR density non-invasively in humans. However, no PET radioligand for the selective imaging of cardiac beta(1)-ARs is clinically available. Here some derivatives of the well characterized beta(1)-AR selective antagonist, ICI 89,406, namely the enantiomers of N-[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N'-(4-hydroxy-phenyl)-urea (5a and 5b) were synthesized and evaluated in vitro. The (R)-isomer 5a was more beta(1)-selective but has lower affinity than its (S)-enantiomer 5b (beta(1)-AR selectivity: 6100 vs 1240; beta(1)-affinity: K-1 = 0.288 nM vs K-1 = 0.067 nM). Etherification of the analogous desmethyl precursors, 5e and 5f, respectively, with [C-11]iodomethane gave C-11-labelled versions of 5a and 5b, namely 5g and 5h, in 44 +/- 5% radiochemical yield (decay-corrected) and 97.4 +/- 1.3 % radiochemical purity with specific radioactivities of 26.4 +/- 9.4 GBq/mu mol within 41.2 +/- 3.4 min from the end of bombardment (n = 14). 5g and 5h are now being evaluated as candidate radioligands for myocardial beta(1)-ARs. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Hosp Munster, Dept Nucl Med, D-48149 Munster, Germany. NIH, Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Wagner, S (reprint author), Univ Hosp Munster, Dept Nucl Med, Albert Schweitzet Str 33, D-48149 Munster, Germany. EM stwagner@uni-muenster.de RI Schober, Otmar/A-8670-2008 NR 33 TC 7 Z9 7 U1 0 U2 0 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 SEP PY 2005 VL 48 IS 10 BP 721 EP 733 DI 10.1002/jlcr.965 PG 13 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 972JF UT WOS:000232449400002 ER PT J AU Musachio, JL Shah, J Pike, VW AF Musachio, JL Shah, J Pike, VW TI Radiosyntheses and reactivities of novel [F-18]2-fluoroethyl arylsulfonates SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE fluorine-18; sulfonate ester; labeling agent ID NCA; RADIOLIGAND; TOSYLATE; BRAIN AB [F-18]2-Fluoroethyl tosylate ([F-18]FEOX, X = Ts) is widely used for labeling radio-tracers for positron emission tomography (PET). Little work has been reported on syntheses of other [F-18]2-fluoroethyl arylsulfonates ([F-18]FEOX) that bear a less electron-rich aryl group, even though these might offer enhanced reactivities. Thus, a series of novel [F-18]FEOX (X = benzenesulfonyl, brosyl, nosyl, 3,4-dibromobenzene-sulfonyl) were synthesized and reactivities compared to [F-18]FEOTs. Precursors for radiolabeling (bis-ethylene glycol arylsulfonates) and reference FEOX were synthesized (alcohol + arylsulfonyl chloride + KOSiMe3 in THF). Regardless of substitution pattern, [F-18]FEOX (110 degrees C, 5 min, acetonitrile) were obtained in similar decay-corrected isolated radiochemical yields (RCY; 47-53%). All [F-18]FEOX gave excellent RCYs (64-87%) of the dopamine uptake radioligand, [F-18]FECNT (130 degrees C, 10 min, acetonitrile). The 3,4-dibromobenzensulfonate gave the highest RCY of [F-18]FECNT (87%) and this HPLC-purified labeling agent was used directly for efficient [F-18]FECNT production. When the secondary aniline of an amyloid probe (HMIMPY) or p-nitrophenol was reacted with [F-18]FEOX, RCYs were appreciably higher for brosylate and nosylate than for tosylate, while 3,4-dibromobenzenesulfonate again gave the highest RCY. Owing to the high reactivity of the new [F-18]FEOX and their ease of syntheses via stable precursors, such agents (particularly 3,4-dibromobenzenesulfonate) should be considered as alternatives to [F-18]FEOTs. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Natl Inst Mental Hlth, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Musachio, JL (reprint author), Natl Inst Mental Hlth, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM john.musachio@nih.gov NR 13 TC 16 Z9 16 U1 0 U2 4 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 SEP PY 2005 VL 48 IS 10 BP 735 EP 747 DI 10.1002/jlcr.991 PG 13 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 972JF UT WOS:000232449400003 ER PT J AU Aue, G Carroll, N Kressel, BR Hardi, R Horne, MK AF Aue, G Carroll, N Kressel, BR Hardi, R Horne, MK TI Disseminated intravascular coagulation in an ambulatory young woman SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; VENOUS THROMBOSIS; TISSUE FACTOR; ENDOTOXEMIA; FIBRINOLYSIS; TOLERANCE; PLASMA AB We are reporting the case of an ambulatory young woman with a 10-year history of recurrent venous thrombosis who presented to us with diffuse intravascular coagulation (DIC). After excluding the recognized causes of DIC, we examined the possibility that her clinically quiescent ulcerative colitis might be the underlying stimulus. We documented sepsis-range endotoxemia in this patient at a time when she was afebrile and had a normal C-reactive protein level. In vitro her serum upregulated tissue factor in cultured endothelial cells. We postulate that she had become tolerant to the systemic effects of endotoxin leaking from her inflamed colon but that the endotoxin stimulated her endothelium and/or monocytes to produce tissue factor that made her intensely hypercoagulable. Her prothrombotic state may have been compounded by the fact that she was heterozygous for prothrombin G20210A and that her plasma clotting time demonstrated resistance to activated protein C. C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Metropolitan Gastroenterol Grp, Washington, DC USA. Washington Oncol Hematol Ctr, Washington, DC USA. RP Horne, MK (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Room 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov NR 30 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD SEP PY 2005 VL 146 IS 3 BP 192 EP 196 DI 10.1016/j.lab.2005.05.006 PG 5 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 963EC UT WOS:000231785200007 PM 16131459 ER PT J AU Litton, P Miller, FG AF Litton, P Miller, FG TI A normative justification for distinguishing the ethics of clinical research from the ethics of medical care SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID PLACEBO-CONTROLLED TRIALS AB The central question in current debates about the moral appropriateness of randomized placebo-control trials and the principle of clinical equipoise for research is whether physician-researchers owe primary loyalty to their patient-subjects, as physicians owe their patients under medical care. We argue that they do not. First, because of the importance of medical research and the scientifically rigorous means needed to produce valid medical knowledge, there is prima facie reason to exclude the duty of therapeutic beneficence from the duties on researchers. Second, that prima facie reason is not trumped by the reasonable expectations of patient-subjects. C1 NIH, Unit Clin Res, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 25 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, SUITE 1634, BOSTON, MA 02215 USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2005 VL 33 IS 3 BP 566 EP + DI 10.1111/j.1748-720X.2005.tb00519.x PG 10 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 965OW UT WOS:000231961000013 PM 16240736 ER PT J AU Lin, YH Salem, N AF Lin, YH Salem, N TI In vivo conversion of 18-and 20-C essential fatty acids in rats using the multiple simultaneous stable isotope method SO JOURNAL OF LIPID RESEARCH LA English DT Article DE stable isotope tracer; alpha-linolenic acid; eicosapentaenoic acid; docosahexaenoic acid; linoleic acid; dihomo-gamma-linolenic acid; arachidonic acid; gas chromatography-mass spectrometry; multiple simultaneous stable isotopes ID ALPHA-LINOLENIC ACID; DIETARY ARACHIDONIC-ACID; DOCOSAHEXAENOIC ACID; LIVER-MICROSOMES; EICOSAPENTAENOIC ACID; DELTA-5 DESATURASE; METABOLISM; BRAIN; LIPIDS; BIOSYNTHESIS AB An important question for mammalian nutrition is the relative efficiency of C18 versus C20 essential fatty acids (EFAs) for supporting the tissue composition of n-3 and n-6 pathway end products. One specific question is whether C22 EFAs are made available to tissues more effectively by dietary alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) or by dietary eicosapentaenoic acid (20:5n-3) and dihomo-gamma-linolenic acid (20:3n-6). To address this question in a direct manner, four stable isotope compounds were given simultaneously in a novel paradigm. A single oral dose of a mixture of H-2(5)-18:3n-3, U-13-20:5n-3, C-13-U-18:2n-6, and (2)H5-20:3n-6 was administered to rats given a defined diet. There was a preferential in vivo conversion of arachidonic acid (20:4n-6) to docosatetraenoic acid (22:4n-6) and of 22:4n-6 to n-6 docosapentaenoic acid (22:5n-6) when the substrates originated from the C18 precursors. However, when the end products docosahexaenoic acid (22:6n-3) or 22:5n-6 were expressed as the total amount in the plasma compartment divided by the dosage, this parameter was 11-fold greater for 20:5n-3 than for 18:3n-3 and 14-fold greater for 20:3n-6 than for 18:2n-6. Thus, on a per dosage basis, the total amounts of n-3 and n-6 end products accreted in plasma were considerably greater for C20 EFA precursors relative to C18. C1 NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Salem, N (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov FU Intramural NIH HHS NR 62 TC 13 Z9 13 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2005 VL 46 IS 9 BP 1962 EP 1973 DI 10.1194/jlr.M500127-JLR200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 955RG UT WOS:000231244200018 PM 15930514 ER PT J AU Lin, YH Pawlosky, RJ Salem, N AF Lin, YH Pawlosky, RJ Salem, N TI Simultaneous quantitative determination of deuterium- and carbon-13-labeled essential fatty acids in rat plasma SO JOURNAL OF LIPID RESEARCH LA English DT Article DE deuterated linolenate; deuterated linoleate; carbon-13-labeled linolenate; carbon-13-labeled linoleate; standard curves; concentration effect curves; gas chromatography-mass spectrometry negative chemical ionization analysis ID CHROMATOGRAPHY MASS-SPECTROMETRY; STABLE ISOTOPES; LINOLENIC ACIDS; IN-VIVO; METABOLISM; DESATURATION; PRECISION AB This study reports methods for the quantitative determination of stable isotope-labeled essential fatty acids ( EFAs) as well as an experiment in which deuterium-labeled linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) were compared with those labeled with carbon-13 in rat plasma in vivo. Standard curves were constructed to compensate for concentration and plasma matrix effects. It was observed that endogenous pools of fatty acids had a greater suppressing effect on the measurements of C-13-U-labeled EFAs relative to those labeled with H-2(5). Using these methods, the in vivo metabolism of orally administered deuterated-linolenate, C-13-U-labeled linolenate, deuterated-linoleate, and C-13-U-labeled linoleate was compared in adult rats (n = 11). There were no significant differences in the concentrations of the H-2 versus C-13 isotopomers of 18:2n-6, 18:3n-3, arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3) in rat plasma samples at 24 h after dosing. Thus, there appears to be little isotope effect for H-2(5) - versus C-13-U-labeled EFAs when the data are calculated using the conventional standard curves and corrected for endogenous fatty acid pool size and matrix effects. C1 NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Salem, N (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov FU Intramural NIH HHS NR 29 TC 14 Z9 15 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2005 VL 46 IS 9 BP 1974 EP 1982 DI 10.1194/jlr.M500128-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 955RG UT WOS:000231244200019 PM 15930513 ER PT J AU Hoffman, RE Becker, ED AF Hoffman, RE Becker, ED TI Temperature dependence of the H-1 chemical shift of tetramethylsilane in chloroform, methanol, and dimethylsulfoxide SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE TMS chemical shift; He-3 resonance; temperature measurement; magnetic susceptibility; shape factor ID MAGNETIC-RESONANCE; SAMPLE ROTATION; NOBLE-GASES; NMR; SUSCEPTIBILITY; RECOMMENDATIONS; THERMOMETER; CALIBRATION; CONVECTION; SOLVENTS AB The chemical shift of tetramethylsilane (TMS) is usually taken to be zero. However, it does vary slightly with temperature, having obvious implications for studies of temperature effects on chemical shifts. In this work, we measure the variation in the chemical shift of TMS with temperature in three solvents, CDCl3, CD3OD, and DMSO-d(6), relative to the resonant frequency of He-3 gas, which can be reasonably assumed to be temperature independent. In all three solvents, the average temperature coefficient over a wide temperature range is about -6 x 10(-4) ppm/degrees C, a factor of five smaller than that previously reported in the literature. Data are included for 3 He resonance frequencies over a temperature range of -110 to +180 degrees C, along with new measurements of volume magnetic susceptibilities of the three solvents and estimates of their temperature dependence. A novel method is used to provide temperature measurement via 2 H resonances of methanol and ethylene glycol samples, which can concurrently be used for field/frequency locking. Published by Elsevier Inc. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Inst Chem, Dept Organ Chem, IL-91904 Jerusalem, Israel. RP Becker, ED (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. EM tbecker@nih.gov NR 24 TC 19 Z9 20 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 2005 VL 176 IS 1 BP 87 EP 98 DI 10.1016/j.jmr.2005.05.015 PG 12 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 959WD UT WOS:000231549100011 PM 15996496 ER PT J AU Aletras, AH Ingkanisorn, WP Mancini, C Arai, AE AF Aletras, AH Ingkanisorn, WP Mancini, C Arai, AE TI DENSE with SENSE SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE myocardial; contraction; cardiac; function; SPAMM; DENSE; HARP; tagging; heart; MRI; strain ID STIMULATED ECHOES; SPATIAL MODULATION; HUMAN HEART; MRI; ACQUISITION; MAGNETIZATION; TRACKING; MOTION AB Displacement encoding with stimulated echoes (DENSE) with a low encoding strength phase-cycled meta-DENSE readout and a two fold SENSE acceleration (R = 2) is described. This combination reduces total breath-hold times for increased patient comfort during cardiac regional myocardial contractility studies. Images from phantoms, normal volunteers, and a patient are provided to demonstrate the SENSE-DENSE combination of methods. The overall breath-hold time is halved while preserving strain map quality. Published by Elsevier Inc. C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Suburban Hosp Healthcare Syst, Bethesda, MD USA. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM AletrasA@nhlbi.nih.gov OI Aletras, Anthony/0000-0002-3786-3817 NR 22 TC 20 Z9 20 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 2005 VL 176 IS 1 BP 99 EP 106 DI 10.1016/j.jmr.2005.05.010 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 959WD UT WOS:000231549100012 PM 15946874 ER PT J AU Davey, F Hill, M Falk, J Sans, N Gunn-Moore, FJ AF Davey, F Hill, M Falk, J Sans, N Gunn-Moore, FJ TI Synapse associated protein 102 is a novel binding partner to the cytoplasmic terminus of neurone-glial related cell adhesion molecule SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebellar granule cells; neurone glial-related cell adhesion molecule; post synaptic density-95/discs-large/ZO-1 domains; synapse associated protein 102 ID D-ASPARTATE RECEPTOR; TANDEM AFFINITY PURIFICATION; DOMAIN-CONTAINING PROTEINS; ANKYRIN-BINDING; PDZ DOMAINS; NR-CAM; IMMUNOGLOBULIN SUPERFAMILY; L1 FAMILY; RGS-GAIP; IN-VIVO AB Neurone glial-related cell adhesion molecule (NrCAM) is a member of the L1 family of transmembrane cell adhesion receptors which are involved in the development and function of the mammalian nervous system. How these receptors interact with intracellular signalling pathways is not understood. To date the only identified binding partner to the cytoplasmic terminus of NrCAM is ankyrin G. We screened a developing rat brain cDNA yeast two-hybrid library with the cytoplasmic domain of NrCAM to identify further intracellular binding partners. We identified synapse associated protein 102 (SAP102) as a new binding partner for NrCAM. The interaction was confirmed biochemically using glutathione S-transferase (GST)-pull-down and tandem affinity purification, and also immunocytochemically as NrCAM and SAP102 co-localized in COS-7 and cerebellar granule cells. Binding was specific to NrCAM as neither neurofascin nor L1 bound SAP102, and this interaction was reliant on the last three amino acids of NrCAM. Additionally, NrCAM constructs whose last three amino acids had been deleted appeared to have a dominant negative effect on neurite extension of cerebellar granule cells. This is the first interaction reported for NrCAM, and its association with SAP102 suggests that it is part of a larger complex which can interact with many different signalling pathways. C1 Univ St Andrews, Sch Biol, St Andrews KY16 9TS, Fife, Scotland. Inst Jean Roche, CNRS UMR NICN 6184, Marseille, France. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD USA. RP Gunn-Moore, FJ (reprint author), Univ St Andrews, Sch Biol, Bute Med Bldg, St Andrews KY16 9TS, Fife, Scotland. EM fjg1@st-and.ac.uk NR 55 TC 22 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2005 VL 94 IS 5 BP 1243 EP 1253 DI 10.1111/j.1471-4159.2005.03271.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 954HY UT WOS:000231147000008 PM 15992371 ER PT J AU Gryder, DS Castaneda, DC Rogawski, MA AF Gryder, DS Castaneda, DC Rogawski, MA TI Evidence for low GluR2 AMPA receptor subunit expression at synapses in the rat basolateral amygdala SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AMPA receptor; basolateral amygdala; electron microscopy; GluR2 subunit; hippocampus; patch clamp recording ID CALCIUM-PERMEABLE AMPA; MEDIATED SYNAPTIC CURRENTS; MESSENGER-RNAS; GLUTAMATE RECEPTORS; HIPPOCAMPAL-NEURONS; CA2+ PERMEABILITY; DOWN-REGULATION; RELATIVE ABUNDANCE; AMPA-GLUR2 SUBUNIT; LATERAL AMYGDALA AB Fast excitatory synaptic responses in basolateral amygdala (BLA) neurons are mainly mediated by ionotropic glutamate receptors of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype. AMPA receptors containing an edited GluR2 subunit are calcium impermeable, whereas those that lack this subunit are calcium permeable and also inwardly rectifying. Here, we sought to determine the extent to which synapses in the rat BLA have AMPA receptors with GluR2 subunits. We assessed GluR2 protein expression in the BLA by immunocytochemistry with a GluR2 subunit-specific antiserum at the light and electron microscopic level; for comparison, a parallel examination was carried out in the hippocampus. We also recorded from amygdala brain slices to examine the voltage-dependent properties of AMPA receptor- mediated evoked synaptic currents in BLA principal neurons. At the light microscopic level, GluR2 immunoreactivity was localized to the perikarya and proximal dendrites of BLA neurons; dense labeling was also present over the pyramidal cell layer of hippocampal subfields CA1 and CA3. In electron micrographs from the BLA, most of the synapses were asymmetrical with pronounced postsynaptic densities (PSD). They contained clear, spherical vesicles apposed to the PSD and were predominantly onto spines (86%), indicating that they are mainly with BLA principal neurons. Only 11% of morphological synapses in the BLA were onto postsynaptic elements that showed GluR2 immunoreactivity, in contrast to hippocampal subfields CA1 and CA3 in which 76% and 71% of postsynaptic elements were labeled (p < 0.001). Synaptic staining in the BLA and hippocampus, when it occurred, was exclusively postsynaptic, and particularly heavy over the PSD. In whole-cell voltage clamp recordings, 72% of BLA principal neurons exhibited AMPA receptor-mediated synaptic currents evoked by external capsule stimulation that were inwardly rectifying. Although BLA principal neurons express perikaryal and proximal dendritic GluR2 immunoreactivity, few synapses onto these neurons express GluR2, and a preponderance of principal neurons have inwardly rectifying AMPA-mediated synaptic currents, suggesting that targeting of GluR2 to synapses is restricted. Many BLA synaptic AMPA receptors are likely to be calcium permeable and could play roles in synaptic plasticity, epileptogenesis and excitoxicity. C1 NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 1C-1002,35 Convent Dr,MSC 3702, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NINDS NIH HHS [Z01 NS002732-19] NR 76 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2005 VL 94 IS 6 BP 1728 EP 1738 DI 10.1111/j.1471-4159.2005.03334.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 959HS UT WOS:000231509400023 PM 16045445 ER PT J AU Temple, JL Wray, S AF Temple, JL Wray, S TI Developmental changes in GABA(A) receptor subunit composition within the gonadotrophin-releasing hormone-1 neuronal system SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE LHRH; migration; olfactory axons; nasal explant; mouse ID TEMPORAL-LOBE EPILEPSY; EXPLANT CULTURES; GNRH NEURONS; LHRH NEURONS; IN-VITRO; EXPRESSION; MODULATION; ACTIVATION; SECRETION; MECHANISM AB It is becoming increasingly evident that GABA plays an important role in the regulation of gonadotrophin-releasing hormone (GnRH)-1 neurones via the GABA(A) receptor. The aim of the present study was to characterise expression of the GABA(A) receptor within the GnRH-1 system across development. The expression pattern of five GABA(A)alpha subunits and one GABA(A)beta subunit was first examined within individual GnRH-1 neurones by the polymerase chain reaction. A significant increase in the expression of GABA(A)alpha(2) and a significant decrease in the expression of GABA(A)alpha(6) over time were found. Of the other subunits examined, two (alpha(1) and alpha(3)) showed no differences in expression and two (alpha(4) and beta(3)) showed variable low incidence of expression. Given the reciprocal relationship of alpha(2) and alpha(6) expression, we hypothesised that there is a developmental switch in the expression of these subunits in GnRH-1 neurones. To investigate this hypothesis, single- and double-label immunocytochemistry for GABA(A)alpha(2) and alpha(6) and GnRH-1 was performed in tissue from ages E12.5 to adulthood, as well as in nasal explants. We show that GABA(A)alpha(2) and alpha(6) are present in the GnRH-1 neuronal system both in vivo and in vitro and that the levels of expression are altered as a function of age. C1 Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, Bethesda, MD USA. RP Wray, S (reprint author), 36 Convent Dr,MSC 4156,Bldg 36,Room 5A10, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov NR 27 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD SEP PY 2005 VL 17 IS 9 BP 591 EP 599 DI 10.1111/j.1365-2826.2005.01348.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 954HX UT WOS:000231146800008 PM 16101898 ER PT J AU Hooper, LC Chin, MS Detrick, B Hooks, JJ AF Hooper, LC Chin, MS Detrick, B Hooks, JJ TI Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-alpha, soluble TNFR2 and altered TNF-alpha signaling SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE viral; cytokine receptors; cytokines; inflammation ID TUMOR-NECROSIS-FACTOR; C VIRUS-INFECTION; FACTOR RECEPTORS; NITRIC-OXIDE; RHEUMATOID-ARTHRITIS; T-CELLS; IN-VIVO; KAPPA-B; DISEASE; DIFFERENTIATION AB Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-alpha plays a role in immune-mediated processes we evaluated the levels of TNF-alpha/TNF-alpha receptors and the downstream signaling molecule nitric oxide (NO) during disease in both retinal degeneration susceptible BALB/c and degeneration resistant CD-1 mice. Following coronavirus injection, TNF-alpha mRNA was detected at higher levels within the retinas, and concentrations of TNF-alpha (p <0.005) and sTNFR1 (p <0.0005) proteins were increased within the sera of BALB/c but not CD-1 mice. While concentrations of sTNFR2 proteins were elevated in both BALB/c (p < 0.00005) and CD-1 (p < 0.005) mice compared to controls, concentrations were higher in BALB/c mice (p <0.0005). Gene expression of iNOS while initially high in BALB/c mice decreased during the acute phase of infection, while it increased in CD-1 mice. These trends are attributable to differences in monocyte TNFR2 release (p<0.0005) between the strains since sTNFR2 decreased (p < 0.01) levels of NO production. These studies demonstrate that retinal degeneration following viral infection is associated with increased release of TNF-alpha/TNF receptors combined with a down-regulation of NO. Furthermore they suggest that these molecules are involved in alterations in immune response leading to autoimmune reactivity. Published by Elsevier B.V. C1 NEI, Immunol Lab, Immunol & Virol Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, Immunol Lab, Immunol & Virol Sect, NIH, NIH Bldg 10,Rm 6N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM hooksj@nei.nih.gov NR 37 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2005 VL 166 IS 1-2 BP 65 EP 74 DI 10.1016/j.jneuroim.2005.05.018 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 958ZQ UT WOS:000231487100008 PM 16039725 ER PT J AU Harris-Love, M Cohen, LG AF Harris-Love, M Cohen, LG TI High level bilateral talks. Focus on "Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition" SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Editorial Material ID HUMAN MOTOR CORTEX; CORTICAL INHIBITION; MULTIPLE-SCLEROSIS; SCHIZOPHRENIA C1 NINDS, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, 10 Ctr Dr,MSC 1428,Bldg 10,Rm 5N226, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov RI Harris-Love, Michelle/J-1388-2014 OI Harris-Love, Michelle/0000-0001-5571-3858 NR 20 TC 0 Z9 0 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2005 VL 94 IS 3 BP 1164 EP 1165 DI 10.1152/jn.00450.2005 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 955WX UT WOS:000231259400002 ER PT J AU Watanabe, K Hikosaka, O AF Watanabe, K Hikosaka, O TI Immediate changes in anticipatory activity of caudate neurons associated with reversal of position-reward contingency SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPPLEMENTARY EYE FIELD; CONDITIONAL OCULOMOTOR ASSOCIATIONS; PRIMATE PREFRONTAL NEURONS; LINKING BASAL GANGLIA; FUNCTIONAL-PROPERTIES; ORBITOFRONTAL CORTEX; CORTICOSTRIATAL PROJECTIONS; SUPERIOR COLLICULUS; DOPAMINE NEURONS; MACAQUE MONKEY AB The primate caudate nucleus plays a crucial role in transforming cognitive/motivational information into eye movement signals. A subset of caudate projection neurons fire before a visual target's onset. This anticipatory activity is sensitive to position-reward contingencies and correlates with saccade latency, which is shorter toward a rewarded position. We recorded single-unit activity of caudate projection neurons to examine the dynamics of change in anticipatory activity immediately after switches of the position-reward contingency. Two monkeys performed a visually guided saccade task where only one position was associated with reward. The position-reward mapping remained constant within a block, but was reversed frequently between blocks without any indication to the monkey. Therefore the switch could be detected only by unexpected reward delivery or unexpected lack of reward. After the switch, both saccade latency and anticipatory activity showed reliable changes already in the second trial, whether or not the first trial was rewarded. However, anticipatory activity in the second trial was generally higher if the first trial was rewarded, and the measured saccade latencies could be better explained by the difference in anticipatory activity between the two caudate nuclei. We suggest that anticipatory activity of caudate neurons reflects the reversal set of reward-position contingency. C1 Natl Inst Adv Ind Sci & Technol, Inst Human Sci & Biomed Engn, AIST Tsukuba Cent 6, Tsukuba, Ibaraki 3058566, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Watanabe, K (reprint author), Natl Inst Adv Ind Sci & Technol, Inst Human Sci & Biomed Engn, AIST Tsukuba Cent 6, 1-1-1 Higashi, Tsukuba, Ibaraki 3058566, Japan. EM katsumi.watanabe@aist.go.jp NR 70 TC 36 Z9 36 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 SEP PY 2005 VL 94 IS 3 BP 1879 EP 1887 DI 10.1152/jn.00012.2005 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 955WX UT WOS:000231259400024 PM 15872072 ER PT J AU Lipsky, RH Sparling, MB Ryan, LM Xu, K Salazar, AM Goldman, D Warden, DL AF Lipsky, RH Sparling, MB Ryan, LM Xu, K Salazar, AM Goldman, D Warden, DL TI Association of COMT Val1.58Met genotype with executive functioning following traumatic brain injury SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; PREFRONTAL FUNCTION; PHARMACOGENETICS; POLYMORPHISM; CORTEX; SCHIZOPHRENIA; PERFORMANCE; DISORDERS; GENE AB Catechol-O-methyltransferase (COMT) is thought to functionally modulate dopamine neurons, thus likely influencing frontal-executive functioning. High enzyme activity (COMT Val) and low enzyme activity (COMT Met) are functional polymorphisms resulting from a G to A transition in exon 4 (codon 158) of the human COMT gene. Decreased cortical dopamine should result in poorer executive functioning. Therefore, the authors hypothesized that individuals with traumatic brain injury (TBI) and the low enzyme activity polymorphism would perform better on tests Of executive functioning than individuals with the high enzyme activity polymorphism. One hundred thirteen individuals referred to the Defense and Veterans Brain Injury Center underwent a comprehensive TBI evaluation and were genotyped for the COMT polymorphism. Comparison of mean differences among the COMT genotype groups for several measures of aspects of executive functioning was conducted using analysis of variance (ANOVA) with adjustment for multiple comparisons. Homozygotes for the higher activity allele made more perseverative responses on the Wisconsin Card Sorting Test, while homozygotes for the lower activity allele had the least number of perseverative responses. While it cannot be determined whether TBI influenced the association of COMT Val158Met to executive functioning, these data extend the known relationship of genotype to executive performance seen in healthy comparison subjects and individuals with schizophrenia to individuals with TBI. C1 Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Dept Neurol, Washington, DC 20012 USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Dept Neurosurg, Washington, DC 20012 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Warden, DL (reprint author), Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Dept Neurol, POB 59181, Washington, DC 20012 USA. EM deborah.warden@na.amedd.army.mil RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 28 TC 47 Z9 50 U1 2 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2005 VL 17 IS 4 BP 465 EP 471 DI 10.1176/appi.neuropsych.17.4.465 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 993PH UT WOS:000233966900004 PM 16387984 ER PT J AU Laurent, C Levinson, DF Schwartz, SA Harrington, PB Markey, SP Caprioli, RM Levitt, P AF Laurent, C Levinson, DF Schwartz, SA Harrington, PB Markey, SP Caprioli, RM Levitt, P TI Direct profiling of the cerebellum by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: A methodological study in postnatal and adult mouse SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE cerebellum; MALDI; mass spectrometry; proteomics ID PROTEOMIC PATTERNS; PROSTATE-CANCER; OVARIAN-CANCER; SERUM; CLASSIFICATION; IONIZATION; EXPRESSION; DESORPTION; DIAGNOSIS AB Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI MS) can detect substantial changes in expression of proteins in tissues, such as cancer cells. A more challenging problem is detecting the smaller changes expected in normal development or complex diseases. Here we address methodological issues regarding the acquisition and analysis of MALDI MS data from tissue sections, in a study of mouse cerebellum at different stages of development. Sections of the cerebellar cortex were analyzed at the peak of granule neuron production [postnatal day (P) 7], during synapse formation (P14), and in adults. Data were acquired (VoyagerDE (TM) STR Biospectrometry Workstation; seven acquisitions of 50 shots per section, 3.5-50 kDa), preprocessed (Data Explorer 4.3), and averaged. Among 846 peaks detected, in at least 50% of at least one group, 122 showed significant group differences (Kruskal-Wallis ANOVA) after Bonferroni correction. Factor analyses revealed two age-related factors, possibly reflecting gradients of expression during development. Predictive analysis of microarrays generated a model from half of the sample that correctly predicted developmental groups for the second half. Intraclass correlation coefficients, measuring within-mouse consistency of peak heights from three tissue sections, were acceptable at lower m/z and for larger peaks at higher m/z. Low mass was the best predictor of significant group differences. The analysis demonstrates that MALDI MS of normal tissue sections at different ages can detect consistent, significant group differences. Further work is needed to increase the sensitivity of the methods and to apply them reliably to brain regions and to subproteomes with relevance to diverse brain functions and diseases. (c) 2005 Wiley-Liss, Inc. C1 Vanderbilt Univ, Sch Med, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. Ohio Univ, Ctr Intelligent Chem Instrumentat, Athens, OH USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Levitt, P (reprint author), Box 40,Peabody,230 Appleton Pl, Nashville, TN 37203 USA. EM pat.levitt@vanderbilt.edu OI Harrington, Peter/0000-0003-0268-8630 FU NICHD NIH HHS [P30HD015052]; NIGMS NIH HHS [R01GM058008]; NIMH NIH HHS [K24MH064197, MH051456] NR 24 TC 12 Z9 12 U1 3 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 2005 VL 81 IS 5 BP 613 EP 621 DI 10.1002/jnr.20590 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 960HF UT WOS:000231580500002 PM 16035104 ER PT J AU Paul, CA Reid, PC Boegle, AK Karten, B Zhang, M Jiang, ZG Franz, D Lin, L Chang, TY Vance, JE Blanchette-Mackie, J Maue, RA AF Paul, CA Reid, PC Boegle, AK Karten, B Zhang, M Jiang, ZG Franz, D Lin, L Chang, TY Vance, JE Blanchette-Mackie, J Maue, RA TI Adenovirus expressing an NPC1-GFP fusion gene corrects neuronal and nonneuronal defects associated with Niemann pick type C disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Niemann Pick disease; cholesterol; neurons; astrocytes; adenovirus ID AXONAL-TRANSPORT; NEURODEGENERATIVE DISEASES; INTRACELLULAR TRAFFICKING; CHOLESTEROL HOMEOSTASIS; LIVER-TRANSPLANTATION; C1-DEFICIENT NEURONS; ALZHEIMERS-DISEASE; LYSOSOMAL STORAGE; NERVOUS-SYSTEM; ANIMAL-MODEL AB Niemann Pick type C (NPC) disease is an autosomal recessive disorder characterized by abnormal cholesterol metabolism and accumulation in lysosomal and endosomal compartments. Although peripheral organs are affected, the progressive neurodegeneration in the brain is typically most deleterious, leading to dystonia, ataxia, seizures, and premature death. Although the two genes underlying this disorder in humans and mouse models of the disease have been identified (NPC1 in 95% and NPC2/HE1 in 5% of human cases), their cellular roles have not Been fully defined, and there is currently no effective treatment for this disorder. To help address these issues, we constructed a recombinant adenovirus, Ad(NPC1-GFP), which contains a cDNA encoding a mouse NPC1 protein with a green fluorescent protein (GFP) fused to its C-terminus. Fluorescence microscopy and cholesterol trafficking assays demonstrate that the GFP-tagged NPC1 protein is functional and detectable in cells from different species (hamster, mouse, human) and of different types (ovary-derived cells, fibroblasts, astrocytes, neurons from peripheral and central nervous systems) in vitro. Combined with results from time-lapse microscopy and in vivo brain injections, our findings suggest that this adenovirus offers advantages for expressing NPC1 and, analyzing its cellular localization, movement, functional properties, and beneficial effects in vitro and in Vivo. (c) 2005 Wiley-Liss, Inc. C1 Dartmouth Coll Sch Med, Dept Physiol, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Univ Alberta, Dept Med, Edmonton, AB, Canada. NIDDK, Lipid Cell Biol Sect, NIH, Bethesda, MD USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Maue, RA (reprint author), Dartmouth Coll Sch Med, Dept Physiol, Hanover, NH 03755 USA. EM robert.maue@dartmouth.edu OI Chang, Ta-Yuan/0000-0002-3249-0468 FU NIDDK NIH HHS [DK7508-17]; NINDS NIH HHS [NS050716, NS04564] NR 68 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 2005 VL 81 IS 5 BP 706 EP 719 DI 10.1002/jnr.20592 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 960HF UT WOS:000231580500011 PM 16015597 ER PT J AU Lonser, RR Buggage, RR Weil, RJ AF Lonser, RR Buggage, RR Weil, RJ TI Malignant cerebellar swelling in Behcet disease - Case illustration SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE Behcet disease; cerebellar; neurological; surgery; pediatric neurosurgery C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2005 VL 103 IS 3 SU S BP 292 EP 292 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 971HJ UT WOS:000232374500017 PM 16238088 ER PT J AU Fowler, JS Logan, J Wang, GJ Volkow, ND Telang, F Zhu, W Franceschi, D Shea, C Garza, V Xu, YW Ding, YS Alexoff, D Warner, D Netusil, N Carter, P Jayne, M King, P Vaska, P AF Fowler, JS Logan, J Wang, GJ Volkow, ND Telang, F Zhu, W Franceschi, D Shea, C Garza, V Xu, YW Ding, YS Alexoff, D Warner, D Netusil, N Carter, P Jayne, M King, P Vaska, P TI Comparison of monoamine oxidase a in peripheral organs in nonsmokers and smokers SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; cigarette smoke; monoamine oxidase; lung; arterial plasma ID CIGARETTE-SMOKING; BRAIN; INHIBITION; NICOTINE; BINDING; METABOLISM; ARTERIAL; HUMANS; NEUROTRANSMISSION; NOREPINEPHRINE AB Smokers have reduced levels of brain monoamine oxidase A (MAO A) leading to speculation that MAO A inhibition by tobacco smoke may underlie some of the neurophysiologic effects of smoking. Because smoking exposes peripheral organs as well as the brain to MAO A-inhibitory compounds, we determined whether smokers would also have reduced MAO A in peripheral organs. Methods: We measured MAO A in peripheral organs in a group of 9 smokers and compared it with a group of nonsmokers studied previously. MAO A was measured using PET and serial scans with the MAO A-specific radiotracers C-11-clorgyline and deuterium-substituted C-11-clorgyline (C-11-clorgyline-D2) using the deuterium isotope effect to assess binding specificity. The time course of radiotracer in the arterial plasma was also measured and data from the tissue timeactivity curves and the arterial input function were analyzed using a 3-compartment model to estimate k(3), which represents the rate-limiting step for the irreversible binding of labeled clorgyline to MAO A. Results: Tracer uptake at plateau was reduced with deuterium substitution for the heart, lungs, and kidneys, indicating specificity for MAO. There was no difference in organ uptake at plateau between nonsmokers and smokers though, for the smokers, the efflux of tracer from peak uptake to plateau was slower for the lungs. The area under the time- activity curve for the arterial plasma was also significantly reduced for smokers versus nonsmokers and the reduction occurred in the first few minutes after radiotracer injection. Smokers had an similar to 50% reduction in k3 when compared with nonsmokers; however, k3 did not differ for nonsmokers and smokers for the heart and the kidneys. Conclusion: Because MAO A breaks down serotonin, norepinephrine, dopamine, and tyramine, and because the lung is a major metabolic organ in degrading some of these substances, reduced lung MAO A may contribute to some of the physiologic effects of smoking. This study also revealed that the concentration of the radictracers in the arterial plasma is significantly lower for the smoker versus the nonsmoker and that this appears to be caused in part by retention of the radiotracer in lungs. If this is generally true for other substances that are administered intravenously, then this needs to be considered as a variable that may contribute to different short-term behavioral responses to intravenously administered drugs for nonsmokers versus smokers. C1 Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Natl Inst Drug Abuse, Bethesda, MD USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. RP Fowler, JS (reprint author), Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. EM fowler@bnl.gov FU NCRR NIH HHS [M01RR10710]; NIBIB NIH HHS [EB002630]; NIDA NIH HHS [DA7092-01] NR 36 TC 21 Z9 24 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 SEP PY 2005 VL 46 IS 9 BP 1414 EP 1420 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 962GZ UT WOS:000231720300008 PM 16157522 ER PT J AU Reedy, J Haines, PS Steckler, A Campbell, MK AF Reedy, J Haines, PS Steckler, A Campbell, MK TI Qualitative comparison of dietary choices and dietary supplement use among older adults with and without a history of colorectal cancer SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE dietary supplements; cancer survivors; qualitative research ID BREAST-CANCER; PHYSICAL-ACTIVITY; HEALTH; SURVIVORS; DIAGNOSIS; NUTRITION; MEDICINE; BEHAVIOR; BELIEFS AB Objective: To explore colorectal cancer survivors' beliefs about diet, dietary supplements, health, and cancer in relation to beliefs of a similar group without colorectal cancer. Design: In-depth, semistructured, open-ended interviews were used to examine perceptions. Participants: Twenty-two participants (10 colorectal cancer survivors and 12 from a comparison group) from the North Carolina Strategies for Improving Diet, Exercise, and Screening Study. Analysis: Verbatim interview transcripts were coded and analyzed. Comparisons were made between colorectal cancer survivors and the comparison group. Results: Three main themes emerged: the influence of significant life events on dietary change, concerns about contaminants in the food supply, and a lack of physician guidance in dietary supplement selection. Conclusion and Implications: The experience of colorectal cancer is significant and may lead to dietary change among some survivors, but these findings do not suggest that it is necessarily more influential than other life events. Participants sought to control diet (for coping or survival) and also felt that diet cannot be controlled (due to the contamination of the food supply). Although many lacked guidance from physicians about dietary supplements, they were comfortable making their own decisions to self-treat. Enhanced understanding of the themes that guide selection of diet and dietary supplements can provide a context for dietitians in practice and researchers conducting behavioral interventions. C1 NCI, Div Canc Control & Populat Sci, Div Canc Prevent, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, Div Canc Prevent, 6130 Execut Blvd,EPN Room 405,MSC 7344, Bethesda, MD 20892 USA. EM reedyj@mail.nih.gov NR 27 TC 16 Z9 17 U1 1 U2 9 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD SEP-OCT PY 2005 VL 37 IS 5 BP 252 EP 258 DI 10.1016/S1499-4046(06)60280-7 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 958ES UT WOS:000231428100007 PM 16053814 ER PT J AU Lai, JS Dineen, K Reeve, BB Von Roem, J Shervin, D McGuire, M Bode, RK Paice, J Cella, D AF Lai, JS Dineen, K Reeve, BB Von Roem, J Shervin, D McGuire, M Bode, RK Paice, J Cella, D TI An item response theory-based pain item bank can enhance measurement precision SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE item banking; Rasch; item response theory; cancer; pain; disease management ID HEALTH-STATUS ASSESSMENT; GUIDELINES; INTENSITY; PATIENT; CARE AB Cancer-related pain is often under-recognized and undertreated. This is partly due to the lack of appropriate assessments, which need to be comprehensive and precise yet easily integrated into clinics. Computerized adaptive testing (CA T) can enable precise-yet-brief assessments by only selecting the most informative items from a calibrated item bank. The purpose of this study was to create such a bank. The sample included 400 cancer patients who were asked to complete 61 pain-related items. Data were analyzed using factor analysis and the Rasch model. The final bank consisted of 43 items which satisfied the measurement requirement of factor analysis and the Rasch model, demonstrated high internal consistency and reasonable item-total correlations, and discriminated patients with differing degrees of pain. We conclude that this bank demonstrates good psychometric properties, is sensitive to pain reported by patients, and can be used as the foundation for a CAT pain-testing platform for use in clinical Practice. C1 Evanston NW Healthcare & NW Univ, CORE, Evanston, IL 60201 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. NW Univ Freinberg, Sch Med, Dept Phys Med & Rehabil, Div Hematol Oncol, Chicago, IL USA. Evanston NW Healthcare, Evanston, IL USA. RP Lai, JS (reprint author), Evanston NW Healthcare & NW Univ, CORE, 1001 Univ Pl,Suite 100, Evanston, IL 60201 USA. OI Paice, Judith/0000-0001-7534-1756 FU NCI NIH HHS [CA60068] NR 35 TC 32 Z9 32 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2005 VL 30 IS 3 BP 278 EP 288 DI 10.1016/j.jpainsymman.2005.03.009 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 974CP UT WOS:000232569200013 PM 16183012 ER PT J AU Wilfond, BS Parad, RB Fost, N AF Wilfond, BS Parad, RB Fost, N TI Balancing benefits and risks for cystic fibrosis newborn screening: Implications for policy decisions SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Workshop on Newborn Screening for Cystic Fibrosis CY NOV 20-21, 2003 CL Atlanta, GA SP Ctr Dis Control & Prevent, Cystic Fibrosis Fdn ID SICKLE-CELL TRAIT; GENETIC-DISORDERS; ETHICAL ISSUES; CHILDREN; MALNUTRITION; MANAGEMENT; DIAGNOSIS; KNOWLEDGE; SURVIVAL; GROWTH AB Policy decisions for newborn screening (NBS) are particularly challenging when the balance of benefits and risks is not tipped dramatically, in 1 direction. When this is the case, as with cystic fibrosis (CF), the traditional approach of mandatory testing of all newborns in all states may not be appropriate. Alternative approaches may produce a substantial reduction ill psychosocial risks, at the cost of a small reduction in medical benefits, and thus improve the benefit/risk balance. At the provider level, this could include greater engagement and discussion with parents before testing. At the program implementation level, specific decisions about tradeoffs between sensitivity and specificity that could result in not identifying all infants with CF may be appropriate. At the policy decision level, deciding whether to implement CF NBS in a particular state could involve consideration of the availability of the financial resources, clinical services, and systems for assessing outcomes. Although CF NBS call be justified in settings in which the specific approach has a favorable benefit/risk balance, all inadequately designed screening program has the potential for being less favorable than the current approach of diagnosis on the basis of clinical criteria or family history. C1 NHGRI, Social & Mebah Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02125 USA. Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Wisconsin, Dept Pediat, Madison, WI USA. Univ Wisconsin, Dept Med Hist & Bioeth, Madison, WI USA. RP Wilfond, BS (reprint author), Bldg 10,Room ICII8,9000 Rockville Pike,MSC 1156, Bethesda, MD 20892 USA. EM wilfond@nhgri.nih.gov RI Parad, Richard/E-8559-2010 NR 42 TC 20 Z9 20 U1 2 U2 4 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 SEP PY 2005 VL 147 IS 3 SU S BP S109 EP S113 DI 10.1016/j.jpeds.2005.08.019 PG 5 WC Pediatrics SC Pediatrics GA 973RT UT WOS:000232541000024 PM 16202773 ER PT J AU McCrae, RR Terracciano, A AF McCrae, RR Terracciano, A CA Personality Profiles Cultures Pro TI Personality profiles of cultures: Aggregate personality traits SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article DE personality; five-factor model; cross-cultural; culture-level analyses ID 5-FACTOR MODEL; CONSENSUAL VALIDATION; SELF-REPORTS; INVENTORY; NATIONS; EXTROVERSION; PSYCHOTICISM; PERSPECTIVE; DISORDERS; COUNTRIES AB Personality profiles of cultures can be operationalized as the mean trait levels of culture members. College students from 51 cultures rated an individual from their country whom they knew well (N = 12,156). Aggregate scores on Revised NEO Personality Inventory (NEO-PI-R) scales generalized across age and sex groups, approximated the individual-level 5-factor model, and correlated with aggregate self-report personality scores and other culture-level variables. Results were not attributable to national differences in economic development or to acquiescence. Geographical differences in scale variances and mean levels were replicated, with Europeans and Americans generally scoring higher in Extraversion than Asians and Africans. Findings support the rough scalar equivalence of NEO-PI-R factors and facets across cultures and suggest that aggregate personality profiles provide insight into cultural differences. C1 NIA, Gerontol Res Ctr, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, NIH, Dept Hlth & Human Serv, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; De Fruyt, Filip/A-3083-2009; Rossier, Jerome/A-3494-2009; Allik, Juri/D-5609-2009; Sanchez-Bernardos, Maria Luisa/C-6038-2011; Avia, Maria Dolores/C-7061-2011; Realo, Anu/M-9524-2016 OI Rossier, Jerome/0000-0002-9924-3672; Allik, Juri/0000-0002-8358-4747; Sanchez-Bernardos, Maria Luisa/0000-0003-4931-867X; FU Intramural NIH HHS [Z99 AG999999] NR 82 TC 255 Z9 259 U1 7 U2 49 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD SEP PY 2005 VL 89 IS 3 BP 407 EP 425 DI 10.1037/0022-3514.89.3.407 PG 19 WC Psychology, Social SC Psychology GA 981MF UT WOS:000233092000010 PM 16248722 ER PT J AU Ni, W Wilhelm, CS Bader, M Murphy, DL Lookingland, K Watts, SW AF Ni, W Wilhelm, CS Bader, M Murphy, DL Lookingland, K Watts, SW TI (+)-Norfenfluramine-induced arterial contraction is not dependent on endogenous 5-hydroxytryptamine or 5-hydroxytryptamine transporter SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SEROTONIN TRANSPORTER; 5-HT2B RECEPTORS; THORACIC AORTA; FENFLURAMINE; METABOLITE; DEXFENFLURAMINE; RELEASE; PATHWAY; MOUSE; MICE AB (+)-Norfenfluramine, the major metabolite of fenfluramine, causes vasoconstriction dependence on the 5-hydroxytryptamine (5-HT)(2A) receptor in rat. (+)-Norfenfluramine was reported as a 5-hydroxytryptamine transporter (5-HTT) substrate and 5-HT releaser. Because the arterial 5-HTT exists and is functional in the rat, we hypothesized that (+)-norfenfluramine causes vasoconstriction by releasing 5-HT from vascular smooth muscle via 5-HTT. The released 5-HT, in turn, activates the 5-HT2A receptor. Isometric contractility experiments showed that (+)-norfenfluramine-induced mouse aortic contraction was reduced by the 5-HTT inhibitor fluoxetine (1 mu M) but not by fluvoxamine (1 mu M). Tryptophan hydroxylase (TPH)-deficient (Tph1-/-) mice lack peripheral 5-HT. (+)-Norfenfluramine (10 nM - 100 mu M)-contracted aorta from wild-type and Tph1-/- mice with equivalent potency (-log EC50 [M], wild type = 5.73 +/- 0.02, Tph1-/- = 5.62 +/- 0.09), and these contractions were inhibited by the 5-HT2A receptor antagonist ketanserin (3 nM) by a similar magnitude in aorta from wild-type and Tph1-/- mice (wild type = 19.4, Tph1-/- = 15.4-fold rightward shift versus control), as did fluoxetine (1 mu M) (wild type = 22.4, Tph1-/- = 28.8-fold rightward shift versus control). To further test the role of 5-HTT in (+)-norfenfluramine-induced aortic contraction, the 5-HTT-targeted mutation mouse was used. (+)-Norfenfluramine induced similar aortic contraction in wild-type and 5-HTT-targeted mutation mice, and these contractions were inhibited by fluoxetine (1 mu M). Thus, (+)-norfenfluramine vasoconstriction is not dependent on 5-HTT-mediated release of endogenous 5-HT but by activating membrane 5-HT2A receptors directly. Understanding of the mechanism by which (+)-norfenfluramine induces vasoconstriction is important to characterize and understand the function of the serotonergic system in peripheral arterial vasculature. C1 Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. Max Delbruck Ctr Mol Med, Berlin, Germany. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Ni, W (reprint author), Michigan State Univ, Dept Pharmacol & Toxicol, B445 Life Sci Bldg, E Lansing, MI 48824 USA. EM niwei@msu.edu OI Bader, Michael/0000-0003-4780-4164 FU NHLBI NIH HHS [HL58489] NR 26 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2005 VL 314 IS 3 BP 953 EP 960 DI 10.1124/jpet.105.087080 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 957IB UT WOS:000231362400003 PM 15901794 ER PT J AU Ruiz-Velasco, V Puhl, HL Fuller, BC Sumner, AD AF Ruiz-Velasco, V Puhl, HL Fuller, BC Sumner, AD TI Modulation of Ca2+ channels by opioid receptor-like 1 receptors natively expressed in rat stellate ganglion neurons innervating cardiac muscle SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ORL1 RECEPTOR; CALCIUM-CHANNELS; SYMPATHETIC NEURONS; NOCICEPTIN RECEPTOR; MOLECULAR-CLONING; SPLICE VARIANTS; BLOOD-PRESSURE; ORPHANIN FQ; HEART-RATE; IN-VITRO AB Postganglionic sympathetic nerve terminals innervate cardiac muscle and express opioid receptor-like 1 (ORL1) receptors, the most recently described member of the opioid receptor subclass. ORL1 receptors are stimulated by the endogenous heptadecapeptide nociceptin (Noc). To better understand how the signaling events by Noc regulate sympathetic neuron excitability, the goal of the present study was to determine whether sympathetic stellate ganglion (SG) neurons, innervating the heart, natively express ORL1 opioid receptors and couple to Ca2+ channels. SG neurons in adult male rats were retrograde-labeled with a fluorescent tracer via injection of the ventricular muscle employing ultrasound imaging. Thereafter, N-type Ca2+ channel modulation was investigated using the whole-cell variant of the patch-clamp technique. Exposure of labeled SG neurons to Noc resulted in a concentration-dependent inhibition of Ca2+ currents (with an estimated EC50 of 193 +/- 14 nM). Pre-exposure of SG neurons to the ORL1 receptor blocker, [Nphe(1), Arg(14), Lys(15)]N/OFQ-NH2 (UFP-101), significantly decreased the Noc-mediated Ca2+ current inhibition. The Ca2+ current inhibition was also blocked by pertussis toxin pretreatment, indicating that signaling occurs via G alpha(i/o) G proteins. Finally, the full-length ORL1 receptor cDNA in SG neurons was cloned and sequenced. Of the two known alternatively spliced variants in rats, sequencing analysis showed that the ORL1 receptor expressed in SG neurons is the short form. Overall, these results suggest that stimulation of postsynaptic ORL1 receptors by Noc in SG neurons regulate cardiac sympathetic activity. C1 Penn State Univ, Coll Med, Dept Anesthesiol, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Med, Hershey, PA 17033 USA. Natl Inst Alcohol Abuse & Alcoholism, Lab Mol Physiol, Bethesda, MD USA. Guthrie Healthcare Syst, Guthrie Vasc Labs, Sayre, PA USA. RP Ruiz-Velasco, V (reprint author), Penn State Univ, Coll Med, Dept Anesthesiol, H187, Hershey, PA 17033 USA. EM vruizvelasco@psu.edu OI Puhl, Henry/0000-0003-3095-7201 FU NHLBI NIH HHS [HL-074311] NR 40 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2005 VL 314 IS 3 BP 987 EP 994 DI 10.1124/jpet.105.089284 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 957IB UT WOS:000231362400007 PM 15937148 ER PT J AU Wang, XY Baumann, MH Xu, H Morales, M Rothman, RB AF Wang, XY Baumann, MH Xu, H Morales, M Rothman, RB TI (+/-)-3,4-Methylenedioxymethamphetamine administration to rats does not decrease levels of the serotonin transporter protein or alter its distribution between endosomes and the plasma membrane SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUBSTITUTED AMPHETAMINES; NEURONAL DEGENERATION; INDUCED NEUROTOXICITY; BRAIN; FENFLURAMINE; ECSTASY; METHYLENEDIOXYMETHAMPHETAMINE; METHAMPHETAMINE AB We showed that the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) reduces brain tissue 5-HT, decreases expression of 5-HT transporter (SERT) protein, and increases expression of glial fibrillary acidic protein (GFAP). In contrast, doses of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) that decrease brain tissue 5-HT fail to alter expression of SERT or GFAP. Using a new and highly sensitive anti-SERT antibody, we determined whether MDMA alters the subcellular distribution of SERT protein by measuring SERT expression in endosomes and plasma membranes 2 weeks after MDMA administration. Rat brain tissues (caudate, cortex, and hippocampus) were collected 3 days and 2 weeks after MDMA (7.5 mg/kg i.p., every 2 h x 3 doses) or 5,7-DHT (150 mu g/rat i.c.v.) administration. Representative results from cortex are as follows. At both 3 days and 2 weeks postinjection, MDMA decreased tissue 5-HT (65%) and had no effect on GFAP expression. MDMA increased heat shock protein 32 (HSP32; a marker for microglial activation) expression (30%) at 3 days, but not 2 weeks. MDMA did not alter SERT expression at either time point and did not alter SERT levels in either endosomes or plasma membranes (2 weeks). 5,7-DHT decreased tissue 5-HT (80%), increased HSP32 expression at both time points (about 50%), and increased GFAP expression at 2 weeks (40%). 5,7-DHT decreased SERT expression (33%) at 2 weeks, but not at 3 days. These findings indicate that a dosing regimen of MDMA that depletes brain 5-HT does not alter SERT protein expression or the distribution of SERT between endosomes and the plasma membrane and does not produce detectable evidence for neurotoxicity. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), Triad Technol Ctr, Clin Psychopharmacol Sect, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov NR 49 TC 45 Z9 45 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 SEP PY 2005 VL 314 IS 3 BP 1002 EP 1012 DI 10.1124/jpet.105.088476 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 957IB UT WOS:000231362400009 PM 15937150 ER PT J AU Chen, YP Kissling, G Negishi, M Goldstein, JA AF Chen, YP Kissling, G Negishi, M Goldstein, JA TI The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4 alpha to synergistically activate the human CYP2C9 promoter SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HUMAN HEPATOCYTE CULTURES; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID RECEPTOR; FACTOR 4-ALPHA; INDUCTION; BINDING; RIFAMPICIN; HNF4-ALPHA; HYPERFORIN AB CYP2C9 is an important human drug-metabolizing enzyme that is expressed primarily in liver. Recent studies in our laboratory have shown that the nuclear receptor pregnane X receptor (PXR) is important in the transcriptional activation of the CYP2C9 promoter by drugs such as rifampicin and that the essential element is a constitutive androstane receptor (CAR)/PXR site -1839 bp upstream of the translation start site. Both CAR and PXR transcriptionally up-regulate the CYP2C9 promoter via these elements. In the present study, we ask whether additional sites in the proximal promoter also play a role in this induction. We identify two proximal hepatic nuclear factor (HNF) 4 alpha binding sites at -152 and -185 bp of the CYP2C9 promoter, both of which bind HNF4 alpha in gel shift assays and transcriptionally up-regulate this promoter in response to HNF4 alpha in HepG2 cells. HNF4 alpha synergizes with CAR and with PXR in HepG2 cells treated with rifampicin. The synergy only occurs when the CAR/PXR binding site at -1839 bp is present. Mutation of the two HNF4 alpha binding sites differentially prevented up-regulation of CYP2C9 promoter by both CAR as well as HNF4 alpha, synergy between the two receptors, and essentially abolished induction by rifampicin in HepG2 cells transfected with PXR. These studies strongly support the hypothesis that there is cross talk between distal CAR/PXR sites and HNF4 alpha binding sites in the CYP2C9 promoter and that the HNF4 alpha sites are required for maximal induction of the CYP2C9 promoter. C1 NIEHS, Human Metab Sect, Chem Pharmacol Lab, Dept Htlh & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Pharmacogenet Sect, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Reprod & Dev Toxicol, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Human Metab Sect, Chem Pharmacol Lab, Dept Htlh & Human Serv,NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012 NR 36 TC 79 Z9 82 U1 0 U2 2 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 SEP PY 2005 VL 314 IS 3 BP 1125 EP 1133 DI 10.1124/jpet.105.087072 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 957IB UT WOS:000231362400023 PM 15919766 ER PT J AU Kristof, AS Pacheco-Rodriguez, G Schremmer, B Moss, J AF Kristof, AS Pacheco-Rodriguez, G Schremmer, B Moss, J TI LY303511 (2-piperazinyl-8-phenyl-4H-1-benzopyran-4-one) acts via phosphatidylinositol 3-kinase-independent pathways to inhibit cell proliferation via mammalian target of rapamycin (mTOR)- and non- mTOR-dependent mechanisms. SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN-KINASE INHIBITORS; PHOSPHOINOSITIDE 3-KINASE; CYCLIN D1; CANCER; LY294002; ACTIVATION; EXPRESSION; GROWTH; TOR; PHOSPHORYLATION AB Mammalian target of rapamycin ( mTOR), a serine/ threonine kinase, regulates cell growth and proliferation in part via the activation of p70 S6 kinase ( S6K). Rapamycin is an antineoplastic agent that, in complex with FKBP12, is a specific inhibitor of mTOR through interaction with its FKBP12-rapamycin binding domain, thereby causing G 1 cell cycle arrest. However, cancer cells often develop resistance to rapamycin, and alternative inhibitors of mTOR are desired. 2-(4- Morpholinyl)-8- phenyl-4H- 1- benzopyran- 4- one ( LY294002) blocks mTOR kinase activity, but it also inhibits phosphatidylinositol 3- kinase ( PI3K), an enzyme that regulates cellular functions other than proliferation. We hypothesized that a close structural analog, 2- piperazinyl8- phenyl- 4H- 1- benzopyran- 4- one ( LY303511) might inhibit mTOR- dependent cell proliferation without unwanted effects on PI3K. In human lung epithelial adenocarcinoma A549) cells, LY303511, like rapamycin, inhibited mTOR- dependent phosphorylation of S6K, but not PI3K- dependent phosphorylation of Akt. LY303511 blocked proliferation in A549 as well as in primary pulmonary artery smooth muscle cells, without causing apoptosis. In contrast to rapamycin, LY303511 reduced G(2)/ M progression as well as G(2)/M- specific cyclins in A549 cells. Consistent with an additional mTOR- independent kinase target, LY303511 inhibited casein kinase 2 activity, a known regulator of G1 and G(2)/M progression. In addition to its antiproliferative effect in vitro, LY303511 inhibited the growth of human prostate adenocarcinoma tumor implants in athymic mice. Given its inhibition of cell proliferation via mTOR- dependent and independent mechanisms, LY303511 has therapeutic potential with antineoplastic actions that are independent of PI3K inhibition. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Kristof, AS (reprint author), McGill Univ, Royal Victoria Hosp, 687 Pine Ave W,Room L3-05, Montreal, PQ H3A 1A1, Canada. EM arnold.kristof@muhc.mcgill.ca NR 40 TC 32 Z9 32 U1 0 U2 2 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 SEP PY 2005 VL 314 IS 3 BP 1134 EP 1143 DI 10.1124/jpet.105.083550 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 957IB UT WOS:000231362400024 PM 15923340 ER PT J AU Lyubimov, AV Carr, SN Brown, AP Art, JJ Crowell, JA Levine, BS AF Lyubimov, AV Carr, SN Brown, AP Art, JJ Crowell, JA Levine, BS TI Evaluation of hydrogen ion concentrations in prostates from rats and dogs using fluorescent confocal microscopy SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE prostate; epithelial cells SNARF-1; confocal microscopy; pH measurements; fluorescent indicators ID HORMONAL-THERAPY; INTRACELLULAR PH; TUMOR-CELLS; CANCER; CHEMOTHERAPY; SECRETION; SEQUESTRATION; INHIBITION; DRUGS; ACID AB The knowledge of intracellular spatial distribution of pH in prostates in animal models reflective of human prostate may have implications for drug development upon pH dependent drug delivery and activity. Freshly dissected prostate tissues (in vitro) or the entire prostate gland (in vivo) were loaded with fluorescent dyes and viewed using confocal microscopy. Images were initially taken in tissues perfused with RPMI-1640 medium. Calibration in situ was performed with high potassium buffers of known pH containing nigericin. Acetoxymethyl ester carboxy-SNARF-1 was visible in epithelial cells (but not stroma) in rat and dog prostates. The pH of lysosomes in prostate epithelial cells was <= 5.2 as determined by fluorescence of Lyso Sensor Green DND-189. A method of in situ confirmation of tissue viability was developed by a secondary loading and visualization of the BCECF fluorescent dye. Besides the direct measurement of the pH in rat and dog tissues (pH approximate to 7.0), a method of pH measurement in prostate tissue (rather than in cell culture) was developed. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Illinois, Toxicol Res Lab, Chicago, IL 60612 USA. Univ Illinois, Dept Anat, Chicago, IL USA. NCI, Div Canac Prevent, Bethesda, MD USA. RP Lyubimov, AV (reprint author), Univ Illinois, Toxicol Res Lab, 1940 W Taylor St MC 868, Chicago, IL 60612 USA. EM Lyubimov@uic.edu FU NCI NIH HHS [N01-CN-95055] NR 26 TC 5 Z9 5 U1 0 U2 8 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD SEP 1 PY 2005 VL 80 IS 3 BP 225 EP 234 DI 10.1016/j.jphotobiol.2005.04.008 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 960GB UT WOS:000231577200008 PM 15982897 ER PT J AU Hendler, RW AF Hendler, RW TI An apparent general solution for the kinetic models of the bacteriorhodopsin photocycles SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SINGULAR-VALUE DECOMPOSITION; WIDE PH RANGE; PURPLE MEMBRANE; PROTON PUMP; HALOBACTERIUM-SALINARIUM; VISIBLE ABSORPTION; LIPID ORGANIZATION; RESONANCE RAMAN; SCHIFF-BASE; 2 FORMS AB For the past decade, the field of Bacteriorhodopsin (BR) research has been influenced by a kinetic view of the photocycle as a reversible, homogeneous, model (RHM) with a linear sequence of intermediates. More recently, we proposed a much different model which consists of essentially unidirectional, parallel (i.e., heterogeneous) cycles (UPM) (Hendler, R. W.; Shrager, R. I.; Bose, S. J. Phys. Chem. B 2001, 105, 33193328). It is important to try to resolve which of the two models is more likely to be correct, because models influence and provide a basis for further experimentation. Therefore, in this communication, we reexamine the basis for the RHM with a focus on the most recent and complete description of this model (van Stokkum, I., H., M.; Lozier, R. J. Phys. Chem. B 2002, 106, 3477-3485) vis a vis the UPM in an in-depth study. We show that (i) the tested RHM does not really work for the data of van Stokkum and Lozier nor ours; (ii) no previously published RHM model has been shown to work for data under any conditions, (iii) there are many published observations that are difficult if not impossible to explain by RHM, but are readily explained by parallel cycles. It is also shown that either a UPM or a parallel cycle model with limited reversibility correctly describes photocycle data collected at pH 5, 7, and 9 and at 10, 20, and 30 degrees and is consistent with all known experimental observations. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hendler, RW (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 61 TC 13 Z9 13 U1 1 U2 6 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 SEP 1 PY 2005 VL 109 IS 34 BP 16515 EP 16528 DI 10.1021/jp052733h PG 14 WC Chemistry, Physical SC Chemistry GA 959DQ UT WOS:000231497500040 PM 16853100 ER PT J AU Wang, DX Xu, WP McGrath, SC Patterson, C Neckers, L Cotter, RJ AF Wang, DX Xu, WP McGrath, SC Patterson, C Neckers, L Cotter, RJ TI Direct identification of ubiquitination sites on ubiquitin-conjugated CHIP using MALDI mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE ubiquitination; CHIP; MALDI mass spectrometry; N-terminal sulfonation ID PROTEIN UBIQUITINATION; UBIQUITYLATION; GUANIDINATION; PEPTIDES; LIGASE AB The study of protein ubiquitination, a post-translational modification by ubiquitin, has emerged as one of the most active areas in biology because of the important role of this type of modification on the regulation of various cellular proteins. Advances in techniques for the determination and site mapping of protein ubiquitination can facilitate the elucidation of molecular mechanisms of this modification. We have recently described a novel method for identifying peptides containing ubiquitinated amino acid residues, based on the MALDI-MS/MS analysis of tryptic peptide derivatives. In particular, we have utilized N-terminal sulfonation of these peptides to provide a unique fragmentation pattern that leads to the direct identification and sequencing of ubiquitin modified peptides. Here we present an application of this new method on the characterization of ubiquitin conjugated C-terminal Hsc70-interacting protein (CHIP), a recently identified U-box containing E3 enzyme. Three peptides bearing ubiquitination sites have been identified from the digest of ubiquitinated CHIP; one of these was a site on CHIP, while the other two were found on the ubiquitin molecules, demonstrating that sulfonation of tryptic peptides is a general and efficient method for characterizing protein ubiquitination. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. NCI, Urol Oncol Branch, NIH, Rockville, MD 20850 USA. Univ N Carolina, Program Mol Cardiol, Chapel Hill, NC 27599 USA. RP Cotter, RJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. EM rrotter@jhmi.edu OI McGrath, Sara/0000-0003-4773-4784 FU NCRR NIH HHS [U54 RR 020839] NR 16 TC 22 Z9 25 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP-OCT PY 2005 VL 4 IS 5 BP 1554 EP 1560 DI 10.1021/pr050104e PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974GK UT WOS:000232579100015 PM 16212406 ER PT J AU Hood, BL Zhou, M Chan, KC Lucas, DA Kim, GJ Issaq, HJ Veenstra, TD Conrads, TP AF Hood, BL Zhou, M Chan, KC Lucas, DA Kim, GJ Issaq, HJ Veenstra, TD Conrads, TP TI Investigation of the mouse serum proteome SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE mouse; serum proteomics; multidimensional fractionation; tandem mass spectrometry ID HUMAN PLASMA PROTEOME; MASS-SPECTROMETRY; CANCER; PROTEINS; CHROMATOGRAPHY; PREDICTION; BIOMARKERS; PATHOLOGY; TOPOLOGY; DISEASE AB With the rapid assimilation of genomic information and the equally impressive developments in the field of proteomics, there is an unprecedented interest in biomarker discovery. Although human biofluids represent increasingly attractive samples from which new and more accurate disease biomarkers may be found, the intrinsic person-to-person variability in these samples complicates their discovery. One of the most extensively used animal models for studying human disease is mouse because, unlike humans, they represent a highly controllable experimental model system. Unfortunately, very little is known about the proteomic composition of mouse serum. In this study, a multidimensional fractionation approach on both the protein and the peptide level that does not require depletion of highly abundant serum proteins was combined with tandem mass spectrometry to characterize proteins within mouse serum. Over 12 300 unique peptides that originate from 4567 unique proteins-approximately 16% of all known mouse proteins-were identified. The results presented here represent the broadest proteome coverage in mouse serum and provide a foundation from which quantitative comparisons can be made in this important animal model. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Conrads, TP (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM conrads@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 35 TC 48 Z9 48 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP-OCT PY 2005 VL 4 IS 5 BP 1561 EP 1568 DI 10.1021/pr050107r PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974GK UT WOS:000232579100016 PM 16212407 ER PT J AU Law, AJ Lipska, B Weickert, S Hyde, TM Straub, RE Hashimoto, R Harrison, PJ Kleinman, JE Weinberger, DR AF Law, AJ Lipska, B Weickert, S Hyde, TM Straub, RE Hashimoto, R Harrison, PJ Kleinman, JE Weinberger, DR TI Neuregulin 1 (NRG1) transcripts are differentially expressed in schizophrenia and regulated by 5 ' SNPS associated with the disease SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychoparmacology CY JUL 24-27, 2005 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RI Law, Amanda/G-6372-2012; Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2005 VL 19 IS 5 SU S BP A31 EP A31 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 971IM UT WOS:000232377400123 ER PT J AU Roiser, JP Blackwell, AD Cools, R Clark, L Rubinsztein, DC Robbins, TW Sahakian, BJ AF Roiser, JP Blackwell, AD Cools, R Clark, L Rubinsztein, DC Robbins, TW Sahakian, BJ TI Vulnerability to loss of motivated action following acute tryptophan depletion: The role of allelic variation at the serotonin transporter gene SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychoparmacology CY JUL 24-27, 2005 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. NIMH, Sect Mood & Anxiety Disorders, Bethesda, MD 20852 USA. Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2XY, England. EM adb43@cam.ac.uk NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2005 VL 19 IS 5 SU S BP A58 EP A58 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 971IM UT WOS:000232377400231 ER PT J AU Roiser, JP Blackwell, AD Cools, R Clark, L Rubinsztein, DC Robbins, TW Sahakian, BJ AF Roiser, JP Blackwell, AD Cools, R Clark, L Rubinsztein, DC Robbins, TW Sahakian, BJ TI Vulnerability to loss of motivated action following acute tryptophan depletion: The role of allelic variation at the serotonin transporter gene SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychoparmacology CY JUL 24-27, 2005 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. NIMH, Sect Mood & Anxiety Disorders, Bethesda, MD 20852 USA. Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2XY, England. EM adb43@cam.acuk NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2005 VL 19 IS 5 SU S BP A50 EP A50 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 971IM UT WOS:000232377400198 ER PT J AU Tunbridge, EM Weinberger, DR Harrison, PJ AF Tunbridge, EM Weinberger, DR Harrison, PJ TI A novel variant of catechol-O-methyltransferase increased in schizophrenia and bipolar disorder and associated with val(158)met genotype SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychoparmacology CY JUL 24-27, 2005 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. NIMH, NIH, Bethesda, MD 20892 USA. EM elizabeth.tunbridge@psych.ox.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2005 VL 19 IS 5 SU S BP A30 EP A30 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 971IM UT WOS:000232377400121 ER PT J AU Stancil, TR Li, CH Hyman, JJ Reid, BC Reichman, ME AF Stancil, TR Li, CH Hyman, JJ Reid, BC Reichman, ME TI Dental insurance and clinical dental outcomes in NHANES III SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE dental caries; dental insurance; national surveys; periodontal attachment loss; propensity score ID HEALTH-INSURANCE; RECENT TRENDS; US ADULTS; VISITS; EXPENDITURES; IMPACT; INCOME; CARE AB Objectives: The National Health and Nutrition Examination Survey (NHANES III) 1988-1994 is one of the few nationally representative data sets with information on both private dental insurance and a clinical dental exam. The objective of this analysis was to examine the possible associations between private denial insurance and clinical exam outcomes, demographic variables, and dental visits. Methods: Using NHANES III data, analysis was limited to persons aged 20 years or older who had a dental exam and reported on their private dental insurance status. Initial analyses were based on comparisons between those with and without private dental insurance. Propensity scoring method was used to examine the effects of dental insurance on clinical exam variables. Results: The percentage of individuals with private dental insurance was significantly greater among non-Hispanic blacks, those with higher educational attainment, those living at/above the federal poverty level, and those with a dental visit in the past year compared to their respective counterparts. Those with untreated caries, those with a loss of attachment of greater than 4 mm, and those with 12-27 missing teeth were significantly less likely to have dental insurance (p < 0. 05) than their respective counterparts. Conclusions: These results suggest that having private dental insurance is associated with better clinical oral health status. C1 Northrop Grumman Informat Technol, Rockville, MD USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Maryland, Baltimore, MD 21201 USA. RP Li, CH (reprint author), 2101 Gaither Rd,Ste 600, Rockville, MD 20850 USA. EM Charles.li@ngc.com NR 14 TC 8 Z9 9 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 2005 VL 65 IS 4 BP 189 EP 195 DI 10.1111/j.1752-7325.2005.tb03017.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 003BH UT WOS:000234656100002 PM 16468459 ER PT J AU Santolaya-Forgas, J De Leon-Luis, J Shen, Z McCorquodale, M AF Santolaya-Forgas, J De Leon-Luis, J Shen, Z McCorquodale, M TI Chromosomal studies on 2 mL of celomic fluid obtained during the fifth week of development in the timed-pregnant baboon model SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE chromosomes; baboons; prenatal diagnosis ID EARLY PRENATAL-DIAGNOSIS; IN-SITU HYBRIDIZATION; FETAL SEX; COELOCENTESIS; GESTATION; CELLS; GENE AB OBJECTIVE: To determine if chromosomal studies could be performed using 2 mL of celomic fluid obtained during the fifth postfertilization week in pregnant baboons. MATERIALS AND METHODS: Nine ultrasound-guided celocenteses were performed. The initial 0.5 mL of celomic fluid was discarded to decrease maternal cell contamination. Approximately 2 mL of celomic fluid was then collected. The fluid was centrifuged and the supernatant removed to a final volume of 0.5 mL. The celomic fluid sample was placed in either a small plastic flaskette chamber slide with a mix of 0.5 mL celomic fluid, I mL of Amniomax (TM), and 1 mL of used fibroblast culture medium to spread on the entire surface (n = 4), or a 3.5 x 1-cm plastic Petri dish with a 24x30-mm glass coverslip to keep the 0.5 mL celomic fluid mixed with I mL of Amniomax (TM) (Invitrogen, Carlsbad, California) within a 1 cm(2) area (n = 5). The medium was changed on day 5 and thereafter every second to third day. The cells were harvested when the number of cells appeared sufficient for chromosomal analysis. RESULTS: Standard chromosomal studies were possible in 5 of the 9 celomic fluid samples. Mean ( +/- SD) celomic fluid volume used for culture was 1.85 +/- 0.3 mL. Mean ( SD) time to karyotype result was 18.8 +/- 1.8 days. CONCLUSION: The findings of this study suggest that there are living cells at 36-42 days of embryonic development in the extraembryonic celomic fluid of primates and that they can be cultured for chromosomal studies. However, significant improvements in understanding the biology of cells present at 5 weeks after fertilization in celomic fluid are needed to improve culture conditions. C1 Wayne State Univ, Sch Med, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. Michael Reese Hosp & Med Ctr, Cytogenet Lab, Chicago, IL 60616 USA. Amarillo Womens Hlth Res Inst, Amarillo, TX USA. RP Santolaya-Forgas, J (reprint author), Wayne State Univ, Sch Med, Perinatol Res Branch, NICHD,NIH,DHHS, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM jsantol@med.wayne.edu NR 22 TC 9 Z9 9 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD SEP PY 2005 VL 50 IS 9 BP 692 EP 696 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 967EN UT WOS:000232074400008 PM 16363757 ER PT J AU Iancu, CV Wright, ER Benjamin, J Tivol, WF Dias, DP Murphy, GE Morrison, RC Heymann, JB Jensen, GJ AF Iancu, CV Wright, ER Benjamin, J Tivol, WF Dias, DP Murphy, GE Morrison, RC Heymann, JB Jensen, GJ TI A "flip-flop" rotation stage for routine dual-axis electron cryotomography SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE tomography; electron microscopy; cryoEM; dual-axis; cryoholder; missing wedge ID CRYOELECTRON TOMOGRAPHY; 3-DIMENSIONAL STRUCTURE; MICROSCOPY; RESOLUTION; VIRUS; SECTIONS; TOOL AB Electron cryotomography can be used to solve the three-dimensional structures of individual large macromolecules, assemblies, and even small intact cells to medium (similar to 4-8 nm) resolution in a near-native state, but restrictions in the range of accessible views are a major limitation. Here we report on the design, characterization, and demonstration of a new "flip-flop" rotation stage that allows facile and routine collection of two orthogonal tilt-series of cryosamples. single- and dual-axis tomograrns of a variety of samples are compared to illustrate qualitatively the improvement produced by inclusion of the second tilt-series. Exact quantitative expressions are derived for the volume of the remaining "missing pyramid" in reciprocal space. When orthogonal tilt-series are recorded to +/-65 degrees in each direction, as this new cryostage permits, only 11% of reciprocal space is left unmeasured. The tomograms suggest that further improvement could be realized, however, through better software to align and merge dual-axis tilt-series of cryosamples. (C) 2005 Elsevier Inc. All rights reserved. C1 CALTECH, Div Biol, Pasadena, CA 91125 USA. Gatan UK, Abingdon OX14 1RL, Oxon, England. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Jensen, GJ (reprint author), CALTECH, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA. EM Jensen@caltech.edu RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326 FU NIGMS NIH HHS [P01 GM66521] NR 24 TC 43 Z9 45 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2005 VL 151 IS 3 BP 288 EP 297 DI 10.1016/j.jsb.2005.07.004 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 973SI UT WOS:000232542500007 PM 16129619 ER PT J AU Sporn, AL Bobb, AJ Gogtay, N Stevens, H Greenstein, DK Clasen, LS Tossell, JW Nugent, T Gochman, PA Sharp, WS Mattai, A Lenane, MC Yanovski, JA Rapoport, JL AF Sporn, AL Bobb, AJ Gogtay, N Stevens, H Greenstein, DK Clasen, LS Tossell, JW Nugent, T Gochman, PA Sharp, WS Mattai, A Lenane, MC Yanovski, JA Rapoport, JL TI Hormonal correlates of clozapine-induced weight gain in psychotic children: An exploratory study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE childhood; weight gain; obesity; clozapine; antipsychotic ID CHILDHOOD-ONSET SCHIZOPHRENIA; SERUM LEPTIN LEVELS; ANTIPSYCHOTIC-DRUGS; BODY-WEIGHT; DOUBLE-BLIND; ATYPICAL ANTIPSYCHOTICS; TRIGLYCERIDE LEVELS; INSULIN LEVELS; OLANZAPINE; HALOPERIDOL AB Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls (HC) were obtained. Levels of leptin, insulin, adiponectin, amylin, ghrelin, and tumor necrosis factor a were measured and compared between the groups. For 23 patients with COS, hormonal levels were measured at background and week 6 of clozapine treatment. Change in body mass index was correlated with levels of clozapine and changes in hormonal levels and clinical ratings. Results: At baseline, COS did not differ significantly from HC on any hormonal measure. Clozapine treatment was associated with significant (7.9% +/- 8.5%) increase in mean body mass index. Only leptin levels increased significantly from baseline to week 6 on clozapine (p = .003). Body mass index increase was significantly correlated with decrease in ghrelin and adiponectin and was positively correlated with clinical improvement. Conclusions: This is the first study of weight gain-related hormones in children on clozapine. Hormonal changes are correlated with weight gain. How effectiveness of clozapine is linked to weight gain remains uncertain. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NICHD, Unit Growth & Obes Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Sporn, AL (reprint author), 103 Mercer St, Princeton, NJ 08540 USA. EM sporna@intra.nimh.nih.gov RI Gogtay, Nitin/A-3035-2008; Stevens, Hanna/M-4104-2016 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999] NR 51 TC 35 Z9 38 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2005 VL 44 IS 9 BP 925 EP 933 DI 10.1097/01.chi.0000170552.15798.dd PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 958EZ UT WOS:000231428800013 PM 16113621 ER PT J AU Goldstein, RB Johnson, MO Rotheram-Borus, MJ Kirshenbaum, SB Pinto, RM Kittel, L Pequegnat, W Mickalian, JD Weinhardt, LS Kelly, JA Lightfoot, M AF Goldstein, RB Johnson, MO Rotheram-Borus, MJ Kirshenbaum, SB Pinto, RM Kittel, L Pequegnat, W Mickalian, JD Weinhardt, LS Kelly, JA Lightfoot, M CA Natl Inst Mental Hlth Healthy Livi TI Psychological distress, substance use, and adjustment among parents living with HIV SO JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE LA English DT Article ID INJECTION-DRUG USERS; UNITED-STATES; DEPRESSIVE SYMPTOMS; POSITIVE WOMEN; ADOLESCENT CHILDREN; MULTIPLE ROLES; MENTAL-HEALTH; INFECTION; MOTHERS; DISEASE AB Background: Being a parent, especially a custodial parent, living with HIV was anticipated to increase psychological distress and challenges to self-care. Methods: Mental health symptoms, substance use, and health care utilization were assessed among 3818 HIV-infected adults, including custodial parents, noncustodial parents, and nonparents, in 4 AIDS epicenters. Results: Custodial parents demonstrated significantly poorer medication adherence and attendance at medical appointments but were similar to nonparents and noncustodial parents in mental health symptoms and treatment utilization for mental health and substance use problems. Noncustodial parents demonstrated the highest levels of recent substance use and substance abuse treatment. Other markers of risk, such as African American ethnicity, lack of current employment income, and injection drug use moderated many of the apparent psychosocial disadvantages exhibited by parents. Conclusions: Interventions specific to the psychosocial stressors facing families living with HIV are needed. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Community Hlth, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. Columbia Univ, New York, NY USA. NIMH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Ctr AIDS Intervent Res, Milwaukee, WI 53226 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3068,MS 9304, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU NIMH NIH HHS [U10-MH57615, P30 MH043520, P30 MH058107, P30 MH062246, P30-MH058107, P30-MH062246, P30-MH43520, P30-MH57226, U10 MH057615, U10 MH057616, U10 MH057631, U10 MH057636, U10-MH57616, U10-MH57631, U10-MH57636] NR 74 TC 7 Z9 9 U1 7 U2 9 PU AMER BOARD FAMILY PRACTICE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 0893-8652 J9 J AM BOARD FAM PRACT JI J. Am. Board Fam. Pract. PD SEP-OCT PY 2005 VL 18 IS 5 BP 362 EP 373 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 962GL UT WOS:000231718900004 PM 16148246 ER PT J AU Maker, AV Attia, P Rosenberg, S AF Maker, AV Attia, P Rosenberg, S TI Cellular mechanisms of anti-tumor responses in patients treated with CTLA-4 blockade SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2005 VL 201 IS 3 SU S BP S86 EP S87 DI 10.1016/j.jamcollsurg.2005.06.204 PG 2 WC Surgery SC Surgery GA 962PX UT WOS:000231745800193 ER PT J AU Ramos-Gomez, F Cruz, GD Watson, MR Canto, MT Boneta, AE AF Ramos-Gomez, F Cruz, GD Watson, MR Canto, MT Boneta, AE TI A research agenda toward eliminating oral health disparities SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID EARLY-CHILDHOOD CARIES; TWINS REARED APART; DENTAL-CARIES; UNITED-STATES; MEXICAN-AMERICANS; LATINO CHILDREN; NHANES-III; CARE; POPULATION; HISPANICS AB Background:. The Hispanic population has become the largest minority group in the United, States, resulting in an increase in oral health care demands. Developing a research agenda and promoting collaboration on Latino oral health issues are crucial., The Hispanic Dental Association and the University of Puerto Rico, School of Dentistry, San Juan, convened a workshop of health care providers and other experts to examine the current state of Hispanic oral health research and identify gaps in existing data and research methods. Participants were asked to break out into small groups to discuss research priorities. Results: The participants discussed the following research areas: population-based studies, social and behavioral sciences, health promotion and communications', gene-environment interactions, and research training and workforce development. Participants emphasized the importance,of understanding variations among subgroups within the Hispanic population in the development of future studies. Conclusions: Participants recommended collaborative research studies to advance existing oral disease prevention and:oral health promotion efforts, with a stronger focus' on the development of a multidisciplinary pipeline of researchers participating in Latino oral health research to address the growing needs of this population. Practice Implications: Building an infrastructure for research training and workforce development would supply researchers with the necessary tools to develop new studies that could affect the overall oral health of the Latino population. The translation and dissemination of these arch findings will benefit clinicians by research leading to a better understanding of new trends and specific population needs, as well a's appropriate targeted interventions. C1 Univ Calif San Francisco, Dept Orofacial Sci, Div Pediat Dent, Ctr Add Dispar Childrens Oral Hlth, San Francisco, CA 94143 USA. NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY USA. Spanish Catholic Ctr, Hlth Clin, Washington, DC USA. US Dept Hlth & Human Serv, Epidemiol Res Program, Clin Res Branch,Natl Inst Dent & Craniofacial Re, Div Clin Res & Hlth Promot,NIH, Bethesda, MD USA. Univ Puerto Rico, Sch Dent, San Juan, PR 00936 USA. RP Ramos-Gomez, F (reprint author), Univ Calif San Francisco, Dept Orofacial Sci, Div Pediat Dent, Ctr Add Dispar Childrens Oral Hlth, 707 Parnassus Ave,Box 0753,Room D1021, San Francisco, CA 94143 USA. EM ramos@itsa.ucsf.edu NR 59 TC 17 Z9 18 U1 1 U2 5 PU AMER DENTAL ASSN 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 SEP PY 2005 VL 136 IS 9 BP 1231 EP 1240 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 964ZP UT WOS:000231919800010 PM 16196228 ER PT J AU Venti, CA Tataranni, PA Salbe, AD AF Venti, CA Tataranni, PA Salbe, AD TI Lack of relationship between calcium intake and body size in an obesity-prone population SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID ASSESSING RISK-FACTORS; DIETARY CALCIUM; PRESCHOOL-CHILDREN; BEVERAGE CHOICES; PIMA-INDIANS; WEIGHT; FAT; QUESTIONNAIRE; CONSUMPTION; CHILDHOOD AB Objective Dietary calcium intake, especially from dairy products, may have a protective effect against obesity. This study aimed to determine if calcium intake is associated with body weight and adiposity in Pima Indians, an obesity-prone population. Research methods and procedures Subjects were 65 Pima Indian adults (35 men/30 women, age 33 8 years [mean +/- standard deviation]) participating in a study of eating behavior and 78 Pima Indian children (36 boys/42 girls, age 10.4 +/- 0.3 years) participating in a study of childhood obesity. Height and weight were measured, and body composition was determined by dual-energy x-ray absorptiometry. Food intake in adults was assessed using the Block 1998 Food Questionnaire; food intake in children was assessed using a 24-hour recall with parental assistance. Results In adults, mean energy intake was 3,163 +/- 1,037 kcal/day, mean percentage of energy from fat was 41% +/- 7%, and calcium intake was 914 +/- 333 mg/day. In children, mean energy intake was 1,988 +/- 733 kcal/day, mean percentage of energy from fat was 36% +/- 9%, and calcium intake was 637 +/- 352 mg/day, half the recommended daily intake for this age group. There were no significant associations between calcium intake and body weight (r=0.05, P=.71; r=0.04, P=.73), body fat (r=0.16, P=.19; r=0.12, P=.42), or body mass index (r=0.01, P-97; r=0.04, P=.77) in either adults or children, respectively. Discussion One explanation for the lack of association between reported calcium intake and body size in Pima Indians may be that the high-fat, high-energy diet consumed by the population overwhelmed the "anti-obesigenic" effect of calcium. Conclusions We were unable to find an association between calcium intake and body size or adiposity in Pima Indian adults and children. Although the essentiality of calcium to bone health is well established, the role of calcium and dairy product intake in obesity and weight management remains uncertain. C1 NIDDKD, CDNS, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA. Sanofi Aventis Pharmaceut, Paris, France. RP Salbe, AD (reprint author), NIDDKD, CDNS, Obes & Diabet Clin Res Sect, NIH, 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. EM ASalbe@mail.nih.gov FU Intramural NIH HHS NR 42 TC 46 Z9 47 U1 1 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2005 VL 105 IS 9 BP 1401 EP 1407 DI 10.1016/j.jada.2005.06.004 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 962CY UT WOS:000231709800012 PM 16129081 ER PT J AU Bretz, WA Weyant, RJ Corby, PM Ren, D Weissfeld, L Kritchevsky, SB Harris, T Kurella, M Satterfield, S Visser, M Newman, AB AF Bretz, WA Weyant, RJ Corby, PM Ren, D Weissfeld, L Kritchevsky, SB Harris, T Kurella, M Satterfield, S Visser, M Newman, AB TI Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE periodontal diseases; periodontal organisms; inflammation; elderly ID DL-ARGININE-NAPHTHYLAMIDE; C-REACTIVE PROTEIN; PORPHYROMONAS-GINGIVALIS; CARDIOVASCULAR-DISEASE; MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; PLAQUE; BACTERIA; HEALTH AB OBJECTIVES: To study the levels of systemic markers for inflammation with parameters of periodontal diseases in older people. DESIGN: A cross-sectional study was conducted in a cohort that is being followed prospectively on the effects of aging and body composition on morbidity. SETTING: University of Pittsburgh, Pittsburgh, and University of Tennessee, Memphis. PARTICIPANTS: One thousand one hundred thirty-one participants (mean age +/- standard deviation 72.7 +/- 2.8); 66% white and 50% male. MEASUREMENTS: Periodontal examination, including probing depth and attachment loss, was performed. Periodontal disease extent was divided into 0% of sites with probing depth of 6 mm or more, 1% to 10% of sites with probing depth of 6 mm or more and more than 10% of sites with probing depth of 6 mm or more. Subgingival plaque samples were collected from four molar teeth, and the levels of periodontal pathogens were determined using the benzoyl-DL-arginine-naphthylamide (BANA) test. Plasma interleukin-6 (IL-6), C-reactive protein (CRP), plasminogen activator inhibitor type-1 (PAI-1), and tumor necrosis factor alpha (TNF-alpha) levels were measured in all participants. Assessments of risk factors associated with elevated levels of markers of systemic inflammation were also determined. Multiple regression analysis was employed to analyze the data. RESULTS: IL-6 levels were significantly higher in participants with more-extensive periodontal disease than in other participants. Periodontal disease extent was significantly associated with higher TNF-alpha plasma levels, controlling for established risk factors for elevated TNF-alpha levels. Participants with BANA-positive species had significantly higher CRP plasma levels when controlling for risk factors for elevated CRP levels. CONCLUSION: Periodontal disease and infection may be modifiable risk indicators for elevated levels of systemic inflammatory markers in older people. C1 Univ Pittsburgh, Div Pediat & Dev Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15261 USA. Wake Forest Univ, Sch Med, Stricht Ctr Aging, Winston Salem, NC 27109 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands. RP Bretz, WA (reprint author), Univ Pittsburgh, Div Pediat & Dev Dent Sci, 3501 Terrace St,Room 380, Pittsburgh, PA 15261 USA. EM wab2@pitt.edu RI Kurella Tamura, Manjula/C-8284-2014; Newman, Anne/C-6408-2013; OI Kurella Tamura, Manjula/0000-0001-5227-2479; Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106, N01-AG-6-210] NR 27 TC 82 Z9 84 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2005 VL 53 IS 9 BP 1532 EP 1537 DI 10.1111/j.1532-5415.2005.53468.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 959HO UT WOS:000231509000012 PM 16137283 ER PT J AU Singh, AS Figg, WD AF Singh, AS Figg, WD TI In vivo models of prostate cancer metastasis to bone SO JOURNAL OF UROLOGY LA English DT Review DE prostate; bone and bones; neoplasm metastasis; prostatic neoplasms ID COMBINED IMMUNODEFICIENT MICE; HUMAN TUMOR-CELLS; ADULT HUMAN BONE; NUDE-MICE; ORTHOTOPIC IMPLANTATION; ANDROGEN-INDEPENDENCE; ZOLEDRONIC ACID; MURINE MODELS; MOUSE MODEL; SCID MICE AB Purpose: The metastasis of prostate cancer to bone is the most significant cause of morbidity and mortality in this disease. An estimated 28,900 men die annually secondary to prostate cancer bone metastasis. Current treatments increase survival for 2 months and only bisphosphonates offer any palliative benefit. This shortcoming is due in part to inadequate models in which to study the molecular biology of the disease and evaluate therapeutic regimens. We examined the breadth of models available that recapitulate the process of prostate cancer metastasis to bone. Materials and Methods: A PubMed search was done for publications concerning prostate cancer metastasis to bone and the imaging of bone metastases. Only studies focusing on model systems of disease progression and imaging of the process were included. Additional studies were found by cross-reference searching. Results: Prostate cancer metastasis to bone is a lengthy, complex process characterized by multiple stages. This has made it difficult to find adequate laboratory models in which to recreate the disease process. Each available model has characteristics of particular phases of disease progression to bone. The most widely used models are transgenic mice, variations of SCID mice, and the traditional orthotopic and xenotransplantation models. Furthermore, investigators have started to adapt their models to incorporate imaging modalities for following the progression of prostate cancer to bone. Conclusions: The development of models of prostate cancer metastasis to bone is an evolving discipline. A deeper understanding of the metastatic process has served to improve current models and it will continue to do so in the future. C1 NCI, Mol Pharmacol Sect, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Ctr Canc Res, Canc Therapeut Branch, Bldg 10,Room 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 69 TC 43 Z9 45 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2005 VL 174 IS 3 BP 820 EP 826 DI 10.1097/01.ju.0000169133.82167.aa PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 956BU UT WOS:000231274700006 PM 16093963 ER PT J AU Grieder, FB Whitehair, LA AF Grieder, FB Whitehair, LA TI Funding opportunities for research and graduate education: How the NIH can help you SO JOURNAL OF VETERINARY MEDICAL EDUCATION LA English DT Article; Proceedings Paper CT AAVMC Symposium 2004 CY MAR 11-15, 2004 CL Washington, DC SP AAVMC C1 NIH, Div Comparat Med, Nat Ctr Res Resources, Bethesda, MD 20814 USA. RP Grieder, FB (reprint author), NIH, Div Comparat Med, Nat Ctr Res Resources, Bethesda, MD 20814 USA. EM griederf@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV TORONTO PRESS INC PI TORONTO PA JOURNALS DIVISION, 5201 DUFFERIN ST, DOWNSVIEW, TORONTO, ON M3H 5T8, CANADA SN 0748-321X J9 J VET MED EDUC JI J. Vet. Med. Educ. PD FAL PY 2005 VL 32 IS 3 BP 314 EP 317 DI 10.3138/jvme.32.3.314 PG 4 WC Education, Scientific Disciplines; Veterinary Sciences SC Education & Educational Research; Veterinary Sciences GA 983SA UT WOS:000233251200008 PM 16261489 ER PT J AU Best, SM Bloom, ME AF Best, SM Bloom, ME TI Pathogenesis of Aleutian mink disease parvovirus and similarities to B19 infection SO JOURNAL OF VETERINARY MEDICINE SERIES B-INFECTIOUS DISEASES AND VETERINARY PUBLIC HEALTH LA English DT Article; Proceedings Paper CT International Parvovirus Meeting 2005 CY JUL 15-16, 2005 CL Leipzig, GERMANY ID ANTIBODY-DEPENDENT ENHANCEMENT; NONSTRUCTURAL PROTEIN NS1; CELL-LINE; MACROPHAGE INFECTION; CASPASE ACTIVATION; INTERFERON-GAMMA; ADULT MINK; VIRUS; REPLICATION; SUPPRESSION AB Aleutian mink disease parvovirus (ADV) is an unusual member of the autonomous parvoviruses in both its replication and pathogenesis. Infection of newborn mink kits results in an acute disease typified by virus replication in type II pneumocytes in the lung. This replication is permissive and cytopathic, characterized by the production of high levels of viral replicative intermediates and infectious progeny. However, infection of adult Aleutian mink leads to a chronic form of the disease termed Aleutian disease (AD). In this case, virus replication occurs predominantly in lymph node macrophages and is restricted, with viral DNA replication, RNA transcription, protein expression and production of infectious progeny occurring at low levels. B19 is the only autonomous parvovirus known to infect humans. The primary site of virus replication in both children and adults is in erythrocyte precursors in the blood and bone marrow, although viral genomes have been detected in various other tissues. B19 infection often causes a self-limiting disease although persistent infection of B19 can occur in both immuno-compromised and -competent people. Perhaps the most striking similarity between infection with ADV or with B19 is the important role the humoral immune response to infection has in pathogenesis. It can be both protective and pathogenic. Due to of the central role of antibody in the disease caused by either virus, understanding the specific roles of antibody production in protection, antibody-mediated enhancement of infection, the establishment of persistent infection and immune-mediated pathology will provide insight into the pathogenesis of these infections. A second similarity between the two viruses is the ability to establish persistent infection. Persistence of ADV is associated with restricted replication. Although many cellular factors may contribute to restricted virus replication, the interactions between the major non-structural protein, NS1, and the cells are likely to be critical. Parallels exist between the expression and post-translational modification of ADV and B19 NS1 proteins that may contribute to restriction of virus replication. Thus, a study of the regulation of NS1 expression and its interactions with cell signalling pathways may lead to increased understanding of the restricted replication of these two viruses, and perhaps of persistent infection. C1 NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Best, SM (reprint author), NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov FU Intramural NIH HHS NR 39 TC 6 Z9 8 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0931-1793 J9 J VET MED B JI J. Vet. Med. Ser. B-Infect. Dis. Vet. Public Health PD SEP PY 2005 VL 52 IS 7-8 BP 331 EP 334 DI 10.1111/j.1439-0450.2005.00864.x PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 979XT UT WOS:000232979100009 PM 16316395 ER PT J AU Hu, K Clement, JF Abrahamyan, L Strebel, K Bouvier, M Kleiman, L Mouland, AJ AF Hu, K Clement, JF Abrahamyan, L Strebel, K Bouvier, M Kleiman, L Mouland, AJ TI A human immunodeficiency virus type 1 protease biosensor assay using bioluminescence resonance energy transfer SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE BRET2; HIV-1; protease; inhibitor; Vif ID VIRAL PROTEASE; LIVING CELLS; HIV-1 GAG; RNA ENCAPSIDATION; TRANSFER BRET; GENOMIC RNA; VIF PROTEIN; CLEAVAGE; EXPRESSION; MATURATION AB A sensitive reporter assay to measure human immunodeficiency virus type 1 (HIV-1) protease (PR) activity is described in this manuscript. This assay measures PR activity as a function of the resonance energy transfer (RE, T) between a donour molecule [humanized sea pansy Renilla reniformis luciferase (hRLuc)] and an energy acceptor molecule, humanized green fluorescent protein (hGFP2) when expressed in mammalian cells. This is a naturally occurring phenomenon and is an emerging and powerful technology that has significant advantages over alternative in vitro PR assays. The HIV-1 Gag-p2/Gag-p7 (p2/p7) PR site was inserted between hGFP2 and hRLuc. The newly created vector, hRLuc-p2/p7h-GFP2 was co-expressed with an HIV-1 codon-optimized PR+ or PR- Gag/Pol expressor. Expression of the hRLuc-p2/p7-hGFP2 alone or with the PR- Gag-Pol expressor generated a BRET2 indicating that the PR cleavage site was not cleaved, whereas the inclusion of the PR+ Gag-Pol produced a significant reduction in the BRET2. The inclusion of PR inhibitors Saquinavir or Amprenavir, or the expression of a p2/p7 PR Substrate mutant also blocked the cleavage to result in a stable BRET2 signal. Because the HIV-1 auxiliary protein Vif has been shown to modulate the HIV-1 p2/p7 cleavage, this assay was then validated in studies in which Vif was expressed. When Vif was overexpressed along with hRLuc-p2/p7-hGFP2 and PR+ Gag-Pol, the decrease in BRET2 was abrogated in a dose-dependent manner, demonstrating that supra-physiologic levels of Vif block p2/p7 cleavage. An accumulation of a Gag processing intermediate was observed, indicating that p2/p7 cleavage was negatively affected. Overexpression of an RNA-binding-defective Staufen protein or a related dsRNA-binding protein TRBP had no effect on PR cleavage activity as shown by Western and BRET2 analyses. The p2/p7 processing data were confirmed by Western blot analyses. BRET is non-invasive and occurs within live cells, is measured in real time, and is not restricted to cellular compartments making it an especially attractive technology to identify small bioactive inhibitory molecules. This PR BRET2 biosensor assay can be adapted for high throughput screening of new HIV-1 PR inhibitors. It can be employed to screen for antiviral compounds that also target the proteases of other viruses. (c) 2005 Elsevier B.V. All rights reserved. C1 Sir Mortimer B Davis Jewish Hosp, HIV 1 RNA Trafficking Lab, Montreal, PQ H3T 1E2, Canada. Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. NIAID, NIH, Bethesda, MD 20892 USA. Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Med Microbiol & Immunol, Montreal, PQ, Canada. McGill Univ, Div Expt Med, Montreal, PQ, Canada. RP Mouland, AJ (reprint author), Sir Mortimer B Davis Jewish Hosp, HIV 1 RNA Trafficking Lab, 3999 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM andrew.mouland@mcgill.ca RI Abrahamyan, Levon/E-1982-2013; Bouvier, Michel/H-2758-2014 OI Abrahamyan, Levon/0000-0002-0849-0134; Bouvier, Michel/0000-0003-1128-0100 NR 47 TC 23 Z9 24 U1 1 U2 9 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 SEP PY 2005 VL 128 IS 1-2 BP 93 EP 103 DI 10.1016/j.jviromet.2005.04.012 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 953DA UT WOS:000231055200014 PM 15951029 ER PT J AU Biacchesi, S Skiadopoulos, MH Yang, LJ Murphy, BR Collins, PL Buchholz, UJ AF Biacchesi, S Skiadopoulos, MH Yang, LJ Murphy, BR Collins, PL Buchholz, UJ TI Rapid human metapneumovirus microneutralization assay based on green fluorescent protein expression SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE recombinant HMPV; microneutralization assay; GFP ID RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A VIRUS; YOUNG-CHILDREN; TRACT DISEASE; IN-VITRO; SERUM; INFECTION; IDENTIFICATION; GLYCOPROTEIN; INHIBITION AB We describe a simple and expedited microneutralization assay for human metapneumovirus virus (HMPV) based on a recombinant HMPV expressing the enhanced green fluorescent protein (rHMPV-GFP). Test serum dilutions were incubated with fixed amounts of rHMPV-GFP and inoculated onto Vero cells, and the growth of non-neutralized rHMPV-GFP was visualized by fluorescent microscopy of living cells. A preliminary titer could be determined following 3 days of incubation. GFP expression was sufficient to be read by an automated scanner after 4-5 days of incubation, which also provided a permanent record. In comparison, the conventional serum neutralization assay requires a longer incubation time plus the additional steps of fixation and staining or immunostaining. rHMPV-GFP-based titers could be determined by the 50% infectivity endpoint method of Reed and Muench [Reed, L.J., Muench, H., 1938. A simple method of estimating fifty per cent endpoint. Am. J. Hyg. 27, 493-497], or by automated scanning and non-linear regression to determine the 50% endpoint of GFP fluorescence. The latter method was two- to three-fold more sensitive. This assay also permits automation and up-scaling, making it suitable for broad HMPV seroepidemiology studies and experiments that require large scale serology, such as vaccine studies. (c) 2005 Elsevier B.V. All rights reserved. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Buchholz, UJ (reprint author), NIAID, Infect Dis Lab, Bldg 50,Room 6505,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov RI Biacchesi, Stephane/A-6924-2010 NR 19 TC 29 Z9 31 U1 1 U2 11 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 SEP PY 2005 VL 128 IS 1-2 BP 192 EP 197 DI 10.1016/j.jviromet.2005.05.005 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 953DA UT WOS:000231055200027 PM 15955576 ER PT J AU Forsell, MNE Li, YX Sundback, M Svehla, K Liljestrom, P Mascola, JR Wyatt, R Hedestam, GBK AF Forsell, MNE Li, YX Sundback, M Svehla, K Liljestrom, P Mascola, JR Wyatt, R Hedestam, GBK TI Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by Semliki Forest virus SO JOURNAL OF VIROLOGY LA English DT Article ID HIGH-LEVEL EXPRESSION; LOUPING-ILL VIRUS; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; RHESUS-MONKEYS; PROTECTIVE EFFICACY; VACCINE PROTECTION; DISULFIDE BONDS; HIV-1 GP120; T-CELLS AB The current lack of envelope glycoprotein immunogens that elicit broadly neutralizing antibody responses remains a major challenge for human immunodeficiency virus type 1 (HIV-1) vaccine development. However, the recent design and construction of stable soluble gp140 trimers have shown that some neutralization breadth can be achieved by using immunogens that better mimic the functional viral spike complex. The use of genetic delivery systems to drive the in vivo expression of such immunogens for the stimulation of neutralizing antibodies against HIV-1 may offer advantages by maintaining the quaternary structure of the trimeric envelope glycoproteins. Here, we describe the biochemical and immunogenic properties of soluble HIV-1 envelope glycoprotein trimers expressed by recombinant Semliki Forest virus (rSFV). The results presented here demonstrate that rSFV supports the expression of stable soluble gp140 trimers that retain recognition by conformationally sensitive antibodies. Further, we show that rSFV particle immunizations efficiently primed immune responses as measured after a single boost with purified trimeric gp140 protein, resulting in a Thl-biased antibody response. This differed from the Th2-biased antibody response obtained after repeated immunizations with purified gp140 protein trimers. Despite this difference, both regimens stimulated neutralizing antibody responses of similar potency. This suggests that rSFV may be a useful component of a viral vector prime-protein boost regimen aimed at stimulating both cell-mediated immune responses and neutralizing antibodies against HIV-1. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Swedish Inst Infect Dis Control, Dept Vaccine Res, SE-17182 Solna, Sweden. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hedestam, GBK (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, Box 280, S-17177 Stockholm, Sweden. EM Nilla.Karlsson@mtc.ki.se OI Liljestrom, Peter/0000-0002-2132-0981 NR 54 TC 26 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 17 BP 10902 EP 10914 DI 10.1128/JVI.79.17.10902-10914.2005 PG 13 WC Virology SC Virology GA 956ML UT WOS:000231303900006 PM 16103142 ER PT J AU Townsley, AC Senkevich, TG Moss, B AF Townsley, AC Senkevich, TG Moss, B TI The product of the vaccinia virus L5R gene is a fourth membrane protein encoded by all poxviruses that is required for cell entry and cell-cell fusion SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR MATURE VIRIONS; SURFACE HEPARAN-SULFATE; A27L PROTEIN; ENVELOPE; MORPHOGENESIS; IDENTIFICATION; PENETRATION; INFECTION; COMPONENT; PATHWAY AB The L5R gene of vaccinia virus is conserved among all sequenced members of the Poxviridae but has no predicted function or recognized nonpoxvirus homolog. Here we provide the initial characterization of the L5 protein. L5 is expressed following DNA replication with kinetics typical of a viral late protein, contains a single intramolecular disulfide bond formed by the virus-encoded cytoplasmic redox pathway, and is incorporated into intracellular mature virus particles, where it is exposed on the membrane surface. To determine whether L5 is essential for virus replication, we constructed a mutant that synthesizes L5 only in the presence of an inducer. The mutant exhibited a conditional-lethal phenotype, as cell-to-cell virus spread and formation of infectious progeny were dependent on the inducer. Nevertheless, all stages of replication occurred in the absence of inducer and intracellular and extracellular progeny virions appeared morphologically normal. Noninfectious virions lacking L5 could bind to cells, but the cores did not enter the cytoplasm. In addition, virions lacking L5 were unable to mediate low-pH-triggered cell-cell fusion from within or without. The phenotype of the L5R conditional lethal mutant is identical to that of recently described mutants in which expression of the A21, A28, and H2 genes is repressed. Thus, L5 is the fourth component of the poxvirus cell entry/fusion apparatus that is required for entry of both the intracellular and extracellular infectious forms of vaccinia virus. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Mem Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 43 TC 58 Z9 61 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 17 BP 10988 EP 10998 DI 10.1128/JVI.79.17.10988-10998.2005 PG 11 WC Virology SC Virology GA 956ML UT WOS:000231303900014 PM 16103150 ER PT J AU Karlsson, I Grivel, JC Chen, SS Karlsson, A Albert, J Fenyo, EM Margolis, LB AF Karlsson, I Grivel, JC Chen, SS Karlsson, A Albert, J Fenyo, EM Margolis, LB TI Differential pathogenesis of primary CCR5-using human immunodeficiency virus type 1 isolates in ex vivo human lymphoid tissue SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; DISEASE PROGRESSION; HIV-INFECTION; IN-VITRO; GASTROINTESTINAL-TRACT; CORECEPTOR USE; MESSENGER-RNA; REPLICATION; LYMPHOCYTES; VARIANTS AB In the course of human immunodeficiency virus (HIV) disease, CCR5-utilizing HIV type 1 (HIV-1) variants (R5), which typically transmit infection and dominate its early stages, persist in approximately half of the infected individuals (nonswitch virus patients), while in the other half (switch virus patients), viruses using CXCR4 (X4 or R5X4) emerge, leading to rapid disease progression. Here, we used a system of ex vivo tonsillar tissue to compare the pathogeneses of sequential primary R5 HIV-1 isolates from patients in these two categories. The absolute replicative capacities of HIV-1 isolates seemed to be controlled by tissue factors. In contrast, the replication level hierarchy among sequential isolates and the levels of CCR5(+) CD4(+) T-cell depletion caused by the R5 isolates seemed to be controlled by viral factors. R5 viruses isolated from nonswitch virus patients depleted more target cells than R5 viruses isolated from switch virus patients. The high depletion of CCR5+ cells by HIV-1 isolates from nonswitch virus patients may explain the steady decline of CD4+ T cells in patients with continuous dominance of R5 HIV-1. The level of R5 pathogenicity, as measured in ex vivo lymphoid tissue, may have a predictive value reflecting whether, in an infected individual, X4 HIV-1 will eventually dominate. C1 Lund Univ, Dept Lab Med, Div Med Microbiol, Virol Unit, S-22362 Lund, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. NIH, NASA, Ctr Dimens Tissue Culture 3, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. Karolinska Univ Hosp, Stockholm, Sweden. Karolinska Inst, Swedish Inst Dis Control, Stockholm, Sweden. Karolinska Inst, Microbiol & Tumorbiol Ctr, Stockholm, Sweden. RP Karlsson, I (reprint author), Lund Univ, Dept Lab Med, Div Med Microbiol, Virol Unit, Solvegatan 23, S-22362 Lund, Sweden. EM Ingrid.Karlsson@mmb.lu.se NR 61 TC 19 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 17 BP 11151 EP 11160 DI 10.1128/JVI.79.17.11151-11160.2005 PG 10 WC Virology SC Virology GA 956ML UT WOS:000231303900030 PM 16103166 ER PT J AU Fletcher, P Kiselyeva, Y Wallace, G Romano, J Griffin, G Margolis, L Shattock, R AF Fletcher, P Kiselyeva, Y Wallace, G Romano, J Griffin, G Margolis, L Shattock, R TI The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; SEXUAL TRANSMISSION; MICROBICIDES; UC781; HISTOCULTURES; STRAINS AB Heterosexual transmission of human immunodeficiency virus remains the major route of transmission worldwide; thus, there is an urgent need for additional prevention strategies, particularly those that could be controlled by women. Using cellular and tissue explant models, we have evaluated the potential activity of thiocarboxanilide nonnucleoside analogue reverse transcriptase inhibitor UC-781 as a vaginal microbicide. We were able to demonstrate a potent dose-dependent effect against R5 and X4 infections of T cells. In human cervical explant cultures, UC-781 was not only able to inhibit direct infection of mucosal tissue but was able to prevent dissemination of virus by migratory cells. UC-781 formulated into a carbopol gel (0.1%) retained significant activity against both direct tissue infection and transinfection mediated by migratory cells. Furthermore, UC-781 demonstrated prolonged inhibitory effects able to prevent both localized and disseminated infections up to 6 days post compound treatment. Additional studies were carried out to determine the concentration of compound that might be required to block a primary infection within draining lymph nodes. While a greater dose of compound was required to inhibit both X4 and R5 infections of lymphoid versus cervical explants, this was equivalent to a 1:3,000 dilution of the 0.1% formulation. Furthermore, a 2-h exposure to the compound prevented infection of lymphoid tissue when challenged up to 2 days later. The prolonged protection observed following pretreatment of both genital and lymphoid tissues with UC-781 suggests that this class of inhibitors may have unique advantages over other classes of potential microbicide candidates. C1 Univ London, Div Infect Dis Cellular & Mol Med, London SW17 0RE, England. Biosyn Inc, Huntingdon Valley, PA USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Shattock, R (reprint author), Univ London, Div Infect Dis Cellular & Mol Med, Cranmer Terrace, London SW17 0RE, England. EM shattock@sgul.ac.uk NR 24 TC 71 Z9 72 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 SEP PY 2005 VL 79 IS 17 BP 11179 EP 11186 DI 10.1128/JVI.79.17.11179-11186.2005 PG 8 WC Virology SC Virology GA 956ML UT WOS:000231303900033 PM 16103169 ER PT J AU Yoshizuka, N Yoshizuka-Chadani, Y Krishnan, V Zeichner, SL AF Yoshizuka, N Yoshizuka-Chadani, Y Krishnan, V Zeichner, SL TI Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-EXPRESSION; T-CELLS; EFFICIENT REPLICATION; TISSUE MACROPHAGES; ACCESSORY PROTEIN; NUCLEAR IMPORT; HIV-1; APOPTOSIS; INFECTION; MECHANISM AB The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G(2), which increases HIV gene expression. Some of Vpr's activities have been well described, but some functions, such as cell cycle arrest, are not yet completely characterized, although components of the ATR DNA damage repair pathway and the Cdc25C and Cdc2 cell cycle control mechanisms clearly play important roles. We investigated the mechanisms underlying Vpr-mediated cell cycle arrest by examining global cellular gene expression profiles in cell lines that inducibly express wild-type and mutant Vpr proteins. We found that Vpr expression is associated with the down-regulation of genes in the MEK2-ERK pathway and with decreased phosphorylation of the MEK2 effector protein ERK. Exogenous provision of excess MEK2 reverses the cell cycle arrest associated with Vpr, confirming the involvement of the MEK2-ERK pathway in Vpr-mediated cell cycle arrest. Vpr therefore appears to arrest the cell cycle at G(2)/M through two different mechanisms, the ATR mechanism and a newly described MEK2 mechanism. This redundancy suggests that Vpr-mediated cell cycle arrest is important for HIV replication and pathogenesis. Our findings additionally reinforce the idea that HIV can optimize the host cell environment for viral replication. C1 Natl Canc Inst, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20817 USA. RP Zeichner, SL (reprint author), Natl Canc Inst, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 10S255 MSC1868, Bethesda, MD 20817 USA. EM zeichner@nih.gov NR 46 TC 25 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2005 VL 79 IS 17 BP 11366 EP 11381 DI 10.1128/JVI.79.17.11366-11381.2005 PG 16 WC Virology SC Virology GA 956ML UT WOS:000231303900052 PM 16103188 ER PT J AU VanCompernolle, SE Taylor, RJ Oswald-Richter, K Jiang, JY Youree, BE Bowie, JH Tyler, MJ Conlon, JM Wade, D Aiken, C Dermody, TS KewalRamani, VN Rollins-Smith, LA Unutmaz, D AF VanCompernolle, SE Taylor, RJ Oswald-Richter, K Jiang, JY Youree, BE Bowie, JH Tyler, MJ Conlon, JM Wade, D Aiken, C Dermody, TS KewalRamani, VN Rollins-Smith, LA Unutmaz, D TI Antimicrobial peptides from amphibian skin potently inhibit human immunodeficiency virus infection and transfer of virus from dendritic cells to T cells SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; DC-SIGN; CYANOVIRIN-N; BATRACHOCHYTRIUM-DENDROBATIDIS; REOVIRUS PARTICLES; CHROMIUM RELEASE; THETA-DEFENSIN; LIPID-BILAYERS; HOST-CELLS; PROTEIN AB Topical antimicrobicides hold great promise in reducing human immunodeficiency virus (HIV) transmission. Amphibian skin provides a rich source of broad-spectrum antimicrobial peptides including some that have antiviral activity. We tested 14 peptides derived from diverse amphibian species for the capacity to inhibit HIV infection. Three peptides (caerin 1.1, caerin 1.9, and maculatin 1.1) completely inhibited HIV infection of T cells within minutes of exposure to virus at concentrations that were not toxic to target cells. These peptides also suppressed infection by murine leukemia virus but not by reovirus, a structurally unrelated nonenveloped virus. Preincubation with peptides prevented viral fusion to target cells and disrupted the HIV envelope. Remarkably, these amphibian peptides also were highly effective in inhibiting the transfer of HIV by dendritic cells (DCs) to T cells, even when DCs were transiently exposed to peptides 8 h after virus capture. These data suggest that amphibian-derived peptides can access DC-sequestered HIV and destroy the virus before it can be transferred to T cells. Thus, amphibian-derived antimicrobial peptides show promise as topical inhibitors of mucosal HIV transmission and provide novel tools to understand the complex biology of HIV capture by DCs. C1 Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. AdvancMed LLC, Lexington, KY 40513 USA. Univ Adelaide, Dept Chem, Adelaide, SA, Australia. Univ Adelaide, Dept Environm Biol, Adelaide, SA, Australia. United Arab Emirates Univ, Dept Biochem, Al Ain, U Arab Emirates. Wade Res Fdn, Somerset, NJ 08873 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Unutmaz, D (reprint author), Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, 21st Ave S,Med Ctr N,Room AA5206, Nashville, TN 37232 USA. EM Derya.Unutmaz@vanderbilt.edu OI Wade, David/0000-0003-3343-510X; Conlon, John Michael/0000-0002-4343-1551 FU NIAID NIH HHS [R01 AI47506, R01 AI032539, R01 AI049131, R01 AI32539] NR 68 TC 73 Z9 78 U1 3 U2 15 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 SEP PY 2005 VL 79 IS 18 BP 11598 EP 11606 DI 10.1128/JVI.79.18.11598-11606.2005 PG 9 WC Virology SC Virology GA 961AI UT WOS:000231633900006 PM 16140737 ER PT J AU Murray, JL Mavrakis, M McDonald, NJ Yilla, M Sheng, JS Bellini, WJ Zhao, LJ Le Doux, JM Shaw, MW Luo, CC Lippincott-Schwartz, J Sanchez, A Rubin, DH Hodge, TW AF Murray, JL Mavrakis, M McDonald, NJ Yilla, M Sheng, JS Bellini, WJ Zhao, LJ Le Doux, JM Shaw, MW Luo, CC Lippincott-Schwartz, J Sanchez, A Rubin, DH Hodge, TW TI Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus SO JOURNAL OF VIROLOGY LA English DT Article ID TRANS-GOLGI NETWORK; LIPID RAFT MICRODOMAINS; PLASMA-MEMBRANE; MATRIX PROTEIN; ENVELOPE GLYCOPROTEIN; MULTIVESICULAR BODIES; PRIMARY MACROPHAGES; CLATHRIN ADAPTER; HIV-1 INFECTION; LATE ENDOSOMES AB Rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. By using gene trap insertional mutagenesis, we identified Rab9, which mediates lateendosome-to-trans-Golgi-network trafficking, among several candidate host genes whose disruption allowed the survival of Marburg virus-infected cells, suggesting that Rab9 is utilized in Marburg replication. Although Rab9 has not been implicated in human immunodeficiency virus (HIV) replication, previous reports suggested that the late endosome is an initiation site for HIV assembly and that TIP47-dependent trafficking out of the late endosome to the trans-Golgi network facilitates the sorting of HIV Env into virions budding at the plasma membrane. We examined the role of Rab9 in the life cycles of HIV and several unrelated viruses, using small interfering RNA (siRNA) to silence Rab9 expression before viral infection. Silencing Rab9 expression dramatically inhibited HIV replication, as did silencing the host genes encoding TIP47, p40, and PlKfyve, which also facilitate late-endosome-to-trans-Golgi vesicular transport. In addition, silencing studies revealed that HIV replication was dependent on the expression of Rab11A, which mediates trans-Golgi-to-plasma-membrane transport, and that increased HIV Gag was sequestered in a CD63(+) endocytic compartment in a cell line stably expressing Rab9 siRNA. Replication of the enveloped Ebola, Marburg, and measles viruses was inhibited with Rab9 siRNA, although the nonenveloped reovirus was insensitive to Rab9 silencing. These results suggest that Rab9 is an important cellular target for inhibiting diverse viruses and help to define a late-endosome-to-plasma-membrane vesicular transport pathway important in viral assembly. C1 Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA. Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Avatar BioSci Inc, Nashville, TN USA. Georgia Tech, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. Emory Univ, Atlanta, GA 30322 USA. VA Tennessee Valley Healthcare Syst, Dept Med Res, Nashville, TN 37212 USA. Hudson Alpha Inst Biotechnol, Huntsville, AL USA. RP Hodge, TW (reprint author), Univ Georgia, Coll Vet Med, Dept Infect Dis, 220 Riverbend Rd,Room 112, Athens, GA 30602 USA. EM thodge@vet.uga.edu NR 60 TC 101 Z9 108 U1 1 U2 10 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 SEP PY 2005 VL 79 IS 18 BP 11742 EP 11751 DI 10.1128/JVI.79.18.11742-11751.2005 PG 10 WC Virology SC Virology GA 961AI UT WOS:000231633900021 PM 16140752 ER PT J AU Onder, G Penninx, BWJH Cesari, M Bandinelli, S Lauretani, F Bartali, B Gori, AM Pahor, M Ferrucci, L AF Onder, G Penninx, BWJH Cesari, M Bandinelli, S Lauretani, F Bartali, B Gori, AM Pahor, M Ferrucci, L TI Anemia is associated with depression in older adults: Results from the InCHIANTI study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID QUALITY-OF-LIFE; CEREBRAL-BLOOD-FLOW; HEMOGLOBIN LEVELS; ELDERLY PERSONS; SYMPTOMS; HEMATOCRIT; DEFICIENCY; MORTALITY; HEALTH; EPIDEMIOLOGY AB Background. Depression is a common disorder among older adults, and it has been associated with adverse outcomes, including increased risk of morbidity and mortality as well as incomplete or delayed recovery from illness and disability. The objective of this study was to examine whether depressive symptoms and anemia are associated among older adults living in the community. Methods. We used data from the "Invecchiare in Chianti" (Aging in the Chianti area, InCHIANTI) study, a prospective population-based study of older people living in the community. Anemia was defined by the World Health Organization (WHO) criteria: hemoglobin concentration below 12 a/dl in women and below 13 g/dl in men. Depressive symptoms were measured by using the Center for Epidemiological Studies Depression Scale (CES-D). Participants with a CES-D score >= 16 were considered to be depressed. Results. Mean age of the 986 participants was 75 years, and 56% were female; 3 13 (32%) study participants were depressed. Anemia was recorded in 48 of the 313 (15%) participants with depression and in 53 of the 673 (8%) participants without depression (p <.001). After adjusting for potential confounders, depression was associated with a significant higher risk of anemia (odds ratio = 1.93; 95% confidence interval, 1.19-3.13). The risk of anemia progressively and significantly increased with increasing CES-D score (signifying more severe depression). Compared with nondepressed participants (CES-D score < 16), the odds ratio for anemia were 1.74, 2.04, and 2. 10 for participants with mild (score= 16-20), moderate (score =21-26), and severe depression (score > 26), respectively (p for linear trend =.01). Conclusions. Depressive symptoms are associated with anemia in a general zpopulation of older persons living in the community. C1 Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Policlin A Gemelli, Dept Geriatr, I-00168 Rome, Italy. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. I Fraticini Natl Res Inst, Dept Geriatr, Florence, Italy. Univ Florence, Dept Clin & Surg Care, Sect Clin Med, Thrombosis Ctr, Florence, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Onder, G (reprint author), Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Policlin A Gemelli, Dept Geriatr, Lgo Francesco Vito 1, I-00168 Rome, Italy. EM graziano_onder@rm.unicatt.it RI Cesari, Matteo/A-4649-2008; Lauretani, Fulvio/K-5115-2016 OI Cesari, Matteo/0000-0002-0348-3664; Gori, annamaria.gori@unifi.it/0000-0001-6857-5861; Lauretani, Fulvio/0000-0002-5287-9972 FU NIA NIH HHS [P30AG021332-01] NR 39 TC 46 Z9 49 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2005 VL 60 IS 9 BP 1168 EP 1172 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 969RO UT WOS:000232252600013 PM 16183958 ER PT J AU Norris, KC Agodoa, LY AF Norris, KC Agodoa, LY TI Unraveling the racial disparities associated with kidney disease SO KIDNEY INTERNATIONAL LA English DT Review DE chronic kidney disease; culture; dialysis; end-stage renal disease; ethnic groups; racial disparities; socioeconomic; transplantation ID STAGE RENAL-DISEASE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; UNITED-STATES; IGA NEPHROPATHY; BLOOD-PRESSURE; AFRICAN-AMERICANS; NEW-ZEALAND; TRANSPLANT RECIPIENTS; DIABETES-MELLITUS AB In the United States, chronic kidney disease (CKD), and in particular end-stage renal disease (ESRD), represent a growing problem. Many other countries also have an increasing number of ESRD cases. Racial/ethnic disparities have been documented globally in the prevalence, incidence, and treatment of CKD, most extensively in the United States, but also in the United Kingdom, Australia, and New Zealand, among others. In many circumstances, these disparities are of a negative nature, that is, certain racial/ethnic groups fare worse than their white counterparts with respect to the treatment or outcome of CKD. However, in a few circumstances, they are of a positive nature, such as the survival advantage seen in minorities with ESRD compared with whites. The reasons for racial disparities in the prevalence, incidence, and treatment of CKD are not fully understood, although they are explained partly by coexisting medical conditions and modifiable risk factors, such as socioeconomic, lifestyle, and cultural. It is likely, however, that the complete picture incorporates a complex interaction between these sociocultural, genetic, and environmental factors. In a global society that prides itself on a high level of sensitivity and equality, there is an ethical and moral imperative to address the continuing racial/ethnic disparities in CKD and many of the factors underlying this epidemic. We review data highlighting the racial/ethnic disparities that exist in the incidence and treatment of CKD, with particular emphasis on ESRD. A better understanding of both the negative and positive racial/ethnic disparities may yield important insights, which can inform future research strategies and improve health outcomes for all patients afflicted with CKD. C1 Charles R Drew Univ Med & Sci, Dept Med, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Norris, KC (reprint author), Charles R Drew Univ Med & Sci, Dept Med, Hawkins Bldg,Room 3080,1731 E 120th St, Los Angeles, CA 90059 USA. EM knorris@ucla.edu FU NCRR NIH HHS [RR019234, RR11145]; NIMHD NIH HHS [MD00182] NR 107 TC 99 Z9 102 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2005 VL 68 IS 3 BP 914 EP 924 DI 10.1111/j.1523-1755.2005.00485.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 952RJ UT WOS:000231022900001 PM 16105022 ER PT J AU Pavkov, ME Bennett, PH Sievers, ML Krakoff, J Williams, DE Knowler, WC Nelson, RG AF Pavkov, ME Bennett, PH Sievers, ML Krakoff, J Williams, DE Knowler, WC Nelson, RG TI Predominant effect of kidney disease on mortality in Pima Indians with or without type 2 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE Pima Indians; kidney disease; type 2 diabetes; mortality ID STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; SERUM CREATININE; HEART-DISEASE; INSUFFICIENCY; PREVALENCE; HEALTH; RISK; PROTEINURIA AB Background. We examined the effect of kidney disease (KD) on mortality in nondiabetic and diabetic Pima Indians aged >= 45 years old. Methods. Deaths and person-years of follow-up were stratified in a time-dependent fashion into categories of (1) no proteinuria and normal serum creatinine (SCr); (2) proteinuria and normal SCr; (3) high SCr [SCr >= 133 mu mol/L (1.5 mg/dL) in men, >= 124 mu mol/L (1.4 mg/dL) in women] but not on renal replacement therapy (RRT); or (4) RRT. Results. Among 1993 subjects, 55.8% had type 2 diabetes at baseline. Overall death rates increased with declining kidney function in both the nondiabetic and diabetic subjects (P < 0.0001). Death rates were similar in nondiabetic and diabetic subjects with comparable levels of kidney function, although the number of deaths among nondiabetic subjects with advanced KD was small. Infections and malignancy were the leading causes of death in nondiabetic subjects with KD. Among diabetic subjects, overall mortality increased with diabetes duration (P= 0.0001) and was highest in those on RRT (P < 0.0001). High SCr was associated with higher death rates from cardiovascular disease (CVD), diabetic nephropathy (DN), infections, and malignancy. Conclusion. Death rates increased comparably with worsening kidney function in both nondiabetic and diabetic subjects and were similar in nondiabetic and diabetic subjects without KD. KD was associated with excess mortality from DN, CVD, infections, and malignancy in diabetic subjects, and from infections in those without diabetes. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Pavkov, ME (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM mpavkov@phx.niddk.nih.gov RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [Z01 DK069000-40] NR 32 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2005 VL 68 IS 3 BP 1267 EP 1274 DI 10.1111/j.1523-1755.2005.00523.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 952RJ UT WOS:000231022900039 PM 16105060 ER PT J AU Dirks, JH De Zeeuw, D Agarwal, SK Atkins, RC Correa-Rotter, R D'Amico, G Bennett, PH El Nahas, M Valdes, RH Kaseje, D Katz, IJ Naicker, S Rodriguez-Iturbe, B Schieppati, A Shaheen, F Sitthi-Amorn, C Solez, K Viberti, G Remuzzi, G Weening, JJ AF Dirks, JH De Zeeuw, D Agarwal, SK Atkins, RC Correa-Rotter, R D'Amico, G Bennett, PH El Nahas, M Valdes, RH Kaseje, D Katz, IJ Naicker, S Rodriguez-Iturbe, B Schieppati, A Shaheen, F Sitthi-Amorn, C Solez, K Viberti, G Remuzzi, G Weening, JJ CA Int Soc of Nephrology Commission TI Prevention of chronic kidney and vascular disease: Toward global health equity - The Bellagio 2004 Declaration SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Bellagio Conference on Prevention of Renal Disease in the Emerging World CY MAR 16-18, 2004 CL Bellagio, ITALY DE chronic kidney disease; diabetes; hypertension; prevention; capacity building ID STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; DIABETIC-NEPHROPATHY; AUSDIAB KIDNEY; MICROALBUMINURIA; PROTEINURIA; RISK; HYPERTENSION; POPULATION; MORTALITY AB Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment. C1 Massey Coll, Toronto, ON, Canada. Univ Med Ctr, Dept Clin Pharmacol, Groningen, Netherlands. AIIMS, Dept Nephrol, New Delhi, India. Monash Med Ctr, Melbourne, Vic, Australia. Inst Nacl Ciencias Med & Nutr, Dept Nefrol, Mexico City, DF, Mexico. San Carlo Borromeo Hosp, Div Nephrol, Milan, Italy. NIDDK, Phoenix, AZ USA. No Gen Hosp, Sheffield Kidney Inst, Sheffield, S Yorkshire, England. Inst Nefrol, Havana, Cuba. TICH, Kisumu, Kenya. Chris Hani Baragwanath Nephrol Unit, Norwood, South Africa. Johannesburg Hosp, Div Nephrol, Johannesburg, South Africa. Hosp Univ Univ Zulia, Maracaibo, Venezuela. Osped Rioniti, Bergamo, Italy. Jeddah Kidney Ctr, Jeddah, Saudi Arabia. Chulalongkorn Univ, Bangkok, Thailand. Univ Alberta, Dept Pathol, Edmonton, AB T6G 2E1, Canada. KCL Guys Hosp, London, England. Mario Negri Inst Pharmacol Res, Negri Bergamo Labs, Bergamo, Italy. Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. RP Weening, JJ (reprint author), Acad Med Ctr, Dept Pathol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM j.j.weening@amc.uva.nl RI de Zeeuw, Dick/E-9080-2014 OI de Zeeuw, Dick/0000-0003-3434-7777 NR 49 TC 60 Z9 65 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2005 VL 68 SU 98 BP S1 EP S6 DI 10.1111/j.1523-1755.2005.09800.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 961OW UT WOS:000231672700001 PM 16108963 ER PT J AU Paul, JT Henson, ES Mai, S Mushinski, JF Cheang, M Gibson, SB Johnston, JB AF Paul, JT Henson, ES Mai, S Mushinski, JF Cheang, M Gibson, SB Johnston, JB TI Cyclin D expression in chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE chronic lymphocytic leukemia; cyclin D1; cyclin D2; cyclin D3; prognostic markers; survival ID MANTLE CELL LYMPHOMA; MULTIPLE-MYELOMA; PROGNOSTIC-SIGNIFICANCE; REGULATORY PROTEINS; INDUCED APOPTOSIS; CDK INHIBITORS; OVEREXPRESSION; FLUDARABINE; PROGRESSION; GENES AB Although the majority of circulating leukemic cells in chronic lymphocytic leukemia (CLL) are in G0/early G1, recent studies have shown that these cells have undergone multiple cell divisions. In this study, we have determined whether there are abnormalities in cell cycle control in CLL by examining the three cyclin D isoforms in 43 patients and correlating the findings with clinical features. Cyclin D mRNA was measured by a sensitive RNase protection assay and the order of expression in CLL cells was D3 > D2 > D1. The mean cyclin D1 and D3 mRNA levels were 4 to 6-fold higher in CLL cells than in normal peripheral blood B cells. In contrast, the levels of cyclin D2 mRNA were similar in CLL and normal B cells. Expression of the cyclin D isoforms was two- to four-fold greater in normal T cells than B cells, and the order of expression for both cell types was D2 > D3 > D1. The relative overexpressions of cyclins D1 and D3 in CLL were unrelated to gene amplification, as assessed by Southern blotting, but structural changes in the genes were seen in four patients. Both cyclin D1 and D3 mRNA levels correlated positively with lymphocyte doubling time ( LDT) and inversely with Rai stage and duration of disease. In addition, a significant correlation was observed between cyclin D mRNA levels and survival, with patients having high levels of cyclin D1, and to a lesser extent cyclin D3, mRNA having the best survival. Thus, cyclin D1 and D3 are relatively overexpressed in CLL cells and patients with higher levels have low stage disease, long LDT and prolonged survival. Further studies should evaluate the predictive value of cyclin D measurements in comparison to other prognostic markers in CLL. C1 Manitoba Inst Cell Biol, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada. Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB, Canada. NCI, Mol Genet Sect, Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Dept Stat, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Dept Physiol, Winnipeg, MB, Canada. Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada. RP Johnston, JB (reprint author), Manitoba Inst Cell Biol, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB R3E 0V9, Canada. EM james.johnston@cancercare.mb.ca RI Mai, Sabine/E-5667-2017; OI Mai, Sabine/0000-0002-5797-2201; Gibson, Spencer/0000-0003-0119-732X NR 42 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2005 VL 46 IS 9 BP 1275 EP 1285 DI 10.1080/10428190500158797 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 956PP UT WOS:000231312600004 PM 16109604 ER PT J AU Frankel, AE Kreitman, RJ AF Frankel, AE Kreitman, RJ TI CLL immunotoxins SO LEUKEMIA RESEARCH LA English DT Editorial Material DE immunotoxins; CLL; leukemia ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PHASE-I TRIAL; HEMATOLOGIC MALIGNANCIES; DENILEUKIN DIFTITOX; INTERLEUKIN-4; IMMUNOBIOLOGY; ANTIBODY; TOXIN AB Immunotoxins composed of cell-selective ligands covalently linked to peptide toxins have been developed for the treatment of chemotherapy relapsed or refractory malignancies including chronic lymphocytic leukemia (CLL). A number of CLL immunotoxins have been clinically tested including T101-ricin A, H65-ricin A, DAB(486)IL2, DAB(389)IL2, RFB4 (dsFv)-PE38 and anti-Tac(Fv)-PE38. Remissions have occurred in some patients without significant myelosuppression, but novel agents continue to be needed. Kay and co-workers in this issue of Leukemia Research have targeted interleukin-4 receptors (IL-4R) on CLL B cells with a recombinant IL4 pseudomonas exotoxin fusion protein (IL-4(38-37)-PE38KDEL). A fraction of patients (19%) had CLL cells that were extremely sensitive to the immunotoxin. This novel agent may provide an important new therapeutic for use in the treatment of CLL. (c) 2005 Elsevier Ltd. All rights reserved. C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. NCI, Bethesda, MD 20892 USA. RP Frankel, AE (reprint author), Wake Forest Univ, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM afrankel@wfubmc.edu NR 22 TC 8 Z9 8 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 SEP PY 2005 VL 29 IS 9 BP 985 EP 986 DI 10.1016/j.leukres.2005.02.008 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 952MN UT WOS:000231007700002 PM 16038723 ER PT J AU Shen, M Rothman, N Berndt, SI He, XZ Yeager, M Welch, R Chanock, S Caporaso, N Lan, Q AF Shen, M Rothman, N Berndt, SI He, XZ Yeager, M Welch, R Chanock, S Caporaso, N Lan, Q TI Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China SO LUNG CANCER LA English DT Article DE folate metabolism; single nucleotide; polymorphism; lung cancer; polycyclic aromatic; hydrocarbon; haplotype ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; COMBUSTION EMISSIONS; COMMON MUTATION; INDOOR COAL; FOLIC-ACID; CBS GENE; HOMOCYSTEINE; DNA; DISEASE; ASSOCIATION AB The aim of this study is to investigate the role of genetic polymorphisms in twelve folate metabolism genes on the risk of Lung cancer in Xuan Wei, China, where the lung cancer mortality rate is among the highest and is mainly caused by indoor smoky coal emissions. A total of 122 incident primary lung cancer cases and 122 matched controls were enrolled. Three single nucleotide polymorphisms were associated with increased risk of Lung cancer including homozygotes of the C allele of CBS Ala360Ala (OR: 4.02; 95% CI: 1.64-9.87), the 222Val allele of MTHFR (OR: 2.32; 95% CI: 1.34-4.03), and the C allele of SLC19A1 Pro232Pro (OR: 1.83; 95% CI: 1.02-3.28). The distribution of CBS and MTHFR haplotypes differed between cases and controls (P=0.002 and P=0.07, respectively). In summary, three genetic variants in folate metabolism genes are associated with an increased risk of lung cancer in Xuan Wei, China. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 DHHS, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NCI,NIH, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. NCI, CCR, DHHS, NIH, Bethesda, MD 20892 USA. RP Shen, M (reprint author), DHHS, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NCI,NIH, MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov NR 43 TC 48 Z9 50 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 2005 VL 49 IS 3 BP 299 EP 309 DI 10.1016/j.lungcan.2005.04.002 PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 965EH UT WOS:000231932500002 PM 15922487 ER PT J AU Lan, Q Shen, M Berndt, SI Bonner, MR He, XZ Yeager, M Welch, R Keohavong, P Donahue, M Hainaut, P Chanock, S AF Lan, Q Shen, M Berndt, SI Bonner, MR He, XZ Yeager, M Welch, R Keohavong, P Donahue, M Hainaut, P Chanock, S TI Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China SO LUNG CANCER LA English DT Article DE polycyclic aromatic hydrocarbons; haplotype; lung-cancer ID MOLECULAR EPIDEMIOLOGY; MUTATIONS; GENE; RECOMBINATION; HAPLOTYPE; ASSOCIATION; POPULATION AB Lung cancer rates in Xuan Wei County are among the highest in China and have been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons (PAHs). The NBS1 gene product participates in DNA double-strand break repair and DNA damage-induced checkpoint activation, which are critical for maintaining genomic integrity. The p53 tumor suppressor gene is known to play key roles both in the maintenance of genomic stability in mammalian cells and in DNA damage surveillance. We examined the association between two common NBS1 polymorphisms (Leu34Leu, GLn185Glu) and lung cancer risk in a population-based case-control study in Xuan Wei, China. Individuals homozygous for the NBS1 34Leu or NBS1 185Glu variants were found to have an increased risk of lung cancer (odds ratio [OR] 2.15, 95% confidence interval [CI]: 0.91-5.10 and OR 2.53, 95% CI: 1.05-6.08, respectively). A haplotype containing the variant alleles from both NBS1 SNPs was associated with increased risk of lung cancer compared with the most common haplotype. Further, the associations were particularly pronounced among cases with over expression of p53 protein. These results suggest that NBS1 could be important in the pathogenesis of lung cancer in this population. However, additional studies in other populations with substantial environmental exposures to PAHs are needed to confirm our findings. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. Chinese Acad Prevent Med, Beijing, Peoples R China. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. Int Agcy Res Canc, F-69372 Lyon, France. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Hainaut, Pierre /B-6018-2012; OI Hainaut, Pierre /0000-0002-1303-1610; Keohavong, Phouthone/0000-0001-7812-4925 NR 26 TC 33 Z9 35 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 2005 VL 49 IS 3 BP 317 EP 323 DI 10.1016/j.lungcan.2005.04.004 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 965EH UT WOS:000231932500004 PM 15921821 ER PT J AU Wen, H Bennett, E Epstein, N Plehn, J AF Wen, H Bennett, E Epstein, N Plehn, J TI Magnetic resonance imaging assessment of myocardial elastic modulus and viscosity using displacement imaging and phase-contrast velocity mapping SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article ID CONGESTIVE HEART-FAILURE; CANINE LEFT-VENTRICLE; SYSTOLIC FUNCTION; VISCOELASTIC PROPERTIES; PRESSURE-GRADIENTS; FIBER ORIENTATION; EJECTION FRACTION; STIMULATED ECHOES; STRAIN ANALYSIS; IN-VIVO AB Approximately half of patients experiencing congestive heart failure present with a normal left ventricular ejection fraction. Perturbations in material properties affecting ventricular pressure/volume relationships likely play an important role in the "stiff heart syndrome" yet noninvasive tools permitting the accurate assessment of myocardial elasticity are extremely limited. We developed an MRI-based technique to examine regional left ventricular stress/strain relationships by incorporating displacement-encoding with stimulated-echoes (DENSE) and phase-contrast (PC) velocity mapping and compared regional elastic moduli (EM) and viscous delay time constants (VDTCs) (N = 10) with immediate postmortem direct strain gauge measurements (N = 8) and global chamber compliance (literature) in normal dogs. EMs by MRI were significantly greater in papillary muscle columns when compared with lateral wall and septal locations by MR1 (7.59 +/- 1.65 versus 3.40 +/- 0.87 versus 2.55 +/- 0.93 kPa, P < 0.0001) and were in agreement with direct strain gauge measurements (3.78 +/- 0.93 and 2.96 +/- 0.88 kPa for the lateral wall and the septum, P = Ins for both versus MRI). MRI-determined VDTCs were similar in the three regions (VDTC = -1.15 +/- 12.37 versus 3.04 +/- 7.25 versus 4.17 +/- 5.76 ms, P = ns) and did not differ from lateral and septal wall strain gauge assessment (VDTC = 3.09 +/- 0.40 and 4.57 +/- 1.86 ms, P = ns for both versus MRI). Viscoelastic measurements obtained in six normal volunteers demonstrated the feasibility of this technique in humans. Noninvasive, regional assessment of myocardial stiffness using DENSE and PC velocity mapping techniques is accurate in a canine model and feasible in humans. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-13] NR 42 TC 22 Z9 22 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2005 VL 54 IS 3 BP 538 EP 548 DI 10.1002/mrm.20589 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 959CH UT WOS:000231494000005 PM 16086299 ER PT J AU van Gelderen, P Wu, CWH de Zwart, JA Cohen, L Hallett, M Duyn, JH AF van Gelderen, P Wu, CWH de Zwart, JA Cohen, L Hallett, M Duyn, JH TI Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; functional imaging; localization; brain imaging; fMRI; BOLD ID ELECTRICAL FINGER STIMULATION; HUMAN SOMATOSENSORY CORTEX; MAGNETIC-RESONANCE; SENSORY STIMULATION; OCULAR DOMINANCE; VISUAL-CORTEX; MOTOR TASK; FMRI; REPRESENTATION; ACTIVATION AB Visual and somatosensory activation studies were performed on normal subjects to compare the spatial discrimination and reproducibility between functional MRI (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a dedicated MRI acquisition technique was developed. Repeated experiments of sensory stimulation of single digits of the right hand showed an average variability of activation amplitude of 25% for BOLD data, and a significantly lower variability of 21% for perfusion data. No significant difference in the variability of the locus of activity was observed between the BOLD and perfusion data. In somatotopy experiments, digits II and V were subjected to passive sensory stimulation. Both the BOLD and perfusion data showed substantial overlap in the activation patterns from the two digits. In a retinotopy study, two stimuli were alternated to excite different patches of V1. Again there was substantial overlap between the activation patterns from both stimuli, although the perfusion performed somewhat better than the BOLD method. Particularly for the visual studies, the overlap in activation patterns was more than expected based on the fine-scale retinotopic mapping of cortical activity, suggesting that both BOLD and perfusion contrast mechanisms contribute substantially to the point-spread function(PSF). C1 NINDS, Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA. RP van Gelderen, P (reprint author), NINDS, Adv MRI, LFMI, NIH, Rm B1D-725,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM gelderen@nih.gov RI Duyn, Jozef/F-2483-2010 NR 37 TC 18 Z9 18 U1 0 U2 2 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 SEP PY 2005 VL 54 IS 3 BP 569 EP 576 DI 10.1002/mrm.20577 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 959CH UT WOS:000231494000008 PM 16086372 ER PT J AU Desper, R Difilippantonio, MJ Ried, T Schaffer, AA AF Desper, R Difilippantonio, MJ Ried, T Schaffer, AA TI A comprehensive continuous-time model for the appearance of CGH signal due to chromosomal missegregations during mitosis SO MATHEMATICAL BIOSCIENCES LA English DT Article DE mitosis; comparative genomic hybridization; cancer cell lines; chromosome missegregation; aneuploidy in cancers; sloppy size models ID COMPARATIVE GENOMIC HYBRIDIZATION; CELL-CYCLE MODEL; NONPOLYPOSIS COLORECTAL-CANCER; TRANSITION-PROBABILITY MODEL; MISMATCH REPAIR DEFECTS; STRAND-BREAK REPAIR; SHORT-TERM CULTURES; GENETIC INSTABILITY; GENERATION TIMES; STOCHASTIC-MODEL AB Aneuploidy, the gain or loss of large regions of the genome, is a common feature in cancer cells. Irregularities in chromosomal copy number caused by missegregations of chromosomes during mitosis can be visualized by cytogenetic techniques including fluorescence in situ hybridization (FISH), spectral karyotyping (SKY) and comparative genomic hybridization (CGH). In the current work, we consider the propagation of irregular copy numbers throughout a cell population as the individual cells progress through ordinary mitotic cell cycles. We use an algebraic model to track the different copy numbers as states in a stochastic process, based on the model of chromosome instability of Gusev, Kagansky, and Dooley, and consider the average copy number of a particular chromosome within a cell population as a function of the cell division rate. We review a number of mathematical models for determining the length of the cell cycle, including the Smith-Martin transition probability model and the 'sloppy size' model of Wheals, Tyson and Diekmann. The program MITOSIM simulates the growth of a population of cells using the aforementioned models of the cell cycle. MITOSIM allows the cell population grow. With occasional resampling, until the average copy number of a given chromosome in the population reaches a preset threshold signifying a positive copy number alteration in this region, MITOSIM calculates the relationship between the missegregation rate and the growth rate of the cell population. This allows the user test hypotheses regarding the effect chromosomal aberrations have upon the cell cycle, cell growth rates, and time to population dominance. Published by Elsevier Inc. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schaffer, AA (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bldg 38A,Room 6S608,8600 Rockville Pike, Bethesda, MD 20892 USA. EM schaffer@helix.nih.gov RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS [Z99 CA999999] NR 70 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD SEP PY 2005 VL 197 IS 1 BP 67 EP 87 DI 10.1016/j.mbs.2005.05.005 PG 21 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 967AD UT WOS:000232063000004 PM 16043196 ER PT J AU Ottinger, MA Mobarak, M Abdelnabi, M Roth, G Proudman, J Ingram, DK AF Ottinger, MA Mobarak, M Abdelnabi, M Roth, G Proudman, J Ingram, DK TI Effects of calorie restriction on reproductive and adrenal systems in Japanese quail: Are responses similar to mammals, particularly primates? SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE calorie restriction; short-lived birds; Japanese quail; reproduction; neurochemistry; primates; neuroendocrine system; hypothalamus ID BROILER BREEDER PERFORMANCE; RHESUS-MONKEYS; LIFE-SPAN; DIETARY RESTRICTION; FEED RESTRICTION; ESTROUS CYCLICITY; GENE-EXPRESSION; PROTEIN-INTAKE; COMMON-TERN; TURKEY HENS AB The benefits of calorie restriction (CR) have been established across a variety of vertebrate and invertebrate species. Although the effects of CR on lifespan in birds have not been examined, it is clear that CR has beneficial effects on reproductive, metabolic, and physiological function in adult poultry. We examined the effects of CR in Japanese quail, a rapidly maturing avian model, on reproductive endocrine and neuroendocrine systems. Male Japanese quail were pair fed at 0% ad libitum (AL), 20%, or 40% CR of AL, recorded for juveniles (3-7 weeks of age) or adults (12-16 weeks of age). Juvenile males on CR matured more slowly, and both juvenile and adult males had reduced plasma luteinizing hormone (LH) with CR. Adults on 40% CR showed evidence of stress, with increased plasma corticosterone and reduced testes weight and circulating androgens. In a separate study, pituitary gland response was tested in juvenile and adult castrated males that had been on the same CR treatments. All birds responded to gonadotropin releasing hormone (GnRH) challenge, with LH release. However, the 40% CR juvenile and adult birds had quantitatively lower responses, suggesting central inhibition of the reproductive axis. This hypothesis was tested by measurement of sexual behavior and catecholamines known to stimulate GnRH in hypothalamic regions that modulate these responses. Results showed reduced norepinephrine in key hypothalamic regions and reduced dopamine in posterior hypothalamus. These data support the hypothesis that CR affects reproductive function, with evidence for effects in the central nervous system. These data are discussed and compared to data collected in mammals, especially the rhesus monkey, on the effects of timing and degree of CR on reproductive and stress responses. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NIA, Gerontol Res Ctr, Lab Expt Gerontol, NIH, Baltimore, MD USA. USDA ARS, Beltsville, MD USA. RP Ottinger, MA (reprint author), Univ Maryland, Dept Anim & Avian Sci, 3115 Anim Sci Bldg, College Pk, MD 20742 USA. EM maotting@umd.edu NR 62 TC 20 Z9 21 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD SEP PY 2005 VL 126 IS 9 BP 967 EP 975 DI 10.1016/j.mad.2005.03.017 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 956YC UT WOS:000231335000008 PM 15935442 ER PT J AU Cheng, A Coksaygan, T Tang, H Khatri, R Balice-Gordon, RJ Rao, MS Mattson, MP AF Cheng, A. Coksaygan, T. Tang, H. Khatri, R. Balice-Gordon, R. J. Rao, M. S. Mattson, M. P. TI The truncated trkB BDNF receptor directs neural stem cells to an astrocyte fate by a novel signaling mechanism SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract C1 [Cheng, A.; Coksaygan, T.; Tang, H.; Khatri, R.; Rao, M. S.; Mattson, M. P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Balice-Gordon, R. J.] Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2005 VL 122 SU 1 BP S182 EP S182 PG 1 WC Developmental Biology SC Developmental Biology GA V11IA UT WOS:000207524100694 ER PT J AU Hoffman, MP Likar, KM Patel, VA Elkins, M Vlodasky, I AF Hoffman, M. P. Likar, K. M. Patel, V. A. Elkins, M. Vlodasky, I TI Heparan sulfate modulates FGF10 function during submandibular gland branching morphogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract C1 [Hoffman, M. P.; Likar, K. M.; Patel, V. A.] NIDCR, Matrix & Morphogenesis Unit, CDBRB, NIH,DHHS, Bethesda, MD USA. [Elkins, M.; Vlodasky, I] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2005 VL 122 SU 1 BP S70 EP S71 PG 2 WC Developmental Biology SC Developmental Biology GA V11IA UT WOS:000207524100261 ER PT J AU Khoo, PL Lewis, SL De Young, RA Bildsoe, H Westphal, H Tam, PPL AF Khoo, P. L. Lewis, S. L. De Young, R. A. Bildsoe, H. Westphal, H. Tam, P. P. L. TI Cell fates and morphogenetic tissue movement in the Dkk1 mutant mouse SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract C1 [Khoo, P. L.; Lewis, S. L.; De Young, R. A.; Bildsoe, H.; Tam, P. P. L.] Childrens Med Res Inst, Embryol Unit, Sydney, NSW, Australia. [Westphal, H.] NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2005 VL 122 SU 1 BP S35 EP S35 PG 1 WC Developmental Biology SC Developmental Biology GA V11IA UT WOS:000207524100121 ER PT J AU Kida, Y Sato, T Nakaya, MA Yamaguchi, TP Ogura, T AF Kida, Y. Sato, T. Nakaya, M. A. Yamaguchi, T. P. Ogura, T. TI Non-canonical Wnt signaling regulates Eph-dependent endocytosis during gastrulation movement of zebrafish embryos SO MECHANISMS OF DEVELOPMENT LA English DT Meeting Abstract C1 [Kida, Y.; Sato, T.; Ogura, T.] Tohoku Univ, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan. [Nakaya, M. A.; Yamaguchi, T. P.] NCI Frederick, Canc & Dev Biol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2005 VL 122 SU 1 BP S82 EP S82 PG 1 WC Developmental Biology SC Developmental Biology GA V11IA UT WOS:000207524100303 ER EF