FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Horne, MK Merryman, PK Cullinane, AM AF Horne, MK Merryman, PK Cullinane, AM TI Histidine-proline-rich glycoprotein binding to platelets mediated by transition metals SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE histidine-proline-rich glycoprotein; platelets; fibrinolysis; zinc ID ENDOTHELIAL-CELLS; IMMUNE-COMPLEXES; ACTIVATION; PLASMINOGEN; PROTEIN; SERUM; ZINC; RECEPTOR; AFFINITY; SURFACE AB Histidine-proline-rich glycoprotein (HPRG) binds zinc, which in turn promotes HPRG binding to lymphocytes and monocytes. We examined the possibility that zinc and other transition metals also promote HPRG binding to platelets. Only non-specific. unsaturable association of HPRG with resting or activated platelets was observed in the absence of transition metals. However, nick-el. cobalt, copper, cadmium, and zinc greatly increased HPRG association with the cells. In the presence of zinc. specific. saturable binding of HPRG to platelets was demonstrated. The cell binding capacity for HPRG could be increased by increasing the zinc saturation of HPRG from 10% to 30% as well as by activating the platelets with thrombin. Because platelets contain relatively high concentrations of secretable zinc, it is possible that significant amounts of HPRG bind to activated platelets at sites of blood clotting and that this has a physiologic function. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bldg 10,Room 2C306, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 7 U1 0 U2 4 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAY PY 2001 VL 85 IS 5 BP 890 EP 895 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 433YJ UT WOS:000168788000023 PM 11372684 ER PT J AU Robbins, J Dunn, JT Bouville, A Kravchenko, VI Lubin, J Petrenko, S Sullivan, KM VanMiddlesworth, L Wolff, J AF Robbins, J Dunn, JT Bouville, A Kravchenko, VI Lubin, J Petrenko, S Sullivan, KM VanMiddlesworth, L Wolff, J TI Iodine nutrition and the risk from radioactive iodine: A workshop report in the Chernobyl long-term follow-up study SO THYROID LA English DT Article ID INDUCED THYROID-CANCER; URINARY IODINE; RADIATION; EXCRETION; CARCINOMA; CHILDHOOD; ACCIDENT; VALUES; VOLUME; GOITER AB The major fallout of radionuclides from the nuclear power station accident at Chernobyl on 26 April, 1986, occurred in regions of Ukraine and Belarus that are believed to be moderately deficient in dietary iodine. On 17 November, 2000, in conjunction with the Ukraine-Belarus-USA study of developing thyroid disease ina cohort of individuals exposed as children, a workshop was held to review what is known about iodine nutrition in the region, how this might influence the risk of thyroid tumor formation from radioiodine, and whether and how iodine nutrition should be monitored in this long-term project. This report is a summary of the workshop proceedings. Although no precise information about iodine intake in 1986 was found, the prevalence of mild goiter in the region's children suggested iodine deficiency and urinary iodine measurements begun in 1990 indicated that mild to moderate deficiency existed. Increased thyroid iodine uptake and increased thyroid size in 1986 resulting from iodine deficiency would have had counteracting influence on the thyroid radiation dose and knowledge of these parameters is required for dose reconstruction. More problematic is the possible role of iodine deficiency in the years following the accident. Theoretically, the resulting increase in thyroid cellular activity might increase the risk of tumorigenesis but experimental or clinical evidence supporting this hypothesis is meager or absent. Despite this limitation it was considered important to monitor iodine nutrition in the cohort subjects in relation to their place of residence and over time. Methods to accomplish this were discussed. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA USA. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Kiev Endocrinol & Metab Res Inst, Kiev, Ukraine. Res Clin Inst Radiat Med & Endocrinol, Minsk, Byelarus. Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. RP Robbins, J (reprint author), NIDDK, NIH, 31 Ctr Dr,MSC 2560, Bethesda, MD 20892 USA. EM jacobr@bdg10.niddk.nih.gov NR 35 TC 26 Z9 27 U1 4 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2001 VL 11 IS 5 BP 487 EP 491 DI 10.1089/105072501300176444 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 437GY UT WOS:000168985000010 PM 11396707 ER PT J AU Sanders, JM Burka, LT Chanas, B Matthews, HB AF Sanders, JM Burka, LT Chanas, B Matthews, HB TI Comparative xenobiotic metabolism between Tg.AC and p53+/- genetically altered mice and their respective wild types SO TOXICOLOGICAL SCIENCES LA English DT Article DE transgenic mouse; Tg.AC mouse; p53+/-; mouse; metabolism; cytochrome P450; GST-alpha; ethoxyquin; benzene; methacrylonitrile ID METHACRYLONITRILE METABOLISM; BENZENE METABOLISM; MOUSE; DISPOSITION; EXPRESSION; SKIN; RATS; INDUCTION; TOXICITY; GENES AB The use of transgenic animals, such as v-Ha-ras activated (Tg.AC) and p53+/- mice, offers great promise for a rapid and more sensitive assay for chemical carcinogenicity. Some carcinogens are metabolically activated; therefore, it is critical that the altered genome of either of these model systems does not compromise their capability and capacity for metabolism of xenobiotics. The present work tests the generally held assumption that xenobiotic metabolism in the Tg.AC and p53+/- mouse is not inherently different from that of the respective wild type, the FVB/N and C57BL/6 mouse, by comparing each genotype's ability to metabolize benzene, ethoxyquin, or methacrylonitrile. Use of these representative substrates offers the opportunity to examine arene oxide formation, aromatic ring opening, hydroxylation, epoxidation. O-deethylation, and a number of conjugation reactions. Mice were treated by gavage with C-14-labeled parent compound. excreta were collected, and elimination routes and rates, as well as C-14-derived metabolite profiles in urine, were compared between relevant treatment groups. Results of this study indicated that metabolism of the 3 parent compounds was not appreciably altered between either FVB/N and Tg.AC mise or C57BL/6 and p53+/-mice. Further, expression of CYP1A2, CYP2E1, CYP3A, and GST-alpha in liver of naive genetically altered mice was similar to that of corresponding wild-type mice. Thus, these results suggest that the inherent ability of Tg.AC and p53+/- mice to metabolize xenobiotics is not compromised by their altered genomes and would not be a factor in data interpretation of toxicity studies using either transgenic mouse line. C1 NIEHS, Natl Toxicol Program, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Sanders, JM (reprint author), NIEHS, Natl Toxicol Program, Lab Pharmacol & Chem, MD C3-02,POB 12233, Res Triangle Pk, NC 27709 USA. NR 18 TC 12 Z9 12 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2001 VL 61 IS 1 BP 54 EP 61 DI 10.1093/toxsci/61.1.54 PG 8 WC Toxicology SC Toxicology GA 423YD UT WOS:000168204600008 PM 11294974 ER PT J AU Smialowicz, RJ Williams, WC Copeland, CB Harris, MW Overstreet, D Davis, BJ Chapin, RE AF Smialowicz, RJ Williams, WC Copeland, CB Harris, MW Overstreet, D Davis, BJ Chapin, RE TI The effects of perinatal/juvenile heptachlor exposure on adult immune and reproductive system function in rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE heptachlor; heptachlor epoxide; developmental immunotoxicity; reproductive toxicity; rats; pesticide; persistent immune suppression ID DELAYED-TYPE HYPERSENSITIVITY; ADIPOSE-TISSUE; SUBACUTE EXPOSURE; RISK ASSESSMENT; MICE; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; METHOXYCHLOR; MODEL; IMMUNOTOXICOLOGY; MECHANISMS AB This study was performed to determine if developmental exposure of rats to heptachlor (H) during the last half of gestation through puberty adversely affects adult functioning of the immune and reproductive systems,Time-bred pregnant female Sprague-Dawley rats were dosed by gavage with H (0, 30, 300, or 3000 mug/kg/day) from gestation day (GD) 12 to postnatal day (PND) 7, followed by direct dosing of the pups with H through PND 42. Separate groups of rats were evaluated with a battery of immune function tests, while other groups of rats were evaluated for reproductive development and function, Additional groups of rats wore euthanized at the end of the dosing period for histological analyses of major organ systems, Some dams and PND 7 pups were euthanized; milk, plasma, fat and/or tissues were assayed for H and heptachlor epoxide B (HEB, a major metabolite of H, The amount of H and HEB found in milk, blood, fat, and tissues was proportional to the dose of H administered. There mere no effects on the number or survival of pups born to H-exposed dams nor to pups exposed postnatally, There were no effects on the number of treated dams delivering litters or on litter size, nor were there any effects on any of the reproductive end points examined in the F-o or F-1 rats. There were no effects of H exposure on lymphoid organ weights, splenic natural killer (NK) cell activity, and splenic lymphoproliferative (LP) responses to mitogens and allogeneic cells in a mixed lymphocyte response (MLR) assay at 8 weeks of age, Ii exposure did not alter delayed or contact hypersensitivity at 10 or 17 weeks of age, respectively. However, the primary IgM antibody response to sheep red blood cells (SRBCs) was suppressed in a dose-dependent manner in males, but not females, at 8 weeks of age. The percentage of B lymphocytes (OX12(+)OX19(-)) in spleen was also reduced in the high-dose males, The anti-SRBC IgM response was reduced only in males er;posed to 30 mug H/kg/day in a separate group of rats I weeks of age. In these same rats, at 26 weeks of age, the secondary IgG antibody response to SRBCs was suppressed in all of the H-exposed males, but not females. These data indicate that perinatal exposure of male rats to H results in suppression of the primary IgM and secondary Ige anti-SRBC responses, Suppression of these antibody responses persisted for up to 20 weeks after the last exposure to H, at a total exposure of approximately 1500 mug H/kg/rat. C1 US EPA, Expt Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIEHS, Reprod Toxicol Grp, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. DuPont Co Inc, Pharmaceut, Newark, DE 19714 USA. RP Smialowicz, RJ (reprint author), US EPA, Expt Toxicol Div, Natl Hlth & Environm Effects Res Lab, ETD MD-92, Res Triangle Pk, NC 27711 USA. EM smialowicz.ralph@epa.gov OI Chapin, Robert/0000-0002-5997-1261 NR 54 TC 31 Z9 32 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2001 VL 61 IS 1 BP 164 EP 175 DI 10.1093/toxsci/61.1.164 PG 12 WC Toxicology SC Toxicology GA 423YD UT WOS:000168204600021 PM 11294987 ER PT J AU Lovekamp, TN Davis, BJ AF Lovekamp, TN Davis, BJ TI Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE ovary; female reproductive toxicity; granulosa cells; phthalates; DEHP; MEHP; aromatase; estradiol; peroxisome proliferation; transcription; RT-PCR ID PEROXISOME PROLIFERATORS; ACTIVATED RECEPTOR; ACID ESTERS; DIFFERENTIATION; CYTOCHROME-P-450; PURIFICATION; INDUCTION; GAMMA AB The female reproductive toxicity of di-(2-ethylhexyl) phthalate and its active metabolite mono-(2-ethylhexyl) phthalate (MEHP) is attributed to suppression of ovarian granulosa cell estradiol production. In these studies, several structurally related phthalates (0-200 muM) and Wy-14,643 (0-100 muM) were compared to MEHP for their effects on granulosa cell estradiol production and transcript levels of cytochrome P450 enzyme CYP 19, also known as aromatase (P450arom), the rate-limiting enzyme in the conversion of androgens to estrogens, Granulosa cells were obtained from 28-day-old Fisher 344 rats and were cultured for 48 h, Test chemical or DMSO was added at the time of culture, along with testosterone as a substrate for aromatase. 17 beta -Estradiol production was measured by standard radioimmunoassay, mRNA was measured by fluorescent RT-PCR, and protein was measured by Western blot analysis. MEHP was unique among the phthalates in its ability to decrease estradiol production, while Wy-14,643 had effects similar to MEHP at 100 muM MEHP and Wy-14,643 also significantly decreased aromatase mRNA levels. The decrease in mRNA was concentration dependent and was paralleled by a decrease in aromatase protein. MEHP did not alter levels of CYP 11A1, the cholesterol side-chain cleavage enzyme (P450scc). Treatment with a cAMP analogue increased expression of P450scc in the presence of MEHP (100 to 200 muM) while the decrease in aromatase remained. Thus, these studies suggest that MEHP is distinct from several structurally related phthalates but similar to the peroxisome proliferator Wy-14,643 in its action on granulosa cell estradiol production. Moreover, the suppression of estradiol by MEHP is likely mediated through its action on aromatase transcript levels independent of cAMP-stimulated regulation. (C) 2001 Academic Press. C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Davis, BJ (reprint author), NIEHS, Lab Womens Hlth, POB 12233,MD A2-01, Res Triangle Pk, NC 27709 USA. NR 31 TC 135 Z9 151 U1 1 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 1 PY 2001 VL 172 IS 3 BP 217 EP 224 DI 10.1006/taap.2001.9156 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 429DQ UT WOS:000168501100008 PM 11312650 ER PT J AU Vega, L Styblo, M Patterson, R Cullen, W Wang, CQ Germolec, D AF Vega, L Styblo, M Patterson, R Cullen, W Wang, CQ Germolec, D TI Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenite; arsenate; MMA; DMA; keratinocytes; cell proliferation; viability; cytokine secretion; metabolism ID CULTURED HUMAN KERATINOCYTES; IN-VITRO METHYLATION; DIMETHYLARSINIC ACID; GROWTH-FACTORS; MONOMETHYLARSONOUS ACID; ENZYMATIC METHYLATION; CHRONIC STIMULATION; ENDOTHELIAL-CELLS; REACTIVE OXYGEN; MAMMALIAN-CELLS AB There is strong evidence from epidemiologic studies of an association between chronic exposure to inorganic arsenic (iAs) and hyperpigmentation, hyperkeratosis, and neoplasia in the skin. Although it is generally accepted that methylation is a mechanism of arsenic detoxification, recent studies have suggested that methylated arsenicals also have deleterious biological effects. In these studies we compare the effects of inorganic arsenicals (arsenite (iAs([I])) and arsenate (iAs(V))) and trivalent and pentavalent methylated arsenicals (methylarsine oxide ((MAsO)-O-III), complex of dimethylarsinous acid with glutathione (DMAs(III)GS), methylarsonic acid (MAsV), and dimethylarsinic acid (DMAsV)) in human keratinocyte cultures. Viability testing showed that the relative toxicities of the arsenicals were as follows: iAs(III) > (MAsO)-O-III > DMAs(III)GS > DMAsV > MAsV > iAs(V). Trivalent arsenicals induced an increase in cell proliferation at concentrations in the 0.001 to 0.01 muM range, while at high concentrations (>0.5 muM) cell proliferation was inhibited. Pentavalent arsenicals did not stimulate cell proliferation. As seen in the viability studies, the methylated forms of As-V were more cytotoxic than iAs(V). Exposure to low doses of trivalent arsenicals stimulated secretion of the growth-promoting cytokines, granulocyte macrophage colony stimulating factor and tumor necrosis factor-alpha. DMAsV reduced cytokine secretion at concentrations at which proliferation and viability were not affected. These data suggest that methylated arsenicals, products of the metabolic conversion of inorganic arsenic, can significantly affect viability and proliferation of human keratinocytes and modify their secretion of inflammatory and growth-promoting cytokines. (C) 2001 Academic Press. C1 NIEHS, Lab Toxicol & Environm Immunol, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. RP Germolec, D (reprint author), 111 TW Alexander Dr,Bldg 101,MD C1-04,POB 12233, Res Triangle Pk, NC 27709 USA. RI Vega, Libia/C-3391-2013 OI Vega, Libia/0000-0002-4993-5267 FU NIDDK NIH HHS [DK 56350] NR 66 TC 167 Z9 177 U1 1 U2 17 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 1 PY 2001 VL 172 IS 3 BP 225 EP 232 DI 10.1006/taap.2001.9152 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 429DQ UT WOS:000168501100009 PM 11312651 ER PT J AU Johnson, ES Shorter, C Bestervelt, LL Patterson, DG Needham, LL Piper, WN Lucier, G Nolan, CJ AF Johnson, ES Shorter, C Bestervelt, LL Patterson, DG Needham, LL Piper, WN Lucier, G Nolan, CJ TI Serum hormone levels in humans with low serum concentrations of 2,3,7,8-TCDD SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE dioxin; hormones; prolactin; sprayers; TCDD; 2,4,5-T ID PITUITARY-ADRENAL-FUNCTION; MALE-RATS; LACTATIONAL EXPOSURE; CANCER MORTALITY; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TCDD; WORKERS; INUTERO; DIOXIN; TESTOSTERONE AB We measured current serum hormone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 37 men who sprayed 2,4,5 trichlorophenoxyacetic acid (2,4,5-T) in the State of Victoria, Australia. TCDD levels were consistently significantly inversely related to prolactin levels in all analyses. In correlation analyses, TCDD levels were also inversely related to triiodothyronine (T3), thyroid-stimulating hormone (TSH), and testosterone levels, and positively associated with glucagon levels. The mean serum TCDD concentration in these sprayers was between 2.6 and 8.1 parts per trillion (ppt). Since such TCDD levels are commonly found in the general population in countries such as the US, the results could suggest that background levels of TCDD in the general population could have an effect on hormone levels. The findings are preliminary and need to be replicated in order to evaluate their full public health significance. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Univ Michigan, Sch Publ Hlth, Dept Environm & Ind Hlth, Toxicol Program, Ann Arbor, MI 48109 USA. Ctr Dis Control & Prevent, Div Environm Hlth Lab Sci, Atlanta, GA 30341 USA. NIEHS, Div Environm Toxicol, Res Triangle Pk, NC 27709 USA. RP Johnson, ES (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, SL 18,1430 Tulane Ave, New Orleans, LA 70112 USA. RI Needham, Larry/E-4930-2011 NR 29 TC 20 Z9 21 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD MAY PY 2001 VL 17 IS 4 BP 105 EP 112 DI 10.1191/0748233701th096oa PG 8 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 621BH UT WOS:000179568300002 PM 12479506 ER PT J AU Aravind, L AF Aravind, L TI The WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SECONDARY STRUCTURE; SIGNALING PATHWAY; RING FINGER; SEQUENCE; DELTEX; PREDICTION; REGULATOR; DATABASE; RECEPTOR; LIGASE AB Sequence profile analysis was used to detect a conserved globular domain in several proteins including deltex, Trip12 and poly-ADP-ribose polymerase homologs. It was named the WWE domain after its most conserved residues and is predicted to mediate specific protein-protein interactions in ubiquitin and ADP-ribose conjugation systems. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20894 USA. NR 21 TC 108 Z9 112 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2001 VL 26 IS 5 BP 273 EP 275 DI 10.1016/S0968-0004(01)01787-X PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432XA UT WOS:000168720000002 PM 11343911 ER PT J AU Browning, KS Gallie, DR Hershey, JWB Hinnebusch, AG Maitra, U Merrick, WC Norbury, C AF Browning, KS Gallie, DR Hershey, JWB Hinnebusch, AG Maitra, U Merrick, WC Norbury, C TI Unified nomenclature for the subunits of eukaryotic initiation factor 3 SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter ID TRANSLATION C1 Univ Texas, Dept Chem, Austin, TX 78712 USA. Univ Texas, Dept Biochem, Austin, TX 78712 USA. Univ Calif Riverside, Riverside, CA 92521 USA. Univ Calif Davis, Davis, CA 95616 USA. NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Imperial Canc Res Fund, Oxford OX3 9DS, England. RP Browning, KS (reprint author), Univ Texas, Dept Chem, Austin, TX 78712 USA. NR 6 TC 57 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2001 VL 26 IS 5 BP 284 EP 284 DI 10.1016/S0968-0004(01)01825-4 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432XA UT WOS:000168720000009 PM 11426420 ER PT J AU Brzostowski, JA Kimmel, AR AF Brzostowski, JA Kimmel, AR TI Signaling at zero G: G-protein-independent functions for 7-TM receptors SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID EXCHANGER REGULATORY FACTOR; METABOTROPIC GLUTAMATE RECEPTORS; POSTSYNAPTIC DENSITY PROTEINS; F9 TERATOCARCINOMA CELLS; II AT(1) RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; TYROSINE KINASE; BETA-ARRESTIN; CHEMOATTRACTANT RECEPTORS; COUPLED RECEPTORS AB Eukaryotic cells, whether free-living, single-celled microbes or components of complex metazoa. can sense environmental cues through specialized seven-transmembrane (7-TM) receptors (also called heptahelical or G-protein-coupled receptors). 7-TM receptors detect 'inputs' such as light. peptide hormones, neurotransmitters, pheromones, odorants, morphogens and chemoattractants, linking extracellular stimuli to intracellular signaling networks via heterotrimeric G proteins. Recently, this obligatory paradigm has been challenged. A growing body of evidence indicates that 7-TM receptors can also transmit extracellular signals through mechanisms that function independently of G-protein coupling. This review discusses pathways and protein interactions for 7-TM receptors signaling 'at zero G' in Dictyostelium acid mammalian cells. C1 NIH, Cellular & Dev Biol Lab, NIDDKD, Bethesda, MD 20892 USA. RP Brzostowski, JA (reprint author), NIH, Cellular & Dev Biol Lab, NIDDKD, Bldg 10, Bethesda, MD 20892 USA. NR 56 TC 114 Z9 123 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2001 VL 26 IS 5 BP 291 EP 297 DI 10.1016/S0968-0004(01)01804-7 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432XA UT WOS:000168720000011 PM 11343921 ER PT J AU Schussheim, DH Skarulis, MC Agarwal, SK Simonds, WF Burns, AL Spiegel, AM Marz, SJ AF Schussheim, DH Skarulis, MC Agarwal, SK Simonds, WF Burns, AL Spiegel, AM Marz, SJ TI Multiple endocrine neoplasia type 1: new clinical and basic findings SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; MEN1 GENE-MUTATIONS; ISLET CELL TUMOR; BILATERAL PHEOCHROMOCYTOMA; ADRENOCORTICAL LESIONS; NEUROENDOCRINE TUMORS; PARATHYROID TUMORS; CARCINOID-TUMORS; HYPERPARATHYROIDISM; JUND AB Multiple endocrine neoplasia type 1 (MEN1) provides a prime example of how a rare disease can advance our understanding of basic cell biology, neoplasia and common endocrine tumors. MEN1 is expressed mainly as parathyroid, enteropancreatic neuroendocrine, anterior pituitary and foregut carcinoid tumors. It is an autosomal dominant disease caused by mutation of the MEN1 gene. Since its identification, the MEN1 gene has been implicated in many common endocrine and non-endocrine tumors. This is a brief overview of recent scientific advances relating to MEN1, including newly recognized clinical features that are now better characterized by genetic analysis, insights into the function of the MEN1-encoded protein menin, and refined recommendations for mutation testing and tumor screening, which highlight our increasing understanding of this complex syndrome. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Schussheim, DH (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 69 TC 107 Z9 111 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 2001 VL 12 IS 4 BP 173 EP 178 DI 10.1016/S1043-2760(00)00372-6 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432XK UT WOS:000168720900013 PM 11295574 ER PT J AU Liu, Y Shaw, S AF Liu, Y Shaw, S TI The human genome: an immuno-centric view of evolutionary strategies SO TRENDS IN IMMUNOLOGY LA English DT Editorial Material ID IMMUNOGLOBULIN FOLD; SEQUENCE; ADHESION AB A hallmark of modern biology is the realization of the fundamental unity of biological processes in all life forms. Consequently,the complete genome sequencing of various bacteria, yeast (Saccharomyces cerevisiae), fly (Drosophila melanogaster) and worm (Caenorhabditis elegans) over the past five years has already had an impact on all of biology. 'Model organisms' have contributed a great deal to immunology; for example, the Toll receptors of the fly provided the impetus for the investigation of Toll-like receptors, which proved to be fundamental elements in the mammalian innate immune system. The recent release of a draft sequence of the human genome provides the first panoramic view of the 30000-35000 human genes in the human genetic blueprint and provides a plethora of new details, the significance of which will take some time to appreciate. The over-riding concepts that emerge from these studies relate primarily to general evolutionary processes that are equally as relevant to immunology as they are to other disciplines of biology. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Liu, Y (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. EM sshaw@nih.gov NR 16 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAY PY 2001 VL 22 IS 5 BP 227 EP 229 DI 10.1016/S1471-4906(01)01902-0 PG 3 WC Immunology SC Immunology GA 453VD UT WOS:000169936400001 PM 11323268 ER PT J AU Barry, CE AF Barry, CE TI Interpreting cell wall 'virulence factors' of Mycobacterium tuberculosis SO TRENDS IN MICROBIOLOGY LA English DT Review ID ROUGH MORPHOLOGICAL VARIANTS; MYCOLIC ACIDS; GENE-CLUSTER; SECRETED PROTEINS; GENOME SEQUENCE; IN-VITRO; IDENTIFICATION; SMEGMATIS; AVIUM; BIOSYNTHESIS AB The complex structure of the cell wall of Mycobacterium tuberculosis clearly contributes to the outcome of the dialogue between this pathogen and its host. The effects of mutations in cell wall components are likely to be quite complex, as individual components of the wall could have indirect effects that extend well beyond the physical integrity of the wall itself. Affected processes include the surface exposure or secretion of the many lipid, glycolipid and proteinaceous molecules that can interact directly with components of the host cell. C1 NIAID, TB Res Sect, LHD, NIH, Rockville, MD 20852 USA. RP Barry, CE (reprint author), NIAID, TB Res Sect, LHD, NIH, 12441 Parklawn Dr,Rm 239, Rockville, MD 20852 USA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 69 TC 61 Z9 61 U1 1 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 2001 VL 9 IS 5 BP 237 EP 241 DI 10.1016/S0966-842X(01)02018-2 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 432WT UT WOS:000168719300014 PM 11336841 ER PT J AU Carlton, JMR Hayton, M Cravo, PVL Walliker, D AF Carlton, JMR Hayton, M Cravo, PVL Walliker, D TI Of mice and malaria mutants: unravelling the genetics of drug resistance using rodent malaria models SO TRENDS IN PARASITOLOGY LA English DT Review ID PLASMODIUM-FALCIPARUM; CHLOROQUINE RESISTANCE; DIHYDROFOLATE-REDUCTASE; CYTOCHROME-B; PYRIMETHAMINE RESISTANCE; DIHYDROPTEROATE SYNTHASE; POINT MUTATIONS; PFMDR1 GENE; IN-VITRO; CHABAUDI AB It is well recognized that drug resistance is the most significant obstacle to gaining effective malaria central. Despite the enormous advances in the knowledge of the biochemistry and molecular biology of malaria parasites, only a few genes determining resistance to the commonly used drugs have been identified. The idea that rodent malaria parasites should be exploited more widely for such work, in view of the practical problems of studying this subject experimentally in human malaria, is presented. C1 NIH, Natl Ctr Biotechnol Res, Natl Lib Med, Bethesda, MD 20892 USA. Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JT, Midlothian, Scotland. RP Carlton, JMR (reprint author), NIH, Natl Ctr Biotechnol Res, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RI Cravo, Pedro/G-3532-2012 OI Cravo, Pedro/0000-0003-1675-4504 NR 63 TC 45 Z9 46 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD MAY PY 2001 VL 17 IS 5 BP 236 EP 242 DI 10.1016/S1471-4922(01)01899-2 PG 7 WC Parasitology SC Parasitology GA 453UE UT WOS:000169934200010 PM 11323308 ER PT J AU Bernstein, SL Russell, P Wong, P Fishelevich, R Smith, LEH AF Bernstein, SL Russell, P Wong, P Fishelevich, R Smith, LEH TI Heat shock protein 90 in retinal ganglion cells: Association with axonally transported proteins SO VISUAL NEUROSCIENCE LA English DT Article DE retinal ganglion cell; trkB; growth factor receptors; axon transport; MAP kinase ID MESSENGER-RNA EXPRESSION; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; VISUAL-SYSTEM; RAT RETINA; CONSTITUTIVE EXPRESSION; NEUROTROPHIN RECEPTORS; STEROID-RECEPTOR; TYROSINE KINASE; HSP90 AB The mRNAs for heat shock protein 90 (HSP90) are found at highest levels (differentially expressed) in the primate retinal fovea, the region of highest visual acuity, compared to the peripheral retina. HSP90 expression and retinal associations were analyzed by immuno-localization, in situ hybridization, and western analysis. Retinal ganglion cells (RGCs) express much of the HSP90 mRNA present in the primate retinal fovea. A large fraction of RGC synthesized HSP90 is apparently present in the axonal compartment. To identify the role of HSP90 protein in the optic nerve and retina, co-immunoprecipitation experiments were performed, using antibodies specific for HSP90 isoforms. The immunoprecipitates were analyzed for neurotrophin receptor and ligand activities, and MAP kinase activity. MAP kinase assay was used to determine the activation state of MAP kinase associated with HSP90. HSP90 proteins selectively associate with the inactive form of full-length tyrosine kinase growth factor receptor trkB, suggesting utilization during anterograde axonal transport. Activated MAP kinase, associated with the trk downstream signaling cascade, was found to co-immunoprecipitate with optic nerve HSP90, suggesting that HSP90 may be utilized in retrograde transport of the secondary messengers associated with neurotrophin signaling. HSP90 can thus be hypothesized to play a role in bidirectional RGC axonal protein transport. C1 Univ Maryland, Sch Med, Dept Ophthalmol, Lab Mol Res, Baltimore, MD 21201 USA. Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. RP Bernstein, SL (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol, Lab Mol Res, MSTF 5-65,10 S Pine St, Baltimore, MD 21201 USA. NR 52 TC 16 Z9 17 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 2001 VL 18 IS 3 BP 429 EP 436 DI 10.1017/S0952523801183094 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 458DH UT WOS:000170177600009 PM 11497419 ER PT J AU Nichols, BJ Kenworthy, AK Polishchuk, RS Lodge, R Roberts, TH Hirschberg, K Phair, RD Lippincott-Schwartz, J AF Nichols, BJ Kenworthy, AK Polishchuk, RS Lodge, R Roberts, TH Hirschberg, K Phair, RD Lippincott-Schwartz, J TI Rapid cycling of lipid raft markers between the cell surface and Golgi complex SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Golgi complex; endocytes; glycosyl phosphatidylinositol anchor; raft; green fluorescent protein ID GPI-ANCHORED PROTEINS; PLASMA-MEMBRANE; SHIGA TOXIN; SKIN FIBROBLASTS; BINDING PROTEIN; LIVING CELLS; CHOLESTEROL; ENDOCYTOSIS; APPARATUS; TRANSPORT AB The endocytic itineraries of lipid raft markers, such as glycosyl phosphatidylinositol (GPI)anchored proteins and glycosphingolipids, are incompletely understood. Here we show that different GPI-anchored proteins have different intracellular distributions; some (such as the folate receptor) accumulate in transferrin-containing compartments, others (such as CD59 and GPI-linked green fluorescent protein [GFP]) accumulate in the Golgi apparatus. Selective photobleaching shows that the Golgi pool of both GPI-GFP and CD59-GFP constantly and rapidly exchanges with the pool of these proteins found on the plasma membrane (PM). We visualized intermediates carrying GPI-GFP from the Golgi apparatus to the PM and separate structures delivering GPI-GFP to the Golgi apparatus. GPI-GFP does not accumulate within endocytic compartments containing transferrin, although it is detected in intracellular structures which are endosomes by the criteria of accessibility to a fluid phase marker and to cholera and shiga toxin B subunits (CTxB and STxB, which are also found in rafts). GPI-GFP and a proportion of the total CTxB and STxB taken up into cells are endocytosed independently of clathrin-associated machinery and are delivered to the Golgi complex via indistinguishable mechanisms, Hence, they enter the Golgi complex in the same intermediates, get there in dependently of both clathrin and rab5 unction, and are excluded from it at 20 degreesC and under conditions of cholesterol sequestration. The PM-Golgi cycling pathway followed by GPI-GFP could serve to regulate lipid raft distribution and function within cells. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20895 USA. Bioinformat Serv, Rockville, MD 20854 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, Bldg 18T,Lib Dr, Bethesda, MD 20895 USA. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 NR 39 TC 406 Z9 413 U1 2 U2 22 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 30 PY 2001 VL 153 IS 3 BP 529 EP 541 DI 10.1083/jcb.153.3.529 PG 13 WC Cell Biology SC Cell Biology GA 428VB UT WOS:000168481400009 PM 11331304 ER PT J AU Lambert, JS Keefer, M Mulligan, MJ Schwartz, D Mestecky, J Weinhold, K Smith, C Hsieh, R Moldoveanu, Z Fast, P Forrest, B Koff, W AF Lambert, JS Keefer, M Mulligan, MJ Schwartz, D Mestecky, J Weinhold, K Smith, C Hsieh, R Moldoveanu, Z Fast, P Forrest, B Koff, W TI A Phase I safety and immunogenicity trial of UBI (R) microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects SO VACCINE LA English DT Article DE HIV; vaccines; mucosal immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERNATIONAL CLINICAL-TRIALS; T-CELL; RECOMBINANT GP160; MUCOSAL IMMUNITY; VACCINE; IMMUNIZATION; ANTIGEN; ANTIBODIES; RESPONSES AB Thirty-three HIV-seronegative adults were recruited into a Phase I safety and immunogenicity HIV-1 vaccine trial. The immunogens were as follows: a synthetic, monovalent, octameric HIV-1 MN V3 peptide in aluminum hydroxide (alum) adjuvant administered by intramuscular delivery: and a similar product encapsulated in biodegradable micro-spheres composed of co-polymers of lactic and glycolic acids, administered by the oral route. These were administered in three sequential oral doses, followed by a parenteral boost. No serious adverse experiences were observed. Oral administration of this vaccine, alone or in combination with parenteral boosting, resulted in no significant humoral, cellular, or mucosal immune responses. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Alabama, Dept Microbiol, Mucosal Immunol Lab, Birmingham, AL USA. Duke Univ, Med Ctr, Durham, NC USA. Emmes Corp, Potomac, MD USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. United Biomed Inc, Hapague, NY USA. RP Lambert, JS (reprint author), Glaxo Wellcome R&D, Greenford Rd, Greenford UB6 0HE, Middx, England. FU NIAID NIH HHS [AI-45209] NR 39 TC 39 Z9 43 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 30 PY 2001 VL 19 IS 23-24 BP 3033 EP 3042 DI 10.1016/S0264-410X(01)00051-2 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 430NA UT WOS:000168579000002 PM 11311997 ER PT J AU Lee, CJ Wang, TR Frasch, CE AF Lee, CJ Wang, TR Frasch, CE TI Immunogenicity in mice of pneumococcal glycoconjugate vaccines using pneumococcal protein carriers SO VACCINE LA English DT Article DE polysaccharide; glycoconjugate; pneumococcal protein ID STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINES; TYPE-19F POLYSACCHARIDE; PROTECTIVE IMMUNITY; ANTIBODY-RESPONSES; PNEUMOLYSIN; INFECTION; AVIDITY; BINDING; STANDARDIZATION AB Antibody response and protective immunity were evaluated in mice immunized with pneumococcal glycoconjugate vaccines using two pneumococcal protein carriers. Mice injected with type 9V polysaccharide (PS) conjugated to inactivated pneumolysin (Ply) or autolysin (Aly) produced high levels of IgG and IgM antibodies to both the PS and the protein carrier. Higher PS antibody titers to the pneumococcal PS conjugates were measured by ELISA using PS-Ply or PS-tetanus toroid (TT) conjugate as a coating antigen compared with PS mixed with methylated human serum albumin. Type 9V PS (10 mug) inhibited most of the 9V IgM and IgG antibody binding to the 9V-TT coated plate. In contrast, absorption with 19F PS did not inhibit 9V antibody binding. The avidity index of Ige antibodies in the: 9V PS-Ply serum was 55.5 +/- 0.9. compared with 47.8 +/- 1.4 for 9V PS-Aly serum. Thus. high avidity of serum antibodies in conjugate-immunized mice can provide more effective functional activity for protection against pneumococcal infection. Mice immunized with these glycoconjugates exhibited rapid bacterial clearance from blood and provided cross-protection against challenge with heterologous serotypes of virulent pneumococci. These results reveal that conjugates using pneumococcal protein carriers can induce opsonophagocytic activity to destroy homologous and heterologous pneumococci. indicating that such conjugates can confer broader protective immunity than conjugates using nonpneumococcal proteins. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH, Bldg 29,Room 405,1401 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 15 Z9 18 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 30 PY 2001 VL 19 IS 23-24 BP 3216 EP 3225 DI 10.1016/S0264-410X(01)00033-0 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 430NA UT WOS:000168579000023 PM 11312018 ER PT J AU Weiss, SC Emanuel, LL Fairclough, DL Emanuel, EJ AF Weiss, SC Emanuel, LL Fairclough, DL Emanuel, EJ TI Understanding the experience of pain in terminally ill patients SO LANCET LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; CANCER PAIN; OPIOID ANALGESICS; FAMILY MEMBERS; HOSPICE; CAREGIVERS; CARE AB Background Terminally ill patients commonly experience substantial pain. Unresolved pain has been cited as evidence that end-of-life care is of poor quality. However, the data on which that conclusion is based are limited. We aimed to provide additional data on the experience of pain in such patients. Methods We interviewed 988 terminally ill patients from six randomly selected US sites. We asked them who had treated their pain in the previous 4 weeks (primary-care physician, pain specialist, or both), and whether they wanted more pain medication than they were receiving, or why they did not want more. Findings 496 (50%) terminally ill patients reported moderate or severe pain. 514 (52%) individuals had seen a primary-care physician for treatment of pain in the previous 4 weeks and 198 (20%) saw a pain specialist. Of those who had been treated by their primary-care physician, 287 (29%) wanted more therapy, 613 (62%) wanted their pain therapy to remain the same, and 89 (9%) wanted to reduce or stop their pain therapy. Several reasons for not wanting additional therapy were offered-fear of addiction, dislike of mental or physical side-effects, and not wanting to take more pills or injections. We saw no association between disease and amount of pain between disease and the desire for more treatment. Black patients were more likely to seek additional pain therapy, see a pain specialist, and refuse additional medication because of fear of addiction than other populations. Interpretation Although half of terminally ill patients experienced moderate to severe pain, only 30% of them wanted additional pain treatment from their primary-care physician. The number of patients experiencing pain remains too high. However, the number is not as large as perceived. Additionally, most are willing to tolerate pain. Furthermore, the experience of pain is constant across major terminal diseases. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL USA. AMC Canc Res Ctr, Ctr Res Methodol & Biometr, Denver, CO USA. RP Weiss, SC (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 31 TC 119 Z9 124 U1 2 U2 8 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 28 PY 2001 VL 357 IS 9265 BP 1311 EP 1315 DI 10.1016/S0140-6736(00)04515-3 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 427ND UT WOS:000168411400008 PM 11343734 ER PT J AU Zambito, AM Wolff, J AF Zambito, AM Wolff, J TI Plasma membrane localization of palmitoylated tubulin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tubulin; palmitoylation; plasma membrane; endoplasmic reticulum; idroxylamine ID MICROTUBULES; CELLS; ASSOCIATION; VESICLES; GLYCOPROTEINS; MITOCHONDRIA; PROTEIN; TOXIN; CILIA; VIRUS AB PC12 pheochromocytoma cells incorporate [H-3]palmitic acid into tubulin in a time- and cell-density-dependent manner. The plasma membrane-enriched fraction contains most of the radioactivity of the membrane pellet. While palmitoylated tubulin is found in both the cytoplasm and particulate fraction, the bulk of [H-3]palmitic acid bound to tubulin is present in the crude membrane pellet and the tubulin extracted from the plasma membrane is more heavily palmitoylated than that extracted from endoplasmic reticulum. Detergent-extracted tubulin from plasma membrane is, to a large extent, polymerization competent; a substantial fraction, increasing as a function of labeling time, is not hydroxylamine-labile. The requirement for detergent extraction, the accompanying changes in tubulin properties and the present findings of preferential incorporation of labeled tubulin into plasma membranes, make it clear that direct incorporation of tubulin into the plasma membrane can occur. (C) 2001 Academic Press. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Zambito, AM (reprint author), NIDDKD, Lab Biochem & Genet, NIH, 9000 Rockville Pike,Bldg 8,Room 2A-23, Bethesda, MD 20892 USA. NR 31 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC 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 APR 27 PY 2001 VL 283 IS 1 BP 42 EP 47 DI 10.1006/bbrc.2001.4735 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 427YR UT WOS:000168434800008 PM 11322765 ER PT J AU Rusnak, M Kvetnansky, R Jelokova, J Palkovits, M AF Rusnak, M Kvetnansky, R Jelokova, J Palkovits, M TI Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats SO BRAIN RESEARCH LA English DT Article DE tyrosine hydroxylase; norepinephrine transporter; vesicular monoamine transporter; gene expression; repeated stress; novel stressor; locus coeruleus; brainstem noradrenergic cell group ID MESSENGER-RNA LEVELS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CORTICOTROPIN-RELEASING HORMONE; INDUCED NOREPINEPHRINE RELEASE; STEM CATECHOLAMINERGIC GROUPS; ACUTE RESTRAINT STRESS; C-FOS EXPRESSION; LOCUS-COERULEUS; DOPAMINE TRANSPORTER; ADRENOCORTICAL AXIS AB Responses of central noradrenergic (NE) neurons to stressors like immobilization (IMO), cold exposure, insulin-induced hypoglycemia, and cellular glucoprivation caused by 2-deoxy-D-glucose (2-DG) were investigated in intact and long-term repeatedly immobilized (LTR, 2 h daily IMO for 41 days) rats. Expression of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and vesicular monoamine transporter (VMAT2) genes were determined by using in situ hybridization histochemistry in brainstem A1, A2, A5 and locus coeruleus (LC) neurons. TH mRNA levels were increased by single IMO or 2-DG administration in all areas studied. Cold was effective only in LC and A2 neurons while insulin had no effect. LTR immobilization elevated TH mRNA levels in all investigated cell groups. These elevations were equally high to those elicited by a single IMO in each noradrenergic group, except the LC where LTR IMO was less effective than the single IMO. The levels of NET and VMAT2 mRNAs were elevated only in the A1 and A2 cell groups of LTR IMO rats. A newly applied IMO in LTR rats did not alter TH, NET, and VMAT2 mRNA levels in any NE cell group investigated. Novel stressors like cold and 2-DG exaggerated the increased TH mRNA levels only in the LC of LTR IMO rats, unlike in the other NE cell groups. The present data indicate that repeated exposure of rats to homotypic stressor induces an adaptation of NE neurons, whereas single exposure of such animals to heterotypic novel stressor produces an exaggerated response of the system at the level of TH (in LC) and NET (in A1, A2) gene expression. Published by Elsevier Science B.V. C1 Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 83306, Slovakia. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Rusnak, M (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 83306, Slovakia. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 79 TC 58 Z9 59 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 27 PY 2001 VL 899 IS 1-2 BP 20 EP 35 DI 10.1016/S0006-8993(01)02126-6 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 427KP UT WOS:000168403600003 PM 11311864 ER PT J AU Song, LS Wang, SQ Xiao, RP Spurgeon, H Lakatta, EG Cheng, HP AF Song, LS Wang, SQ Xiao, RP Spurgeon, H Lakatta, EG Cheng, HP TI beta-adrenergic stimulation synchronizes intracellular Ca2+ release during excitation-contraction coupling in cardiac myocytes SO CIRCULATION RESEARCH LA English DT Article DE excitation-contraction coupling; beta-adrenergic receptor; L-type Ca2+ channel current; ryanodine receptors; heart cells ID RAT VENTRICULAR MYOCYTES; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTOR; CALCIUM-RELEASE; HEART-CELLS; PHOSPHOLAMBAN PHOSPHORYLATION; LOCAL-CONTROL; CHANNEL; SPARKS; MUSCLE AB To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by beta -adrenergic receptor (beta -AR) stimulation, we examined local Ca2+ release function, ie, Ca2+ spikes at individual transverse tubule-sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique for release flux measurement. beta -AR stimulation by norepinephrine plus an alpha (1)-adrenergic blocker, prazosin, increased the amplitude of SR Ca2+ release flux (J(SR)), its running integral (integralJ(SR)), and L-type Ca2+ channel current (I-Ca), and it shifted their bell-shaped voltage dependence leftward by approximate to 10 mV, with the relative effects ranking I-Ca> J(SR)>integralJ(SR). Confocal imaging revealed that the bell-shaped voltage dependence of SR Ca2+ release is attributable to a graded recruitment of T-SR junctions as well as to changes in Ca2+ spike amplitudes. beta -AR stimulation increased the fractional T-SR junctions that fired Ca2+ spikes and augmented Ca2+ spike amplitudes, without altering the SR Ca2+ load, suggesting that more release units were activated synchronously among and within T-SR junctions. Moreover, beta -AR stimulation decreased the latency and temporal dispersion of Ca2+ spike occurrence at a given voltage, delivering most of the Ca2+ at the onset of depolarization rather than spreading it out throughout depolarization. Because the synchrony of Ca2+ spikes affects Ca2+ delivery per unit of time to contractile myofilaments, and because the myofilaments display a steep Ca2+ dependence, our data suggest that synchronization of SR Ca2+ release represents a heretofore unappreciated mechanism of beta -AR modulation of cardiac inotropy. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. RP Cheng, HP (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 NR 39 TC 106 Z9 110 U1 1 U2 8 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 APR 27 PY 2001 VL 88 IS 8 BP 794 EP 801 DI 10.1161/hh0801.090461 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 428WW UT WOS:000168485500009 PM 11325871 ER PT J AU Forbes, RA Steenbergen, C Murphy, E AF Forbes, RA Steenbergen, C Murphy, E TI Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism SO CIRCULATION RESEARCH LA English DT Article DE reactive oxygen species; cardioprotection; intracellular pH; dichlorofluorescin diacetate ID K-ATP CHANNEL; PRECONDITIONED RAT HEARTS; SULFHYDRYL MODIFICATION; OXYGEN RADICALS; MITOCHONDRIAL-FUNCTION; REPERFUSION INJURY; POTASSIUM CHANNEL; HYDROGEN-PEROXIDE; INTRACELLULAR PH; OXIDANT STRESS AB Diazoxide, a selective opener of the mitochondrial ATP-sensitive potassium channel, has been shown to elicit tolerance to ischemia in cardiac myocytes and in perfused heart. However, the mechanism of this cardioprotection is poorly understood. Because reactive oxygen species (ROS) are recognized as important intracellular signaling molecules and have been implicated in ischemic preconditioning, we examined diazoxide-induced ROS production in adult cardiomyocytes, Cells treated with 50 mu mol/L diazoxide showed a 173% increase in ROS production relative to baseline. 5-Hydroxydecanoate was found to attenuate the diazoxide-induced increase in ROS generation. The diazoxide-induced increase in ROS also was abrogated by the addition of either the antioxidant N-acetylcysteine (NAC) or N-mercaptopropionylglycine. We also examined the ability of NAC to block the protective effects of diazoxide in the perfused rat heart. After 20 minutes of global ischemia and 20 minutes of reflow, hearts perfused with 100 mu mol/L diazoxide before ischemia showed significantly improved postischemic contractile function relative to untreated hearts (84% versus 29% of initial left ventricular developed pressure, respectively). Hearts treated with diazoxide in the presence of 4 mmol/L NAC recovered 53% of initial left ventricular developed pressure, whereas hearts treated with NAC alone recovered 46% of preischemic function. Using P-31 NMR spectroscopy, we found that, similar to preconditioning, diazoxide significantly attenuated ischemia-induced intracellular acidification and enhanced postischemic recovery of phosphocreatine levels, both of which were blocked by cotreatment with NAG. These data suggest that the cardioprotective actions of diazoxide are mediated by generation of a pro-oxidant environment. C1 NIEHS, NIH, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Murphy, E (reprint author), NIEHS, NIH, Lab Signal Transduct, MD 2-03,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752, R01-HL-39752] NR 44 TC 294 Z9 313 U1 2 U2 8 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 APR 27 PY 2001 VL 88 IS 8 BP 802 EP 809 DI 10.1161/hh0801.089342 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 428WW UT WOS:000168485500010 PM 11325872 ER PT J AU Oz, M Tchugunova, YB Dunn, SMJ AF Oz, M Tchugunova, YB Dunn, SMJ TI Direct inhibition of voltage-dependent Ca2+ fluxes by ethanol and higher alcohols in rabbit T-tubule membranes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Ca2+ channel; ethanol; alcohol; skeletal muscle ID SKELETAL-MUSCLE; CALCIUM CHANNELS; BIOCHEMICAL-CHARACTERIZATION; DIHYDROPYRIDINE-BINDING; HOMOLOGOUS SERIES; ACTION-POTENTIALS; CA-2+ CHANNELS; NERVOUS-SYSTEM; ION CHANNELS; CURRENTS AB The effects of ethanol and higher alcohols on Ca-45(2+) fluxes, mediated by voltage-dependent Ca2+ channels (VDCCs), were investigated in inside-out transverse (T)-tubule membrane vesicles from rabbit skeletal muscle. Ca-45(2+) effluxes were induced by membrane potentials generated via establishing K+ gradients across the vesicles, and were significantly inhibited by the inorganic Ca2+ channel blocker La3+ (1 mM) and the Ca2+ channel antagonist nifedipine (1-10 muM), Ethanol, in the concentration range of 100-400 mM, caused a significant suppression of depolarization-induced Ca-45(2+) fluxes. Ethanol also functionally modulated the effect of nifedipine (1-10 muM) and the Ca2+ channel agonist Bay K 8644 (1 muM) on Ca2+ effluxes. Pretreatment with pertussis toxin (5 mug/ml) or phorbol 12-myrstate 13-acetate (PMA, 50 nM) did not affect the ethanol inhibition of Ca-45(2+) fluxes. Further experiments with alcohols revealed that butanol, hexanol, octanol and decanol also significantly inhibited Ca-45(2+) effluxes. However, undecanol and dodecanol did not cause any significant change on Ca-45(2+) fluxes, indicating that the effects of alcohols on Ca-45(2+) effluxes exhibit a cut-off phenomenon. In radioligand binding studies, it was found that at the concentrations used in flux studies, alcohols did not alter the characteristics of the specific binding of [H-3]PN 200-110 to T-tubule membranes. Results indicate that ethanol directly inhibits the function of voltage-dependent Ca2+ channels without modulating the specific binding of Ca2+ channel ligands of the dihydropyridine class, and that this inhibition is independent of intracellular Ca2+ levels. (C) 2001 Published by Elsevier Science B.V. C1 Leob Res Inst, Ottawa, ON K1Y 4K9, Canada. Univ Alberta, Fac Med, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada. RP Oz, M (reprint author), NIDA, Cellular Neurobiol Branch, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Oz, Murat/E-2148-2012 NR 37 TC 16 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 27 PY 2001 VL 418 IS 3 BP 169 EP 176 DI 10.1016/S0014-2999(01)00945-1 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 431JF UT WOS:000168627500002 PM 11343686 ER PT J AU Oshima, Y Puri, RK AF Oshima, Y Puri, RK TI A novel interleukin-13 (IL-13) antagonist that blocks the biological activity of human IL-13 in immune and nonimmune cells SO FASEB JOURNAL LA English DT Article DE pleiotropic cytokine; inflammatory disease ID RECEPTOR-ALPHA CHAIN; HIGH-AFFINITY INTERLEUKIN-4; REED-STERNBERG CELLS; HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; ERYTHROPOIETIN RECEPTOR; PROLIFERATIVE ACTIVITY AB The pleiotropic cytokine interleukin-13 (IL-13) plays a major role in the pathogenesis of inflammatory diseases, including allergic rhinitis, atopic dermatitis, allergic asthma, and malignancies. Therefore, specific inhibitors of IL-13 may have important clinical applications. We have previously produced a super agonist of IL-13 (termed IL-13R112D) by single amino acid substitution changing Arg to Asp at position 112. In an effort to create a cell-selective IL-13 agonist, we performed a second mutation in the IL-13R112D molecule substituting Lys for Glu at position 13. Unexpectedly, rather than an agonist, this novel double mutein (IL-13 DM, termed IL-13E13KR112D, turned out to be an IL-13 antagonist. It competes for I-125-IL-13 binding sites as effectively as wtIL-13. Designation of IL-13E13KR112D as an IL-13 antagonist is supported further by a second assay involving a fusion protein consisting of the bacterial cytotoxic molecule PE38QQR as well as wtIL-13 (IL-13-PE38QQR or IL-13 cytotoxin). IL-13E13KR112D neutralizes the cytotoxic activity of IL-13 cytotoxin exhibited in U251 and PM-RCC cancer cell lines. In addition, IL-13E13KR112D inhibits the proliferative activity of wtIL-13 in TF-1 and L1236 hematopoietic cell lines, neutralizes wtIL-13 induced inhibition of CD14 expression on primary monocytes, and prevents wtIL-13 induced activation of signal transducer and activator of transcription (STAT-6) protein in KSY-1 and THP-1 cell lines. Thus, IL-13E13KR112D may be a useful agent for the study of interaction between IL-13 and its cognate receptors and may contribute to the development of new treatments for inflammatory diseases, even malignancies, in which IL-13 plays a central role. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, 29 Lincoln Dr,NIH Bldg 29B,Room 2NN10, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 66 TC 6 Z9 6 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 27 PY 2001 VL 15 IS 6 BP 1469 EP + DI 10.1096/fj.00-0711fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 519BV UT WOS:000173705800007 PM 11387260 ER PT J AU Sampath, V Zhao, XJ Caughey, WS AF Sampath, V Zhao, XJ Caughey, WS TI Anesthetic-like interactions of nitric oxide with albumin and hemeproteins - A mechanism for control of protein function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C-OXIDASE; HUMAN SERUM-ALBUMIN; SOLUBLE GUANYLATE-CYCLASE; INFRARED-SPECTROSCOPY; NITROUS-OXIDE; TRYPTOPHAN FLUORESCENCE; MOLECULE ENVIRONMENTS; HALOTHANE BINDING; CARBON-MONOXIDE; HEMOGLOBIN AB Noncovalent bonding interactions of nitric oxide (NO) with human serum albumin (HSA), human hemoglobin A,bovine myoglobin, and bovine cytochrome c oxidase (CcO) have been explored. The anesthetic nitrous oxide (NNO) occupies multiple sites within each protein, but does not bind to heme iron. Infrared (IR) spectra of NNO molecules sequestered within albumin, with NO present, support the binding of NO and NNO to the same sites with comparable affinities. Perturbations of IR spectra of the Cys(34) thiol of HSA indicate NO, NNO, halothane, and chloroform can induce similar changes in protein structure. Experiments evaluating the relative affinities of binding of NO and carbon monoxide (CO) to iron(II) sites of the hemeproteins led to evidence of NO binding to noniron, nonsulfur sites as well. With HbA, IR spectra of cysteine thiols and/or the iron(II) N-O stretching region denote changes in protein structure due to NO, NNO, or CO occupying noniron sites with an order of decreasing affinities of NO > NNO > CO. Loss of NO from some, not all, noniron sites in hemeproteins is very slow (t(1/2) similar to hours). These findings provide examples in which NO and anesthetics alter the structure and properties of protein similarly, and support the hypothesis that some physiological effects of NO land possibly CO) result from anesthetic-like noncovalent bonding to sites within protein or other tissue components. Such bonding may be involved in mechanisms for control of oxygen transport, mitochondrial respiration, and activation of soluble guanylate cyclase by NO. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. RP Caughey, WS (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 4th St, Hamilton, MT 59840 USA. FU NHLBI NIH HHS [HL-15890] NR 51 TC 19 Z9 19 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 13635 EP 13643 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600020 PM 11278308 ER PT J AU Wong, AHT Durbin, JE Li, SY Dever, TE Decker, T Koromilas, AE AF Wong, AHT Durbin, JE Li, SY Dever, TE Decker, T Koromilas, AE TI Enhanced antiviral and antiproliferative properties of a STAT1 mutant unable to interact with the protein kinase PKR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED-RNA; TUMOR-SUPPRESSOR P53; VACCINIA VIRUS; TRANSCRIPTIONAL ACTIVATION; TARGETED DISRUPTION; GAMMA-INTERFERON; INNATE IMMUNITY; IFN-GAMMA; GENE; CELLS AB We have previously reported a physical association between STAT1 and the protein kinase double-stranded RNA-activated protein kinase (PKR). PKR inhibited STAT1 function in a manner independent of PKR kinase activity. In this report, we have further characterized the properties of both molecules by mapping the sites of their interaction. A STAT1 mutant unable to interact with PKR displays enhanced interferon gamma (IFN-gamma)-induced transactivation capacity compared with STAT1. This effect appears to be mediated by the higher capacity of STAT1 mutant to heterodimerize with STAT3. Furthermore, expression of STAT1 mutant in STAT1(-/-) cells enhances both the antiviral and antiproliferative effects of IFNs as opposed to STAT1. We also provide evidence that STAT1 functions as an inhibitor of PKR in vitro and in vivo. That is, phosphorylation of eIF-2 alpha is enhanced in STAT1(-/-) than STAT1(+/+) cells in vivo, and this correlates with higher activation capacity of PKR in STAT1(-/-) cells. Genetic experiments in yeast demonstrate the inhibition of PKR activation and eIF-2 alpha phosphorylation by STAT1 but not by STAT1 mutant. These data substantiate our previous findings on the inhibitory effects of PKR on STAT1 and implicate STAT1 in translational control through the modulation of PKR activation and eIF-2 alpha phosphorylation. C1 Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Terry Fox Mol Oncol Grp, Montreal, PQ H3T 1E2, Canada. Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA. Ohio State Univ, Childrens Hosp Res Fdn, Columbus, OH 43205 USA. NICHD, Lab Eukaryot Gene Express, NIH, Bethesda, MD 20892 USA. Vienna Bioctr, Inst Microbiol & Genet, A-1030 Vienna, Austria. RP Koromilas, AE (reprint author), Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Terry Fox Mol Oncol Grp, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. NR 46 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 13727 EP 13737 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600032 PM 11278865 ER PT J AU Mato, IP del Pino, MMS Chamberlin, ME Mudd, SH Mato, JM Corrales, FJ AF Mato, IP del Pino, MMS Chamberlin, ME Mudd, SH Mato, JM Corrales, FJ TI Biochemical basis for the dominant inheritance of hypermethioninemia associated with the R264H mutation of the MAT1A gene - A monomeric methionine adenosyltransferase with tripolyphosphatase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-ADENOSYLMETHIONINE SYNTHETASE; ISOLATED PERSISTENT HYPERMETHIONINEMIA; RAT-LIVER; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; I/III DEFICIENCY; MESSENGER-RNA; PURIFICATION; SITE AB Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet), the main alkylating agent in living cells. Additionally, in the liver, MAT is also responsible for up to 50% of methionine catabolism. Humans with mutations in the gene MAT1A, the gene that encodes the catalytic subunit of MAT I and III, have decreased MAT activity in liver, which results in a persistent hypermethioninemia without homocystinuria. The hypermethioninemic phenotype associated with these mutations is inherited as an autosomal recessive trait. The only exception is the dominant mild hypermethioninemia associated with a G-A transition at nucleotide 791 of exon VII, This change yields a MAT1A-encoded subunit in which arginine 264 is replaced by histidine, Our results indicate that in the homologous rat enzyme, replacement of the equivalent arginine 265 by histidine (R265H) results in a monomeric MAT with only 0.37% of the AdoMet synthetic activity. However the tripolyphosphatase activity is similar to that found in the wild type (WT) MAT and is inhibited by PP,, Our in vivo studies demonstrate that the R265H MAT I/III mutant associates with the WT subunit resulting in a dimeric R265H-WT MAT unable to synthesize AdoMet. Tripolyphosphatase activity is maintained in the hybrid MAT, but is not stimulated by methionine and ATP, indicating a deficient binding of the substrates. Our data indicate that the active site for tripolyphosphatase activity is functionally active in the monomeric R265H MAT I/III mutant. Moreover, our results provide a molecular mechanism that might explain the dominant inheritance of the hypermethioninemia associated with the R264H mutation of human MAT I/III. C1 Univ Navarra, Div Hepatol & Gene Therapy, Pamplona 31008, Spain. Univ Tennessee, Sch Med, Vet Affairs Med Ctr, Memphis, TN 38104 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Corrales, FJ (reprint author), Univ Navarra, Div Hepatol & Gene Therapy, Irunlarrea 1, Pamplona 31008, Spain. RI MATO, JOSE/A-5187-2011; Sanchez del Pino, Manuel/I-3977-2015 OI Sanchez del Pino, Manuel/0000-0001-9696-7600 NR 44 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 13803 EP 13809 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600043 ER PT J AU Manickan, E Satoi, JJ Wang, TC Liang, TJ AF Manickan, E Satoi, JJ Wang, TC Liang, TJ TI Conditional liver-specific expression of simian virus 40 T antigen leads to regulatable development of hepatic neoplasm in transgenic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; MAMMALIAN-CELLS; HEPATOCELLULAR-CARCINOMA; IN-VIVO; SYSTEM; MOUSE; HEPATOCARCINOGENESIS; CARCINOGENESIS; DOXYCYCLINE; PROTEINS AB Adaptive epigenetic changes and toxicity often accompany constitutive expression of a transgene or knockout of an endogenous gene in mice. These considerations potentially limit the usefulness of transgenic technology in studying the in vivo functions of a gene. Using conditional gene expression technology, it is possible to override such restrictions to achieve temporal and tissue-specific manipulation of gene expression in vivo. Based on the tetracycline regulatory system, we established a binary transgenic model in which the conditional expression of two transgenes, SV40 T antigen (TAg) and lacZ, can be tightly regulated in the liver by administration of tetracycline. The mouse albumin or mouse major urinary protein promoter was used to achieve liver-specific expression of the tetracycline-responsive transcriptional activator (tTA) in one set of transgenic mice. These mice were crossed with transgenic mice carrying either TAg or lacZ under the control of the tTA-regulated promoter. Analyses of mice transgenic for both tTA and TAg (or lacZ) revealed that the liver-specific expression of the transgenes could be suppressed to undetectable levels and regulated in a reversible fashion by tetracycline administration and withdrawal. Mice with tTA and TAg transgenes developed hepatocellular adenomas and hyperplasia that could be prevented by continuous tetracycline administration. Our report demonstrates the value of this binary transgenic model in studying the physiological functions of any potential genes of interest in a liver-specific manner. C1 NIDDK, Liver Dis Sect, DDB, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, DDB, NIH, Bldg 10,Rm 9B16,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. NR 33 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 13989 EP 13994 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600067 PM 11278564 ER PT J AU Atabey, N Gao, Y Yao, ZJ Breckenridge, D Soon, L Soriano, JV Burke, TR Bottaro, DP AF Atabey, N Gao, Y Yao, ZJ Breckenridge, D Soon, L Soriano, JV Burke, TR Bottaro, DP TI Potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion and branching morphogenesis by antagonists of Grb2 Src homology 2 domain interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASE; FACTOR SCATTER FACTOR; PHOSPHATE-CONTAINING LIGANDS; PAPILLARY RENAL CARCINOMAS; C-MET RECEPTOR; EPITHELIAL-CELLS; SH2 DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; FACTOR ISOFORMS; DOCKING SITE AB Hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets during development, homeostasis and tissue regeneration. Inappropriate HGF signaling occurs in several human cancers, and the ability of HGF to initiate a program of protease production, cell dissociation, and motility has been shown to promote cellular invasion and is strongly linked to tumor metastasis. Upon HGF binding, several tyrosines within the intracellular domain of its receptor, c-Met, become phosphorylated and mediate the binding of effector proteins, such as Grb2. Grb2 binding through its SH2 domain is thought to link. c-Met with downstream mediators of cell proliferation, shape change, and motility. We analyzed the effects of Grb2 SH2 domain antagonists on HGF signaling and observed potent blockade of cell motility, matrix invasion, and branching morphogenesis, with ED50 values of 30 nM or less, but only modest inhibition of mitogenesis. These compounds are 1000-10,000-fold more potent anti-motility agents than any previously characterized Grb2 SH2 domain antagonists. Our results suggest that SH2 domain-mediated c-Met-Grb2 interaction contributes primarily to the motogenic and morphogenic responses to HGF, and that these compounds may have therapeutic application as anti-metastatic agents for tumors where the HGF signaling pathway is active. C1 NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), EntreMed Inc, 9640 Med Ctr Dr, Rockville, MD 20850 USA. RI Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 OI Bottaro, Donald/0000-0002-5057-5334; NR 46 TC 75 Z9 78 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 14308 EP 14314 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600105 PM 11278639 ER PT J AU Liu, YF Paz, K Herschkovitz, A Alt, A Tennenbaum, T Sampson, SR Ohba, M Kuroki, T LeRoith, D Zick, Y AF Liu, YF Paz, K Herschkovitz, A Alt, A Tennenbaum, T Sampson, SR Ohba, M Kuroki, T LeRoith, D Zick, Y TI Insulin stimulates PKC zeta-mediated phosphorylation of insulin receptor substrate-1 (IRS-1) - A self-attenuated mechanism to negatively regulate the function of IRS proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE-C-ZETA; TYROSINE PHOSPHORYLATION; GLUCOSE-TRANSPORT; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; PHOSPHOTYROSINE PROTEIN; JUXTAMEMBRANE REGION; S6 KINASE; ACTIVATION; DOMAIN AB Incubation of rat hepatoma Fao cells with insulin leads to a transient rise in Tyr phosphorylation of insulin receptor substrate (IRS) proteins. This is followed by elevation in their P-Ser/Thr content, and their dissociation from the insulin receptor (IR), Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, abolished the increase in the P-Ser/Thr content of IRS-1, its dissociation from the IR, and the decrease in its P-Tyr content following 60 min of insulin treatment, indicating that the Ser kinases that negatively regulate IRS-l function are downstream effectors of PI3K. PKC zeta fulfills this criterion, being an insulin-activated downstream effector of PI3K, Overexpression of PKC zeta in Fao cells, by infection of the cells with adenovirus-based PKC zeta construct, had no effect on its own, but it accelerated the rate of insulin-stimulated dissociation of IR IRS-1 complexes and the rate of Tyr dephosphorylation of IRS-1, The insulin-stimulated negative regulatory role of PKC zeta was specific and could not be mimic by infecting Fao cells with adenoviral constructs encoding for PKC alpha, delta, or eta. Because the reduction in P-Tyr content of IRS-1 was accompanied by a reduced association of IRS-1 with p85, the regulatory subunit of PI3K, it suggests that this negative regulatory process induced by PKC zeta has a built-in attenuation signal. Hence, insulin triggers a sequential cascade in which PI3K-mediated activation of PKC zeta inhibits IRS-1 functions, reduces complex formation between IRS-1 and PI3K, and inhibits further activation of PKC zeta itself. These findings implicate PKC zeta as a key element in a multistep negative feedback control mechanism of IRS-1 functions. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Bar Ilan Univ, Gonda Goldschmied Ctr, Fac Life Sci, IL-52900 Ramat Gan, Israel. Showa Univ, Inst Mol Oncol, Shinagawa Ku, Tokyo 1428555, Japan. NIDDK, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Zick, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RI Kuroki, Toshio/A-9500-2011 OI Kuroki, Toshio/0000-0001-6369-4351 NR 46 TC 149 Z9 152 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 14459 EP 14465 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600125 PM 11278339 ER PT J AU Watanabe, H de Caestecker, MP Yamada, Y AF Watanabe, H de Caestecker, MP Yamada, Y TI Transcriptional cross-talk between Smad, ERK1/2, and p38 mitogen-activated protein kinase pathways regulates transforming growth factor-beta-induced aggrecangene expression in chondrogenic ATDC5 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-2; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; CHONDROCYTE DIFFERENTIATION; MICROMASS CULTURES; MESENCHYMAL CELLS; TUMOR-SUPPRESSOR; LINE ATDC5; IN-VITRO; RECEPTORS AB In chondrogenesis, members of the transforming growth factor-beta (TGF-beta) superfamily play critical roles by inducing gene expression of cartilage-specific molecules. By using a chondrogenic cell line, ATDC5, we investigated the TGF-beta -mediated signaling pathways involved in expression of the aggrecan gene (Agc). At confluency, TGF-beta induced Age expression within 3 h, and cycloheximide blocked this induction, indicating that de novo protein synthesis is essential for this response. At this stage, TGF-beta induced rapid, transient phosphorylation of Smad2, extracellular signal-activated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK). Inhibition of the Smad pathways by transfection with a dominant negative Smad4 construct significantly reduced TGF-beta -induced Age expression, indicating that Smad signaling is essential for this response. Furthermore, an inhibitor of the ERK1/2 pathway, U0126, or inhibitors of the p38 MAPK pathway, SB203580 and SKF86002, repressed TGF-beta -induced Age expression in a dose-dependent manner, indicating that ERK1/2 or p38 MAPK activation is also required for TGF-beta -induced Agc expression in confluent ATDC5 cells. In differentiated ATDC5 cells, persistently high basal levels of ERK1/2 and p38 MAPK phosphorylation correlated with elevated basal Age expression, which was inhibited by incubation with inhibitors of these pathways. Whereas Smad2 was rapidly phosphorylated by TGF-beta and involved in the initial activation of Agc expression in confluent cells, Smad2 activation was not required for maintaining the high level of Age expression. Taken together, these results suggest an important role for transcriptional cross-talk between Smad and MAPK pathways in expression of early chondrocytic phenotypes and identify important changes in the regulation of Age expression following chondrocyte differentiation. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Yamada, Y (reprint author), NICDR, NIH, Bldg 30,Rm 405,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. NR 62 TC 214 Z9 224 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2001 VL 276 IS 17 BP 14466 EP 14473 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426PB UT WOS:000168356600126 PM 11278290 ER PT J AU Shibusawa, Y Yanagida, A Isozaki, M Shindo, H Ito, Y AF Shibusawa, Y Yanagida, A Isozaki, M Shindo, H Ito, Y TI Separation of apple procyanidins into different degrees of polymerization by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; apples; procyanidins; catechins; tannins ID LIQUID PARTITION CHROMATOGRAPHY; SOLID SUPPORT; FRACTIONATION; POLYPHENOLS; OLIGOMERS; TANNINS; PROTEIN; CELLS AB Apple procyanidins were fractionated by high-speed counter-current chromatography in a one-step operation from apple condensed tannins using a type-J multilayer coil planet centrifuge. The separation of procyanidins was performed with a two-phase solvent system composed of methyl acetate-water (1:1) by eluting the upper phase at a flow-rate of 1.0 ml/min. Each fraction was examined by time-of-flight mass spectrometry. Procyanidins were separated according to their degrees of polymerization. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, Hachioji, Tokyo 1920392, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. NR 19 TC 31 Z9 32 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 27 PY 2001 VL 915 IS 1-2 BP 253 EP 257 DI 10.1016/S0021-9673(01)00575-1 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 423YZ UT WOS:000168206500026 PM 11358256 ER PT J AU Gomeza, J Zhang, L Kostenis, E Felder, CC Bymaster, FP Brodkin, J Shannon, H Xia, B Duttaroy, A Deng, CX Wess, J AF Gomeza, J Zhang, L Kostenis, E Felder, CC Bymaster, FP Brodkin, J Shannon, H Xia, B Duttaroy, A Deng, CX Wess, J TI Generation and pharmacological analysis of M-2 and M-4 muscarinic receptor knockout mice SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 9th International Symposium on Subtypes of Muscarinic Receptors CY OCT 31-NOV 04, 2000 CL HOUSTON, TEXAS SP Boston Univ Sch Med DE gene targeting; oxotremorine; analgesia; locomotor activity; striatum; Parkinson's disease; dopamine receptor ID RAT SPINAL-CORD; ACETYLCHOLINE-RECEPTORS; ANTINOCICEPTION; DOPAMINE; PROTEINS; SUBTYPES; NEURONS; D1; M2; M1 AB Muscarinic acetylcholine receptors (M-1-M-5) play important roles in the modulation of many key functions of the central and peripheral nervous system. To explore the physiological roles of the two G(i)-coupled muscarinic receptors, we disrupted the M-2 and M-4 receptor genes in mice by using a gene targeting strategy, pharmacological and behavioral analysis of the resulting mutant mice showed that the M-2 receptor subtype is critically involved in mediating three of the most striking central muscarinic effects, tremor, hypothermia, and analgesia. These studies also indicated that M-4 receptors are not critically involved in these central muscarinic responses. However, M-4 receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses following drug-induced activation of D1 dopamine receptors, This observation is consistent with the concept that M-4 receptors exert inhibitory control over D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are known to be coexpressed. These findings emphasize the usefulness of gene targeting approaches to shed light on the physiological and pathophysiological roles of the individual muscarinic receptor subtypes. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Wess, J (reprint author), NIDDKD, Bioorgan Chem Lab, Bldg 8A,Room B1A-05,8 Ctr Dr MSC 0810, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 22 TC 40 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 BP 2457 EP 2466 DI 10.1016/S0024-3205(01)01039-6 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200002 PM 11392613 ER PT J AU Bymaster, FP Carter, PA Zhang, L Falcone, JF Stengel, PW Cohen, ML Shannon, HE Gomeza, J Wess, J Felder, CC AF Bymaster, FP Carter, PA Zhang, L Falcone, JF Stengel, PW Cohen, ML Shannon, HE Gomeza, J Wess, J Felder, CC TI Investigations into the physiological role of muscarinic M-2 and M-4 muscarinic and M-4 receptor subtypes using receptor knockout mice SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 9th International Symposium on Subtypes of Muscarinic Receptors CY OCT 31-NOV 04, 2000 CL HOUSTON, TEXAS SP Boston Univ Sch Med DE muscarinic receptor; gene knockout; hypothermia; salivation; tremor; atria; muscarinic M-2; receptors; muscarinic M-4 receptors ID BRAIN; GENE AB Determination of muscarinic agonist-induced parasympathomimetic effects in wild type and M-2 and M-4 muscarinic receptor knockout mice revealed that M-2 receptors mediated tremor and hypothermia, but not salivation. The M-4 receptors seem to play a modest role in salivation, but did not alter hypothermia and tremor. In the M-2 knockout mice, agonist-induced bradycardia in isolated spontaneously beating atria was completely absent compared to their wild type litter mates, whereas agonist-induced bradycardia was similar in the M-4 knockout and wild type mice. The potency of carbachol to stimulate contraction of isolated stomach fundus, urinary bladder and trachea was reduced by a factor of about 2 in the M-2 knockout mice, but was unaltered in the M-4 knockout mice. The binding of the muscarinic agonist, [H-3]-oxotremorine-M, was reduced in cortical tissue from the M-2 knockout mice and to a lesser extent from the M-4 knockout mice, and was reduced over 90% in the brain stem of M-2 knockout mice. The data demonstrate the usefulness of knockout mice in determining the physiological function of peripheral and central muscarinic receptors. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Eli Lilly & Co, Lilly Res Labs, Neurosci Res Div, Indianapolis, IN 46285 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Bymaster, FP (reprint author), Eli Lilly & Co, Lilly Res Labs, Neurosci Res Div, Indianapolis, IN 46285 USA. NR 15 TC 32 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 BP 2473 EP 2479 DI 10.1016/S0024-3205(01)01041-4 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200004 PM 11392615 ER PT J AU Shapiro, MS Gomeza, J Hamilton, SE Hille, B Loose, MD Nathanson, NM Roche, JP Wess, J AF Shapiro, MS Gomeza, J Hamilton, SE Hille, B Loose, MD Nathanson, NM Roche, JP Wess, J TI Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 9th International Symposium on Subtypes of Muscarinic Receptors CY OCT 31-NOV 04, 2000 CL HOUSTON, TEXAS SP Boston Univ Sch Med DE muscarinic receptor; G protein; Ca2+ channel; M current ID CALCIUM CHANNELS; VOLTAGE DEPENDENCE; CURRENT INHIBITION; KNOCKOUT MICE; N-TYPE; ACTIVATION; MODULATION; NEUROTRANSMITTERS; SUPPRESSION; DISRUPTION AB Many different G protein-coupled receptors modulate the activity of Ca2+ and K+ channels in a variety of neuronal types. There art: five known subtypes (M-1-M-5) Of muscarinic acetylcholine receptors. Knockout mice lacking the M-1, M-2, or M-4 subtypes are studied to determine which receptors mediate modulation of voltage-gated Ca2+ channels in mouse sympathetic neurons. In these cells, muscarinic agonists modulate N- and L-type Ca2+ channels and the M-type K+ channel through two distinct, G-protein mediated pathways. The fast and voltage-dependent pathway is lacking in the M-2 receptor knockout mice. The slow acid voltage-independent pathway is absent in the M-1 receptor knockout mice. Neither pathway is affected in the M-4 receptor knockout mice. Muscarinic modulation of the M current is absent in the M-1 receptor knockout mice, and can be reconstituted in a heterologous expression system using cloned channels and M-1 receptors. Our results using knockout mice are compared with pharmacological data in the rat. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Oberlin Coll, Program Neurosci, Oberlin, OH 44074 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shapiro, MS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, MS 7756,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDA NIH HHS [DA11322]; NINDS NIH HHS [NS08174, NS26920] NR 33 TC 45 Z9 45 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 BP 2481 EP 2487 DI 10.1016/S0024-3205(01)01042-6 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200005 PM 11392616 ER PT J AU Felder, CC Porter, AC Skillman, TL Zhang, L Bymaster, FP Nathanson, NM Hamilton, SE Gomeza, J Wess, J AF Felder, CC Porter, AC Skillman, TL Zhang, L Bymaster, FP Nathanson, NM Hamilton, SE Gomeza, J Wess, J TI Elucidating the role of muscarinic receptors in psychosis SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 9th International Symposium on Subtypes of Muscarinic Receptors CY OCT 31-NOV 04, 2000 CL HOUSTON, TEXAS SP Boston Univ Sch Med DE muscarinic receptor subtypes; cognition; psychosis; GTP binding; startle reflex; schizophrenia ID KNOCKOUT MICE; HYPOTHESIS; AGONISTS; CELLS AB Muscarinic receptors have been implicated in the regulation of cognition and psychosis based on pharmacological evidence from pre-clinical and clinical studies. Muscarinic agonists have shown promise in the clinic in improving cognition and reducing psychotic episodes in Alzheimer's patients. However, lack of selective muscarinic ligands has limited their use due to troublesome side effects observed at higher doses. Without selective ligands, it has been difficult to assign a specific muscarinic receptor subtype to these high order mental processes. Recent development of muscarinic receptor knockout mice has provided additional tools to investigate cognition and psychosis in behavioral assays and to determine the receptor subtypes associated with parasympathomimetic physiology. Biochemical studies indicate that the M-1 receptor plays a significant role in regulating G alphaq-mediated signal transduction in the hippocampus and cortex. Behavioral studies suggest that the M-4 receptor is involved in movement regulation and prepulse inhibition of the startle reflex, a measure of attention. These findings support a role for the development of M-1 and M-4 receptor agonists for diseases in which symptoms include cognitive impairment and psychotic behaviors. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Lilly Corp Ctr, Eli Lilly Res Labs, Div Neurosci, Indianapolis, IN 46285 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. NIDDK, Lab Bioorgan Chem, Bethesda, MD 20892 USA. RP Felder, CC (reprint author), Lilly Corp Ctr, Eli Lilly Res Labs, Div Neurosci, Drop 0510, Indianapolis, IN 46285 USA. NR 19 TC 72 Z9 74 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 BP 2605 EP 2613 DI 10.1016/S0024-3205(01)01059-1 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200022 PM 11392633 ER PT J AU Berkeley, JL Hamilton, SE Nathanson, NM Wess, J Levey, AI AF Berkeley, JL Hamilton, SE Nathanson, NM Wess, J Levey, AI TI M1 muscarinic acetylcholine receptors activate MAPK in brain SO LIFE SCIENCES LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. RI Levey, Allan/F-2104-2011 OI Levey, Allan/0000-0002-3153-502X NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 MA 19 BP 2624 EP 2624 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200042 ER PT J AU Duttaroy, A Gomeza, J Gan, JW Basile, AS Harman, WD Smith, PL Felder, CC Levey, AI Wess, J AF Duttaroy, A Gomeza, J Gan, JW Basile, AS Harman, WD Smith, PL Felder, CC Levey, AI Wess, J TI Evaluation of muscarinic agonist-induced analgesia in muscarinic receptor knockout mice SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22903 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RI Levey, Allan/F-2104-2011 OI Levey, Allan/0000-0002-3153-502X NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 MA 34 BP 2631 EP 2631 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200057 ER PT J AU Jagoda, EM Kiesewetter, DO Shimoji, K Gomeza, J Wess, J Eckelman, WC AF Jagoda, EM Kiesewetter, DO Shimoji, K Gomeza, J Wess, J Eckelman, WC TI Regional brain uptake of the muscarinic ligand, [F-18]FP-TZTP, is decreased in M2 knockout but not in M4 knockout mice. SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIDDK, PET Dept, NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 MA 40 BP 2634 EP 2634 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200063 ER PT J AU Felder, CC Bymaster, FP Wess, J Zang, L Shaw, DB McKinzie, DL AF Felder, CC Bymaster, FP Wess, J Zang, L Shaw, DB McKinzie, DL TI Enhanced sensitivity to the lomotor-activating and disrupting effects of phencyclidine in M4 muscarinic receptor knock-out mice SO LIFE SCIENCES LA English DT Meeting Abstract C1 Eli Lilly Res Labs, Div Neurosci, Indianapolis, IN 46285 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 MA 44 BP 2636 EP 2636 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200067 ER PT J AU Erlenbach, I Kostenis, E Schmidt, C Hamdan, F Pausch, MH Wess, J AF Erlenbach, I Kostenis, E Schmidt, C Hamdan, F Pausch, MH Wess, J TI Functional expression of M-1, M-3, and M-5 muscarinic acetylcholine receptors in yeast SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Wyeth Ayerst Res, Mol Genet Screen Design, Princeton, NJ 08543 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 27 PY 2001 VL 68 IS 22-23 MA 51 BP 2640 EP 2640 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 430KZ UT WOS:000168574200074 ER PT J AU Conway, JF Wikoff, WR Cheng, N Duda, RL Hendrix, RW Johnson, JE Steven, AC AF Conway, JF Wikoff, WR Cheng, N Duda, RL Hendrix, RW Johnson, JE Steven, AC TI Virus maturation involving large subunit rotations and local refolding SO SCIENCE LA English DT Article ID DEPENDENT CONFORMATIONAL-CHANGES; DOUBLE-STRANDED-RNA; STRUCTURAL TRANSITIONS; CAPSID PROTEIN; DENSITY MAPS; BACTERIOPHAGE-T4; BINDING; STATES; VISUALIZATION; RESOLUTION AB Large-scale conformational changes transform viral precursors into infectious virions. The structure of bacteriophage HK97 capsid, Head-II, was recently solved by crystallography, revealing a catenated cross-linked topology. We have visualized its precursor, Prohead-II, by cryoelectron microscopy and modeled the conformational change by appropriately adapting Head-II. Rigid-body rotations (similar to 40 degrees) cause switching to an entirely different set of interactions; in addition, two motifs undergo refolding. These changes stabilize the capsid by increasing the surface area buried at interfaces and bringing the cross-link-forming residues, initially similar to 40 angstroms apart, close together. The inner surface of Prohead-II is negatively charged, suggesting that the transition is triggered electrostatically by DNA packaging. C1 NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA. Inst Biol Struct JP Ebel, F-38027 Grenoble, France. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. RP Steven, AC (reprint author), NIH, Bldg 6,Room B2-34,6 Ctr Dr MSC 2717, Bethesda, MD 20892 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 FU NIAID NIH HHS [AI40101]; NIGMS NIH HHS [R01 GM47795] NR 33 TC 151 Z9 156 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 27 PY 2001 VL 292 IS 5517 BP 744 EP 748 DI 10.1126/science.1058069 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 428TX UT WOS:000168478300057 PM 11326105 ER PT J AU Nishizuka, S Winokur, ST Simon, M Martin, J Tsujimoto, H Stanbridge, EJ AF Nishizuka, S Winokur, ST Simon, M Martin, J Tsujimoto, H Stanbridge, EJ TI Oligonucleotide microarray expression analysis of genes whose expression is correlated with tumorigenic and non-tumorigenic phenotype of HeLa X human fibroblast hybrid cells SO CANCER LETTERS LA English DT Article DE oligonucleotide microarray; HeLa x fibroblast hybrid cell; tumorigenicity; differential gene expression; gene expression profiling ID INTESTINAL ALKALINE-PHOSPHATASE; TUMOR-ASSOCIATED ANTIGEN; IDENTIFICATION; GENOME; ARRAYS; HYBRIDIZATION; CHROMOSOME-11; SUPPRESSION AB In order to understand the differences and similarities between tumorigenic and non-tumorigenic HeLa x human fibroblast hybrids, gene expression profiles were examined with synthetic oligonucleotide arrays containing nearly 7000 gene probe sets. We used two pairs of genetically related hybrids, each pair representing individual clones of non-tumorigenic and tumorigenic segregant hybrids, respectively. Analysis of six possible comparisons, utilizing two algorithms, identified 204 genes with differential expression. The greater number of differentially expressed genes was observed when non-tumorigenic hybrids were compared with tumorigenic segregants. Fifteen and 14 genes, respectively, were consistently found to be differentially expressed in non-tumorigenic and tumorigenic cells. Among those 29 differentially expressed genes, three (intestinal alkaline phosphatase, caveolin-1, and solute carrier family2, member3) have been reported previously to be associated with the tumorigenic phenotype, using the same hybrid pairs. In addition, among the genes previously detected by differential display, 78% of them exhibited more than 5-fold change, demonstrating a high consistency between the two methods of differential gene expression. These findings suggest that synthetic oligonucleotide arrays are a powerful and highly reproducible tool to identify those genes whose expression is associated with certain phenotypes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. Kyoto Prefectural Univ Med, Dept Surg Gastroenterol, Kamigyo Ku, Kyoto 6020841, Japan. Univ Calif Irvine, Dept Mol Genet & Microbiol, Irvine, CA 92697 USA. RP Nishizuka, S (reprint author), NCI, NIH, Mol Pharmacol Lab, Bldg 37,Room 4C-09,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA19104] NR 27 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 26 PY 2001 VL 165 IS 2 BP 201 EP 209 DI 10.1016/S0304-3835(01)00437-2 PG 9 WC Oncology SC Oncology GA 428BK UT WOS:000168441100011 PM 11275370 ER PT J AU Shi, GB Blaszczyk, J Ji, XH Yan, HG AF Shi, GB Blaszczyk, J Ji, XH Yan, HG TI Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: Synthesis and biochemical and crystallographic studies SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; 7,8-DIHYDRO-6-HYDROXYMETHYLPTERIN-PYROPHOSPHOKINASE; COMPLEX; KINASE AB 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading to the biosynthesis of folate cofactors. Like other enzymes in the folate pathway, HPPK is an ideal target for the development of antimicrobial agents because the enzyme is essential for microorganisms but is absent from human and animals. Three bisubstrate analogues have been synthesized for HPPK and characterized by biochemical and X-ray crystallographic analyses. All three bisubstrate analogues consist of a pterin, an adenosine moiety, and a link composed of 2-4 phosphoryl groups. P-1-(6-Hydroxymethylpterin)-P-2-(5 ' -adenosyl)diphosphate (HP(2)A, 5) shows little affinity and inhibitory activity for E. coli HPPK, P-1-(6-Hydroxymethylpterin)-P-4-(5 ' -adenosyl)triphosphate (H(P)3A, 6) shows moderate affinity and inhibitory activity with K-d = 4.25 muM in the presence of Mg2+ and IC50 = 1.27 muM. P-1-(6-Hydroxymethylpterin)-P-4-(5 ' -adenosyl)tetraphosphate (HP(4)A, 7) shows the highest affinity and inhibitory activity with K-d = 0.47 muM in the presence of Mg2+ and IC50 = 0.44 muM The affinity of MgHP(4)A for HPPK is similar to 116 and 76 times higher than that of MgADP and 6-hydroxymethylpterin, respectively. The crystal structure of HPPK in complex with 7 (HPPK MgHP4A) has been determined at 1.85 Angstrom resolution with a crystallographic R factor of 0.185. The crystal structure shows that 7 occupies both HP- and ATP-binding sites and induces significant conformational changes in HPPK. The biochemical and structural studies of the bisubstrate analogues indicate that the bisubstrate analogue approach can produce more potent inhibitors for HPPK and the minimum length of the link for a bisubstrate analogue is similar to7 Angstrom. C1 NCI, Frederick Canc Res & Dev Ctr, Macromol Crystallog Lab, Frederick, MD 21702 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. RP Ji, XH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Macromol Crystallog Lab, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM51901] NR 39 TC 34 Z9 34 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 26 PY 2001 VL 44 IS 9 BP 1364 EP 1371 DI 10.1021/jm0004493 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 428CG UT WOS:000168443100007 PM 11311059 ER PT J AU McLamore, S Ullrich, T Rothman, RB Xu, H Dersch, C Coop, A Davis, P Porreca, F Jacobson, AE Rice, KC AF McLamore, S Ullrich, T Rothman, RB Xu, H Dersch, C Coop, A Davis, P Porreca, F Jacobson, AE Rice, KC TI Effect of N-alkyl and N-alkenyl substituents in noroxymorphindole, 17-substituted-6,7-dehydro-4,5 alpha-epoxy-3,14-dihydroxy-6,7 : 2 ',3 '-indolomorphinans, on opioid receptor affinity, selectivity, and efficacy SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MESSAGE-ADDRESS CONCEPT; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE.; MEDIATED PHENOMENA; AGONIST EFFICACY; IN-VITRO; NALTRINDOLE; BINDING; LIGANDS; PYRROLOOCTAHYDROISOQUINOLINES; ANTAGONIST AB The N-alkyl analogues (N-ethyl through N-heptyl), branched N-alkyl chain analogues (N-isopropyl, N-2-methylpropyl, and N-3-methylbutyl), and N-alkenyl analogues ((E)-N-3-methylallyl (crotyl), N-2-methylallyl, and N-3,3-dimethylallyl) were prepared in the noroxymorphindole series (17-substituted-6,7-dehydro-4,5 alpha -epoxy-3,12-dihydroxy-6,7:2 ' ,3 ' -indolomorphinans), and the effect of the N-substituent on opioid receptor affinity, selectivity, and efficacy was examined using receptor binding assays, [S-35]GTP gammaS efficacy determinations, and smooth muscle functional assays (electrically stimulated mouse vas deferens and guinea pig ileum). All of the compounds acted as opioid antagonists, including those with N-substituents which usually confer either weak agonist-antagonist behavior (N-ethyl) or potent opioid agonist activity (N-pentyl) in morphinan-like ligands which interact with the mu -receptor. Several N-substituted noroxymorphindoles were found to be more mu/delta -selective than naltrindole (NTI). The N-2-methylallylnoroxymorphindole, in particular, was found to be more selective than NTI in receptor binding assays (mu/delta = 1700 vs 120; kappa/delta = 810 vs 140), as an antagonist in the GTP gammaS assay (mu/delta = 170 vs 140; kappa/delta = 620 vs 160), and considerably more selective than NTI in the functional assays (mu/delta > 2200 vs 90), It also had high affinity for the delta -opioid receptor (K-i = 4.7 nM in the binding assay) and high antagonist potency (1.2 nM in the GTP gammaS assay; 8.9 nM in the MVD assay). C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. Univ Arizona, Hlth Sci Ctr, Dept Pharmacol, Tucson, AZ 85724 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Room B1-23, Bethesda, MD 20892 USA. NR 18 TC 20 Z9 20 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 26 PY 2001 VL 44 IS 9 BP 1471 EP 1474 DI 10.1021/jm000511w PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 428CG UT WOS:000168443100019 PM 11311071 ER PT J AU Andurkar, SV Beguin, C Stables, JP Kohn, H AF Andurkar, SV Beguin, C Stables, JP Kohn, H TI Synthesis and structural studies of aza analogues of functionalized amino acids: New anticonvulsant agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID N-BENZYLACETAMIDE DERIVATIVES; ENZYME-INHIBITORS AB We have reported that functionalized amino acids 1 display potent anticonvulsant activities in mice and rats, and that the activity resides primarily in the D-isomer. In this study we investigated whether selectively replacing the C(2) tetrahedral atom with a trivalent nitrogen provides compounds with comparable activity. Six functionalized N(2)-substituted semicarbazides (3) were prepared. X-ray crystallographic analysis of 1-acetyl-4-benzyl-2-(thiazol-2-yl)semicarbazide (13) showed that it lost asymmetry and adopted a configuration midway between the corresponding D- and L-amino acid derivatives. Evaluation of 3 in both mice (ip) and rats (po) showed that the compounds exhibited significant anticonvulsant activities but in most cases at levels lower than their amino acid counterparts. One of the semicarbazides, 13, displayed excellent activity in mice and rats that compared favorably to that of phenytoin. C1 Univ Houston, Dept Chem, Houston, TX 77204 USA. NINDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. RP Kohn, H (reprint author), Univ Houston, Dept Chem, Univ Pk, Houston, TX 77204 USA. EM harold_krohn@unc.edu NR 17 TC 25 Z9 26 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 26 PY 2001 VL 44 IS 9 BP 1475 EP 1478 DI 10.1021/jm0005171 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 428CG UT WOS:000168443100020 PM 11311072 ER PT J AU Hendler, RW Shrager, RI Bose, S AF Hendler, RW Shrager, RI Bose, S TI Theory and procedures for finding a correct kinetic model for the bacteriorhodopsin photocycle SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SINGULAR-VALUE DECOMPOSITION; SPECTROSCOPY; TRANSITIONS AB In this paper, we present the implementation and results of new methodology based on linear algebra. The theory behind these methods is covered in detail in the Supporting Information, available electronically (Shrager and Hendler), In brief, the methods presented search through all possible forward sequential submodels in order to find candidates that can be used to construct a complete model for the BR-photocycle. The methodology is limited only to forward sequential models. If no such models are compatible with the experimental data, none will be found, The procedures apply objective tests and filters to eliminate possibilities that cannot be correct, thus cutting the total number of candidate sequences to be considered. In the current application, which uses six exponentials, the total sequences were cut from 1950 to 49. The remaining sequences were further screened using known experimental criteria. The approach led to a solution which consists of a pair of sequences, one with 5 exponentials showing BR* --> L-f --> M-f --> N --> O --> BR and the other with three exponentials showing BR* --> L-s --> M-s --> BR. The deduced complete kinetic model for the BR photocycle is thus either a single photocycle branched at the L intermediate or a pair of two parallel photocycles, Reasons for preferring the parallel photocycles are presented. Synthetic data constructed on the basis of the parallel photocycles were indistinguishable from the experimental data in a number of analytical tests that were applied. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. CIT, Math & Stat Comp Lab, NIH, Bethesda, MD 20892 USA. RP Hendler, RW (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 15 TC 28 Z9 28 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 26 PY 2001 VL 105 IS 16 BP 3319 EP 3328 DI 10.1021/jp002362z PG 10 WC Chemistry, Physical SC Chemistry GA 428BU UT WOS:000168441900023 PM 23776957 ER PT J AU Lin, FYC Ho, VA Khiem, HB Trach, DD Bay, PV Thanh, TC Kossaczka, Z Bryla, DA Shiloach, J Robbins, JB Schneerson, R Szu, SC Lanh, MN Hunt, S Trinh, L Kaufman, JB AF Lin, FYC Ho, VA Khiem, HB Trach, DD Bay, PV Thanh, TC Kossaczka, Z Bryla, DA Shiloach, J Robbins, JB Schneerson, R Szu, SC Lanh, MN Hunt, S Trinh, L Kaufman, JB TI The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE; IMMUNOLOGICAL PROPERTIES; PUBLIC-HEALTH; FEVER; IMMUNOGENICITY; PREVENTION; IMMUNIZATION; TAJIKISTAN; RESISTANCE AB Background: Typhoid fever is common in developing countries. The licensed typhoid vaccines confer only about 70 percent immunity, do not protect young children, and are not used for routine vaccination. A newly devised conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old. Methods: In a double-blind, randomized trial, we evaluated the safety, immunogenicity, and efficacy of the Vi-rEPA vaccine in children two to five years old in 16 communes in Dong Thap Province, Vietnam. Each of the 11,091 children received two injections six weeks apart of either Vi-rEPA or a saline placebo. Cases of typhoid, diagnosed by the isolation of S. typhi from blood cultures after 3 or more days of fever (a temperature of 37.5 degreesC or higher), were identified by active surveillance over a period of 27 months. We estimated efficacy by comparing the attack rate of typhoid in the vaccine group with that in the placebo group. Results: S. typhi was isolated from 4 of the 5525 children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children who received both injections of placebo (efficacy, 91.5 percent; 95 percent confidence interval, 77.1 to 96.6 percent; P<0.001). Among the 771 children who received only one injection, there was 1 case of typhoid in the vaccine group and 8 cases in the placebo group. Cases were distributed evenly among all age groups and throughout the study period. No serious adverse reactions were observed. In all 36 children studied four weeks after the second injection of the vaccine, levels of serum IgG Vi antibodies had increased by a factor of 10 or more. Conclusions: The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than 90 percent efficacy in children two to five years old. The antibody responses and the efficacy suggest that this vaccine should be at least as protective in persons who are more than five years old. (N Engl J Med 2001;344:1263-9.) Copyright (C) 2001 Massachusetts Medical Society. C1 NICHHD, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Dong Thap Prov Hosp, Cao Lanh, Vietnam. Inst Pasteur, Ho Chi Minh City, Vietnam. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. RP Lin, FYC (reprint author), NICHHD, Rm 7B03,6100 Execut Blvd, Bethesda, MD 20892 USA. OI Hunt, Steven/0000-0003-3533-0627 FU NICHD NIH HHS [N01-HD-3269] NR 37 TC 214 Z9 221 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2001 VL 344 IS 17 BP 1263 EP 1269 DI 10.1056/NEJM200104263441701 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 424UM UT WOS:000168252400001 PM 11320385 ER PT J AU Walkup, JT Labellarte, MJ Riddle, MA Pine, DS Greenhill, L Klein, R Davies, M Sweeney, M Abikoff, H Hack, S Klee, B McCracken, J Bergman, L Piacentini, J March, J Compton, S Robinson, J O'Hara, T Baker, S Vitiello, B Ritz, LA Roper, M AF Walkup, JT Labellarte, MJ Riddle, MA Pine, DS Greenhill, L Klein, R Davies, M Sweeney, M Abikoff, H Hack, S Klee, B McCracken, J Bergman, L Piacentini, J March, J Compton, S Robinson, J O'Hara, T Baker, S Vitiello, B Ritz, LA Roper, M CA Res Unit Pediat Psychopharmacology TI Fluvoxamine for the treatment of anxiety disorders in children and adolescents SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED TRIAL; MEDICAL LITERATURE; EARLY EXPERIENCE; USERS GUIDES; FLUOXETINE; DEPRESSION; VALIDITY; SCALE; RELIABILITY AB Background: Drugs that selectively inhibit serotonin reuptake are effective treatments for adults with mood and anxiety disorders, but limited data are available on the safety and efficacy of serotonin-reuptake inhibitors in children with anxiety disorders. Methods: We studied 128 children who were 6 to 17 years of age; who met the criteria for social phobia, separation anxiety disorder, or generalized anxiety disorder; and who had received psychological treatment for three weeks without improvement. The children were randomly assigned to receive fluvoxamine (at a maximum of 300 mg per day) or placebo for eight weeks and were evaluated with rating scales designed to assess the degree of anxiety and impairment. Results: Children in the fluvoxamine group had a mean (+/-SD) decrease of 9.7+/-6.9 points in symptoms of anxiety on the Pediatric Anxiety Rating Scale (range of possible scores, 0 to 25, with higher scores indicating greater anxiety), as compared with a decrease of 3.1+/-4.8 points among children in the placebo group (P<0.001). On the Clinical Global Impressions-Improvement scale, 48 of 63 children in the fluvoxamine group (76 percent) had a response to the treatment, as indicated by a score of less than 4, as compared with 19 of 65 children in the placebo group (29 percent, P<0.001). Five children in the fluvoxamine group (8 percent) discontinued treatment because of adverse events, as compared with one child in the placebo group (2 percent). Conclusions: Fluvoxamine is an effective treatment for children and adolescents with social phobia, separation anxiety disorder, or generalized anxiety disorder. (N Engl J Med 2001;344:1279-85.) Copyright (C) 2001 Massachusetts Medical Society. C1 NIMH, Intramural Res Program, Program Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Columbia Univ, New York, NY 10027 USA. New York State Psychiat Inst, New York, NY 10032 USA. NYU, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Duke Univ, Durham, NC 27706 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Program Mood & Anxiety Disorders, Bldg 10,Rm 4N-222,MSC-1381, Bethesda, MD 20892 USA. RI Piacentini, John/C-4645-2011 NR 47 TC 322 Z9 326 U1 3 U2 20 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2001 VL 344 IS 17 BP 1279 EP 1285 DI 10.1056/NEJM200104263441703 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 424UM UT WOS:000168252400003 ER PT J AU Inskip, PD Tarone, RE Linet, MS AF Inskip, PD Tarone, RE Linet, MS TI Cellular telephones and brain tumors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Inskip, PD (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2001 VL 344 IS 17 BP 1332 EP 1332 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 424UM UT WOS:000168252400020 ER PT J AU Boulanger, CA Smith, GH AF Boulanger, CA Smith, GH TI Reducing mammary cancer risk through premature stem cell senescence SO ONCOGENE LA English DT Article DE mammary; stem cell; cancer risk; cellular senescence; MMTV ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE; TUMOR VIRUS; EXPRESSION; MICE; GLAND; DIFFERENTIATION; TISSUES AB The reproductive capacity of the mammary epithelial stem cell is reduced coincident with the number of symmetric divisions it must perform. In a study of FVB/ N mice with the transgene, WAP-TGF beta1, we discovered that mammary epithelial stem tells were prematurely aged due to ectopic expression of TGF-beta1. To test whether premature aging of mammary epithelial stem cells would have an impart on susceptibility or resistance to mammary cancer, female littermates from FVB/ N x WAP-TGF-beta1 mating were injected with mouse mammary tumor virus (MMTV) at 8-10 weeks of age. A total of 44 females were inoculated, maintained as breeders and observed for tumor development for up to 18 months. Only one mammary tumor appeared in 17 TGF-beta1 females while 15 were collected from 29 wild type sisters. Premalignant mammary epithelial cells in infected glands were identified by transplantation of single cell(1 x 10(5)) suspensions into nulliparous hosts and testing for hyperplastic outgrowth. Although the number of positive takes was significantly reduced with TGF-beta1 cells, both MMTV-infected TGF-beta1 and wild type cells produced hyperplastic outgrowths suggesting that premalignant transformation was achieved in each group. The results suggest a positive correlation between the procreative life-span of mammary epithelial stem cells and mammary cancer risk. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NIH, Bldg 10,Room 8H07,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 63 Z9 63 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 26 PY 2001 VL 20 IS 18 BP 2264 EP 2272 DI 10.1038/sj.onc.1204312 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 427KZ UT WOS:000168404500008 PM 11402321 ER PT J AU Calis, KA Daniels, CE AF Calis, KA Daniels, CE TI Safety reporting in clinical trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. RP Calis, KA (reprint author), NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2001 VL 285 IS 16 BP 2076 EP 2076 DI 10.1001/jama.285.16.2076 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 422QW UT WOS:000168131600015 PM 11311085 ER PT J AU Nansel, TR Overpeck, M Pilla, RS Ruan, WJ Simons-Morton, B Scheidt, P AF Nansel, TR Overpeck, M Pilla, RS Ruan, WJ Simons-Morton, B Scheidt, P TI Bullying behaviors among US youth - Prevalence and association with psychosocial adjustment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SCHOOL-AGE-CHILDREN; BULLY/VICTIM PROBLEMS; SELF-ESTEEM; BULLIES; VICTIMS; VICTIMIZATION; ADOLESCENTS; DEPRESSION; EXPERIENCE; STUDENTS AB Context Although violence among US youth is a current major concern, bullying is infrequently addressed and no national data on the prevalence of bullying are available. Objectives To measure the prevalence of bullying behaviors among US youth and to determine the association of bullying and being bullied with indicators of psychosocial adjustment, including problem behavior, school adjustment, social/emotional adjustment, and parenting. Design, Setting, and Participants Analysis of data from a representative sample of 15686 students in grades 6 through 10 in public and private schools throughout the United States who completed the World Health Organization's Health Behaviour in School-aged Children survey during the spring of 1998. Main Outcome Measure Self-report of involvement in bullying and being bullied by others. Results A total of 29.9% of the sample reported moderate or frequent involvement in bullying, as a bully (13.0%), one who was bullied (10.6%), or both (6.3%). Males were more likely than females to be both perpetrators and targets of bullying. The frequency of bullying was higher among 6th- through 8th-grade students than among 9th- and 10th-grade students. Perpetrating and experiencing bullying were associated with poorer psychosocial adjustment (P<.001); however, different patterns of association occurred among bullies, those bullied, and those who both bullied others and were bullied themselves. Conclusions The prevalence of bullying among US youth is substantial. Given the concurrent behavioral and emotional difficulties associated with bullying, as well as the potential long-term negative outcomes for these youth, the issue of bullying merits serious attention, both for future research and preventive intervention. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Nansel, TR (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7805,MSC 7510, Bethesda, MD 20892 USA. OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z99 HD999999] NR 43 TC 1281 Z9 1299 U1 51 U2 426 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2001 VL 285 IS 16 BP 2094 EP 2100 DI 10.1001/jama.285.16.2094 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 422QW UT WOS:000168131600029 PM 11311098 ER PT J AU Polettini, A Huestis, MA AF Polettini, A Huestis, MA TI Simultaneous determination of buprenorphine, norbuprenorphine, and buprenorphine-glucuronide in plasma by liquid chromatography-tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE buprenophine; nobuprenophine ID BODY-FLUIDS; ELECTROSPRAY-IONIZATION; DEALKYLATED METABOLITE; MORPHINE METABOLITES; CODEINE-GLUCURONIDE; ACTIVE METABOLITE; BIOLOGICAL-FLUIDS; 6-MONOACETYLMORPHINE; HUMANS; HEROIN AB For the first time, an LC-MS-MS method has been developed for the simultaneous analysis of buprenorphine (BUP), norbuprenorphine (NBUP), and buprenorphine-glucuronide (BUPG) in plasma. Analytes were isolated from plasma by C-18 SPE and separated by gradient RP-LC. Electrospray ionization and MS-MS analyses were carried out using a PE-Sciex API-3000 tandem mass spectrometer. The m/z 644-->m/z 468 transition was monitored for BUPG, whereas for BUP, BUP-d(4), NBUP, and NBUP-d(3) it was necessary to monitor the surviving parent ions in order to achieve the required sensitivity. The method exhibited good linearity from 0.1 to 50 ng/ml (r(2)greater than or equal to0.998). Extraction recovery was higher than 77% for BUPG and higher than 88% for both BUP and NBUP. The LOQ was established at 0.1 ng/ml for the three analytes. The method was validated on plasma samples collected in a controlled intravenous and sublingual buprenorphine administration study. Norbuprenorphine-glucuronide was also tentatively detected in plasma by monitoring the m/z 590-->m/z 414 transition. Published by Elsevier Science B.V. C1 NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 50 Z9 52 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 25 PY 2001 VL 754 IS 2 BP 447 EP 459 DI 10.1016/S0378-4347(01)00029-9 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 420UN UT WOS:000168023800018 PM 11339288 ER PT J AU Chou, JJ Bax, A AF Chou, JJ Bax, A TI Protein side-chain rotamers from dipolar couplings in a liquid crystalline phase SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NMR; MACROMOLECULES; CALMODULIN; VALIDATION C1 NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RI Chou, James/N-9840-2013 NR 16 TC 34 Z9 35 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 25 PY 2001 VL 123 IS 16 BP 3844 EP 3845 DI 10.1021/ja015660y PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 428CA UT WOS:000168442500035 PM 11457127 ER PT J AU Rathore, D Wahl, AM Sullivan, M McCutchan, TF AF Rathore, D Wahl, AM Sullivan, M McCutchan, TF TI A phylogenetic comparison of gene trees constructed from plastid, mitochondrial and genomic DNA of Plasmodium species SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE gene trees; genomic DNA; mitochondrial DNA; phylogenetic comparison; Plasmodium species; plastid DNA ID SUBUNIT RIBOSOMAL-RNA; APICOMPLEXAN PARASITES; EXTRACHROMOSOMAL DNA; EVOLUTIONARY ORIGIN; MALARIA PARASITES; CIRCUMSPOROZOITE PROTEIN; CIRCULAR DNA; FALCIPARUM; SEQUENCE; INHERITANCE AB Gene trees of Plasmodium species have been reported, for the nuclear encoded genes (e.g. the Small Subunit rRNA) and a mitochondrial encoded gene, cytochrome b. Here, we have analyzed a plastid gene coding for caseinolytic protease ClpC, whose structure, function and evolutionary history have been studied in various organisms. This protein possesses a 220-250 amino acid long AAA domain (ATPases associated with a variety of cellular activities) that belongs to the Walker super family of ATPases and GTPases. We have sequenced the AAA motif of this gene, encoding the protein from nine different species of Plasmodium infecting rodents, birds, monkeys, and humans. The codon usage and GC content of each gene were nearly identical in contrast to the widely varying nucleotide composition of genomic DNAs. Phylogenetic trees derived from both DNA and inferred protein sequences have consistent topologies. We have used the ClpC sequence to analyze the phylogenetic relationship among Plasmodium species and compared it with those derived from mitochondrial and genomic sequences. The results corroborate well with the trees constructed using the mitochondrially encoded cytochrome b. However, an important element distinguishes the trees: the placement of Plasmodium elongatum near the base of the plastid tree, indicating an ancient lineage of parasites in birds that branches from the tree prior to other lineages of avian malaria and the human parasite, P. falciparum (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP McCutchan, TF (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr MSC 0445, Bethesda, MD 20892 USA. NR 31 TC 48 Z9 49 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD APR 25 PY 2001 VL 114 IS 1 BP 89 EP 94 DI 10.1016/S0166-6851(01)00241-9 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 433ZW UT WOS:000168791500009 PM 11356517 ER PT J AU Kim, KM Giedt, CD Basanez, G O'Neill, JW Hill, JJ Han, YH Tzung, SP Zimmerberg, J Hockenbery, DM Zhang, KYJ AF Kim, KM Giedt, CD Basanez, G O'Neill, JW Hill, JJ Han, YH Tzung, SP Zimmerberg, J Hockenbery, DM Zhang, KYJ TI Biophysical characterization of recombinant human Bcl-2 and its interactions with an inhibitory ligand, antimycin A SO BIOCHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; HIGH-LEVEL EXPRESSION; PROTEIN THERMOSTABILITY; ESCHERICHIA-COLI; FAMILY PROTEINS; ION-CHANNEL; APOPTOSIS; BINDING; BCL-X(L); DOMAINS AB Apoptosis is an essential physiological process, regulated by the family of Bcl-2-related proteins. However, the molecular mechanism by which Bcl-2 regulates apoptosis still remains elusive. Here we report the functional studies of recombinant human Bcl-2 with the deletion of 22 residues at the C-terminal membrane-anchoring region (rhBcl-2 Delta 22). Characterization of rhBcl-2 Delta 22 showed that the recombinant protein is homogeneous and monodisperse in nondenaturing solutions, stable at room temperature in the presence of a metal chelator, and an or-helical protein with unfolding of secondary structure at a T, of 62.8 degreesC. Optimal membrane pore formation by rhBcl-2 Delta 22 required negatively charged phospholipids. The existence of a hydrophobic groove in rhBcl-2 Delta 22 was demonstrated by the fluorescence enhancement of the hydrophobic ANS probe with which a pro-apoptotic Bak BH3 peptide competed. The respiratory inhibitor antimycin A also bound to the hydrophobic groove of rhBcl-2 Delta 22 with a K-d of 0.82 muM The optimal binding conformation of antimycin A was predicted from molecular docking of antimycin A with the hBcl-2 model created by homology modeling. Antimycin A selectively induces apoptosis in cells overexpressing Bcl-2, suggesting that hydrophobic groove-binding compounds may act as selective apoptotic triggers in tumor cells. C1 Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. ICOS Corp, Dept Prot Biochem, Bothell, WA 98021 USA. RP Zhang, KYJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA. RI Zhang, Kam/B-3552-2012; Basanez, Gorka/L-9509-2014 OI Zhang, Kam/0000-0002-9282-8045; Basanez, Gorka/0000-0002-7475-7861 FU NCI NIH HHS [CA15704-26] NR 68 TC 65 Z9 68 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 24 PY 2001 VL 40 IS 16 BP 4911 EP 4922 DI 10.1021/bi002368e PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 424XD UT WOS:000168258500003 PM 11305906 ER PT J AU Gonzalez, M Weiler, S Ferretti, JA Ginsburg, A AF Gonzalez, M Weiler, S Ferretti, JA Ginsburg, A TI The vnd/NK-2 homeodomain: Thermodynamics of reversible unfolding and DNA binding for wild-type and with residue replacements H52R and H52R/T56W in helix III SO BIOCHEMISTRY LA English DT Article ID DODECAMERIC GLUTAMINE-SYNTHETASE; DIFFERENTIAL SCANNING CALORIMETRY; ESCHERICHIA-COLI; NK-2 HOMEODOMAIN; STRUCTURAL BASIS; HOMEOBOX GENES; PROTEINS; DROSOPHILA; TRANSITIONS; MUTATIONS AB The conformational stabilities of the vnd (ventral nervous system defective)/NK-2 homeodomain [HD(wt); residues 1-80 that encompass the 60-residue homeodomain] and those harboring mutations in helix UI of the DNA recognition site [HD(H52R) and HD(H52R/T56W)] have been investigated by differential scanning calorimetry (DSC) and ellipticity changes at 222 nm. Thermal unfolding reactions at pH 7.4 are reversible and repeatable in the presence of 50-500 mM NaCl with DeltaC(p) = 0.52 +/- 0.04 kcal K-1 mol(-1). A substantial stabilization of HD(wt) is produced by 50 mM phosphate or by the addition of 100-500 mM NaCl to 50 mM Hepes, pH 7.4, buffer (from T-m = 35.5 degreesC to T-m 43-51 degreesC; DeltaH(vH) congruent to 47 +/- 5 kcal mol(-1)). The order of stability is HD(H52R/T56W) > HD(H52R) > HD(wt), irrespective of the anions present. Progress curves for ellipticity changes at 222 nm as a function of increasing temperature are fitted well by a two-state unfolding model, and the cooperativity of secondary structure changes is greater for mutant homeodomains than for HD(wt) and also is increased by adding 100 mM NaCl to Hepes buffer. A 33% quench of the intrinsic tryptophanyl residue fluorescence of HD(wt) by phosphate binding (K-D' = 2.6 +/- 0.3 mM phosphate) is reversed similar to 60% by DNA binding. Thermodynamic parameters for vnd/NK-2 homeodomain proteins binding sequence-specific 18 bp DNA have been determined by isothermal titration calorimetry (10-30 degreesC). Values of DeltaC(p) are +0.25, -0.17, and -0.10 +/- 0.04 kcal K-1 mol(-1) for HD(wt), HD(H52R), and HD(H52R/T56W) binding duplex DNA. respectively. Interactions of homeodomains with DNA are enthalpically controlled at 298 K and pH 7.4 with corresponding DeltaH values of -6.6 +/- 0.5, -10.8 +/- 0.1, and -9.0 +/- 0.6 kcal mol-1 and DeltaG ' values of -11.0 +/- 0.1, -11.0 +/- 0.1, and -11.3 +/- 0.3 kcal mol-l with a binding stoichiometry of 1.0 +/-. 0.1. Thermodynamic parameters for DNA binding are not predicted from homeodomain structural changes that occur upon complexing to DNA and must reflect also solvent and possibly DNA rearrangements. C1 NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ginsburg, A (reprint author), NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bldg 3,Room 208, Bethesda, MD 20892 USA. NR 34 TC 14 Z9 14 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 24 PY 2001 VL 40 IS 16 BP 4923 EP 4931 DI 10.1021/bi0022341 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 424XD UT WOS:000168258500004 PM 11305907 ER PT J AU Lin, MC Nahin, R Gershwin, ME Longhurst, JC Wu, KK AF Lin, MC Nahin, R Gershwin, ME Longhurst, JC Wu, KK TI State of complementary and alternative medicine in cardiovascular, lung, and blood research - Executive summary of a workshop SO CIRCULATION LA English DT Article DE acupuncture; medicine, herbal; cardiovascular diseases; alternative medicine; meditation AB The National Heart, Lung, and Blood Institute and the National Center for Complementary and Alternative: Medicine recently cosponsored a workshop on the use of complementary and alternative medicine (CAM) in cardiovascular, lung, and blood research. In view of the increasing use of CAM by the general public, it is imperative to promote credible research by the established biomedical community. The goal of this workshop was to enhance the exchange of information and ideas between alternative medicine practitioners and scientists in cardiovascular, lung, and blood research and to foster collaborative research among these researchers. The workshop focused on 5 areas of research, including a historical and cultural perspective of CAM, methodological issues in clinical trials, herbal medicine, chelation therapy, mind/body (meditation) therapy, and acupuncture. CAM has become widely used without rigorously proven efficacy and safety, To protect the public. it was recommended that the fundamental mechanistic research for these CAM approaches be vigorously pursued and that any large-scale clinical trial be carefully executed to avoid any waste of resources and any unnecessary risk. It was felt that standardization of botanical products and procedure-based CAM intervention, such as acupuncture and meditation, is essential for meaningful basic and clinical research. Although botanical products properly consumed are perceived as generally safe, potential herb-drug interactions are a major safety concern. Clearly, many challenges need to be addressed by the scientific community before the public can be assured of the proper use of CAM. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Univ Texas, Dept Internal Med & Hematol, Houston, TX USA. RP Lin, MC (reprint author), NHLBI, NIH, 6701 Rockledge Dr,Suite 10193,MSC 7956, Bethesda, MD 20892 USA. NR 0 TC 48 Z9 49 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 24 PY 2001 VL 103 IS 16 BP 2038 EP 2041 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 427AU UT WOS:000168383300012 PM 11319191 ER PT J AU Exner, DV Pinski, SL Wyse, DG Renfroe, EG Follmann, D Gold, M Beckman, KJ Coromilas, J Lancaster, S Hallstrom, AP AF Exner, DV Pinski, SL Wyse, DG Renfroe, EG Follmann, D Gold, M Beckman, KJ Coromilas, J Lancaster, S Hallstrom, AP CA AVID Investigators TI Electrical storm presages nonsudden death - The antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Article DE defibrillation; heart failure; tachycardia; fibrillation ID SUDDEN CARDIAC DEATH; TROPONIN-I LEVELS; CARDIOVERTER-DEFIBRILLATORS; VENTRICULAR-TACHYCARDIA; MYOCARDIAL INJURY; SURVIVAL; FIBRILLATION; DISCHARGES; PREVENTION; AMIODARONE AB Background-Electrical storm, multiple temporally related episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), is a frequent problem among recipients of implantable cardioverter defibrillators (ICDs). However, insufficient data exist regarding its prognostic significance. Methods and Results-This analysis includes 457 patients who received an ICD in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial and who were followed for 31+/-13 months. Electrical storm was defined as greater than or equal to3 separate episodes of VT/VF within 24 hours. Characteristics and survival of patients surviving electrical storm (n=90) those with VT/VF unrelated to electrical storm (n=184), and the remaining patients (n=183) were compared. The 3 groups differed in terms of ejection fraction, index arrhythmia, revascularization status, and baseline medication use. Survival was evaluated using time-dependent Cox modeling, Electrical storm occurred 9.2+/-11.5 months after ICD implantation, and most episodes (86%) were due to VT. Electrical storm was a. significant risk factor for subsequent death, independent of ejection fraction and other prognostic variables (relative risk [RR], 2.4; 95% confidence interval [CI], 1.3 to 4.2; P=0.003), but VT/VF unrelated to electrical storm was not (RR, 1.0; 95% CI, 8.6 to 1.7; P=0.9). The risk of death was greatest 3 months after electrical storm (RR, 1.9; 95% CI, 1.0 to 12.3; P=0.0001) and diminished beyond this time (RR, 1.9; 95% CI, 1.0 to 3.6; P=0.04), Conclusions-Electrical storm is an important, independent marker for subsequent death among ICD recipients particularly in the first 3 months after its occurrence, However the development of VT/VF unrelated to electrical storm does not seem to be associated with an increased risk of subsequent death. C1 Univ Calgary, Calgary, AB, Canada. Rush Med Coll, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Washington, AVID Clin Trial Ctr, Seattle, WA 98195 USA. NHLBI, Bethesda, MD 20892 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. RP Exner, DV (reprint author), 3330 Hosp Dr NW,Room G208, Calgary, AB T2N 4N1, Canada. FU NHLBI NIH HHS [N01 HC-25117] NR 35 TC 159 Z9 176 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 24 PY 2001 VL 103 IS 16 BP 2066 EP 2071 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 427AU UT WOS:000168383300017 PM 11319196 ER PT J AU Hademenos, GJ Alberts, MJ Awad, I Mayberg, M Shephard, T Jagoda, A Latchaw, RE Todd, HW Viste, K Starke, R Girgus, MS Walker, M Marler, J Emr, M Hart, N AF Hademenos, GJ Alberts, MJ Awad, I Mayberg, M Shephard, T Jagoda, A Latchaw, RE Todd, HW Viste, K Starke, R Girgus, MS Walker, M Marler, J Emr, M Hart, N TI Advances in the genetics of cerebrovascular disease and stroke SO NEUROLOGY LA English DT Review ID EHLERS-DANLOS-SYNDROME; POLYCYSTIC KIDNEY-DISEASE; ACTIVATED PROTEIN-C; SYNDROME TYPE-IV; FAMILIAL INTRACRANIAL ANEURYSMS; HEREDITARY HEMORRHAGIC TELANGIECTASIA; FACTOR-V-LEIDEN; CEREBRAL CAVERNOUS MALFORMATION; ARTERY FIBROMUSCULAR DYSPLASIA; POOR ANTICOAGULANT RESPONSE AB MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be mure difficult because their inheritance is complex, multigenic, and heterogeneous, However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test-a statistical method for detection of linkage between a marker and a disease-susceptibility locus. C1 Amer Heart Assoc, Natl Ctr, Off Sci & Med, Dallas, TX 75231 USA. Amer Stroke Assoc, Denver, CO USA. Stroke Belt Consortium, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Org Brain Attack Coalit, Dallas, TX 75231 USA. Amer Assoc Neurol Surg & Congress Neurol Surg, Irving, TX USA. Amer Assoc Neurosci Nurses, Irving, TX USA. Amer Coll Emergency Phys, Irving, TX USA. Amer Soc Neuroradiol, Englewood, CO USA. Natl Stroke Assoc, Englewood, CO USA. Amer Acad Neurol, St Paul, MN USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Hademenos, GJ (reprint author), Amer Heart Assoc, Natl Ctr, Off Sci & Med, 7272 Greenville Ave, Dallas, TX 75231 USA. OI Mayberg, Marc/0000-0002-6718-7143 NR 176 TC 46 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 24 PY 2001 VL 56 IS 8 BP 997 EP 1008 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 424ZN UT WOS:000168264000005 PM 11339244 ER PT J AU Magdinier, F Wolffe, AP AF Magdinier, F Wolffe, AP TI Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HISTONE DEACETYLASE COMPLEX; CANCER CELL-LINES; DNA METHYLATION; TRANSCRIPTIONAL REPRESSOR; GENE-EXPRESSION; BREAST-CANCER; HYPERMETHYLATION; INACTIVATION; PROMOTER; ISLAND AB DNA methylation of tumor suppressor genes is a common feature of human cancer. The cyclin-dependent kinase inhibitor gene p16/Ink4A is hypermethylated in a wide range of malignant tissues and the p14/ARF gene located 20 kb upstream on chromosome 9p21 is also methylated in carcinomas. p14/ARF (ARF, alternative reading frame) does not inhibit the activities of cyclins or cyclin-dependent kinase complexes; however, the importance of the two gene products in the etiology of cancer resides in their involvement in two major cell cycle regulatory pathways: p53 and the retinoblastoma protein, Rb, respectively. Distinct first exons driven from separate promoters are spliced onto the common exons 2 and 3 and the resulting proteins are translated in different reading frames. Both genes are expressed in normal cells but can be alternatively or coordinately silenced when their CpG islands are hypermethylated. Herein, we examined the presence of methyl-CpG binding proteins associated with aberrantly methylated promoters, the distribution of acetylated histones H3 and H4 by chromatin immunoprecipitation assays, and the effect of chemical treatment with 5-aza-2 ' -deoxycytidine (5aza-dC) and trichostatin A on gene induction in colon cell lines by quantitative reverse transcriptase-PCR. We observed that the methyl-CpG binding protein MBD2 is targeted to methylated regulatory regions and excludes the acetylated histones H3 and H4, resulting in a localized inactive chromatin configuration. When methylated, the genes can be induced by 5aza-dC but the combined action of 5aza-dC and trichostatin A results in robust gene expression. Thus, methyl-CpG binding proteins and histone deacetylases appear to cooperate in vivo, with a dominant effect of DNA methylation toward histone acetylation, and repress expression of tumor suppressor genes hypermethylated in cancers. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Magdinier, F (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. RI Magdinier, Frederique/I-4735-2016 OI Magdinier, Frederique/0000-0002-0159-9559 NR 41 TC 157 Z9 164 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 4990 EP 4995 DI 10.1073/pnas.101617298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500036 PM 11309512 ER PT J AU Jin, YH Obert, R Burgers, PMJ Kunkel, TA Resnick, MA Gordenin, DA AF Jin, YH Obert, R Burgers, PMJ Kunkel, TA Resnick, MA Gordenin, DA TI The 3 '-> 5 ' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BACTERIOPHAGE-T7 DEOXYRIBONUCLEIC-ACID; DOUBLE-STRAND BREAKS; RNA PRIMER REMOVAL; SACCHAROMYCES-CEREVISIAE; MUTATION AVOIDANCE; REPLICATION FORK; PROOFREADING ACTIVITY; RECOMBINATION; YEAST; REPAIR AB Many DNA polymerases (Pol) have an intrinsic 3 ' -->5 ' exonuclease (Exo) activity which corrects polymerase errors and prevents mutations. We describe a role of the 3 ' -->5 ' fro of Pol delta as a supplement or backup for the Rad27/Fen1 5' flap endonuclease. A yeast rad27 null allele was lethal in combination with Pol delta mutations in fro I, fro II, and fro III motifs that inactivate its exonuclease, but it was viable with mutations in other parts of Pol delta, The rad27-p allele, which has little phenotypic effect by itself, was also lethal in combination with mutations in the Pol delta fro I and fro II motifs. However, rad27-p Pol delta fro III double mutants were viable. They exhibited strong synergistic increases in CAN1 duplication mutations, intrachromosomal and interchromosomal recombination, and required the wild-type double-strand break repair genes RAD50, RAD51, and RAD52 for viability. Observed effects were similar to those of the rad27-null mutant deficient in the removal of 5' flaps in the lagging strand. These results suggest that the 3 ' -->5 ' fro activity of Pol delta is redundant with Rad27/Fen1 for creating ligatable nicks between adjacent Okazaki fragments, possibly by reducing the amount of strand-displacement in the lagging strand. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Gordenin, DA (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. FU NIGMS NIH HHS [R01 GM032431, GM48434, R01 GM058534] NR 52 TC 99 Z9 101 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5122 EP 5127 DI 10.1073/pnas.091095198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500059 PM 11309502 ER PT J AU Perera, LP Goldman, CK Waldmann, TA AF Perera, LP Goldman, CK Waldmann, TA TI Comparative assessment of virulence of recombinant vaccinia viruses expressing IL-2 and IL-15 in immunodeficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NATURAL-KILLER ACTIVITY; NK CELLS; ANTIVIRAL DEFENSE; INTERFERON-GAMMA; IMMUNE-RESPONSES; IN-VIVO; INTERLEUKIN-15; INFECTION; RECEPTOR; HOMEOSTASIS AB IL-2 and -15 belong to the four cu-helix bundle family of cytokines and display a spectrum of overlapping immune functions because of shared signal transducing receptor components of the IL-2 receptor complex. However, recent evidence suggests a nonredundant unique role for IL-15 in the establishment and perhaps maintenance of peripheral natural killer (NK) cell populations in vivo. To explore the contribution of locally released IL-15 on peripheral NK-cell-mediated innate immune responses, we generated a recombinant vaccinia virus that expresses IL-15 and evaluated the course of Vaccinial disease in athymic nude mice. Coexpression of IL-15 resulted in the attenuation of virulence of vaccinia virus, and mice inoculated with 10(5) plaque-forming units or less resolved the infection successfully. In contrast, mice inoculated with a similar dose of the control vaccinia virus failed to eliminate the virus and died of generalized vaccinial disease. Enhanced expression of IL-12 and IFN-gamma as well as induction of chemokines were evident in the mice inoculated with IL-15-expressing vaccinia virus in addition to an increase in NK cells in the spleen. However. in this model system, the degree of attenuation in viral virulence attained with coexpression of IL-15 was much less than that achieved with coexpression of IL-2. suggesting that the peripheral NK-cell-mediated events are more responsive to IL-2 than to IL-15. C1 NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Perera, LP (reprint author), NCI, Metab Branch, Div Clin Sci, Bldg 10,Room 4840,10 Ctr Dr,MSC 1374, Bethesda, MD 20892 USA. NR 36 TC 31 Z9 32 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5146 EP 5151 DI 10.1073/pnas.081080298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500063 PM 11296252 ER PT J AU Mayer, DCG Kaneko, O Hudson-Taylor, DE Reid, ME Miller, LH AF Mayer, DCG Kaneko, O Hudson-Taylor, DE Reid, ME Miller, LH TI Characterization of a Plasmodium falciparum erythrocyte-binding protein paralogous to EBA-175 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MALARIA MEROZOITE INVASION; GLYCOPHORIN-C; BLOOD-GROUP; ANTIGEN; VIVAX; PARASITES; DOMAINS; IDENTIFICATION; JUNCTION; RECEPTOR AB A member of a Plasmodium receptor family for erythrocyte invasion was identified on chromosome 13 from the Plasmodium falciparum genome sequence of the Sanger Centre (Cambridge, U.K.). The protein (named BAEBL) has homology to EBA-175, a P. falciparum receptor that binds specifically to sialic acid and the peptide backbone of glycophorin A on erythrocytes. Both EBA-175 and BAEBL localize to the micronemes, organelles at the invasive ends of the parasites that contain other members of the family. Like EBA-175. the erythrocyte receptor for BAEBL is destroyed by neuraminidase and trypsin, indicating that the erythrocyte receptor is a sialoglycoprotein. Its specificity, however, differs from that of EBA-175 in that BAEBL can bind to erythrocytes that lack glycophorin A, the receptor for EBA-175. It has reduced binding to erythrocytes with the Gerbich mutation found in another erythrocyte, sialoglycoprotein (glycophorin C/D). The interest in BAEBL's reduced binding to Gerbich erythrocytes derives from the high frequency of the Gerbich phenotype in some regions of Papua New Guinea where P, falciparum is hyperendemic. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Ehime Univ, Sch Med, Dept Mol Parasitol, Shigenobu, Ehime 7910295, Japan. New York Blood Ctr, Immunohematol Lab, New York, NY 10021 USA. RP Miller, LH (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. NR 30 TC 125 Z9 127 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5222 EP 5227 DI 10.1073/pnas.081075398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500076 PM 11309486 ER PT J AU Muriaux, D Mirro, J Harvin, D Rein, A AF Muriaux, D Mirro, J Harvin, D Rein, A TI RNA is a structural element in retrovirus particles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE murine leukemia virus; packaging cell lines; retrovirus assembly; RNA packaging; Semliki Forest virus gene expression system ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; VITRO ASSEMBLY PROPERTIES; PRIMER-BINDING-SITE; ROUS-SARCOMA VIRUS; IN-VITRO; NUCLEOCAPSID PROTEIN; GENOMIC RNA; BASIC RESIDUES; TYPE-1 AB A single retroviral protein, Gag, is sufficient for virus particle assembly. While Gag is capable of specifically packaging the genomic RNA into the particle, this RNA species is unnecessary for particle assembly in vivo. In vitro, nucleic acids profoundly enhance the efficiency of assembly by recombinant Gag proteins, apparently by acting as "scaffolding" in the particle. To address the participation of RNA in retrovirus assembly in vivo, we analyzed murine leukemia virus particles that lack genomic RNA because of a deletion in the packaging signal of the viral RNA. We found that these particles contain cellular mRNA in place of genomic RNA. This result was particularly evident when Gag was expressed by using a Semliki Forest virus-derived vector: under these conditions, the Semliki Forest virus vector-directed mRNA became very abundant in the cells and was readily identified in the retroviral virus-like particles. Furthermore, we found that the retroviral cores were disrupted by treatment with RNase. Taken together, the data strongly suggest that RNA is a structural element in retrovirus particles. C1 NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 48 TC 216 Z9 220 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5246 EP 5251 DI 10.1073/pnas.091000398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500080 PM 11320254 ER PT J AU Sora, I Hall, FS Andrews, AM Itokawa, M Li, XF Wei, HB Wichems, C Lesch, KP Murphy, DL Uhl, GR AF Sora, I Hall, FS Andrews, AM Itokawa, M Li, XF Wei, HB Wichems, C Lesch, KP Murphy, DL Uhl, GR TI Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NOREPINEPHRINE UPTAKE SITES; NUCLEUS-ACCUMBENS DOPAMINE; MICE LACKING; RAT STRIATUM; ATTENUATES COCAINE; 5-HT1B RECEPTORS; SELF-STIMULATION; LIGAND-BINDING; MEDIAN RAPHE; BRAIN AB Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET), Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT, However, knockouts of neither DAT. SERT, or NET reduce cocaine reward/reinforcement. leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioural features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement. as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. Penn State Univ, Dept Chem, University Pk, PA 16802 USA. RP Uhl, GR (reprint author), NIDA, Intramural Res Program, NIH, Box 5180, Baltimore, MD 21224 USA. RI Andrews, Anne/B-4442-2011; Hall, Frank/C-3036-2013; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Hall, Frank/0000-0002-0822-4063; Lesch, Klaus-Peter/0000-0001-8348-153X NR 57 TC 291 Z9 299 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5300 EP 5305 DI 10.1073/pnas.091039298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500089 PM 11320258 ER PT J AU Rocha, GM Michea, LF Peters, EM Kirby, M Xu, YH Ferguson, DR Burg, MB AF Rocha, GM Michea, LF Peters, EM Kirby, M Xu, YH Ferguson, DR Burg, MB TI Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acetaminophen; aspirin; salicylic acid; indomethacin; caffeine ID ANALGESIC NEPHROPATHY; MAMMALIAN-CELLS; DNA-DAMAGE; MECHANISMS; APOPTOSIS; PARACETAMOL; FAILURE; DEATH; RISK AB Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin. and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of phenacetin), caffeine, and other related drugs individually and in combination on mouse inner medullary collecting duct cells (mIMCD3). The number of rapidly proliferating cells was reduced by approximate to 50% by 0.5 mM ASA, salicylic acid, or APAF, The drugs had less effect on confluent cells, which proliferate slowly. Thus, the slow in vivo turnover of IMCD cells could explain why clinical toxicity requires very high doses of these drugs over a very long period. Caffeine greatly potentiated the effect of acetaminophen. pointing to a potential danger of the mixture. Cyclooxygenase (COX) inhibitors, indomethacin and NS-398, did not reduce cell number except at concentrations greatly in excess of those that inhibit COX. Therefore, COX inhibition alone is not toxic, APAF arrests most cells in late G(1) and S and produces a mixed form of cell death with both oncosis (swollen cells and nuclei) and apoptosis. APAF is known to inhibit the synthesis of DNA and cause chromosomal aberrations due to inhibition of ribonucleotide reductase, Such effects of APAF might account for renal medullary cell death in vivo and development of uroepithelial tumors from surviving cells that have chromosomal aberrations. C1 NHLBI, Lab Kidney & Electrolytes Metab, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Microscope Core Facil, Bethesda, MD 20892 USA. Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England. RP Burg, MB (reprint author), NIH, Bldg 10,Room 6N260, Bethesda, MD 20892 USA. NR 28 TC 27 Z9 30 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5317 EP 5322 DI 10.1073/pnas.091057698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500092 PM 11320259 ER PT J AU Hampton, RR AF Hampton, RR TI Rhesus monkeys know when they remember SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEMORY; SYSTEMS; ANIMALS; MODELS; HUMANS AB Humans are consciously aware of some memories and can make verbal reports about these memories. Other memories cannot be brought to consciousness, even though they influence behavior. This conspicuous difference in access to memories is central in taxonomies of human memory systems but has been difficult to document in animal studies, suggesting that some forms of memory may be unique to humans. Here I show that rhesus macaque monkeys can report the presence or absence of memory. Although it is probably impossible to document subjective, conscious properties of memory in nonverbal animals, this result objectively demonstrates an important functional parallel with human conscious memory. Animals able to discern the presence and absence of memory should improve accuracy if allowed to decline memory tests when they have forgotten, and should decline tests most frequently when memory is attenuated experimentally. One of two monkeys examined unequivocally met these criteria under all test conditions, whereas the second monkey met them in all but one case. Probe tests were used to rule out "cueing" by a wide variety of environmental and behavioral stimuli, leaving detection of the absence of memory per se as the most likely mechanism underlying the monkeys' abilities to selectively decline memory tests when they had forgotten. C1 NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Hampton, RR (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bldg 49,Room 18-80, Bethesda, MD 20892 USA. NR 14 TC 194 Z9 201 U1 12 U2 57 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2001 VL 98 IS 9 BP 5359 EP 5362 DI 10.1073/pnas.071600998 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 425VC UT WOS:000168311500099 PM 11274360 ER PT J AU Bergwitz, C Wendlandt, T Kispert, A Brabant, G AF Bergwitz, C Wendlandt, T Kispert, A Brabant, G TI Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE collagen type II gene expression; Wnt family (Wnt-1, Wnt-3a, Wnt-4, Wnt-7a, Wnt-7b, Wnt-5a, Wnt-11); RCJ3.1(C5.18) rat calvaria cell; chlorate; secreted frizzled-related protein; differentiation; chondrocyte; protein kinase C ID PROTEIN-KINASE-C; CHICK LIMB BUD; IN-VITRO; CARTILAGE DIFFERENTIATION; SKELETAL DEVELOPMENT; SIGNAL-TRANSDUCTION; PATTERN-FORMATION; POTENT INHIBITOR; GENE-EXPRESSION; PATHWAY AB The wingless- and int-related proteins (Wnts) have an important role during embryonic development and limb patterning. To investigate their function during chondrocyte differentiation, we used NIH3T3 cells producing seven members of the Wnt family and secreted frizzled-related protein (sFRP-2) for co-culture experiments with the rat chondrogenic cell line pColl(II)-EGFP-5. Pilot experiments showed a negative effect of Wnt-7a on the proliferation of three rodent chondrogenic cell lines, RCJ3.1(C5.18), CFK-2, and C1. To establish a reporter system for chondrogenic differentiation we then produced a stably transfected chondrogenic cell line based on RCJ3.1(C5.18) for further experiments, which expresses green fluorescence protein (EGFP) under the collagen type II promoter (pColl(II)-EGFP-5). This cell line permits convenient observation of green fluorescence as a marker for differentiation in lift cultures. The colony size of this cell line in agarose suspension cultures was reduced to 20-40% of control, when exposed to Wnt-1, 3a, 4, 7a, and 7b for 14 days. Similarly, reporter gene expression and the synthesis of cartilage-specific proteoglycans were inhibited by this group of Wnts. In contrast, pColl(II)-EGFP-5 cells exposed to Wnt-5a and Wnt-11 reached 140% of control, and reporter gene expression and proteoglycan synthesis were stimulated. The effects of Wnt-7a and Wnt-5a were additive in pColl(II)-EGFP-5 cells and some but not all Wnt effects were antagonized by the inhibition of proteoglycan sulfation with chlorate, by sFRP-2. which may modulate Wnt receptor binding, or by inhibitors of protein kinase C. These results suggest two functional Wnt subclasses that differentially regulate proliferation and chondrogenic differentiation in vitro which may have implications for cartilage differentiation in vivo. Since some, but not all Wnt effects were sensitive to inhibitors of proteoglycan synthesis or protein kinase C, multiple modes of signal transduction may be involved. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Med Hsch Hannover, Abt Klin Endokrinol, D-30625 Hannover, Germany. Max Planck Inst Immunol, Abt Mol Embryol, D-79108 Freiburg, Germany. RP Bergwitz, C (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. NR 58 TC 36 Z9 37 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 23 PY 2001 VL 1538 IS 2-3 BP 129 EP 140 DI 10.1016/S0167-4889(00)00123-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 429LT UT WOS:000168519100003 PM 11336784 ER PT J AU Qiao, LX Zhao, LY Rong, SB Wu, XW Wang, SM Fujii, T Kazanietz, MG Rauser, L Savage, J Roth, BL Flippen-Anderson, J Kozikowski, AP AF Qiao, LX Zhao, LY Rong, SB Wu, XW Wang, SM Fujii, T Kazanietz, MG Rauser, L Savage, J Roth, BL Flippen-Anderson, J Kozikowski, AP TI Rational design, synthesis, and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PROTEIN-KINASE-C; ACTIVATOR-BINDING DOMAIN; ESTER-INDUCED APOPTOSIS; PHORBOL ESTER; SIGNAL-TRANSDUCTION; ALPHA EXPRESSION; 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED APOPTOSIS; INDOLACTAM-V; PKC-DELTA; IDENTIFICATION AB In view of its role in tumor promotion and signal transduction, protein kinase C (PKC) has proven to be an exciting target for cancer therapy. With the aid of molecular modeling, we rationally designed and stereoselectively synthesized a new class of rigidified pyrrolidone-based PKC activators. Pyrrolidone 15 was found to exhibit reasonable affinity for PKC delta, with lower affinity for the other isozymes tested. Pyrrolidone 2 causes the dose-dependent induction of apoptosis in LNCaP prostate cancer cells. This apoptotic effect could be markedly potentiated by the use of LNCaP cells overexpressing the PKC alpha or delta isozymes. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Georgetown Univ, Ctr Med, Dept Neurol, Drug Discovery Program, Washington, DC 20007 USA. Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Dept Biochem & Neurosci, NIMH, Psychioact Drug Screening Program, Cleveland, OH 44106 USA. USN, Res Lab, Washington, DC 20375 USA. RP Kozikowski, AP (reprint author), Georgetown Univ, Ctr Med, Dept Neurol, Drug Discovery Program, Washington, DC 20007 USA. RI Roth, Bryan/F-3928-2010; Wang, Shaomeng/E-9686-2010 FU NCI NIH HHS [CA79601]; NIMH NIH HHS [MH 01366] NR 22 TC 24 Z9 24 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 23 PY 2001 VL 11 IS 8 BP 955 EP 959 DI 10.1016/S0960-894X(01)00097-X PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 422TW UT WOS:000168136200001 PM 11327599 ER PT J AU Coxon, B Reynolds, RC AF Coxon, B Reynolds, RC TI Boat conformations part IV - Synthesis, NMR spectroscopy, and molecular dynamics of methyl 4,6-O-benzylidene-3-deoxy-3-phthalimido-alpha-D-altropyranoside derivatives SO CARBOHYDRATE RESEARCH LA English DT Article DE altropyranoside; boat conformations; H-1 NMR spectroscopy; molecular dynamics; phthalimido derivative; simulated annealing; skew boat conformations; vicinal coupling constants ID H-1-NMR AB Addition of the elements of phthalimide to methyl 2,3-anhydro-4,6-O-benzylidene-alpha -D-mannopyranoside (1) under fusion conditions has yielded methyl 4,6-O-benzylidene-3-deoxy-3-phthalimido-alpha -D-altropyranoside (2). The conformation of the pyranose ring of 2 has been shown to be non-chair by H-1 NMR spectroscopy, in contrast to the conformations of related derivatives having smaller substituents at C-3. Molecular dynamics simulations of 2 in explicit chloroform-d solvent have indicated four principal conformational possibilities. Of these, the C-7(5)/S-1(5) chair/skew boat form 2d has the lowest potential energy, and is largely consistent with the observed vicinal H-1-H-1 NMR coupling constants. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Coxon, B (reprint author), NICHHD, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 17 TC 8 Z9 9 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD APR 23 PY 2001 VL 331 IS 4 BP 461 EP 467 DI 10.1016/S0008-6215(01)00036-2 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 427BC UT WOS:000168384100012 PM 11398989 ER PT J AU Tullio, AN Bridgman, PC Tresser, NJ Chan, CC Conti, MA Adelstein, RS Hara, Y AF Tullio, AN Bridgman, PC Tresser, NJ Chan, CC Conti, MA Adelstein, RS Hara, Y TI Structural abnormalities develop in the brain after ablation of the gene encoding nonmuscle myosin II-B heavy chain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE nonmuscle myosin II-B; hydrocephalus; cell adhesion; brain development; cytoskeleton; rosette formation ID CENTRAL-NERVOUS-SYSTEM; GROWTH CONES; N-CADHERIN; CELLS; LOCALIZATION; ISOFORMS; NEURONS; L1; NEURAMINIDASE; MIGRATION AB Ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice results in severe hydrocephalus with enlargement of the lateral and third ventricles. All B*/B* mice died either during embryonic development or on the day of birth (PO). Neurons cultured from superior cervical ganglia of B*/B* mice between embryonic day (E) 18 and P0 showed decreased rates of neurite outgrowth, and their growth cones had a distinctive narrow morphology compared with those from normal mice. Serial sections of E12.5, E13.5, and E15 mouse brains identified developmental defects in the ventricular neuroepithelium. On E12.5, disruption of the coherent ventricular surface and disordered cell migration of neuroepithelial and differentiated cells were seen at various points in the ventricular walls. These abnormalities resulted in the formation of rosettes in various regions of the brain and spinal cord. On E13.5 and E15, disruption of the ventricular surface and aberrant protrusions of neural cells into the ventricles became more prominent. By E18.5 and P0, the defects in cells lining the ventricular wall resulted in an obstructive hydrocephalus due to stenosis or occlusion of the third ventricle and cerebral aqueduct. These defects may be caused by abnormalities in the cell adhesive properties of neuroepithelial cells and suggest that NMHC-B is essential for both early and late developmental processes in the mammalian brain. Published 2001 Wiley-Liss, inc.(dagger). C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Human Gene Sci Ctr, Mol Neurobiol Lab, Bunkyo Ku, Tokyo 1138510, Japan. RP Hara, Y (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. OI azmitia, efrain/0000-0002-8806-1064 FU NINDS NIH HHS [NS26150] NR 30 TC 80 Z9 80 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 23 PY 2001 VL 433 IS 1 BP 62 EP 74 DI 10.1002/cne.1125 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 417LG UT WOS:000167836000006 PM 11283949 ER PT J AU Gerecke, KM Wyss, JM Karavanova, I Buonanno, A Carroll, SL AF Gerecke, KM Wyss, JM Karavanova, I Buonanno, A Carroll, SL TI ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE neuregulin; glial growth factor; heregulin; development; acetylcholine receptor inducing activity ID EPIDERMAL GROWTH-FACTOR; EPSILON-SUBUNIT GENE; ACETYLCHOLINE-RECEPTOR; NEUREGULIN RECEPTORS; NEURITE OUTGROWTH; NEURONAL DIFFERENTIATION; NEUROMUSCULAR-JUNCTIONS; SIGNAL-TRANSDUCTION; CARDIAC DEVELOPMENT; PUTATIVE RECEPTORS AB The neuregulin (NRG) family of growth and differentiation factors and their erbB receptors contribute importantly to the development of the nervous system, but their distribution and function in the adult brain are poorly understood. The present study showed that erbB2, erbB3, and erbB4, transcripts and protein are distributed throughout all areas of adult rat; brain. These three receptors were differentially expressed in neurons and glia. Some neurons expressed only a subset of erbB kinases, whereas other neurons expressed all three erbB receptors but sequestered each of these polypeptides into distinct cellular compartments. In synapse-rich regions, erbB immunoreactivity appeared as punctate-, axon-, and/or dendrite-associated staining, suggesting that NRGs are involved in the formation and maintenance of synapses in adult brain. ErbB labeling also was present in neuronal some, indicating that NRGs act at sites in addition to the synapse. Glia in adult brain also differentially expressed erbB3 and erbB4. Approximately half of the erbB3 labeling in white matter was associated with S100 beta+/glial fibrillary acidic protein negative macroglia (i.e., oligodendrocytes or glial fibrillary acidic protein negative astrocytes). In contrast, macroglia in gray matter did not express erbBS. The remaining erbBS immunoreactivity in white matter and erbB3 glial staining seemed to be associated with microglia. These results showed that erbB receptors are expressed widely in adult rat brain and that each erbB receptor subtype has a distinct distribution. The differential distributions of erbB receptors in neurons and glia and the known functional differences between these kinases suggest that NRGs have distinct effects on these cells. The continued expression of NRGs and their erbB receptors in mature brain also implies that these molecules perform important functions in the brain throughout life. (C) 2001 Wiley-Liss, Inc. C1 Univ Alabama, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Carroll, SL (reprint author), Univ Alabama, Dept Pathol, Div Neuropathol, 1720 7th Ave S,SC843, Birmingham, AL 35294 USA. FU NIA NIH HHS [1 P50 AG16582] NR 80 TC 97 Z9 98 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 23 PY 2001 VL 433 IS 1 BP 86 EP 100 DI 10.1002/cne.1127 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 417LG UT WOS:000167836000008 PM 11283951 ER PT J AU Obsil, T Ghirlando, R Klein, DC Ganguly, S Dyda, F AF Obsil, T Ghirlando, R Klein, DC Ganguly, S Dyda, F TI Crystal structure of the 14-3-35 zeta : serotonin N-acetyltransferase complex: A role for scaffolding in enzyme regulation SO CELL LA English DT Article ID MULTIPLE SIGNALING PATHWAYS; 14-3-3 PROTEIN; SERINE PHOSPHORYLATION; MELATONIN PRODUCTION; CATALYTIC MECHANISM; ANGSTROM RESOLUTION; CELL-SURVIVAL; BRAIN 14-3-3; PINEAL-GLAND; ZETA-ISOFORM AB Serotonin N-acetyltransferase (AANAT) controls the daily rhythm in melatonin synthesis. When isolated from tissue, AANAT copurifies with isoforms epsilon and zeta of 14-3-3. We have determined the structure of AANAT bound to 14-3-3 zeta, an association that is phosphorylation dependent. AANAT is bound in the central channel of the 14-3-3 zeta dimer, and is held in place by extensive interactions both with the amphipathic phosphopeptide binding groove of 14-3-3 zeta and with other parts of the central channel. Thermodynamic and activity measurements, together with crystallographic analysis, indicate that binding of AANAT by 14-3-3 zeta modulates AANAT's activity and affinity for its substrates by stabilizing a region of AANAT involved in substrate binding. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009; Obsil, Tomas/B-7142-2012 OI Obsil, Tomas/0000-0003-4602-1272 NR 53 TC 239 Z9 246 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 20 PY 2001 VL 105 IS 2 BP 257 EP 267 DI 10.1016/S0092-8674(01)00316-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 427BE UT WOS:000168384300012 PM 11336675 ER PT J AU Arima, N Kao, CY Licht, T Padmanabhan, R Sasaguri, Y Padmanabhan, R AF Arima, N Kao, CY Licht, T Padmanabhan, R Sasaguri, Y Padmanabhan, R TI Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; TETRACYCLINE-REGULATED SYSTEM; NON-B-HEPATITIS; IN-VITRO; NON-A; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; MOLECULAR CLONE; GENE-EXPRESSION; MAMMALIAN-CELLS AB Hepatitis C virus nonstructural protein, NS5A, is a phosphoprotein produced from the processing of the viral polyprotein precursor, NS5A associates with several cellular proteins in mammalian cells, and the biological consequences of this interaction are currently unknown. To this end, five stable NS5A-expressing murine and human cell lines were established, Tetracycline-regulated NIH3T3 cells and rat liver epithelial cells as well as the constitutive, NS5A-expressing, human Chang liver, HeLa, and NIH3T3 cells all exhibited cell growth retardation compared with the control cells. Cell cycle analysis by flow cytometry indicated that the NSSA-expressing human epitheloid tumor cells had a reduced S phase and an increase in the G(2)/M phase, which could be explained by a p53-dependent induction of p21(Waf1/Cip1) protein and mRNA levels. NS5A interacts with Cdk1 in vivo and in vitro, and a significant portion of the p21(Waf1/Cip1) was found to be in a complex with Cdk2 in the NS5A-expressing human hepatic cell line, Cdk1 and cyclin B1 proteins were also reduced in human Chang liver cells consistent with the increase in G(2)/M phase. Our results suggest that the NS5A protein causes growth inhibition and cell cycle perturbations by targeting the Cdk1/2-cyclin complexes. C1 Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Occupat & Environm Hlth, Dept Pathol & Cell Biol, Kitakyushu, Fukuoka 807, Japan. RP Padmanabhan, R (reprint author), Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM rpadmana@kumc.edu FU NIAID NIH HHS [R03-AI-44036] NR 65 TC 78 Z9 79 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 APR 20 PY 2001 VL 276 IS 16 BP 12675 EP 12684 DI 10.1074/jbc.M008329200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600029 PM 11278402 ER PT J AU Aguilar, RC Boehm, M Gorshkova, I Crouch, RJ Tomita, K Saito, T Ohno, H Bonifacino, JS AF Aguilar, RC Boehm, M Gorshkova, I Crouch, RJ Tomita, K Saito, T Ohno, H Bonifacino, JS TI Signal-binding specificity of the mu 4 subunit of the adaptor protein complex AP-4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; SORTING SIGNALS; MEDIUM CHAINS; CLATHRIN; DISTINCT; RECOGNITION; TGN38; REQUIREMENTS; TRANSPORT; SEQUENCE AB The medium (p) chains of the adaptor protein (AP) complexes AP-1, AP-2, and AP-3 recognize distinct subsets of tyrosine-based (YXX phi) sorting signals found within the cytoplasmic domains of integral membrane proteins. Here, we describe the signal-binding specificity and affinity of the medium subunit mu4 of the recently described adaptor protein complex AP-4. To elucidate the determinants of specificity, we screened a two-hybrid combinatorial peptide library using mu4 as a selector protein. Statistical analyses of the results revealed that mu4 prefers aspartic acid at position Y+1, proline or arginine at Y+2, and phenylalanine at Y-1 and Y+3 (phi). In addition, we examined the interaction of mu4 with naturally occurring YXX phi signals by both two-hybrid and in vitro binding analyses. These experiments showed that mu4 recognized the tyrosine signal from the human lysosomal protein LAMP-2, HTGYEQF. Using surface plasmon resonance measurements, we determined the apparent dissociation constant for the mu4-YXX phi interaction to be in the micromolar range. To gain insight into a possible role of AP-4 in intracellular trafficking, we constructed a Tac chimera bearing a mu4-specific YXX phi signal. This chimera was targeted to the endosomal-lysosomal system without being internalized from the plasma membrane. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Chiba Univ, Grad Sch Med, Dept Mol Genet, Chuo Ku, Chiba 2608670, Japan. Kanazawa Univ, Canc Res Inst, Div Mol Membrane Biol, Kanazawa, Ishikawa 9200934, Japan. RP Bonifacino, JS (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. RI Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014 OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661 NR 34 TC 80 Z9 82 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2001 VL 276 IS 16 BP 13145 EP 13152 DI 10.1074/jbc.M010591200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600095 PM 11139587 ER PT J AU Bouma, P Cabral, WA Cole, WG Marini, JC AF Bouma, P Cabral, WA Cole, WG Marini, JC TI COL5A1 exon 14 splice acceptor mutation causes a functional null allele, haploinsufficiency of alpha 1(V) and abnormal heterotypic interstitial fibrils in Ehlers-Danlos syndrome II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLLAGEN GENE COL5A1; V COLLAGEN; CHAIN; ORGANIZATION; PROCOLLAGEN; FIBRILLOGENESIS; EXPRESSION; DIGESTION; NOSOLOGY; SITE AB We studied four affected individuals from a family of three generations with Ehlers-Danlos Syndrome II. Type V collagen transcripts of affected individuals were screened by reverse transcriptase-polymerase chain reaction. Amplification of the exon 9-28 region of alpha1(V) yielded normal and larger products from the proband, Sequencing of cDNA revealed a 100-base pair insertion from the 3'-end of intron 13 between exons 13 and 14 in one allele. The genomic defect was identified as an A(-2)-->G substitution at the exon 14 splice acceptor site. A cryptic acceptor site -100 nucleotide within intron 13 is used instead of the mutant splice site. The insertion shifts the reading frame +1 and results in a stop codon within exon 17. The mutant transcript was much less abundant than normal allele product in untreated cultured fibroblasts but was approximately equimolar in cycloheximide treated cells, suggesting that the mutation causes nonsense-mediated decay of mRNA. By RNase protection experiments, the level of mutant transcript was determined to be 8% that of the normal transcript in untreated proband fibroblasts, Relative to type I collagen, proband fibroblasts secreted only 65% of the amount of type V collagen secreted by normal controls. Selective salt precipitation of proband secreted collagen provided supportive evidence that the alpha chain composition of type V collagen remains alpha1(V)(2)alpha2(V) even in the context of alpha1(V) haploinsufficiency. Type V collagen incorporates into type I collagen fibrils in the extracellular matrix and is thought to regulate fibril diameter. Transmission electron micrographs of type I collagen fibrils in a proband dermal biopsy showed greater heterogeneity in fibril diameter than in a matched control. The proband had a greater proportion of both larger and smaller fibrils and occasional fibrils with a cauliflower configuration. Unlike the genotype/phenotype relationship seen for type I collagen defects and osteogenesis imperfecta, the null allele in this family appears to cause clinical features similar to those seen in cases with structural alterations in type V collagen. C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Div Orthopaed, Toronto, ON M5G 1X8, Canada. RP Marini, JC (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 22 Z9 23 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2001 VL 276 IS 16 BP 13356 EP 13364 DI 10.1074/jbc.M011742200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600122 PM 11278977 ER PT J AU Keller, JE Neale, EA AF Keller, JE Neale, EA TI The role of the synaptic protein SNAP-25 in the potency of botulinum neurotoxin type A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT NEUROMUSCULAR-JUNCTION; BOVINE CHROMAFFIN CELLS; MEMBRANE-FUSION COMPLEX; SPINAL-CORD CELLS; NEUROTRANSMITTER RELEASE; TRANSMITTER RELEASE; TETANUS TOXIN; CLOSTRIDIAL NEUROTOXINS; VESICLE DOCKING; SEROTYPE-A AB Botulinum neurotoxin serotype A (BoNT/A) is distinguished from BoNT/E by longer duration of paralysis and greater potency. The proteolytic activity of BoNT/A in cultures of dissociated spinal cord neurons persists beyond 80 days, whereas BoNT/E activity persists for less than 1 day (Keller, J, E,, Neale, E, A Oyler, G., and Adler, M, (1999) FEES Lett. 456, 137-142), This single quality of toxin activity can account for the differences observed in the duration of muscle block. In the present work we sought to understand the basis for the apparent greater potency of BoNT/A BoNT/E cleaves a 26-amino acid fragment from the C terminus of the synaptic protein SNAP-25 whereas BoNT/A removes only nine residues creating a 197-amino acid fragment (P197) that is 95% the length of SNAP-25, We show that inhibition of neurotransmitter release by BoNT/E is equivalent to the damage caused to SNAP-25, However, synaptic blockade by BoNT/A is greater than the extent of SNAP-25 proteolysis. These findings can be explained if P197 produces an inhibitory effect on neurotransmitter release. A mathematical model of the experimentally determined relationship between SNAP-25 damage and blockade of neurotransmission supports this interpretation. Furthermore, neurotransmitter release following complete cleavage of SNAP-25 can be achieved by P197, but with about 5-fold less sensitivity to external Ca2+. In this case, vesicular release is restored by increasing intracellular Ca2+. These data demonstrate that P197 competes with intact SNAP-25, but is unable to initiate normal synaptic vesicle fusion in physiological concentrations of Ca2+. C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 72 TC 62 Z9 64 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2001 VL 276 IS 16 BP 13476 EP 13482 DI 10.1074/jbc.M010992200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VN UT WOS:000168198600137 PM 11278807 ER PT J AU Jaskiw, GE Lipska, BK Karoum, F Weinberger, DR AF Jaskiw, GE Lipska, BK Karoum, F Weinberger, DR TI Exposure of a 'witness rat' to one treated with beta-carboline FG 7142 does not increase dopamine turnover in the medial prefrontal cortex of the 'witness rat' SO NEUROSCIENCE LETTERS LA English DT Article DE stress; dopamine; prefrontal cortex ID IBOTENIC ACID LESIONS; NUCLEUS-ACCUMBENS; SELECTIVE INCREASE; SOCIAL-INTERACTION; DIAZEPAM; FG-7142; METABOLISM; NEURONS; STRESS; BEHAVIOR AB A method for selectively activating the dopaminergic field of the prefrontal cortex would be highly useful for studies of mesocortical dopamine systems. When a rat ('witness' rat) is exposed to a rat that is undergoing footshock, prefrontocortical dopamine metabolism is selectively increased in the witness rat. Since the anxiogenic beta -carboline FG 7142 mimics many of the effects of footshock, we hypothesized that exposure of a witness-rat to a rat treated with FG 7142 would also increase dopamine metabolism in the prefrontal cortex. We found that while as expected, FG 7142 itself increased prefrontal cortex dopamine metabolism, there was no significant change in dopamine metabolism in the witness rat. Thus exposure to a rat treated with FG 7142 does not selectively activate the mesocortical dopamine system. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Case Western Reserve Univ, Vet Adm Med Ctr, Cleveland, OH 44141 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44141 USA. NIMH, Clin Brain Disorders Branch 2, Bethesda, MD 20892 USA. RP Jaskiw, GE (reprint author), Case Western Reserve Univ, Vet Adm Med Ctr, 10000 Brecksville Rd, Cleveland, OH 44141 USA. RI Lipska, Barbara/E-4569-2017 NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 20 PY 2001 VL 302 IS 2-3 BP 151 EP 153 DI 10.1016/S0304-3940(01)01689-5 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 422VH UT WOS:000168139600022 PM 11290409 ER PT J AU Goldin, DS Dahl, CA Olsen, KL Ostrach, LH Klausner, RD AF Goldin, DS Dahl, CA Olsen, KL Ostrach, LH Klausner, RD TI Biomedicine - The NASA-NCI collaboration on biomolecular sensors SO SCIENCE LA English DT Editorial Material C1 NCI, Off Technol & Ind Relat, Bethesda, MD 20892 USA. NASA, Off Biol & Phys Res, Washington, DC 20546 USA. RP Dahl, CA (reprint author), NCI, Off Technol & Ind Relat, Bethesda, MD 20892 USA. NR 3 TC 8 Z9 8 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 20 PY 2001 VL 292 IS 5516 BP 443 EP 444 DI 10.1126/science.1059744 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 423QB UT WOS:000168187300025 PM 11330296 ER PT J AU Nabel, GJ AF Nabel, GJ TI Challenges and opportunities for development of an AIDS vaccine SO NATURE LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; ANTIBODY-DEPENDENT ENHANCEMENT; CYTOTOXIC T-LYMPHOCYTES; VIVO GENE DELIVERY; HIV-1 NEF PROTEIN; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; DNA IMMUNIZATION; NONHUMAN-PRIMATES; IMMUNE-RESPONSE AB Among the devastating consequences of AIDS has been its epidemic spread in the developing world. The disease has caused unprecedented suffering, debilitation, loss of life anti disruption of family, social and economic stability. Because of the considerable expense and logistical difficulty in providing antiviral drugs to populations infected with the human immunodeficiency virus throughout the world, the biomedical community is looking towards vaccines to help solve this compelling problem. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 97 TC 149 Z9 157 U1 1 U2 16 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 19 PY 2001 VL 410 IS 6831 BP 1002 EP 1007 DI 10.1038/35073500 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 423AG UT WOS:000168152300061 PM 11309631 ER PT J AU Weinberger, DR AF Weinberger, DR TI Anxiety at the frontier of molecular medicine. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RECEPTOR C1 NIMH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Bethesda, MD 20892 USA. NR 6 TC 28 Z9 29 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 19 PY 2001 VL 344 IS 16 BP 1247 EP 1249 DI 10.1056/NEJM200104193441612 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 422PM UT WOS:000168127600012 PM 11309643 ER PT J AU Gorelick, DA AF Gorelick, DA TI Managing depression in outpatients. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Gorelick, DA (reprint author), NIDA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 19 PY 2001 VL 344 IS 16 BP 1252 EP 1252 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 422PM UT WOS:000168127600016 PM 11314689 ER PT J AU Wendler, D Dickert, N AF Wendler, D Dickert, N TI Attitudes and practices in postmortem organ procurement - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIMH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIMH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 18 PY 2001 VL 285 IS 15 BP 1959 EP 1959 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 420FY UT WOS:000167995900013 ER PT J AU Chen, DT Worrall, BB Meschia, JF AF Chen, DT Worrall, BB Meschia, JF TI Protecting the privacy of family members in research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Liaison Psychiat Serv, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Chen, DT (reprint author), NIH, Liaison Psychiat Serv, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 18 PY 2001 VL 285 IS 15 BP 1961 EP 1962 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 420FY UT WOS:000167995900018 PM 11308427 ER PT J AU Wu, ZR Tjandra, N Bax, A AF Wu, ZR Tjandra, N Bax, A TI P-31 chemical shift anisotropy as an aid in determining nucleic acid structure in liquid crystals SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DIPOLAR COUPLING INTERACTIONS; NMR; MACROMOLECULES; PHASE; RNA; DNA C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 14 TC 49 Z9 51 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 18 PY 2001 VL 123 IS 15 BP 3617 EP 3618 DI 10.1021/ja015650x PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 424XP UT WOS:000168259500034 PM 11472143 ER PT J AU Pacak, K Fojo, T Goldstein, DS Eisenhofer, G Walther, MM Linehan, WM Bachenheimer, L Abraham, J Wood, BJ AF Pacak, K Fojo, T Goldstein, DS Eisenhofer, G Walther, MM Linehan, WM Bachenheimer, L Abraham, J Wood, BJ TI Radiofrequency ablation: A novel approach for treatment of metastatic pheochromocytoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID CANCER C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Anesthesiol, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Rm 10N236,10 Ctr Dr,MSC-1583, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 7 TC 46 Z9 47 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 18 PY 2001 VL 93 IS 8 BP 648 EP 649 DI 10.1093/jnci/93.8.648 PG 2 WC Oncology SC Oncology GA 421VT UT WOS:000168084800017 PM 11309443 ER PT J AU Delon, J Germain, RN AF Delon, J Germain, RN TI The immunological synapse: required for T cell receptor signalling or directing T cell effector function? Response SO CURRENT BIOLOGY LA English DT Editorial Material ID ACTIVATION C1 NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Delon, J (reprint author), NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 17 PY 2001 VL 11 IS 8 BP R290 EP R291 DI 10.1016/S0960-9822(01)00166-X PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 433ET UT WOS:000168746800006 ER PT J AU Benyassi, A Schwartz, C Ducouret, B Falcon, J AF Benyassi, A Schwartz, C Ducouret, B Falcon, J TI Glucocorticoid receptors and serotonin N-acetyltransferase activity in the fish pineal organ SO NEUROREPORT LA English DT Article DE arylalkylamine N-acetyltransferase; dexamethasone; fish; glucocorticoid receptors; melatonin; pineal organ; RU486 ID PARTIAL AGONIST ACTIVITY; CORTISOL-LEVELS; MELATONIN PRODUCTION; GENE-EXPRESSION; ATLANTIC SALMON; CELLS; MIFEPRISTONE; PHOTOPERIOD; ESTROGENS; GOLDFISH AB This study aimed to determine whether glucocorticoid receptors are expressed in the photosensitive trout pineal organ, and whether glucocorticoids modulate melatonin secretion. On Western blots from pineal extracts, an antibody directed against trout glucocorticoid receptor labeled a single band at the expected size (similar to 100 kDa). Dexamethasone inhibited pineal arylalkylamine N-acetyltransferase activity (AANAT2; serotonin --> N-acetylserotonin) in a dose-dependent manner after 6 h of culture in the dark (IC50 2.10(-8)M). RU486 (10(-7) M ) alone had a partial agonistic activity, whereas it antagonized the effects of 10(-8) M dexamethasone. Hydroxyindole-O-methyltransferase activity (N-acetylserotonin --> melatonin) remained unaffected. This is the first demonstration that glucocorticoid receptors are present in the pineal organ and that glucocorticoids modulate melatonin production. Neuro-Report 12:889-892 (C) 2001 Lippincott Williams & Wilkins. C1 Univ Paris 06, Lab Arago, Observ Oceanol, CNRS,UMR 7628, Banyuls sur Mer, France. Fac Sci Fes, Physiol Anim Lab, Fes, Morocco. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Inst Biol & Ecol Poissons Rennes, CNRS, UPRESA 6026, Rennes, France. RP Falcon, J (reprint author), Univ Paris 06, Lab Arago, Observ Oceanol, CNRS,UMR 7628, BP 44, Banyuls sur Mer, France. RI FALCON, Jack/I-5302-2013 OI FALCON, Jack/0000-0002-7572-6581 NR 26 TC 17 Z9 17 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 17 PY 2001 VL 12 IS 5 BP 889 EP 892 DI 10.1097/00001756-200104170-00004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 418RR UT WOS:000167905600005 PM 11303753 ER PT J AU Tachibana, T Ling, QD Ruda, MA AF Tachibana, T Ling, QD Ruda, MA TI Increased Fos induction in adult rats that experienced neonatal peripheral inflammation SO NEUROREPORT LA English DT Article DE c-fos; development; Fos; inflammation; neonate; pain; spinal cord ID SPINAL-CORD; C-FOS; NOXIOUS-STIMULATION; PAIN; NEURONS; EXPRESSION; PROTEIN; PRETERM; BIOLOGY AB The response to noxious stimulation was compared in adult rats that had peripheral inflammation as neonates and untreated rats. On postnatal day 1, rat pups experienced complete Freund's adjuvant (CFA)-induced inflammation of the left hind paw. At 8 weeks of age, these rats and neonatal untreated rats received a bilateral injection of CFA into their hind paws. Fos-like immunoreactivity (Fos-LI) was used as a measure of neuronal activity in dorsal horn nociceptive pathways. A significant increase in Fos-LI was found on the left side of the lumbar spinal cord of neonatal treated rats as compared to neonatal untreated rats. These results suggest that the experience of neonatal peripheral inflammation may result in an increase in the response of spinal cord neurons to peripheral inflammation as adults. NeuroReport 12:925-927 (C) 2001 Lippincott Williams & Wilkins. C1 NIDCR, Cellular Neurosci Sect, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Ruda, MA (reprint author), NIDCR, Cellular Neurosci Sect, Pain & Neurosensory Mech Branch, NIH, Bldg 49-1A11,49 Convent Dr, Bethesda, MD 20892 USA. NR 21 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 17 PY 2001 VL 12 IS 5 BP 925 EP 927 DI 10.1097/00001756-200104170-00012 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 418RR UT WOS:000167905600013 PM 11303761 ER PT J AU Borlongan, CV AF Borlongan, CV TI Presidential election and cell recount SO NEUROREPORT LA English DT Editorial Material C1 NIDA, Cellular Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. RP Borlongan, CV (reprint author), NIDA, Cellular Neurobiol Branch, NIH, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 17 PY 2001 VL 12 IS 5 BP A29 EP A29 DI 10.1097/00001756-200104170-00002 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 418RR UT WOS:000167905600003 PM 11303777 ER PT J AU Tseng, TC Marfatia, SM Bryant, PJ Pack, S Zhuang, ZP O'Brien, JE Lin, LH Hanada, T Chishti, AH AF Tseng, TC Marfatia, SM Bryant, PJ Pack, S Zhuang, ZP O'Brien, JE Lin, LH Hanada, T Chishti, AH TI VAM-1: a new member of the MAGUK family binds to human Veli-1 through a conserved domain SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE membrane-associated guanylate kinase homologue; Veli-associated membrane-associated guanylate kinase homologue-1; guanylate kinase; Veli-1; LIN-7; p55 ID BASOLATERAL MEMBRANE; SIGNALING PATHWAYS; EPITHELIAL-CELLS; NMDA RECEPTOR; GLYCOPHORIN-C; WILMS-TUMOR; PROTEINS; COMPLEX; HETEROZYGOSITY; 7P AB The MAGUKs (membrane associated guanylate kinase homologues) constitute a Family of peripheral membrane proteins that function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. Here, we report the characterization of the human vam-1 gene that encodes a novel member of the p55 subfamily of MAGUKs. The complete cDNA sequence of VAM-1, tissue distribution of its mRNA, genomic structure. chromosomal localization, and Veli-1 binding properties are presented. The vam-1 gene is composed of 12 exons and spans approx. 115 kb. By fluorescence in situ hybridization the vam-1 gene was localized to 7p15-21, a chromosome region frequently disrupted in some human cancers. VAM-1 mRNA was abundant in human testis, brain, and kidney with lower levels detectable in other tissues. The primary structure of VAM-1, predicted from cDNA sequencing, consists of 540 amino acids including a single PDZ domain near the N-terminus, a central SH3 domain, and a C-terminal GUK (guanylate kinase-like) domain. Sequence alignment, heterologous transfection, GST pull-down experiments, and blot overlay assays revealed a conserved domain in VAM-1 that binds to Veli-1, the human homologue of the LIN-7 adaptor protein in Caenorhabditis. LIN-7 is known to play an essential role in the basolateral localization of the LET-23 tyrosine kinase receptor, by linking the receptor to LIN-2 and LIN-10 proteins. Our results therefore suggest that VAM-I may function by promoting the assembly of a Veli-1 containing protein complex in neuronal as well as epithelial cells. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Tufts Univ, St Elizabeths Med Ctr, Sch Med, Ctr Biomed Res,Dept Med,Sect Hematol Oncol Res, Boston, MA 02135 USA. Tufts Univ, St Elizabeths Med Ctr, Sch Med, Ctr Biomed Res,Dept Anat & Cellular Biol, Boston, MA 02135 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Chishti, AH (reprint author), Tufts Univ, St Elizabeths Med Ctr, Sch Med, Ctr Biomed Res,Dept Med,Sect Hematol Oncol Res, CBR404, Boston, MA 02135 USA. RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [CA66263]; NHLBI NIH HHS [HL60755] NR 28 TC 27 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 16 PY 2001 VL 1518 IS 3 BP 249 EP 259 DI 10.1016/S0167-4781(01)00191-9 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 428NY UT WOS:000168468800004 PM 11311936 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Sequence recognition in the pairing of DNA duplexes SO PHYSICAL REVIEW LETTERS LA English DT Article ID B-DNA; HOMOLOGOUS RECOMBINATION; HELICAL REPEAT; CONDENSATION; ATTRACTION; BINDING; POLYELECTROLYTES; COUNTERIONS; RESOLUTION; COMPLEXES AB Pairing of DNA fragments with homologous sequences occurs in gene shuffling, DNA repair, and other vital processes. While chemical individuality of base pairs is hidden inside the double helix, x ray and NMR revealed sequence-dependent modulation of the structure of DNA backbone. Here we show that the resulting modulation of the DNA surface charge pattern enables duplexes longer than similar to 50 base pairs to recognize sequence homology electrostatically at a distance of up to several water layers. This may explain the local recognition observed in pairing of homologous chromosomes and the observed length dependence of homologous recombination. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Res Ctr Julich, D-52425 Julich, Germany. RP Leikin, S (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 35 TC 65 Z9 65 U1 0 U2 7 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD APR 16 PY 2001 VL 86 IS 16 BP 3666 EP 3669 DI 10.1103/PhysRevLett.86.3666 PG 4 WC Physics, Multidisciplinary SC Physics GA 422GH UT WOS:000168109800052 PM 11328049 ER PT J AU Sharaf, BL Pepine, CJ Kerensky, RA Reis, SE Reichek, N Rogers, WJ Sopko, G Kelsey, SF Holubkov, R Olson, M Miele, NJ Williams, DO Merz, CNB AF Sharaf, BL Pepine, CJ Kerensky, RA Reis, SE Reichek, N Rogers, WJ Sopko, G Kelsey, SF Holubkov, R Olson, M Miele, NJ Williams, DO Merz, CNB CA WISE Study Grp TI Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored women's ischemia syndrome evaluation [WISE] study angiographic core laboratory) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; FLOW RESERVE; ENDOTHELIAL DYSFUNCTION; VASOMOTOR RESPONSE; GENDER DIFFERENCES; SEX-DIFFERENCES; BYPASS-SURGERY; RISK-FACTORS; ATHEROSCLEROSIS; ANGIOPLASTY AB The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant (>50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in <10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p <0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk. (C) 2001 by Excerpta Medico, Inc. C1 Brown Univ, Div Cardiol, Rhode Isl Hosp, Providence, RI 02903 USA. Univ Florida, Gainesville, FL USA. Univ Pittsburgh, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Sharaf, BL (reprint author), Brown Univ, Div Cardiol, Rhode Isl Hosp, APC 814,593 Eddy St, Providence, RI 02903 USA. RI Reis, Steven/J-3957-2014 FU NHLBI NIH HHS [HV-91-09, HV-90-07, HV-90-08, HV-91-05, HV-91-06, HV-91-07, HV-91-08, HV-91-10, HV-91-11, HV-91-12, HV-91-13, HV-91-14] NR 29 TC 136 Z9 139 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2001 VL 87 IS 8 BP 937 EP 941 DI 10.1016/S0002-9149(01)01424-2 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 421AJ UT WOS:000168039700001 PM 11305981 ER PT J AU Yeh, HC Matanoski, GM Wang, NY Sandler, DP Comstock, GW AF Yeh, HC Matanoski, GM Wang, NY Sandler, DP Comstock, GW TI Cancer incidence after childhood nasopharyngeal radium irradiation: A follow-up study in Washington County, Maryland SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE nasopharynx; neoplasms; radiation; radium ID THYROID-CANCER; RADIATION; MORTALITY; COHORT; TUMORS AB A population from a hearing clinic in Washington County, Maryland, in 1943-1960 was followed to assess the risk of developing neoplasms from radium treatment of the nasopharynx for adenoid hypertrophy. Of the 2,925 subjects who attended the clinic, 904 received radium treatment. A nonconcurrent prospective study compared the cancer incidence among the irradiated persons with that among persons with other treatments. Seven brain tumor cases (three malignant and four benign) were identified in the irradiated group versus none in the nonirradiated group (relative risk = 14.8, 95% confidence interval: 0.76, 286.3). A nonsignificant excess risk of thyroid cancer was detected in the irradiated group based on two cases in the exposed group and one case in the nonexposed group (relative risk = 4.2, 95% confidence interval: 0.38, 46.6). Decreased risks of breast cancer, female genital cancers, and prostate cancer were observed among the irradiated individuals, although these deficits were not statistically significant individually. The decreased risk of sex hormone-related cancers in the irradiated group suggests possible radiation damage to the pituitary, with consequent reduction in pituitary hormone output and alterations in sexual and other hormonal development in early life. This hypothesis needs further evaluation. C1 Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Yeh, HC (reprint author), Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA. OI Wang, Nae-Yuh/0000-0001-6513-9730; Sandler, Dale/0000-0002-6776-0018 FU NHLBI NIH HHS [HL 21670] NR 29 TC 22 Z9 23 U1 2 U2 5 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 APR 15 PY 2001 VL 153 IS 8 BP 749 EP 756 DI 10.1093/aje/153.8.749 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 422AC UT WOS:000168094900004 PM 11296146 ER PT J AU Zhang, J Brenner, RA Klebanoff, MA AF Zhang, J Brenner, RA Klebanoff, MA TI Differences in birth weight and blood pressure at age 7 years among twins SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth weight; blood pressure; twins ID FETAL-ORIGINS HYPOTHESIS; HEART-DISEASE; COHORT; ASSOCIATION AB Blood pressure later in life has been inversely associated with birth weight. However, concerns have been raised about whether this association merely reflects common environmental risk factors for both fetal growth restriction and high blood pressure or whether there is a genetic tendency to give birth to small babies and have high blood pressure. This study examined whether difference in birth weight of twins is associated with difference in blood pressure at age 7 years. The authors used data from the Collaborative Perinatal Project, United States, 1959-1966, which included 119 pairs of monozygotic and 86 pairs of same-sex dizygotic twins. The smaller twin in each pair had an average 300-9 lower birth weight and was substantially thinner than the larger twin (p < 0.001). At age 7 years, body size and blood pressure were similar. Multiple linear regression was used to examine the association between difference in birth size and difference in blood pressure, adjusting for difference in body weight at age 7 years. None of the associations was statistically significant, and the direction of the associations was inconsistent. Further analyses stratified by birth weight, race, and sex revealed a similar, inconsistent pattern. The authors' findings fail to support the hypothesis that an unfavorable intrauterine environment adversely affects blood pressure in children. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 14 TC 33 Z9 33 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 APR 15 PY 2001 VL 153 IS 8 BP 779 EP 782 DI 10.1093/aje/153.8.779 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 422AC UT WOS:000168094900008 PM 11296150 ER PT J AU Gorshkova, II Rausch, JW Le Grice, SFJ Crouch, RJ AF Gorshkova, II Rausch, JW Le Grice, SFJ Crouch, RJ TI HIV-1 reverse transcriptase interaction with model RNA-DNA duplexes SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE HIV-1; reverse transcriptase; primer templates; binding; kinetics; surface plasmon resonance; RNase H ID HUMAN-IMMUNODEFICIENCY-VIRUS; SURFACE-PLASMON RESONANCE; STATE KINETIC CHARACTERIZATION; STEADY-STATE; NUCLEOTIDE INCORPORATION; REPLICATION FIDELITY; EXPERIMENTAL-DESIGN; TEMPLATE-PRIMER; NUCLEIC-ACID; H DOMAIN AB HIV-I reverse transcriptase (HIV-1 RT) is a multifunctional enzyme responsible for converting viral RNA into preintegrative DNA during the early stages of viral infection. DNA polymerase and RNase H activities are required, and several conformationally distinct primer-templates must be accommodated by the enzyme during the process. Parameters of interaction between model substrates (ligands) and HIV-1 RT (wild type p66/p51 and the RNase H-deficient mutant p66(E478Q)/p51) (analytes) were estimated by surface plasmon resonance at 25 degreesC, pH 8.0, Binding of RT to the ligands is specific and can be analyzed using a conventional 1:1 binding algorithm. RNA-DNA hybrids with 5 ' -template overhangs of 6 and 12 nucleotides bind to RT approximately one order of magnitude stronger than the corresponding 36-mer with blunt ends due to slower dissociation. Immobilization of the latter through either the 5 ' -end of RNA or DNA strand does not change the equilibrium constant (K-D) for wild-type RT but the values of kinetic constants of association and dissociation differ significantly. For the p66(E478Q)/p51 enzyme, orientation effects are notable even altering the K, value. Binding of the p66E478B/p51 to any RNA-DNA hybrids is slightly stronger compared with wild type. Data can be interpreted in terms of the mechanism of reverse transcription. (C) 2001 Academic Press. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Resistance Mech Lab, Frederick, MD USA. RP Gorshkova, II (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 40 TC 23 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2001 VL 291 IS 2 BP 198 EP 206 DI 10.1006/abio.2001.5053 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 424VZ UT WOS:000168255800002 PM 11401293 ER PT J AU Liebes, L Conaway, CC Hochster, H Mendoza, S Hecht, SS Crowell, J Chung, FL AF Liebes, L Conaway, CC Hochster, H Mendoza, S Hecht, SS Crowell, J Chung, FL TI High-performance liquid chromatography-based determination of total isothiocyanate levels in human plasma: Application to studies with 2-phenethyl isothiocyanate SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE PEITC; PEITC-NAC; PEITC-GSH; phenethyl isothiocyanate; pharmacokinetics; HPLC; plasma assay; isothiocyanates ID PHENETHYL ISOTHIOCYANATE; BRUSSELS-SPROUTS; CANCER RISK; F344 RATS; GLUTATHIONE; METABOLISM; LUNG; INHIBITION; CYCLOCONDENSATION; TUMORIGENICITY AB Dietary and pharmacologic isothiocyanates (ITCs) may play a role in reducing the risk of certain cancers. The quantification of ITCs in humans is important both for epidemiological and pharmacokinetic studies. We describe a modification of an HPLC-based assay of urinary ITCs for use with human plasma The assay utilizes the cyclocondensation reaction of 1,2-benzenedithiol with ITCs present in human plasma, followed by a two-step hexane extraction and analysis by HPLC using W detection at 365 nm. The method shows linearity and reproducibility with human plasma over a range of 49-3003 nM phenethyl isothiocyanate (PEITC) (r(2) = 0.996 +/- 0.003). A similar degree of linearity was seen with two other biologically occurring conjugates of PEITC: PEITC-N-acetylcysteine (PEITC-NAC) and PEITC-glutathione (PEITC-GSH). The recovery of PEITC assessed on multiple days was 96.6 +/- 1.5% and was 100% for PEITC-GSH and PEITC-NAC. The reproducibility of the assay on multiday samplings showed a mean %CV of 6.5 +/- 0.3% for PEITC, 6.4 +/- 4.3 for PEITC-NAC and 12.3 +/- 3.9 for PEITC-GSH. In clinical studies, mean plasma ITC level of 413 +/- 193 nM PEITC equivalents was determined for a non-dietary-controlled group of 23 subjects. Multiday analysis data from pharmacokinetic plasma sets of 3 subjects taking a single dose of PEITC at 40 mg showed a good CV (range: 16-21%). The applicability of the methodology to pharmacokinetic studies of PEITC in humans is demonstrated. (C) 2001 Academic Press. C1 NYU Med Ctr, Kaplan Comprehens Canc Ctr, Dept Med, Div Oncol, New York, NY 10016 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Liebes, L (reprint author), NYU Med Ctr, Kaplan Comprehens Canc Ctr, Dept Med, Div Oncol, Bellevue C&D Bldg,Room 556,462 1st Ave, New York, NY 10016 USA. OI Hecht, Stephen/0000-0001-7228-1356 FU NCI NIH HHS [CA 46535, CA-166081-21, P01 CA046535]; NCPDCID CDC HHS [NCI-CN-55120]; NCRR NIH HHS [CRC-RR-00096, M01 RR000096] NR 34 TC 65 Z9 69 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2001 VL 291 IS 2 BP 279 EP 289 DI 10.1006/abio.2001.5030 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 424VZ UT WOS:000168255800011 PM 11401302 ER PT J AU Toyofuku, K Wada, I Spritz, RA Hearing, VJ AF Toyofuku, K Wada, I Spritz, RA Hearing, VJ TI The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation SO BIOCHEMICAL JOURNAL LA English DT Article DE calnexin; mutant protein; protein transport ID ENDOPLASMIC-RETICULUM; PROTEIN-DEGRADATION; SACCHAROMYCES-CEREVISIAE; QUALITY-CONTROL; MELANOMA-CELLS; PROTEASOME; CALNEXIN; MUTATIONS; OLIGOSACCHARIDE; GLYCOPROTEINS AB Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disease resulting from mutations of the tyrosinase gene (TYR), To elucidate the molecular basis of OCA1 phenotypes, we analysed the early processing and maturation of several different types of mutant tyrosinase with various degrees of structural abnormalities (i.e. two large deletion mutants, two missense mutants that completely destroy catalytic function and three missense mutants that have a temperature-sensitive phenotype). When expressed in COS7 cells, all mutant tyrosinases were sensitive to endoglycosidase H digestion, and immunostaining showed their localization in the endoplasmic reticulum (ER) and their failure to be sorted further to their target organelles. Pulse-chase experiments showed that all mutant tyrosinases were retained by calnexin in the ER and that they were degraded at similarly rapid rates, which coincided with their dissociation from calnexin. Temperature-sensitive mutant enzymes were sorted more efficiently at 31 degreesC than at 37 degreesC, and their degradation was accelerated at 37 degreesC compared with 31 degreesC. Thus in contrast to the current concept that mutant tyrosinases are transported to melanosomes but are functionally inactive there. our results suggest that mutant tyrosinases may not be transported to melanosomes in the first place. We conclude that a significant component of mutant tyrosinase malfunction in OCA 1 results from their retention and degradation in the ER compartment. This quality-control process is highly sensitive to minimal changes in protein folding, and so even relatively minor mutations in peripheral sequences of the enzyme not involved with catalytic activity may result in a significant reduction of functional enzyme in melanosomes. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Sapporo Med Univ, Dept Biochem, Chu Ou Ku, Sapporo, Hokkaido 0608556, Japan. Univ Colorado, Hlth Sci Ctr, Human Med Genet Program, Denver, CO 80262 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. NR 47 TC 70 Z9 70 U1 2 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 2001 VL 355 BP 259 EP 269 DI 10.1042/0264-6021:3550259 PN 2 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 426QW UT WOS:000168360700002 PM 11284711 ER PT J AU Chun, YS Yeo, EJ Choi, E Teng, CM Bae, JM Kim, MS Park, JW AF Chun, YS Yeo, EJ Choi, E Teng, CM Bae, JM Kim, MS Park, JW TI Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE YC-1; hypoxia; hypoxia-inducible factor 1 ID SOLUBLE GUANYLATE-CYCLASE; INDUCIBLE FACTOR-I; NITRIC-OXIDE; CARBON-MONOXIDE; FACTOR GENE; ACTIVATION; ELEMENT AB YC-1 is a newly developed agent that inhibits platelet aggregation and vascular contraction. Although its effects are independent of nitric oxide (NO), it mimics some of the biological actions of NO. For example, it stimulates soluble guanylate cyclase (sGC) and increases intracellular cGMP concentration. Here, we tested the possibility that YC-1 inhibits hypoxia-inducible factor (HIF)-1-mediated hypoxic responses, as does NO. Hep3B cells were used during the course of this work to observe hypoxic induction of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the effects of YC-1 were compared with those of a NO donor, sodium nitropurruside (SNP). In hypoxic cells, YC-1 blocked the induction of EPO and VEGF mRNAs, and inhibited the DNA-binding activity of HIF-1. It suppressed the hypoxic accumulation of HIF-1 alpha, but not its mRNA level. It also reduced HIF-1 alpha accumulation induced by cobalt and desferrioxamine. Treatment with antioxidants did not recover the HIF-1 alpha suppressed by YC-1. We examined whether these effects of YC-1 are related to the sGC/cGMP signal transduction system. Two sGC inhibitors examined failed to block the effects of YC-1, and 8-bromo-cGMP did not mimic actions of YC-1. The effects of YC-1 on the hypoxic responses were comparable with those of SNP. These results suggest that YC-1 and SNP suppressed the hypoxic responses by post-translationally inhibiting HIF-1 alpha accumulation. The YC-1 effect may be linked with the metal-related oxygen sensing pathway, and is not due to the stimulation of sGC. This observation implies that the inhibitory effects of YC-1 on hypoxic responses can be developed to suppress EPO-overproduction by tumor cells and tumor angiogenesis. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Heart Res Inst, Seoul 110799, South Korea. Natl Taiwan Univ, Coll Med, Inst Pharmacol, Taipei, Taiwan. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD USA. RP Park, JW (reprint author), Seoul Natl Univ, Coll Med, Dept Pharmacol, 28 Yongon-dong, Seoul 110799, South Korea. RI Park, Jong-Wan/J-2758-2012; Chun, Yang Sook/J-2789-2012; OI TENG, CHE-MING/0000-0002-9719-7334 NR 26 TC 119 Z9 128 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2001 VL 61 IS 8 BP 947 EP 954 DI 10.1016/S0006-2952(01)00564-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 420UZ UT WOS:000168024800003 PM 11286986 ER PT J AU Hyman, SE AF Hyman, SE TI Dopamine, gene expression, and the molecular mechanisms of addiction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 3 BP 1S EP 1S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000004 ER PT J AU Manji, HK Rohlff, C AF Manji, HK Rohlff, C TI Proteomics in molecular medicine - Applications in central nervous system disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Oxford Glycosci, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 6 BP 2S EP 2S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000007 ER PT J AU Herning, RI Tate, K Better, W Cadet, JL AF Herning, RI Tate, K Better, W Cadet, JL TI EEG, cerebral blood flow and depression in chronic cocaine abusers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 25 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000025 ER PT J AU Herkenham, M Brady, LS Winterhoff, H Butterweck, V AF Herkenham, M Brady, LS Winterhoff, H Butterweck, V TI Selective effects of long-term administration of St. John's wort and hypericin on gene transcription in brain areas involved in HPA axis control SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. WWU Muenster, Inst Pharmacol & Toxicol, Munster, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 28 BP 8S EP 8S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000028 ER PT J AU Cohen, RM Small, C Lalonde, F Linker, G Podruchny, TA Sunderland, T AF Cohen, RM Small, C Lalonde, F Linker, G Podruchny, TA Sunderland, T TI The effect of the ApoE4 allele on hippocampal volumes in aging healthy women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 66 BP 19S EP 19S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000066 ER PT J AU Castellanos, FX Giedd, JN Jeffries, NO Sharp, W Blumenthal, J Clasen, L Zijdenbos, A Paus, T Evans, AC Rapoport, JL AF Castellanos, FX Giedd, JN Jeffries, NO Sharp, W Blumenthal, J Clasen, L Zijdenbos, A Paus, T Evans, AC Rapoport, JL TI Longitudinal mri in attention-deficit-hyperactivity disorder (ADHD): Effects of prior stimulant treatment in cerebellum and total brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD USA. NINDS, Biostat Branch, NIH, Bethesda, MD USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 68 BP 20S EP 20S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000068 ER PT J AU Williams, KA Smith, MJ Leong, YM Kazuba, DM Murphy, DL AF Williams, KA Smith, MJ Leong, YM Kazuba, DM Murphy, DL TI The obsessive compulsive status exam: Validation and preliminary findings SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Adult OCD Res Unit, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 81 BP 23S EP 23S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000081 ER PT J AU Stastny, J Schwarz, M Rosenthal, NE Vitouch, O Kasper, S Neumeister, A AF Stastny, J Schwarz, M Rosenthal, NE Vitouch, O Kasper, S Neumeister, A TI Relationship between central monoaminergic mechanisms and immunological parameters in patients with seasonal affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Dept Gen Psychiat, Vienna, Austria. Univ Munich, Biochem Lab, D-80539 Munich, Germany. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 117 BP 33S EP 33S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000115 ER PT J AU Butterweck, V Winterhoff, H Herkenham, M AF Butterweck, V Winterhoff, H Herkenham, M TI Selective effects of long-term administration of St. John's wort and hypericin on gene transcription in brain areas involved in HPA axis control SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 WWU Muenster, Inst Pharmacol & Toxicol, Munster, Germany. NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 125 BP 36S EP 36S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000123 ER PT J AU Nguyen, MB Smith, MJ Trachtenberg, B Williams, KA Hamer, D Wassermann, EM AF Nguyen, MB Smith, MJ Trachtenberg, B Williams, KA Hamer, D Wassermann, EM TI Cortical excitability in sibling pairs SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Sci Lab, Unit Obsess & Compuls Disorders, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 139 BP 40S EP 40S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000137 ER PT J AU Malhotra, AK Kestler, LJ Mazzanti, C Bates, JA Goldberg, T Goldman, D AF Malhotra, AK Kestler, LJ Mazzanti, C Bates, JA Goldberg, T Goldman, D TI A functional COMT polymorphism and cognitive performance of healthy volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. Hillside Hosp, Unit Mol Psychiat, Glen Oaks, NY 11004 USA. NIAA, Neurogenet Lab, NIH, Bethesda, MD USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 143 BP 41S EP 41S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000141 ER PT J AU Obrocea, GV Dunn, RT Frye, MA Ketter, TA Luckenbaugh, DA Leverich, GS Speer, AM Osuch, EA Jajodia, K Post, RM AF Obrocea, GV Dunn, RT Frye, MA Ketter, TA Luckenbaugh, DA Leverich, GS Speer, AM Osuch, EA Jajodia, K Post, RM TI Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Boston, MA 02130 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 175 BP 50S EP 50S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000172 ER PT J AU Moore, GJ Glitz, DA Hussain, S Cortese, B Zajac-Benitez, C Marine, L Manji, HK AF Moore, GJ Glitz, DA Hussain, S Cortese, B Zajac-Benitez, C Marine, L Manji, HK TI In vivo monitoring of the neurotrophic effects of mood stabilizers in the human brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Wayne State Univ, Sch Med, Detroit, MI USA. NIMH, Bethesda, MD 20892 USA. RI Moore, Gregory/E-7184-2010 OI Moore, Gregory/0000-0001-8541-3194 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 184 BP 52S EP 52S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000181 ER PT J AU Lipska, BK Segal, PN Caruso, A Weinberger, DR AF Lipska, BK Segal, PN Caruso, A Weinberger, DR TI Reversible inactivation of the neonatal ventral hippocampus disrupts behavior in the adult rat SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, IRP, CBDB, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 201 BP 57S EP 57S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000198 ER PT J AU Moeller, FG Dougherty, DM Barratt, ES Swann, AC Hanis, CL Bjork, JM AF Moeller, FG Dougherty, DM Barratt, ES Swann, AC Hanis, CL Bjork, JM TI Impulsivity: Is it a genetic disorder? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Houston, TX USA. Univ Texas, Med Branch, Dept Psychiat, Galveston, TX USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 241 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000236 ER PT J AU Cuthbert, BN Heinssen, R AF Cuthbert, BN Heinssen, R TI Translational research: Future directions for studying the schizophrenia prodrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Div Mental Disorders Behav Res & AIDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 253 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000248 ER PT J AU Rasooly, R AF Rasooly, R TI The need for guidelines in conducting DNA array-based research in postmortem brain: Perspectives from the National Institute for Drug Abuse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Natl Inst Drug Abuse Cell Biol & Genet, Div Neurobiol & Behav Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 255 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000250 ER PT J AU Chuang, DM AF Chuang, DM TI Neuroprotective roles of lithium in cultured cells and animal models SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 259 BP 74S EP 74S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000254 ER PT J AU Ketter, TA Wang, PW Sachs, N Kimbrell, TA Little, JT George, MS Post, RM AF Ketter, TA Wang, PW Sachs, N Kimbrell, TA Little, JT George, MS Post, RM TI Brain imaging studies of medication effects and baseline markers of response in bipolar disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 280 BP 80S EP 80S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000275 ER PT J AU Polesskaya, OO Sokolov, BP AF Polesskaya, OO Sokolov, BP TI Low expression of the C(102) allele of the 5-HT2A gene may underlie its association with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 11029 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 293 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000288 ER PT J AU Smith, MJ Nguyen, MB Greenberg, BD Justement, L Murphy, DL Wassermann, EM AF Smith, MJ Nguyen, MB Greenberg, BD Justement, L Murphy, DL Wassermann, EM TI Abnormal cortical excitability in OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Adult OCD Res Unit, Clin Sci Lab, NIH, Bethesda, MD USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 300 BP 86S EP 87S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000295 ER PT J AU Vythilingam, M Charles, CH Tuppler, LA Blitchington, T Kelly, L Krishnan, KRR AF Vythilingam, M Charles, CH Tuppler, LA Blitchington, T Kelly, L Krishnan, KRR TI Whole brain choline inreased in major depression: An automated proton magnetic resonance spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 350 BP 101S EP 101S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000345 ER PT J AU Noaghiul, SF Hibbeln, JR Weissman, MM AF Noaghiul, SF Hibbeln, JR Weissman, MM TI Seafood consumption and cross-national prevalence rates of bipolar disorders and schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 New York State Psychiat Inst, New York, NY 10032 USA. NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 384 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000377 ER PT J AU Fricke, ST Mitchell, TR Chen, G Manji, HK Moore, GJ AF Fricke, ST Mitchell, TR Chen, G Manji, HK Moore, GJ TI Quantitative in vivo MRS of the mouse brain: Monitoring of lithium and valproate induced neurochemical changes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Wayne State Univ, Sch Med, Detroit, MI USA. NIMH, Bethesda, MD 20892 USA. RI Moore, Gregory/E-7184-2010; Chen, Guang/A-2570-2017 OI Moore, Gregory/0000-0001-8541-3194; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 399 BP 114S EP 115S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000392 ER PT J AU Winterer, G Jones, DW Gorey, JG Lee, KS Higley, JD Pushkas, J Bradley, MO Swindell, CS Weinberger, DR AF Winterer, G Jones, DW Gorey, JG Lee, KS Higley, JD Pushkas, J Bradley, MO Swindell, CS Weinberger, DR TI Oral N-docosahexaenoyl-clozapine reduces striatal dopamine receptor availability as measured by [I-123]IBZM SPECT in nonhuman primates SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Unit Mol Neuroimaging, Intramural Res Program, Bethesda, MD 20892 USA. NIAAA, Lab Clin Studies, Primate Sect, Intramural Res Program, Bethesda, MD USA. Protarga Inc, Conshohocken, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 403 BP 116S EP 116S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000396 ER PT J AU Thompson, PM Egbufoama, S Holmes, D Freed, WJ Vawter, MP AF Thompson, PM Egbufoama, S Holmes, D Freed, WJ Vawter, MP TI Selective presynaptic pathology in hippocampus of patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 447 BP 128S EP 129S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000440 ER PT J AU Goldman, D Malhotra, A Egan, M Warden, D Lipsky, R Salazar, A Xu, K Goldberg, T Weinberger, D AF Goldman, D Malhotra, A Egan, M Warden, D Lipsky, R Salazar, A Xu, K Goldberg, T Weinberger, D TI COMT, schizophrenia, and prefrontal cognitive function: Genetic analysis of a complex psychiatric disorder using intermediate phenotypes and a candidate allele SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 464 BP 134S EP 134S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000457 ER PT J AU Suomi, SJ AF Suomi, SJ TI Uptight, laid-back, and jumpy monkeys: How genetic and environmental factors shape biobehavioral development SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 466 BP 134S EP 134S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000459 ER PT J AU Grillon, C Morgan, CA AF Grillon, C Morgan, CA TI Associative learning in humans exposed to highly intense stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 480 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000473 ER PT J AU Morgan, CA Wang, S Thayer, J AF Morgan, CA Wang, S Thayer, J TI Heart rate variability and performance in soldiers anticipating high intensity stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 479 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000472 ER PT J AU Kleinman, JE AF Kleinman, JE TI Cellular and molecular neuropathology of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, IRP,CBDB, Sect Neuropathol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 498 BP 144S EP 144S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000491 ER PT J AU Babak, B Rothman, D Petroff, OAC Mason, G Appel, M Wu, C Duynn, J Cohen, L AF Babak, B Rothman, D Petroff, OAC Mason, G Appel, M Wu, C Duynn, J Cohen, L TI Involvement of GABA in rapid experience-dependent plasticity in the human visual cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06520 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 510 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000503 ER PT J AU Vawter, MP Becker, KG Webster, MJ Freed, WJ AF Vawter, MP Becker, KG Webster, MJ Freed, WJ TI Identification of candidate molecules involved in neurodevelopmental and morphoregulatory processes in schizophrenia: Focus on cell recognition, proteolysis, and signaling using microarray and immunochemical methods SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA, Sect Plast & Dev Cellular Neurobiol, NIH, Baltimore, MD 21224 USA. NIA, DNA Array Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Lab Brain Res, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 516 BP 150S EP 150S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000509 ER PT J AU Bertolino, A Sciota, D Brudaglio, F Scarabino, T Callicott, JH van der Veen, JW Barnett, AS Duyn, JH Weinberger, DR Nardini, M AF Bertolino, A Sciota, D Brudaglio, F Scarabino, T Callicott, JH van der Veen, JW Barnett, AS Duyn, JH Weinberger, DR Nardini, M TI Proton magnetic resonance spectroscopic imaging in first episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Bari, Dipartimento Sci Neurol & Psichiat, I-70121 Bari, Italy. Osped Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 532 BP 155S EP 155S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000525 ER PT J AU Benson, BE Willis, MW Ketter, TA Kimbrell, TA Speer, AM Repella, JD Herscovitch, P Post, RM AF Benson, BE Willis, MW Ketter, TA Kimbrell, TA Speer, AM Repella, JD Herscovitch, P Post, RM TI Functional connectivity of the subgenual anterior cingulate in bipolar and unipolar illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Vet Affairs Med Ctr, N Little Rock, AR 72114 USA. NIH, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 537 BP 156S EP 157S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000530 ER PT J AU Bastain, TM Stevens, J Lewczyk, CM Walter, JM Sharp, WS James, RS Eagen, PB Meck, J Chan, WY Smith, ACM Sidransky, ER Rapoport, JL Castellanos, FX AF Bastain, TM Stevens, J Lewczyk, CM Walter, JM Sharp, WS James, RS Eagen, PB Meck, J Chan, WY Smith, ACM Sidransky, ER Rapoport, JL Castellanos, FX TI Cytogenic abnormalities and attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NHGRI, Off Clin Director, Off Clin Liaison, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 544 BP 159S EP 159S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000537 ER PT J AU Smith, MJ Keel, JC Adams, LF Schmidt, PJ Rubinow, DR Wassermann, EM AF Smith, MJ Keel, JC Adams, LF Schmidt, PJ Rubinow, DR Wassermann, EM TI Follicular phase estradiol dependence of cortical excitability in cycling women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Adult OCD Res Unit, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 561 BP 163S EP 164S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000553 ER PT J AU Iwata, N Vallejoa, RL Virkkunen, M Long, JC Suizuki, T Ozaki, N Goldman, D AF Iwata, N Vallejoa, RL Virkkunen, M Long, JC Suizuki, T Ozaki, N Goldman, D TI Evidence for linkage of genetic variants at the serotonin 2B receptor gene (HTR2B) with Finnish alcoholics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Fujita Hlth Univ, Sch Med, Dept Psychiat, Aichi, Japan. NIAAA, Neurogenet Lab, DICBR, Bethesda, MD USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 563 BP 164S EP 164S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000555 ER PT J AU Roca, CA Harlow, BL Davis, C Schmidt, PJ Goldman, D Rubinow, DR AF Roca, CA Harlow, BL Davis, C Schmidt, PJ Goldman, D Rubinow, DR TI Role of polymorphisms in the estrogen receptor alpha (ER alpha) and progesterone receptor (PR) genes in premenstrual dysphoric disorder (PMDD) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 564 BP 164S EP 164S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000556 ER PT J AU Keel, JC Smith, MJ Wassermann, EM AF Keel, JC Smith, MJ Wassermann, EM TI A safety screening questionnaire for transcranial magnetic stimulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Brain Stimulat Unit, Off Clin Director, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 575 BP 167S EP 167S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000566 ER PT J AU Bartus, CL Akil, M Sherman, TG Crook, JM Hyde, TM Kleinman, JE AF Bartus, CL Akil, M Sherman, TG Crook, JM Hyde, TM Kleinman, JE TI Gene expression of group II metabotropic glutamate receptors in the prefrontal cortex of schizophrenic subjects and controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2001 VL 49 IS 8 SU S MA 599 BP 174S EP 174S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 423ET UT WOS:000168163000590 ER PT J AU Miller, JD Stacy, T Liu, PP Speck, NA AF Miller, JD Stacy, T Liu, PP Speck, NA TI Core-binding factor beta (CBF beta), but not CBF beta-smooth muscle myosin heavy chain, rescues definitive hematopoiesis in CBF beta-deficient embryonic stem SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; IN-VITRO DIFFERENTIATION; TRANSCRIPTION FACTOR; YOLK-SAC; DNA-BINDING; MOUSE EMBRYOS; RUNT DOMAIN; AML1 GENE AB Core-binding factor beta (CBF beta) is the non-DNA-binding subunit of the heterodimeric CBFs. Genes encoding CBF beta (CBFB), and one of the DNA-binding CBF alpha subunits, Runx1 (also known as CBF alpha2, AML1, and PEBP2 alphaB), are required for normal hematopoiesis and are also frequent targets of chromosomal translocations in acute leukemias in humans. Homozygous disruption of either the Runx1 or Cbfb gene in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system, and severely impairs fetal liver hematopoiesis. Results of this study show that Cbfb-deficient mouse embryonic stem (ES) cells can differentiate into primitive erythroid colonies in vitro, but are impaired in their ability to produce definitive erythroid and myeloid colonies, mimicking the in vivo defect. Definitive hematopoiesis is restored by ectopic expression of full-length Cbfb transgenes, as well as by a transgene encoding only the heterodimerization domain of CBF beta. In contrast, the CBF beta -smooth muscle myosin heavy chain (SMMHC) fusion protein generated by the inv(16) associated with acute myeloid leukemias (M4Eo) cannot rescue definitive hematopoiesis by Cbfb-deficient ES cells. Sequences responsible for the inability of CBF beta -SMMHC to rescue definitive hematopoiesis reside in the SMMHC portion of the fusion protein. Results also show that the CBF beta -SMMHC fusion protein transdominantly inhibits definitive hematopoiesis, but not to the same extent as homozygous loss of Runx1 or Cbfb. CBF beta -SMMHC preferentially inhibits the differentiation of myeloid lineage cells, while increasing the number of blastlike cells in culture. (Blood. 2001;97: 2248-2256) (C) 2001 by The American Society of Hematology. C1 Dartmouth Coll, Sch Med, Dept Biochem, Hanover, NH 03755 USA. NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Speck, NA (reprint author), Dartmouth Coll, Sch Med, Dept Biochem, Hanover, NH 03755 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [CA75611, R01 CA58343]; NIAID NIH HHS [T32 AI07363] NR 65 TC 24 Z9 26 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 APR 15 PY 2001 VL 97 IS 8 BP 2248 EP 2256 DI 10.1182/blood.V97.8.2248 PG 9 WC Hematology SC Hematology GA 429KN UT WOS:000168516100008 PM 11290585 ER PT J AU Zoeteweij, JP Moses, AV Rinderknecht, AS Davis, DA Overwijk, WW Yarchoan, R Orenstein, JM Blauvelt, A AF Zoeteweij, JP Moses, AV Rinderknecht, AS Davis, DA Overwijk, WW Yarchoan, R Orenstein, JM Blauvelt, A TI Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus SO BLOOD LA English DT Article ID LYMPHOMA CELL-LINE; EPSTEIN-BARR-VIRUS; ACQUIRED IMMUNODEFICIENCY SYNDROME; MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; A-SENSITIVE INDUCTION; DNA-SEQUENCES; B-CELLS; CYCLOSPORINE-A; T-CELLS AB Kaposi sarcoma-associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in single cells was determined by quantitative flow cytometry. Viral particle production was determined by electron microscope analyses and detection of minor capsid protein in culture supernatants. Agents that mobilized Intracellular calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle-associated proteins and led to increased virus production. Calcium-mediated virus reactivation was blocked by specific inhibitors of calcineurin-dependent signal transduction (cyclosporine, FK506). Similarly, calcium-mediated virus reactivation in KSHV-infected dermal microvascular endothelial cells was blocked by cyclosporine, Furthermore, retroviral transduction with plasmid DNA encoding VIVIT, a peptide specifically blocking calcineurin-NFAT interactions, inhibited calcium-de-pendent KSHV reactivation. By contrast, chemical induction of lytic-phase infection by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate was blocked by protein kinase C inhibitors, but not by calcineurin inhibitors. In summary, calcineurin-dependent signal transduction, an important signaling cascade in vivo, induces calcium-dependent KSHV replication, providing a possible target for the design of antiherpesvirus strategies in KSHV-infected patients. (Blood, 2001;97: 2374-2380) (C) 2001 by The American Society of Hematology. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Rm 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. NR 49 TC 37 Z9 38 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 APR 15 PY 2001 VL 97 IS 8 BP 2374 EP 2380 DI 10.1182/blood.V97.8.2374 PG 7 WC Hematology SC Hematology GA 429KN UT WOS:000168516100023 PM 11290600 ER PT J AU Drobyski, WR Morse, HC Burns, WH Casper, JT Sandford, G AF Drobyski, WR Morse, HC Burns, WH Casper, JT Sandford, G TI Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY BARRIERS; NATURAL-KILLER-CELLS; EFFECTOR MECHANISMS; CD8 CELLS; IN-VIVO; MICE; LYMPHOCYTES; LEUKEMIA; ENGRAFTMENT AB Donor T cells play a pivotal role in facilitating alloengraftment but also cause graft-versus-host disease (GVHD). Ex vivo T-cell depletion (TCD) of donor marrow is the most effective strategy for reducing GVHD but can compromise engraftment. This study examined an approach whereby donor T cells are selectively eliminated in vivo after transplantation using transgenic mice in which a thymidine kinase (TK) suicide gene is targeted to the T cell using a CD3 promoter/ enhancer construct. Lethally irradiated B10.BR mice transplanted with major histocompatibility complex (MHC)-incompatible TCD C57BL/6 (B6) bone marrow (BM) plus TK+ T cells were protected from GVHD after treatment with ganciclovir (GCV) in a schedule-dependent fashion. To examine the effect of GCV treatment on alloengraftment, sublethally irradiated AKR mice underwent transplantation with TCD B6 BM plus limiting numbers (5 x 10(5)) of B6 TK+ T cells. Animals treated with GCV had comparable donor engraftment but significantly reduced GVHD when compared with untreated mice. These mice also had a significantly increased number of donor splenic T cells when assessed 4 weeks after bone marrow transplantation. Thus, the administration of GCV did not render recipients T-cell deficient, but rather enhanced lymphocyte recovery. Adoptive transfer of spleen cells from GCV-treated chimeric mice into secondary AKR recipients failed to cause GVHD indicating that donor T cells were tolerant of recipient alloantigens. These studies demonstrate that administration of TK gene-modified donor T cells can be used as an approach to mitigate GVHD without compromising alloengraftment. (Blood, 2001;97:2506-2513) (C) 2001 by The American Society of Hematology. C1 Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Bone Marrow Transplant Program, Milwaukee, WI 53226 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Drobyski, WR (reprint author), Froedtert Mem Lutheran Hosp, Bone Marrow Transplant Program, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 41 TC 24 Z9 31 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 APR 15 PY 2001 VL 97 IS 8 BP 2506 EP 2513 DI 10.1182/blood.V97.8.2506 PG 8 WC Hematology SC Hematology GA 429KN UT WOS:000168516100039 PM 11290616 ER PT J AU Aoki, Y Tosato, G Fonville, TW Pittaluga, S AF Aoki, Y Tosato, G Fonville, TW Pittaluga, S TI Serum viral interleukin-6 in AIDS-related multicentric Castleman disease SO BLOOD LA English DT Letter ID HERPESVIRUS-ENCODED INTERLEUKIN-6; KAPOSIS; LYMPHOMA; CELLS C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. St Vincent Hosp & Med Ctr, Dept Med, New York, NY USA. NCI, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Aoki, Y (reprint author), NCI, Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 50 Z9 50 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 APR 15 PY 2001 VL 97 IS 8 BP 2526 EP 2527 DI 10.1182/blood.V97.8.2526 PG 2 WC Hematology SC Hematology GA 429KN UT WOS:000168516100044 PM 11307774 ER PT J AU Feldman, AL Pak, H Yang, JC Alexander, HR Libutti, SK AF Feldman, AL Pak, H Yang, JC Alexander, HR Libutti, SK TI Serum endostatin levels are elevated in patients with soft tissue sarcoma SO CANCER LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Society-for-Biological-Therapy CY OCT 26-29, 2000 CL SEATTLE, WASHINGTON SP Soc Biol Therapy DE soft tissue sarcoma; angiogenesis; endostatin; vascular endothelial growth factor; fibroblast growth factor ID ENDOTHELIAL GROWTH-FACTOR; BASEMENT-MEMBRANE ZONES; ANTIANGIOGENIC FACTORS; TUMOR ANGIOGENESIS; COLLAGEN-XVIII; EXPRESSION; CARCINOMA; METASTASES; INHIBITOR; CANCER AB BACKGROUND, Solid tumors are angiogenesis dependent, and elevated levels of proangiogenic cytokines have been reported in a variety of histologies. Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII. Because antiangiogenic protein fragments may be generated by tumor-derived proteases, the authors sought to determine whether circulating levels of endostatin were elevated in patients with localized soft tissue sarcoma. METHODS, The authors analyzed preoperative serum levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate using a competitive enzyme immunoassay. Serum levels were compared with levels from 34 age-matched and gender-matched volunteer blood donors. RESULTS. Endostatin levels were significantly higher in sera from sarcoma patients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002; Mann-Whitney U test). Significant elevations also were noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels > 2 standard deviations above the control mean (55 ng/mL) were associated with an increased risk of tumor recurrence after resection (P = 0.047; log-rank test). CONCLUSIONS, Serum endostatin, VEGF, and bFGF levels are elevated in patients with soft tissue sarcoma. Elevated endostatin levels appear to be associated with tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as potential targets for therapy warrants further study. Cancer 2001;91:1525-9. (C) 2001 American Cancer Society. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 23 TC 74 Z9 87 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2001 VL 91 IS 8 BP 1525 EP 1529 DI 10.1002/1097-0142(20010415)91:8<1525::AID-CNCR1161>3.0.CO;2-P PG 5 WC Oncology SC Oncology GA 421UD UT WOS:000168081200016 PM 11301401 ER PT J AU Dayhoff, JE DeLeo, JM AF Dayhoff, JE DeLeo, JM TI Artificial neural networks - Opening the black box SO CANCER LA English DT Article; Proceedings Paper CT Conference on Prognostic Factors and Staging in Cancer Management CY SEP 27-28, 1999 CL ARLINGTON, VIRGINIA DE artificial neural networks; computational methodology; medicine; paradigm ID APPROXIMATION; ACCURACY; MEDICINE; CANCER; PLOTS AB Artificial neural networks now are used in many fields. They have become well established as viable, multipurpose, robust computational methodologies with solid theoretic support and with strong potential to be effective in any discipline, especially medicine. For example, neural networks can extract new medical information from raw data, build computer models that are useful for medical decision making, and aid in the distribution of medical expertise. Because many important neural network applications currently are emerging, the authors have prepared this article to bring a clearer understanding of these biologically inspired computing paradigms to anyone interested in exploring their use in medicine. They discuss the historical development of neural networks and provide the basic operational mathematics for the popular multilayered perceptron. The authors also describe good training, validation, and testing techniques, and discuss measurements of performance and reliability, including the use of bootstrap methods to obtain confidence intervals. Because it is possible to predict outcomes for individual patients with a neural network, the authors discuss the paradigm shift that is taking place from previous "bin-model" approaches, in which patient outcome and management is assumed from the statistical groups in which the patient fits. The authors explain that with neural networks it is possible to mediate predictions for individual patients with prevalence and misclassification cost considerations using receiver operating characteristic methodology. The authors illustrate their findings with examples that include prostate carcinoma detection, coronary heart disease risk prediction, and medication dosing. The authors identify and discuss obstacles to success, including the need for expanded databases and the need to establish multidisciplinary teams. The authors believe that these obstacles can be overcome and that neural networks have a very important role in future medical decision support and the patient management systems employed in routine medical practice. Cancer 2001;91:1615-35. (C) 2001 American Cancer Society. C1 Complex Res Solut Inc, Silver Spring, MD 20906 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Dayhoff, JE (reprint author), Complex Res Solut Inc, 12657 English Orchard Court, Silver Spring, MD 20906 USA. NR 60 TC 205 Z9 217 U1 1 U2 30 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2001 VL 91 IS 8 SU S BP 1615 EP 1635 DI 10.1002/1097-0142(20010415)91:8+<1615::AID-CNCR1175>3.0.CO;2-L PG 21 WC Oncology SC Oncology GA 422AB UT WOS:000168094800006 PM 11309760 ER PT J AU Bostwick, DG Burke, HB AF Bostwick, DG Burke, HB TI Prediction of individual patient outcome in cancer - Comparison of artificial neural networks and Kaplan-Meier methods SO CANCER LA English DT Article; Proceedings Paper CT Conference on Prognostic Factors and Staging in Cancer Management CY SEP 27-28, 1999 CL ARLINGTON, VIRGINIA DE outcome; survival; artificial neural network; Kaplan-Meier; life table; prediction; prognosis ID MULTILAYER FEEDFORWARD NETWORKS AB BACKGROUND. There is a great need for accurate treatment and outcome prediction in cancer. Two methods for prediction, artificial neural networks and Kaplan-Meier plots, have not, to the authors' knowledge, been compared previously. METHODS. This review compares the advantages and disadvantages of the use of artificial neural networks and Kaplan-Meier curves for treatment and outcome prediction in cancer. RESULTS. Artificial neural networks are useful for prediction of outcome for individual patients with cancer because they are as accurate as the best traditional statistical methods, are able to capture complex phenomena without a priori knowledge, and can be reduced to a simpler model if the phenomena are not complex. Kaplan-Meier plots are of limited accuracy for prediction because they require partitioning of variables, require cutting continuous variables into discrete pieces, and can only handle one or two variables effectively. CONCLUSIONS. Artificial neural networks are an efficient statistical method for outcome prediction in cancer that utilizes all available powerful prognostic factors and maximizes predictive accuracy. Use of Kaplan-Meier plots for predictions is discouraged because of serious technical limitations and low accuracy. Cancer 2001;91:1643-6. (C) 2001 American Cancer Society. C1 Bostwick Labs, Richmond, VA 23294 USA. Urol Virginia, Norfolk, VA USA. Virginia Urol Ctr, Richmond, VA USA. NCI, Urol Oncol Div, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA USA. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. New York Med Coll, Dept Oncol, Valhalla, NY 10595 USA. RP Bostwick, DG (reprint author), Bostwick Labs, 2807 N Parham Rd, Richmond, VA 23294 USA. NR 4 TC 17 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2001 VL 91 IS 8 SU S BP 1643 EP 1646 DI 10.1002/1097-0142(20010415)91:8+<1643::AID-CNCR1177>3.0.CO;2-I PG 4 WC Oncology SC Oncology GA 422AB UT WOS:000168094800008 PM 11309762 ER PT J AU Fisher, ER Anderson, S Tan-Chiu, E Fisher, B Eaton, L Wolmark, N AF Fisher, ER Anderson, S Tan-Chiu, E Fisher, B Eaton, L Wolmark, N TI Fifteen-year prognostic discriminants for invasive breast carcinoma - National Surgical Adjuvant Breast and Bowel Project Protocol-06 SO CANCER LA English DT Article; Proceedings Paper CT Conference on Prognostic Factors and Staging in Cancer Management CY SEP 27-28, 1999 CL ARLINGTON, VIRGINIA DE breast; invasive carcinoma; pathology; treatment; survival; local recurrence ID RANDOMIZED CLINICAL-TRIAL; COMPARING TOTAL MASTECTOMY; PATHOLOGICAL FINDINGS; LOCAL RECURRENCE; CONSERVATIVE SURGERY; DISTANT METASTASES; TUMOR RECURRENCE; RADIATION-THERAPY; TREATED BREAST; CANCER AB BACKGROUND. This report updated previous findings, at the 15-year mark, of the National Surgical Breast and Bowel Project (NSAPB) Protocol B-06 with respect to the treatment of invasive breast carcinoma and the effects of pathologic features and the effects of some clinical features on its natural history. METHODS. Thirty-one pathologic and 6 clinical features that were observed in a pathologic subset of 1039 evaluable patients were assessed as to their value in predicting survival, in predicting ipsilateral breast tumor recurrence (IBTR), and in predicting the necessity for local breast irradiation after lumpectomy. The patients had been randomly assigned to treatment by lumpectomy without local irradiation or to treatment by lumpectomy with local irradiation of the breast. A traditional and another statistical method were used for this purpose. RESULTS. Multivariate analyses revealed that the presence of IBTR, race, histologic tumor type, nodal status, nuclear grade, and blood vessel invasion affected survival independently. Treatment, patient age, nuclear grade, presence of intraductal carcinoma, and a lymphocytic tumor infiltrate were features that predicted IBTR by multivariate analyses. Irradiation reduced IBTR from 36% to 12% in the analyzed cohort. A test of interaction failed to reveal any pathologic or clinical feature that might have allowed for the omission of local irradiation of the breast after lumpectomy. CONCLUSIONS, In addition to the influence of pathologic and clinical features on patient survival and IBTR, the site, histopathologic features, and time of occurrence of the latter allowed for insights into some important biologic considerations concerning invasive breast carcinoma. Cancer 2001;91:1679-87, (C) 2001 American Cancer Society. C1 NSABP, Pathol Ctr, Pittsburgh, PA USA. NSABP, Ctr Stat, Pittsburgh, PA USA. NSABP, Operat Ctr, Pittsburgh, PA USA. RP Fisher, ER (reprint author), Allegheny Univ, Allegheny Gen Hosp, Continuing Care Ctr, 5th Floor,320 E North Ave, Pittsburgh, PA 15212 USA. OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10-CA-12070, U10-CA-37377, U10-CA-39086] NR 34 TC 118 Z9 122 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2001 VL 91 IS 8 SU S BP 1679 EP 1687 DI 10.1002/1097-0142(20010415)91:8+<1679::AID-CNCR1183>3.0.CO;2-8 PG 9 WC Oncology SC Oncology GA 422AB UT WOS:000168094800014 PM 11309768 ER PT J AU Shen, HB Sturgis, EM Khan, SG Qiao, YW Shahlavi, T Eicher, SA Xu, YC Wang, XR Strom, SS Spitz, MR Kraemer, KH Wei, QY AF Shen, HB Sturgis, EM Khan, SG Qiao, YW Shahlavi, T Eicher, SA Xu, YC Wang, XR Strom, SS Spitz, MR Kraemer, KH Wei, QY TI An intronic poly (AT) polymorphism of the DNA repair gene XPC and risk of squamous cell carcinoma of the head and neck: A case-control study SO CANCER RESEARCH LA English DT Article ID PIGMENTOSUM GROUP-C; NUCLEOTIDE EXCISION-REPAIR; LUNG-CANCER; BREAST-CANCER; L1 ELEMENT; XRCC1; EXON; FREQUENCY; INSERTION; CAPACITY AB Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and genetic susceptibility to cancer. In a hospital-based case-control study of 287 non-Hispanic white patients with newly diagnosed SCCHN and 311 control subjects matched on age, sex, ethnicity, and smoking status, we investigated the role of a newly identified variant allele of XPC, XPC-PAT+. We found that the frequency of the XPC-PAT+ allele was higher in the cases (0.409) than in the controls (0.333; P = 0.007). Fifty cases (17.4%) and 37 controls (11.9%) were XPC-PAT+/+, and 135 (47.0%) cases and 133 controls (42.8%) were XPC-PAT+/-, XPC-PAT+/- and XPC-PAT+/+ subjects were at significantly increased risk for SCCHN [adjusted odds ratios = 1.44 and 1.85, respectively (95% confidence intervals, 1.01-2.05 and 1.12-3.05, respectively; trend test, P = 0,007)]. We did not find ethnic difference in the frequency of XPC-PAT+ allele among four groups aged between 19 and 75 years: non-Hispanic whites, 294; African-Americans, 178; Hispanic-Americans, 103; and native Chinese, 119 (0.333, 0.281, 0.296, and 0.353, respectively), The case-control findings support the hypothesis that the XPC-PAT+ allele may contribute to the risk of developing SCCHN. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Stat, Nanjing 210029, Peoples R China. NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Wei, QY (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd,Box 189, Houston, TX 77030 USA. FU Intramural NIH HHS [Z01 BC004517-31]; NCI NIH HHS [CA70242, CA86390, CA55769, CA70334, CA16672, CA74851, P50 CA097007] NR 28 TC 100 Z9 108 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2001 VL 61 IS 8 BP 3321 EP 3325 PG 5 WC Oncology SC Oncology GA 424CR UT WOS:000168215000018 PM 11309287 ER PT J AU Rashid, A Gao, YT Bhakta, S Shen, MC Wang, BS Deng, J Fraumeni, JF Hsing, AW AF Rashid, A Gao, YT Bhakta, S Shen, MC Wang, BS Deng, J Fraumeni, JF Hsing, AW TI beta-catenin mutations in biliary tract cancers: A population-based study in China SO CANCER RESEARCH LA English DT Article ID ADENOMATOUS POLYPOSIS; APC; GALLBLADDER; CARCINOMA; ACTIVATION; PROTEIN AB beta -Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta -catenin gene, at the phosphorylation sites for ubiquitination and degradation of beta -catenin, are present in a variety of cancers. Because alterations of the adenomatous polyposis coli (APC) gene are present in biliary tract cancers and the APC protein modulates levels of beta -catenin, we evaluated the role of beta -catenin in biliary tract cancer by sequencing the third exon of the beta -catenin gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population-based study in China. Point mutations of serine or threonine phosphorylation sites in exon 3 of beta -catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of beta -catenin were more frequent in ampullary and gallbladder carcinomas than in bile duct carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological types of carcinomas (P = 0.02). These results suggest that the molecular pathways of biliary tract neoplasms vary by anatomical subsite and histological subtype. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Shanghai Canc Hosp, Shanghai Canc Inst, Shanghai, Peoples R China. Shanghai Canc Hosp, Dept Pathol, Shanghai, Peoples R China. Zhongshan Hosp, Dept Gen Surg, Shanghai, Peoples R China. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Rashid, A (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd,Box 85, Houston, TX 77030 USA. NR 22 TC 36 Z9 41 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2001 VL 61 IS 8 BP 3406 EP 3409 PG 4 WC Oncology SC Oncology GA 424CR UT WOS:000168215000031 PM 11309300 ER PT J AU Sullivan, SA Akers, L Moody, SA AF Sullivan, SA Akers, L Moody, SA TI foxD5a, a Xenopus winged helix gene, maintains an immature neural ectoderm via transcriptional repression that is dependent on the C-terminal domain SO DEVELOPMENTAL BIOLOGY LA English DT Review DE organizer; Nieuwkoop Center; XFD-12 '; winged helix; neural induction; tail bud ID FORK HEAD DOMAIN; LAEVIS EMBRYOS; HOMEOBOX GENE; SPEMANNS-ORGANIZER; MESODERM INDUCTION; NEURONAL DETERMINATION; AXIS SPECIFICATION; DORSOVENTRAL AXIS; CORTICAL ROTATION; SIGNALING PATHWAY AB Xenopus foxD5a, the full-length fork head gene previously described as a PCR fragment (XFLIP), is first detectable at stage II of oogenesis. Low-abundance maternal transcripts are localized to the animal hemisphere of the cleavage embryo, and protein can be translocated to the nucleus prior to the onset of zygotic transcription. Zygotic expression is strongest in the presumptive neural ectoderm at gastrula and neural plate stages, but there is minor paraxial mesodermal expression during primary gastrulation that becomes significant in the tail bud during secondary gastrulation. Expression of foxD5a in animal cap explants induces elongation and expression of mesodermal, neural-inducing, and early neural-specifying genes, indicating a role in dorsal axis formation. Zygotic foxD5a expression is induced strongly by siamois, moderately by cerberus, weakly by Wnt8 and noggin, and not by chordin in animal cap explants. Expression of foxD5a in whole embryos has differential dorsal and ventral effects. Ventral mRNA injection induces partial secondary axes composed of expanded mesodermal and epidermal tissues, but does not induce ectopic neural tissues. Dorsal mRNA injection causes hypertrophy of the neural plate and expansion of early neural genes (sox3 and otx2), but this is not the result of increased proliferation or expanded neural-inducing mesoderm. The neural plate appears to be maintained in an immature state because otx2 expression is expanded and expression of en2, Krox20, proneural genes (Xnrgn1, neuroD) and a neural differentiation gene (In-tubulin) is repressed in foxD5a-expressing cells. These results indicate that foxD5a maintains an undifferentiated neural ectoderm after neural induction. Expression of foxD5a constructs fused with the engrailed repressor domain or with the VP16 activation domain demonstrates that FoxD5a acts as a transcriptional repressor in axis formation and neural plate expansion. Deletion constructs indicate that this activity requires the C-terminal domain of the protein. (C) 2001 Academic Press. C1 George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Inst Biomed Sci, Washington, DC 20037 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Moody, SA (reprint author), George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Inst Biomed Sci, Washington, DC 20037 USA. OI Moody, Sally/0000-0003-4192-1087 FU NICHD NIH HHS [F32 HD08055]; NINDS NIH HHS [R01 NS23158] NR 113 TC 47 Z9 49 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2001 VL 232 IS 2 BP 439 EP 457 DI 10.1006/dbio.2001.0191 PG 19 WC Developmental Biology SC Developmental Biology GA 424YL UT WOS:000168261500014 PM 11401404 ER PT J AU Reeves, WR McDonald, TJ Bordelon, NR George, SE Donnelly, KC AF Reeves, WR McDonald, TJ Bordelon, NR George, SE Donnelly, KC TI Impacts of aging on in vivo and in vitro measurements of soil-bound polycyclic aromatic hydrocarbon availability SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID TAR-CONTAMINATED SOILS; BIOAVAILABILITY; METABOLITES; RAT; PHARMACOKINETICS; KINETICS; PYRENE; URINE; PAH AB Ingestion of contaminated soil is an exposure pathway at approximately one-half of the Superfund sites in the United States. This study was designed to evaluate the impacts of aging in soil on the availability of polycyclic aromatic hydrocarbons (PAHs). Two coal tar (CT)-amended soils were prepared. One was aged for 270 days and the other was not aged. Both of these treatments were incorporated into pellets and fed to male Fischer 344 rats. Excretion of l-hydroxypyrene (1-OHP) in urine and PAH concentrations in the liver were monitored as end points. Additionally, soil:water partitioning and desorption were measured as comparisons to the in vivo results. After 5 days of ingesting their respective treatments, rats in the aged soil group excreted 4.41 +/- 1.67 ppm 1-OHP/mg of pyrene ingested while rats in the unaged soil group excreted 5.27 +/- 1.37 ppm/mg of pyrene ingested. Animals fed aged CT soil had 0.051 +/- 0.011 ppm carcinogenic PAHs in livers/mg ingested while rats fed unaged CT soil had 0.063 +/- 0.037 ppm carcinogenic PAHs in livers/mg ingested. Partitioning and desorption results revealed a similar results. These results indicate that, at high application rates, soil contact time may not play as significant a role in determining availability as simple dispersion and sorption on soil. C1 Texas A&M Univ, Dept Vet Anat & Publ Hlth, College Stn, TX 77843 USA. Texas A&M Univ, Dept Civil Engn, College Stn, TX 77843 USA. NIEHS, Res Triangle Pk, NC 27711 USA. US EPA, Res Triangle Pk, NC 27711 USA. RP Donnelly, KC (reprint author), Texas A&M Univ, Dept Vet Anat & Publ Hlth, College Stn, TX 77843 USA. FU NIEHS NIH HHS [ES04917] NR 15 TC 19 Z9 23 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD APR 15 PY 2001 VL 35 IS 8 BP 1637 EP 1643 DI 10.1021/es0017110 PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 422BX UT WOS:000168099000013 PM 11329714 ER PT J AU de Souza-Pinto, NC Hogue, BA Bohr, VA AF de Souza-Pinto, NC Hogue, BA Bohr, VA TI DND repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals; mitochondria; DNA repair; 8-oxodG; aging ID BASE EXCISION-REPAIR; OXIDATIVE DAMAGE; ESCHERICHIA-COLI; ABASIC SITES; RAT; ENDONUCLEASE; MUTATIONS; 8-OXOGUANINE; NUCLEOTIDE; CELLS AB 8-oxo-deoxyguanosine (8-oxodG) is one of the major DNA lesions formed upon oxidative attack of DNA. It is a mutagenic adduct that has been associated with pathological states such as cancer and aging. Base excision repair (BER) is the main pathway for the repair of 8-oxodG. There is a great deal of interest in the question about age-associated accumulation of this DNA lesion and its intracellular distribution, particularly with respect to mitochondrial or nuclear localization. We have previously shown that 8-oxodG-incision activity increases with age in rat mitochondria obtained from both liver and heart. In this study, we have investigated the age-associated changes in DNA repair activities in both mitochondrial and nuclear extracts obtained from mouse liver. We observed that 8-oxodG incision activity of mitochondrial extracts increases significantly with age, from 13.4 +/- 2.2 fmoles of oligomer/100 mug of protein/16 h at 6 to 18.6 +/- 4.9 at 14 and 23.7 +/- 3.8 at 23 months of age. In contrast, the nuclear 8-oxoda incision activity showed no significant change with age, and in fact slightly decreased from 11.8 +/- 3 fmoles/50 mug of protein/2 h at 6 months to 9.7 +/- 0.8 at 14 months. Uracil DNA glycosylase and endonuclease G activities did not change with age in nucleus or mitochondria. Our results show that the repair of 8-oxodG is regulated differently in nucleus and mitochondria during the aging process. The specific increase in 8-oxodG-incision activity in mitochondria, rather than a general up-regulation of DNA metabolizing enzymes in those organelles, suggests that this pathway may be up regulated during aging in mice. (C) 2001 Elsevier Science inc. C1 NIA, Mol Genet Lab, GRC, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, GRC, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 30 TC 60 Z9 64 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2001 VL 30 IS 8 BP 916 EP 923 DI 10.1016/S0891-5849(01)00483-X PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 421KG UT WOS:000168063100011 PM 11295534 ER PT J AU Ozbun, LL You, L Kiang, S Angdisen, J Martinez, A Jakowlew, SB AF Ozbun, LL You, L Kiang, S Angdisen, J Martinez, A Jakowlew, SB TI Identification of differentially expressed nucleolar TGF-beta 1 target (DENTT) in human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily SO GENOMICS LA English DT Article ID TRANSFORMING GROWTH-FACTOR; TGF-BETA RECEPTOR; PLASMINOGEN-ACTIVATOR INHIBITOR; NUCLEOSOME-ASSEMBLY PROTEIN; EUKARYOTIC MESSENGER-RNA; EXTRACELLULAR-MATRIX; TRANSFERASE-ALPHA; GENE-EXPRESSION; MAMMALIAN-CELLS; CARCINOMA-CELLS AB The transforming growth factor-beta1 (TGF-beta1) responsive epithelial non-small-cell lung cancer (NSCLC) cell line NCI-H727 was used to identify potential target genes involved in TGF-pi-mediated responses. Comparative cDNA expression patterns between cells treated with TGF-beta1 and those treated with vehicle were generated by differential mRNA display, One 496-bp fragment, differentially increased threefold by TGF-beta1 and hybridizing to a 2.7-kb mRNA species in NCI-H727 cells by Northern analysis, revealed no significant match to any known gene sequence, The mRNA transcript of this novel gene that we named differentially expressed nucleolar TGF-beta1 target (DENTT) is expressed in several normal human tissues, with the highest level of expression in brain. Human brain cDNA library screening and 5 ' rapid amplification of cDNA ends yielded fall-length DENTT cDNA containing an 1899-bp open reading frame encoding a predicted 633-amino-acid protein with four potential nuclear localization signals (NLSs) and two coiled-coil regions. DENTT contains a conserved 191-residue domain that shows significant identity to, and defines, the TSPY/TSPY-like/SET/NAP-1 superfamily, Enhanced green fluorescent protein (EGFP)-tagged full-length DENTT transfected into COS-7 cells showed nucleolar and cytoplasmic localization. Transfection of EGFP-tagged DENTT NLS deletion constructs lacking the bipartite NLS-1 were excluded from the nucleolus. While NLS-1 is necessary for nucleolar localization of DENTT, it is not sufficient for sole nucleolar localization. Our data show that DENTT mRNA induction by TGF-beta1 correlates with induction of TGF-beta1 mRNA, induction of extracellular matrix gene expression, and inhibition of colony formation in soft agarose in TGF-beta1 responsive NSCLC cells when exposed to TGF-beta1, TOE-pi does not induce DENTT mRNA expression in TGF-beta1 nonresponsive NSCLC cells, Our data suggest that this novel TGF-beta1 target gene has distinct domains for direction to different subnuclear locations, (C) 2001 Academic Press. C1 NCI, Med Branch, Dept Cell & Canc Biol, Rockville, MD 20850 USA. RP Jakowlew, SB (reprint author), NCI, Med Branch, Dept Cell & Canc Biol, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 78 TC 38 Z9 45 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 2001 VL 73 IS 2 BP 179 EP 193 DI 10.1006/geno.2001.6505 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 428DU UT WOS:000168446700006 PM 11318608 ER PT J AU Acierno, JS Kennedy, JC Falardeau, JL Leyne, M Bromley, MC Colman, MW Sun, M Bove, C Ashworth, LK Chadwick, LH Schiripo, T Ma, S Goldin, E Schiffmann, R Slaugenhaupt, SA AF Acierno, JS Kennedy, JC Falardeau, JL Leyne, M Bromley, MC Colman, MW Sun, M Bove, C Ashworth, LK Chadwick, LH Schiripo, T Ma, S Goldin, E Schiffmann, R Slaugenhaupt, SA TI A physical and transcript map of the MCOLN1 gene region on human chromosome 19p13.3-p13.2 SO GENOMICS LA English DT Article ID MUCOLIPIDOSIS TYPE-IV; MUTATIONS; 19P; IDENTIFICATION; FAMILIES; LOCUS; DISEASE AB Mutations in IMCOLN1 have been found to cause mucolipidosis type IV (MLIV; MIM 252650), a rare autosomal recessive lysosomal storage disorder found primarily in the Ashkenazi Jewish population. As a part of the successful cloning of MCOLN1, we constructed a 1.4-Mb physical map containing 14 BACs and 4 cosmids that encompasses the region surrounding MCOLN1 on human chromosome 19p13.3-p13.2-a region to which linkage or association has been reported for multiple diseases. Here we detail the precise physical mapping of 28 expressed sequence tags that represent unique UniGene clusters, of which 15 are known genes. We present a detailed transcript map of the MCOLN1 gene region that includes the genes KIAA0521, neuropathy target esterase (NTE), a novel zinc finger gene, and two novel transcripts in addition to MCOLN1. We also report the identification of eight new polymorphic markers between D19S406 and D19S912, which allowed us to pinpoint the location of MCOLN1 by haplotype analysis and which will facilitate future fine-mapping in this region, Additionally, we briefly describe the correlation between the observed haplotypes and the mutations found in MCOLN1. The complete 14-marker haplotypes of non-Jewish disease chromosomes, which are crucial for the genetic diagnosis of MLIV in the non-Jewish population, are presented here for the first time. (C) 2001 Academic Press. C1 Harvard Univ, Inst Human Genet, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Lawrence Livermore Natl Lab, Human Genome Ctr, Livermore, CA 94550 USA. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Inst Human Genet, Sch Med, HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [R01-NS39945] NR 23 TC 6 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 2001 VL 73 IS 2 BP 203 EP 210 DI 10.1006/geno.2001.6526 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 428DU UT WOS:000168446700008 PM 11318610 ER PT J AU Sood, R Bonner, TI Makalowska, I Stephan, DA Robbins, CM Connors, TD Morgenbesser, SD Su, K Faruque, MU Pinkett, H Graham, C Baxevanis, AD Klinger, KW Landes, GM Trent, JM Carpten, JD AF Sood, R Bonner, TI Makalowska, I Stephan, DA Robbins, CM Connors, TD Morgenbesser, SD Su, K Faruque, MU Pinkett, H Graham, C Baxevanis, AD Klinger, KW Landes, GM Trent, JM Carpten, JD TI Cloning and characterization of 13 novel transcripts and the human RC58 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus SO GENOMICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; VARA-PERICARDITIS SYNDROME; JAW TUMOR SYNDROME; SUSCEPTIBILITY LOCUS; PRIMARY HYPERPARATHYROIDISM; CHROMOSOME 1Q42.2-43; ALLELIC IMBALANCE; RGS PROTEINS; HIGH-RISK; SEQUENCES AB The aim of this study was to develop a saturated transcript map of the region encompassing the HPC1 locus to identify the susceptibility genes involved in hereditary prostate cancer (OMIM 176807) and hyperparathyroidism-jaw tumor syndrome (OMIM 145001), We previously reported the generation of a 6-Mb BAC/PAC contig of the candidate region and employed various strategies, such as database searching, exon-trapping, direct cDNA hybridization, and sample sequencing of BACs, to identify all potential transcripts. These efforts led to the identification and precise localization on the BAC contig of 59 transcripts representing 22 known genes and 37 potential transcripts represented by ESTs and exon traps. Here we report the detailed characterization of these ESTs into full-length transcript sequences, their expression pattern in various tissues, their genomic organization, and their homology to known genes. We have also identified an Alu insertion polymorphism in the intron of one of the transcripts. Overall, data on 13 novel transcripts and the human RGS8 gene (homologue of the rat RGS8 gene) are presented in this paper. Ten of the 13 novel transcripts are expressed in prostate tissue and represent positional candidates for HPC1, (C) 2001 Academic Press. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Genzyme Corp, Genet, Framingham, MA 01701 USA. RP Sood, R (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 36,Room 3D05,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pinkett, Heather/M-9235-2014 NR 44 TC 43 Z9 56 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 2001 VL 73 IS 2 BP 211 EP 222 DI 10.1006/geno.2001.6500 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 428DU UT WOS:000168446700009 PM 11318611 ER PT J AU Lovas, G Li, W Pott, U Verga, T Hudson, LD AF Lovas, G Li, W Pott, U Verga, T Hudson, LD TI Expression of the Kruppel-type zinc finger protein rKr2 in the developing nervous system SO GLIA LA English DT Article ID CELL-DIFFERENTIATION; TRANSCRIPTION FACTOR; SONIC HEDGEHOG; NEURAL-TUBE; GLI GENE; MOUSE; BRAIN; OLIGODENDROCYTES; PATTERN; ANTIBODIES AB Zinc finger transcription factors of the Kruppel-class figure prominently in cell fate specification and differentiation in the nervous system. One of the Kruppel-type genes that was originally cloned from an oligodendrocyte library by virtue of its homology with the prototypic Kruppel motif is the rat rKr2 gene (Pott et al,, 1995), In primary cultures of rat glial cells, the rKr2 protein was only present in the oligodendrocyte lineage, predominantly in progenitors. Ninety percent of A2B5(+) oligodendrocyte progenitors displayed rKr2 immunoreactivity, while most MBP+ oligodendrocytes lacked detectable rKr2. A similar pattern was found in vivo, in which the peak expression of rKr2 in the oligodendrocyte lineage of rats coincided with the wave of progenitor proliferation in early postnatal life. The subventricular zone, a source of neuronal and glial progenitors, displayed intense staining for rKr2 at late embryonic and postnatal stages. In the adult, cells within the remnants of this germinal zone continued to express rKr2 protein strongly. Some populations of mature neurons also displayed rKr2 immunostaining. Astrocytes and microglia were not labeled with the polyclonal anti-rKr2 antibody in vitro or in vivo. At all developmental stages, the rKr2 protein was localized to the nucleus. The stage-specific expression pattern and the subcellular localization of rKr2 recommend a role for this Kruppel-type gene in the progression of neural stem cells and in the early development of the oligodendrocyte lineage. GLIA 34:110-120, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. RP Hudson, LD (reprint author), NINDS, Lab Dev Neurogenet, NIH, Bldg 36,Room 5D02,36 convent Dr,MSC 4160, Bethesda, MD 20892 USA. NR 29 TC 3 Z9 3 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD APR 15 PY 2001 VL 34 IS 2 BP 110 EP 120 DI 10.1002/glia.1046 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 429NH UT WOS:000168523500005 PM 11307160 ER PT J AU Husain, SR Joshi, BH Puri, RK AF Husain, SR Joshi, BH Puri, RK TI Interleukin-13 receptor as a unique target for anti-glioblastoma therapy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE glioblastoma; interleukin-13 receptor; IL-13 toxin; in vivo tumor model; tumor regression ID CELL CARCINOMA-CELLS; CIRCULARLY PERMUTED INTERLEUKIN-4; KAPOSIS-SARCOMA CELLS; PSEUDOMONAS EXOTOXIN; PHASE-I; ANTITUMOR-ACTIVITY; FUSION-PROTEIN; CANCER-CELLS; BRAIN-TUMORS; IMMUNOTOXIN AB Surgery, radiotherapy and chemotherapy have minimally altered survival of glioblastoma patients. We explored a specific approach for glioblastoma therapy in which cellular interleukin-13 (IL-13) receptors were targeted by an IL-13 cytotoxin. A wide array of human glioblastoma cell lines expressing the receptor for IL-13 were effectively killed by an IL-13 cytotoxin, a chimeric protein composed of human IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin). Daily (qd) intratumoral injections of IL-13 toxin (50 and 100 mug/kg/day) for 5 consecutive days into subcutaneous human U251 glioblastoma tumors (approx. 30 mm(2)) in nude mice resulted in complete regression of tumors in 4/5 and 5/5 mice, respectively. Tumor regression persisted for at least 221 days postimplantation. Three alternate day injections (qod) of IL-13 toxin (250 mug/kg/day) into other subcutaneous U87 glioblastoma tumors also produced durable complete responses (CR) in all 5 mice. Twice daily (bid) intraperitoneal injections of IL-13 toxin at 25 or 50 mug/kg/dose for 5 days (total doses = 10) regressed U251 tumors by 45% and 58% with 1/5 and 2/5 CRs, respectively, on day 54. Intraperitoneal administration of IL-13 toxin with an identical schedule at a dose of 50 mug/kg injected into mice bearing U87 xenografts reduced tumor burden by one-half on day 36. Similar doses (25 or 50 mug/kg) with a daily schedule (qd x 5) by the intravenous route also suppressed growth of U251 subcutaneous tumors by 75% and 81% with 1/6 CR in either group by day 34. All mice tolerated therapy well without any visible signs of toxicity. On the basis of these studies, we have initiated a Phase I clinical trial using IL13-PE38QQR in patients with recurrent glioblastoma. Published 2001 Wiley-Liss, Inc.(dagger). C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bldg 29B,Room 2nn10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 36 TC 91 Z9 98 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2001 VL 92 IS 2 BP 168 EP 175 DI 10.1002/1097-0215(200102)9999:9999<::AID-IJC1182>3.0.CO;2-N PG 8 WC Oncology SC Oncology GA 414GA UT WOS:000167656800002 PM 11291041 ER PT J AU Rogers, AS Lindsey, JC Donfield, S D'Angelo, LJ AF Rogers, AS Lindsey, JC Donfield, S D'Angelo, LJ TI HIV-1 RNA levels and development of clinical disease in two different adolescent populations SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV disease progression; HIV-1 viral load; adolescents ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTES; UNINFECTED ADOLESCENTS; HUMAN-PAPILLOMAVIRUS; HEMOPHILIA GROWTH; TYPE-1 INFECTION; CELL COUNT; VIRAL LOAD; AIDS; PLASMA AB HIV infection rates in American youth continue to increase unabated. As adolescent-specific therapeutic interventions are planned, information on HIV infection's course and its predictors becomes critically important for valid and precise study design. We report on age-specific disease rates stratified by estimated time since infected and predictors of HIV disease progression through four clinical categories in two distinct adolescent populations. Adolescents with hemophilia infected through contaminated blood products showed disease progression rates of 18 to 23 events per 100 person-years (PYs) by age and years infected. Predictors of first progression included HIV-1 RNA >30,000 copies/ml (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.5-3.9), antiretroviral monotherapy (RR, 2.4; 95% CI, 1.7-3.3); Latino/a ethnicity (RR, 2.2; 95% CI, 1.2-4.2) and initial intermediate clinical status (RR, 1.9; 95% CI, 1.3-2.9). Sexually-infected adolescents >18 years who had been infected >3 to 6 years had a disease progression rate of 16 events per 100 PY. For these youths, the sole predictor of first progression was viral load (VL) (RR for VL >30,000 copies per ml, 8.4; 95% CI, 2.8-25.1). This article examines the predictive capacity of viral load and evaluates other cofactors for disease progression in different adolescent populations. These data will be of value in clinical trial design. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Rho Inc, Chapel Hill, NC USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Rogers, AS (reprint author), NICHD, PAMAB, CRMC, NIH, 6100 Execut Blvd Rm 4B11,MSC 7510, Bethesda, MD 20892 USA. FU NIAID NIH HHS [1UO1-AI-41110]; NICHD NIH HHS [N01-HD-3-3162] NR 32 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 15 PY 2001 VL 26 IS 5 BP 449 EP 457 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433QP UT WOS:000168771500007 PM 11391164 ER PT J AU Daar, ES Lynn, H Donfield, S Gomperts, E Hilgartner, MW Hoots, WK Chernoff, D Arkin, S Wong, WY Winkler, CA AF Daar, ES Lynn, H Donfield, S Gomperts, E Hilgartner, MW Hoots, WK Chernoff, D Arkin, S Wong, WY Winkler, CA CA Hemophilia Growth Dev Study TI Relation between HIV-1 and hepatitis C viral load in patients with hemophilia SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1 viral load; HCV viral load; HIV-1 pathogenesis; hepatitis C virus; human immunodeficiency virus; hepatitis ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; DISEASE PROGRESSION; DRUG-USERS; LIVER-DISEASE; IMMUNE-RESPONSES; RNA LEVELS; HCV RNA; INFECTION; VIREMIA AB Coinfection with hepatitis C virus (HCV) and HIV-1 is common in patients with hemophilia and in intravenous drug users. Little, however, is known about the relation between HIV-1 and HCV coinfection and the effects on HCV clearance and pathogenesis. We examined data from 207 HIV-1-infected and 126 HIV-1-uninfected patients with hemophilia enrolled in the multicenter Hemophilia Growth and Development Study. Participants were observed during prospective follow-up for approximately 7 years with annual measurements of alanine aminotransferase (ALT), CD4(+) cells, and HCV and HIV-1 RNA levels. Clearance of HCV was more likely to occur in those uninfected with HIV-1 (14.3 versus 2.5%; odds ratio [OR] 4.79: 95% confidence interval [CI], 1.63-14.08. p = .005) and was more common with decreasing age (OR, 1.23; 95% CI, 1.04-1.47; p = .017). HCV RNA levels were higher throughout the 7 years of follow-up in those HIV-1-infected (p < .001). In the HIV-1-infected participants, baseline CD4(+) cells were inversely related to HCV RNA with every 100-cell increase associated with a 0.19 log(10) copy/ml decrease in HCV RNA (p = .002), and HIV-1 and HCV RNA levels were directly related (p = .008). Increasing HCV RNA levels were also associated with significantly higher ALT levels regardless of HIV-1 infection status. These results demonstrate that HIV-1/HCV coinfection is associated with a reduced likelihood of HCV clearance and that higher levels of HCV RNA are associated with increased hepatic inflammation. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Cedars Sinai Burns & Allen Res Inst, Dept Med, Div Infect Dis, Los Angeles, CA USA. Rho Inc, Chapel Hill, NC USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. New York Hosp, Cornell Med Ctr, Div Pediat Hematol & Oncol, New York, NY USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. Univ Texas, Sch Med, Dept Internal Med, Houston, TX USA. Chiron Corp, Emeryville, CA 94608 USA. Schneider Childrens Hosp, Div Pediat Hematol Oncol & Stem Cell Transplantat, New Hyde Park, NY USA. NCI, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Daar, ES (reprint author), Cedars Sinai Med Ctr, Div Infect Dis, 1130E,8700 Beverly Blvd, Los Angeles, CA 90048 USA. FU NCI NIH HHS [N01-CO-56000]; NCRR NIH HHS [MO1-RR00059, MO1-RR00071, MO1-RR02558, MO1-RR06020]; NICHD NIH HHS [N01-HD-4-3200] NR 46 TC 83 Z9 87 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 15 PY 2001 VL 26 IS 5 BP 466 EP 472 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433QP UT WOS:000168771500010 PM 11391167 ER PT J AU Hendel, H Winkler, C An, P Roemer-Binns, E Nelson, G Haumont, P O'Brien, S Khalilli, K Zagury, D Rappaport, J Zagury, JF AF Hendel, H Winkler, C An, P Roemer-Binns, E Nelson, G Haumont, P O'Brien, S Khalilli, K Zagury, D Rappaport, J Zagury, JF TI Validation of genetic case-control studies in AIDS and application to the CX3CR1 polymorphism SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; case-control; chemokine receptor; CX3CR1; fractalkine; HIV; genetic; GRIV; progression; polymorphism ID PROTEIN-COUPLED RECEPTOR; CHEMOKINE RECEPTORS; HIV-1 INFECTION; PROGRESSION; CX(3)CR1; IDENTIFICATION; PATHOGENESIS; FRACTALKINE; RESTRICTION; INDIVIDUALS AB New polymorphisms have been recently identified in CX3CR1, a coreceptor for some HIV-1 strains, one of which was associated with a strong acceleration of HIV disease progression. This effect was observed both by a case-control study involving 63 nonprogressors (NP) from the asymptomatic long-term (ALT) cohort and Kaplan-Meier analysis of 426 French seroconverters (SEROCO cohort). These results prompted us to analyze these polymorphisms in 244 nonprogressors (NPs) and 80 rapid progressors (RPs) from the largest case-control cohort known to date. the GRIV cohort. Surprisingly, the genetic frequencies found were identical for both groups under all generic models (p > .8). The discrepancy with the previous work stemmed only from the difference between GRIV NPs versus ALT NPs. We hypothesized this might be due to the limited number of NPs in ALT (n = 63) and in this line we reanalyzed the data previously collected on GRIV for over 100 different genetic polymorphisms: we effectively observed that the genetic frequencies of some poly morphisms could vary by as much as 10% (absolute percentage) when computing them on the first 50 NP subjects enrolled, on the first 100, or on all the NPs tested (240 study subjects). This observation emphasizes the need for caution in cast-control studies involving small numbers of subjects: p values should be low or other control groups should be used. However, the association of the CX3CR1 polymorphism with progression seems quite significant in the Kaplan-Meier analysis of the SEROCO cohort (426 individuals), and the difference observed with GRIV might be explained by a delayed effect of the polymorphism on disease. Further studies on other seroconverter cohorts are needed to confirm the reported association with disease progression. C1 Univ Paris 06, Lab Physiol Cellulaire, F-75005 Paris, France. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Temple Univ, Ctr Neurovirol, Philadelphia, PA 19122 USA. RP Zagury, JF (reprint author), Univ Paris 06, Lab Physiol Cellulaire, 4 Pl Jussieu, F-75005 Paris, France. FU NCI NIH HHS [N01-CO-56000] NR 20 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 15 PY 2001 VL 26 IS 5 BP 507 EP 511 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433QP UT WOS:000168771500017 PM 11391174 ER PT J AU Sagui, C Darden, T AF Sagui, C Darden, T TI Multigrid methods for classical molecular dynamics simulations of biomolecules SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ELECTRONIC-STRUCTURE CALCULATIONS; PARTICLE-MESH EWALD; FAST MULTIPOLE ALGORITHM; SYSTEMS; SUMS; EQUATIONS; FORCES AB We present an O(N) multigrid-based method for the efficient calculation of the long-range electrostatic forces needed for biomolecular simulations, that is suitable for implementation on massively parallel architectures. Along general lines, the method consists of: (i) a charge assignment scheme, which both interpolates and smoothly assigns the charges onto a grid; (ii) the solution of Poisson's equation on the grid via multigrid methods; and (iii) the back interpolation of the forces and energy from the grid to the particle space. Careful approaches for the charge assignment and the force interpolation, and a Hermitian approximation of Poisson's equation on the grid allow for the generation of the high-accuracy solutions required for high-quality molecular dynamics simulations. Parallel versions of the method scale linearly with the number of particles for a fixed number of processors, and with the number of processors, for a fixed number of particles. (C) 2001 American Institute of Physics. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Sagui, C (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 40 TC 93 Z9 94 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 15 PY 2001 VL 114 IS 15 BP 6578 EP 6591 DI 10.1063/1.1352646 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 418VG UT WOS:000167914400012 ER PT J AU Dowlati, A Hoppel, CL Ingalls, ST Majka, S Li, XL Sedransk, N Spiro, T Gerson, SL Ivy, P Remick, SC AF Dowlati, A Hoppel, CL Ingalls, ST Majka, S Li, XL Sedransk, N Spiro, T Gerson, SL Ivy, P Remick, SC TI Phase I clinical and pharmacokinetic study of rebeccamycin analog NSC 655649 given daily for five consecutive days SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-18, 1999 CL ATLANTA, GEORGIA SP Amer Soc Clin Oncol ID ANTIMICROBIAL PROPERTIES; TOPOISOMERASE-I; ANTITUMOR; DERIVATIVES; INHIBITION; DNA AB Purpose: Rebeccamycin analog (NSC 655649) is active against a variety of both solid and nonsolid tumor cell lines. We performed a phase I trial to determine the maximum-tolerated dose (MTD) of rebeccamycin analog when given on a daily x 5 schedule repeated every 3 weeks, characterize the toxicity profile using this schedule, observe patients for antitumor response, and determine the pharmacokinetics of the agent and pharmacodynamic interactions. Patients and Methods: Thirty assessable patients received a total of 153 cycles according to the following dose escalation schema: 60, 80, 106, 141, and 188 mg/m(2)/d x 5 days. Results: Grade 2 phlebitis occurred in all patients before the use of central venous access, placed at dose level 4 and higher. Dose-limiting toxicity (DLT), grade 4 neutropenia, occurred at 188 mg/m2/d x 5 days in both previously treated and chemotherapy-naive patients. Pharmacokinetic analysis revealed a three-compartmental model of drug elimination and a long terminal half-life (154 +/- 55 hours). The percentage drop in absolute neutrophil count correlates with the area under the curve infinity. The presence of a second peak during the elimination phase as well as a high concentration of NSC 655649 in biliary fluid compared with the corresponding plasma measurement tone patient) is suggestive of enterohepatic circulation. Two partial responses, two minor responses, and six prolonged (> 6 months) cases of stable disease were observed. Of these, three patients with gallbladder cancer and one patient with cholangiocarcinoma experienced either a minor response or a significant period of freedom from progression. Conclusion: The recommended phase II dose for NSC 665649 on a daily x 5 every 3 weeks schedule is 141 and 165 mg/m(2)/d for patients with prior and no prior therapy, respectively, with DLT being neutropenia. During this phase I trial, encouraging antitumor activity was been observed. (C) 2001 by American Society of Clinical Oncology. C1 Univ Hosp Cleveland, Ireland Canc Ctr, Div Hematol Oncol & Clin Pharmacol, Dev Therapeut Program, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vet Adm Med Ctr, Cleveland, OH 44106 USA. Natl Canc Inst, Bethesda, MD USA. RP Remick, SC (reprint author), Univ Hosp Cleveland, Div Hematol Oncol, 11100 Euclid Ave, Cleveland, OH 44106 USA. FU NCI NIH HHS [U01 CA62502-06, P30 CA43703]; NCRR NIH HHS [MO1-RR-00080] NR 16 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2001 VL 19 IS 8 BP 2309 EP 2318 PG 10 WC Oncology SC Oncology GA 423LT UT WOS:000168178300024 PM 11304785 ER PT J AU Sausville, EA Arbuck, SG Messmann, R Headlee, D Bauer, KS Lush, RM Murgo, A Figg, WD Lahusen, T Jaken, S Jing, XX Roberge, M Fuse, E Kuwabara, T Senderowicz, AM AF Sausville, EA Arbuck, SG Messmann, R Headlee, D Bauer, KS Lush, RM Murgo, A Figg, WD Lahusen, T Jaken, S Jing, XX Roberge, M Fuse, E Kuwabara, T Senderowicz, AM TI Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROTEIN-KINASE-C; HUMAN EPIDERMOID CARCINOMA; DNA-DAMAGE CHECKPOINT; CELL-CYCLE; 7-HYDROXYSTAUROSPORINE UCN-01; RADIOSENSITIZING AGENT; SELECTIVE INHIBITOR; STAUROSPORINE; EXPRESSION; ACTIVATION AB Purpose: To define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of the novel protein kinase inhibitor, UCN-01 (7-hydroxystaurosporine), administered as a 72-hour continuous intravenous infusion(CIV). Patients and Methods: Forty-seven patients with refractory neoplasms received UCN-01 during this phase I trial. Total, free plasma, and salivary concentrations were determined; the latter were used to address the influence of plasma protein binding on peripheral tissue distribution. The phosphorylation state of the protein kinase C (PKC) substrate alpha-adducin and the abrogation of DNA damage checkpoint also were assessed. Results: The recommended phase II dose of UCN-01 as a 72-hour CIV is 42.5 mg/m(2)/d for 3 days. Avid plasma protein binding of UCN-01,as measured during the trial, dictated a change in dose escalation and administration schedules. Therefore, nine patients received drug on the initial 2-week schedule, and 38 received drug on the recommended 4-week schedule. DLTs at 53 mg/m(2)/d for 3 days included hyperglycemia with resultant metabolic acidosis, pulmonary dysfunction, nausea, vomiting, and hypotension. Pharmacokinetic determinations at the recommended dose of 42.5 mg/m(2)/d for 3 days included mean total plasma concentration of 36.4 muM (terminal elimination half-life range, 447 to 1176 hours), steady-state volume of distribution of 9.3 to 14.2 L, and clearances of 0.005 to 0.033 L/h. The mean total salivary concentration was 111 nmol/L of UCN-01. One partial response was observed in a patient with melanoma, and one protracted period ( > 2.5 years) of disease stability was observed in a patient with alk-positive anaplastic large-cell lymphoma. Preliminary evidence suggests UCN-01 modulation of both PKC substrate phosphorylation and the DNA damage-related Gp checkpoint. Conclusion: UCN-01 can be administered safely as an initial 72-hour CIV with subsequent monthly doses administered as 36-hour infusions. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Clin Trials Unit,Med Branch, Rockville, MD 20852 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Shizuoka, Japan. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Clin Trials Unit,Med Branch, Execut Plaza N Bldg,Ste 8000,6130 Execut Blvd, Rockville, MD 20852 USA. RI Figg Sr, William/M-2411-2016 NR 40 TC 229 Z9 234 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2001 VL 19 IS 8 BP 2319 EP 2333 PG 15 WC Oncology SC Oncology GA 423LT UT WOS:000168178300025 PM 11304786 ER PT J AU Prasad, SA Norbury, CC Chen, WS Bennink, JR Yewdell, JW AF Prasad, SA Norbury, CC Chen, WS Bennink, JR Yewdell, JW TI Cutting edge: Recombinant adenoviruses induce CD8 T cell responses to an inserted protein whose expression is limited to nonimmune cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXOGENOUS ANTIGEN; DENDRITIC CELLS; IMMUNE-RESPONSE; VIRAL VECTORS; IN-VIVO; GENE; HELP; CTL; MHC AB CD8 T cells (TCD8+) play a crucial role in immunity to viruses. Current understanding of activation of naive T cells entails Ag presentation by professional APCs (pAPCs). What happens, however, when viruses evolve to avoid infecting pAPCs? We have studied the consequences of this strategy by generating recombinant adenoviruses that express influenza A virus nucleoprotein under the control of tissue-specific promoters. We show that the immunogenicity of such viruses requires their delivery to organs capable of expressing nucleoprotein. This indicates that infection of pAPCs is not required for adenoviruses to elicit a TCD8+ response, probably due to a cross-priming via pAPCs. While this bodes well for recombinant adenoviruses as vaccines, it dims their prospects as gene therapy vectors. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bennink, JR (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 213,9000 Rockville Pike, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012 NR 21 TC 45 Z9 45 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 APR 15 PY 2001 VL 166 IS 8 BP 4809 EP 4812 PG 4 WC Immunology SC Immunology GA 471VA UT WOS:000170948300001 PM 11290753 ER PT J AU Liu, KB Hodes, RJ Weng, NP AF Liu, KB Hodes, RJ Weng, NP TI Cutting edge: Telomerase activation in human T lymphocytes does not require increase in telomerase reverse transcriptase (hTERT) protein but is associated with hTERT phosphorylation and nuclear translocation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CATALYTIC SUBUNIT GENE; HEMATOPOIETIC-CELLS; B-CELL; EXPRESSION; CANCER; IMMORTALIZATION; LENGTH; PROLIFERATION; MECHANISM; TISSUES AB Capacity for cellular replication is critically important for lymphocyte function and can be regulated by telomerase-dependent maintenance of telomere length. In contrast to most normal human somatic cells that do not express telomerase due to the failure to transcribe telomerase reverse transcriptase (hTERT), lymphocytes express telomerase in a highly regulated fashion yet constitutively transcribe hTERT during development and activation. Here, we report that hTERT protein is present in both thymocytes and blood T cells at equivalent levels despite their substantial differences in telomerase activity, and that induction of telomerase activity in resting CD4(+) T cells is not dependent on net hTERT protein increase. Moreover, hTERT is phosphorylated and translocated from cytoplasm to nucleus during CD4(+) T cell activation. Thus, human T lymphocytes regulate telomerase function through novel events independent of hTERT protein levels, and hTERT phosphorylation and nuclear translocation may play a role in regulation of telomerase function in lymphocytes. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. OI Liu, Kebin/0000-0003-1965-7240 NR 37 TC 165 Z9 173 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 4826 EP 4830 PG 5 WC Immunology SC Immunology GA 471VA UT WOS:000170948300005 PM 11290757 ER PT J AU Alpan, O Rudomen, G Matzinger, P AF Alpan, O Rudomen, G Matzinger, P TI The role of dendritic cells, B cells, and M cells in gut-oriented immune responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOLLICLE-ASSOCIATED EPITHELIUM; ANTIGEN-PRESENTING CELLS; MOUSE PEYERS-PATCH; SUPPRESSOR T-CELLS; ORAL TOLERANCE; DEFICIENT MICE; IN-VIVO; BYSTANDER SUPPRESSION; PERIPHERAL TOLERANCE; IMMUNOGLOBULIN-A AB Although induction of T cell responses to fed Ag (oral tolerance) is thought to happen within the organized lymphoid tissue of the gut, we found that mice lacking Peyer's patches, B cells, and the specialized Ag-handling M cells had no defect in the induction of T cell responses to fed Ag, whether assayed in vitro by T cell proliferation or cytokine production, or in vivo by delayed-type hypersensitivity or bystander suppression against mycobacterial Ags in CFA. Feeding of Ag had a major influence on dendritic cells from fed wild-type or mu MT mice, such that these APCs were able to elicit a different class of response from naive T cells in vitro. These results suggest that systemic immune responses to soluble oral Ags do not require an organized gut-associated lymphoid tissue but are most likely induced by gut-conditioned dendritic cells that function both to initiate the gut-oriented response and to impart the characteristic features that discriminate it from responses induced parenterally. C1 NIAID, Cellular & Mol Immunol Lab, Sect T Cell Tolerance & Memory,Ghost Lab, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Univ Hosp, Med Ctr, Microscopy Imaging Ctr, Stony Brook, NY 11794 USA. RP Alpan, O (reprint author), NIAID, Cellular & Mol Immunol Lab, Sect T Cell Tolerance & Memory,Ghost Lab, NIH, Bldg 4,Room 111,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 71 TC 122 Z9 124 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 4843 EP 4852 PG 10 WC Immunology SC Immunology GA 471VA UT WOS:000170948300008 PM 11290760 ER PT J AU Payet-Jamroz, M Helm, SLT Wu, JH Kilmon, M Fakher, M Basalp, A Tew, JG Szakal, AK Noben-Trauth, N Conrad, DH AF Payet-Jamroz, M Helm, SLT Wu, JH Kilmon, M Fakher, M Basalp, A Tew, JG Szakal, AK Noben-Trauth, N Conrad, DH TI Suppression of IgE responses in CD23-transgenic animals is due to expression of CD23 on nonlymphoid cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; FC-EPSILON-RII; LOW-AFFINITY RECEPTOR; MOUSE B-CELLS; T-CELL; DEPENDENT ANTIGEN; IN-VITRO; CD23-DEFICIENT MICE; ANTIBODY-RESPONSE; HUMAN-LYMPHOCYTES AB Serum IgE is suppressed in CD23-transgenic (Tg) mice where B cells and some T cells express high levels of CD23, suggesting that CD23 on B and T cells may cause this suppression. However, when Tg B lymphocytes were compared with controls in B cell proliferation and IgE synthesis assays, the two were indistinguishable. Similarly, studies of lymphokine production suggested that T cell function in the Tg animals was normal. However, adoptive transfer studies indicated that suppression was seen when normal lymphocytes were used to reconstitute Tg mice, whereas reconstitution of controls with Tg lymphocytes resulted in normal IgE responses, suggesting that critical CD23-bearing cells are irradiation-resistant, nonlymphoid cells. Follicular dendritic cells (FDC) are irradiation resistant, express surface CD23, and deliver iccosomal Ag to B cells, prompting us to reason that Tg FDC may be a critical cell. High levels of transgene expression were observed in germinal centers rich in FDC and B cells, and IgE production was inhibited when Tg FDCs were cultured with normal B cells. In short, suppressed TgE production in CD23-Tg mice appears to be associated with a population of radioresistant nonlymphoid cells. FDCs that interface with B cells in the germinal center are a candidate for explaining this CD23-mediated IgE suppression. C1 Virginia Commonwealth Univ, Dept Microbiol & Immunol, MCV Stn, Richmond, VA 23298 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Conrad, DH (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, MCV Stn, Sanger Hall,1101 E Marshall St,Box 980678, Richmond, VA 23298 USA. FU NIAID NIH HHS [AI34631, AI18697, AI07407] NR 44 TC 23 Z9 23 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 APR 15 PY 2001 VL 166 IS 8 BP 4863 EP 4869 PG 7 WC Immunology SC Immunology GA 471VA UT WOS:000170948300010 PM 11290762 ER PT J AU Iwasaki, A Kelsall, BL AF Iwasaki, A Kelsall, BL TI Unique functions of CD11b(+), CD8 alpha(+), and double-negative Peyer's patch dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; SPLEEN; DIFFERENTIATION; ACTIVATION; TOLERANCE; THYMUS AB We have recently demonstrated the presence of three populations of dendritic cells (DC) in the murine Peyer's patch. CD11b(+)/CD8 alpha (-) (myeloid) DCs are localized in the subepithelial dome, CD11b(-)/CD8 alpha (+) (lymphoid) DCs in the interfollicular regions, and CD11b(-)/CD8 alpha (-) (double-negative; DN) DCs at both sites. We now describe the presence of a novel population of intraepithelial DN DCs within the follicle-associated epithelium and demonstrate a predominance of DN DCs only in mucosal lymphoid tissues. Furthermore, we demonstrate that all DC subpopulations maintain their surface phenotype upon maturation in vitro, and secrete a distinct pattern of cytokines upon exposure to T cell and microbial stimuli. Only myeloid DCs from the PP produce high levels of IL-10 upon stimulation with soluble CD40 ligand(-) trimer, or Staphylococcus aureus and IFN-gamma. In contrast, lymphoid and DN, but not myeloid DCs, produce IL-12p70 following microbial stimulation, whereas no DC subset produces IL-12p70 in response to CD40 ligand trimer. Finally, we show that myeloid DCs from the PP are particularly capable of priming naive T cells to secrete high levels of IL-4 and IL-10, when compared with those from nonmucosal sites, while lymphoid and DN DCs from all tissues prime for IFN-gamma production. These findings thus suggest that DC subsets within mucosal tissues have unique immune inductive capacities. C1 NIAID, Clin Invest Lab, Mucosal Immun Sect, Immune Cell Interact Unit,NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), NIAID, Clin Invest Lab, Mucosal Immun Sect, Immune Cell Interact Unit,NIH, 10 Ctr Dr,Room 11N238, Bethesda, MD 20892 USA. NR 18 TC 326 Z9 340 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 4884 EP 4890 PG 7 WC Immunology SC Immunology GA 471VA UT WOS:000170948300013 PM 11290765 ER PT J AU Riley, JL Blair, PJ Musser, JT Abe, R Tezuka, K Tsuji, T June, CH AF Riley, JL Blair, PJ Musser, JT Abe, R Tezuka, K Tsuji, T June, CH TI ICOS costimulation requires IL-2 and can be prevented by CTLA-4 engagement SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; MONOCLONAL-ANTIBODIES; CD28 COSTIMULATION; LYMPHOCYTES-T; GROWTH-FACTOR; CUTTING EDGE; PROTEIN ICOS; MOLECULE; EXPRESSION; ANTIGEN AB We investigated the relationship between ICOS, CD28, CTLA-4, and IL-2 to gain a better understanding of this family of costimulatory receptors in the immune response. Using magnetic beads coated with anti-CD3 and varying amounts of anti-ICOS and anti-CTLA-4 Abs, we show that CTLA-4 ligation blocks ICOS costimulation. In addition to inhibiting cellular proliferation, CTLA-4 engagement prevented ICOS-costimulated T cells from producing IL-4, IL-10, and IL-13. Both an indirect and direct mechanism of CTLA-4's actions were examined. First, CTLA-4 engagement on resting cells was found to indirectly block ICOS costiniulation by interferring with the signals needed to induce ICOS cell surface expression. Second, on preactivated cells that had high levels of ICOS expression, CTLA-4 ligation blocked the ICOS-mediated induction of IL-4, IL-10, and IL-13, suggesting an interference with downstream signaling pathways. The addition of IL-2 not only overcame both mechanisms, but also greatly augmented the level of cellular activation suggesting synergy between ICOS and IL-2 signaling. This cooperation between ICOS and IL-2 signaling was explored further by showing that the minimum level of IL-2 produced by ICOS costimulation was required for T cell proliferation. Finally, exogenous IL-2 was required for sustained growth of ICOS-costimulated T cells. These results indicate that stringent control of ICOS costimulation is maintained initially by CTLA-4 engagement and later by a requirement for exogenous IL-2. C1 Univ Penn, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. NIDDK, USN, Med Res Ctr, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. Sci Univ Tokyo, Res Inst Biol Sci, Chiba, Japan. JT Inc, Pharmaceut Frontier Res Labs, Kanagawa, Japan. RP Riley, JL (reprint author), Univ Penn, Dept Mol & Cellular Engn, 421 Curie Blvd,Biomed Res Bldg 2-3,Room 508, Philadelphia, PA 19104 USA. RI Tsuji, Takashi/N-6086-2015; OI Riley, James/0000-0002-1057-576X NR 35 TC 89 Z9 97 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 4943 EP 4948 PG 6 WC Immunology SC Immunology GA 471VA UT WOS:000170948300020 PM 11290772 ER PT J AU Ortaldo, JR Bere, EW Hodge, D Young, HA AF Ortaldo, JR Bere, EW Hodge, D Young, HA TI Activating Ly-49 NK receptors: Central role in cytokine and chemokine production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; PROTEIN-TYROSINE KINASE; SIGNAL-TRANSDUCTION; MYELOID CELLS; CUTTING EDGE; MICE; PHOSPHORYLATION; CYTOTOXICITY; PHOSPHATASE; MIGRATION AB In an attempt to understand potential novel functions of receptors in vivo, we evaluated gene expression after cross-linking the activating Ly-49D mouse NK receptor. Gene expression was evaluated using a mouse GEM 2 microarray chip (Incyte Genomics, St. Louis, MO). Each chip displays a total of 8734 elements. The strongly induced genes fell into two categories: 1) soluble factors and 2) apoptotic genes. The majority of the strongly induced mRNAs as analyzed by microarray hybridization were chemokine genes. RNase protection assays and chemokine protein production analysis validated the microarray results, as cross-linking the Ly-49D mouse NK receptor induced high levels of IFN-gamma, lymphotactin, macrophage-inflammatory protein (MIP)1 alpha, and MIP1 beta. This gene expression was specific because other chemokines were not induced by anti-Ly-49D receptors. In addition, a series of pharmacological inhibitors were used to identify the key signaling pathways involved in the cellular response. The primary Ly-49D signaling for IFN-gamma production is predominately mediated through Src kinase pathways involving membrane proximal events, whereas MIP1 alpha and MIP1 beta gene induction is more complex and may involve multiple biochemical pathways. Thus, we conclude that a primary role for the activating NK receptors in vivo may be to trigger soluble factor production and regulation of the immune response. This would place NK cells and their activating Ly-49 receptors as important initiators of microbial immunity and key elements of the innate immune system. The Journal of Immunology, 2001. C1 NCI, Expt Immunol Lab, Frederick, MD 21702 USA. RP Ortaldo, JR (reprint author), NCI, Expt Immunol Lab, Bldg 560,Room 31-93, Frederick, MD 21702 USA. NR 39 TC 48 Z9 48 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 4994 EP 4999 PG 6 WC Immunology SC Immunology GA 471VA UT WOS:000170948300027 PM 11290779 ER PT J AU Makrigiannis, AP Pau, AT Saleh, A Winkler-Pickett, R Ortaldo, JR Anderson, SK AF Makrigiannis, AP Pau, AT Saleh, A Winkler-Pickett, R Ortaldo, JR Anderson, SK TI Class I MHC-Binding characteristics of the 129/J Ly49 repertoire SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MURINE NK CELLS; MOUSE STRAINS; TARGET-CELLS; INBRED MICE; RECEPTOR; EXPRESSION; RECOGNITION; MOLECULES; FAMILY AB The Ly49 family of NK cell receptors and its MHC-binding characteristics have only been well characterized in C57BL/6 (B6) mice. Previous studies have shown that 129/J mice express unique Ly49 genes that are not found in the B6 strain. Screening of a 129/J cDNA library led to the discovery of 10 distinct full-length Ly49-related coding sequences (Ly49c, g, i, o, p, r, s, t, u, and v). Although 129/J mice share identical class I MHC (K-b and D-b) transcripts with B6 mice, only one Ly49 is identical in the two strains (Ly49E). In addition to the previously characterized Ly49P, two new activating Ly49 proteins were discovered, Ly49R and U. The MHC specificity of the total 129J Ly49 repertoire was evaluated with soluble class I MHC tetramers and found to be distinct compared with the B6 Ly49 repertoire. Ly49V bound to many types of class I MHC, suggesting that Ly49V(+) NK cells may monitor host cells for a global down-regulation in MHC levels. An activating receptor, Ly49R, was shown to bind soluble class I molecules to a moderate degree, a result not previously observed for other activating Ly49 proteins. Furthermore, tetramer-binding results were confirmed functionally with cytotoxicity assays using sorted 129/J NK cells. This study shows that the Ly49 repertoire and its MHC-binding characteristics can be very different among inbred mouse strains. Ly49 divergence should be considered when using 129-derived embryonic stern cells for the production of gene-targeted mice, especially when an immune or NK-derived phenotype is under scrutiny. The Journal of Immunology, 2001. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Intramural Res Support Program, Bldg 560,Room 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-56000] NR 60 TC 69 Z9 70 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 APR 15 PY 2001 VL 166 IS 8 BP 5034 EP 5043 PG 10 WC Immunology SC Immunology GA 471VA UT WOS:000170948300032 PM 11290784 ER PT J AU Gaspar, R Bagossi, P Bene, L Matko, J Szollosi, J Tozser, J Fesus, L Waldmann, TA Damjanovich, S AF Gaspar, R Bagossi, P Bene, L Matko, J Szollosi, J Tozser, J Fesus, L Waldmann, TA Damjanovich, S TI Clustering of class IHLA oligomers with CD8 and TCR: Three-dimensional models based on fluorescence resonance energy transfer and crystallographic data SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULES; T-CELL RECEPTOR; MHC CLASS-I; HISTOCOMPATIBILITY ANTIGEN; PLASMA-MEMBRANE; SURFACE; COMPLEX; PEPTIDE; ASSOCIATION; ACTIVATION AB Fluorescence resonance energy transfer (FRET) data, in accordance with lateral mobility measurements, suggested the existence of class I HLA dimers and oligomers at the surface of live human cells, including the B lymphoblast cell line (JY) used in the present study. Intra- and intermolecular class I HLA epitope distances were measured on JY B cells by FRET using fluorophore-conjugated Ag-binding fragments of mAbs W6/32 and L368 directed against structurally well-characterized heavy and light chain epitopes, respectively. Out-of-plane location of these epitopes relative to the membrane-bound BODIPY-PC (2-(4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine) was also determined by FRET. Computer-simulated docking of crystallographic structures of class I HLA and epitope-specific Ag-binding fragments, with experimentally determined interepitope and epitope to cell surface distances as constraints, revealed several sterically allowed and FRET-compatible class I HLA dimeric and tetrameric arrangements. Extension of the tetrameric class I HLA model with interacting TCR and CD8 resulted in a model of a supramolecular cluster that may exist physiologically and serve as a functionally significant unit for a network of CD8-HLA-I complexes providing enhanced signaling efficiency even at low MHC-peptide concentrations at the interface of effector and APCs. The Journal of Immunology, 2001. C1 Univ Debrecen, Hungarian Acad Sci, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, H-4012 Debrecen, Hungary. Univ Debrecen, Hungarian Acad Sci, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, Debrecen, Hungary. Univ Debrecen, Hungarian Acad Sci, Med & Hlth Sci Ctr, Biophys Res Grp, Debrecen, Hungary. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Gaspar, R (reprint author), Univ Debrecen, Hungarian Acad Sci, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, POB 39, H-4012 Debrecen, Hungary. RI Tozser, Jozsef/A-7840-2008; Damjanovich, Sandor/A-9284-2011; Matko, Janos/C-9008-2013; OI Tozser, Jozsef/0000-0003-0274-0056; Matko, Janos/0000-0001-9434-934X; Tozser, Jozsef/0000-0001-5076-8729 NR 52 TC 31 Z9 31 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2001 VL 166 IS 8 BP 5078 EP 5086 PG 9 WC Immunology SC Immunology GA 471VA UT WOS:000170948300037 PM 11290789 ER PT J AU Mendez, S Gurunathan, S Kamhawi, S Belkaid, Y Moga, MA Skeiky, YAW Campos-Neto, A Reed, S Seder, RA Sacks, D AF Mendez, S Gurunathan, S Kamhawi, S Belkaid, Y Moga, MA Skeiky, YAW Campos-Neto, A Reed, S Seder, RA Sacks, D TI The potency and durability of DNA- and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSE; PROTECTIVE IMMUNITY; PLASMID DNA; CIRCUMSPOROZOITE PROTEIN; MURINE LEISHMANIASIS; GENETIC IMMUNIZATION; CELLULAR-IMMUNITY; INTERFERON-GAMMA AB DNA- and protein- based vaccines against cutaneous leishmaniasis due to Leishmania major were evaluated using a challenge model that more closely reproduces the pathology and immunity associated with sand fly-transmitted infection. C57BL/6 mice were vaccinated s.c. with a mixture of plasmid DNAs encoding the Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or with autoclaved L major promastigotes (ALM) plus rIL-12, and the mice were challenged by inoculation of 100 metacyclic promastigotes in the ear dermis. When challenged at 2 wk postvaccination, mice receiving AgDNA or ALM/rIL-12 were completely protected against the development of dermal lesions, and both groups had a 100-fold reduction in peak dermal parasite loads compared with controls. When challenged at 12 wk, mice vaccinated with ALM/rIL-12 maintained partial protection against dermal lesions and their parasite loads were no longer significantly reduced, whereas the mice vaccinated with AgDNA remained completely protected and had a 1000-fold reduction in dermal parasite loads. Mice vaccinated with AgDNA also harbored few, if any, parasites in the skin during the chronic phase, and their ability to transmit L major to vector sand flies was completely abrogated. The durable protection in mice vaccinated with AgDNA was associated with the recruitment of both CD8(+) and CD4(+) T cells to the site of intradermal challenge and with IFN-gamma production by CD8(+) T cells in lymph nodes draining the challenge site. These data suggest that under conditions of natural challenge, DNA vaccination has the capacity to confer complete protection against cutaneous leishmaniasis and to prevent the establishment of infection reservoirs. The Journal of Immunology, 2001. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Immunol Lab, NIH, Bethesda, MD 20892 USA. Infect Dis Res Inst, Seattle, WA 98104 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. NR 31 TC 101 Z9 103 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 APR 15 PY 2001 VL 166 IS 8 BP 5122 EP 5128 PG 7 WC Immunology SC Immunology GA 471VA UT WOS:000170948300042 PM 11290794 ER PT J AU Ariga, T Kondoh, T Yamaguchi, K Yamada, M Sasaki, S Nelson, DL Ikeda, H Kobayashi, K Moriuchi, H Sakiyama, Y AF Ariga, T Kondoh, T Yamaguchi, K Yamada, M Sasaki, S Nelson, DL Ikeda, H Kobayashi, K Moriuchi, H Sakiyama, Y TI Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FLOW CYTOMETRIC ANALYSIS; SYNDROME PROTEIN; REPEAT POLYMORPHISM; WASP GENE; ACTIN POLYMERIZATION; CARRIER STATUS; CELL LINES; T-CELL; LYMPHOCYTES; BLOOD AB The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease, arising from mutations of the WAS-protein (WASP) gene. Previously, we have reported that mononuclear cells from WAS patients showed lack/reduced of the intracellular WASP (WASp(dim)) by flow cytometric analysis, and analysis of WASP by flow cytometry (FCM-WASP) was useful for WAS diagnosis. In this study, we report a WAS patient who showed the unique pattern of FCM-WASP. The patient bad the small population of normal expression of WASP (WASp(bright)) mononuclear cells together with the major WASP(dim) population. The WASP(bright) cells were detected in T cells, not in B cells or in monocytes. Surprisingly, the molecular studies of the WASP(bright) cells revealed that the inherited mutation of WASP gene was reversed to normal. His mother was proved as a WAS carrier, and HLA studies and microsatellite polymorphic studies proved that the WASP(bright) cells were derived from the patient himself. Therefore, we concluded that the WASP(bright) cells were resulted from spontaneous in vivo reversion of the inherited mutation. Furthermore, the scanning electron microscopic studies indicated that WASP-positive cells from the patient restored the dense microvillus surface projections that were hardly observed in the WASP(dim) cells. This case might have significant implications regarding the prospects of the future gene therapy for WAS patients. C1 Hokkaido Univ, Sch Med, Dept Human Gene Therapy, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Nagasaki Univ, Sch Med, Dept Pediat, Nagasaki 852, Japan. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Hokkaido Red Cross, Blood Ctr, Sapporo, Hokkaido, Japan. RP Ariga, T (reprint author), Hokkaido Univ, Sch Med, Dept Human Gene Therapy, Kita Ku, N-14,W-5, Sapporo, Hokkaido 0608638, Japan. RI Ariga, Tadashi/A-4252-2012 NR 34 TC 65 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 APR 15 PY 2001 VL 166 IS 8 BP 5245 EP 5249 PG 5 WC Immunology SC Immunology GA 471VA UT WOS:000170948300057 PM 11290809 ER PT J AU Freitag, C Chougnet, C Schito, M Near, KA Shearer, GM Li, C Langhorne, J Sher, A AF Freitag, C Chougnet, C Schito, M Near, KA Shearer, GM Li, C Langhorne, J Sher, A TI Malaria infection induces virus expression in human immunodeficiency virus transgenic mice by CD4 T cell-dependent immune activation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 28-DEC 02, 1999 CL WASHINGTON, D.C. SP Amer Soc Trop Med & Hyg ID PLASMODIUM-CHABAUDI-CHABAUDI; NECROSIS-FACTOR-ALPHA; BLOOD-STAGE MALARIA; DENDRITIC CELLS; IN-VIVO; MYCOBACTERIUM-TUBERCULOSIS; TYPE-1 REPLICATION; GAMMA-INTERFERON; POTENTIAL ROLE; B-CELLS AB To test the capacity of malaria parasites to trigger virus expression in vivo, human immunodeficiency virus (HIV) transgenic mice were infected with Plasmodium chabaudi chabaudi clone AS. Splenocytes recovered during peak parasitemia showed a dramatic elevation in viral p24 production that returned to baseline by day 15 and failed to rebound at recrudescence or after reinfection. The major sources of virus expression were antigen-presenting cells (APCs) rather than T lymphocytes. Nevertheless, T cells from infected mice stimulated with plasmodial antigen triggered 5-10-fold increases in p24 production from dendritic cells in vitro, which suggests that viral induction stems from interaction of malaria-specific T lymphocytes with HIV-expressing APCs. Indeed, depletion of CD4 T cells resulted in a 70% reduction in the p24 response stimulated by malaria in vivo. These findings demonstrate the ability of Plasmodium species to immunologically activate latently integrated HIV in vivo but suggest that this process may be restricted to acute infection. C1 NIAID, LPD, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. NIAID, LPD, Malaria Vaccine Sect, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. RP Sher, A (reprint author), NIAID, LPD, Immunobiol Sect, NIH, 4 Ctr Dr,Rm 4-126, Bethesda, MD 20892 USA. NR 47 TC 23 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2001 VL 183 IS 8 BP 1260 EP 1268 DI 10.1086/319686 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414PE UT WOS:000167674600012 PM 11262209 ER PT J AU Liesi, P Fried, G Stewart, RR AF Liesi, P Fried, G Stewart, RR TI Neurons and glial cells of the embryonic human brain and spinal cord express multiple and distinct isoforms of laminin SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE brain; human embryo; isoforms of laminin; neurite outgrowth; spinal cord ID OUTGROWTH-PROMOTING DOMAIN; COLORECTAL-CANCER DCC; NEURITE OUTGROWTH; S-LAMININ; CHROMOSOMAL ASSIGNMENT; NERVOUS-SYSTEM; AXON GUIDANCE; MICE LACKING; B2 CHAIN; BASEMENT-MEMBRANES AB We have identified by immunocytochemistry, Western blotting, and RT-PCR the isoforms of laminin expressed by glial cells and neurons cultured from human embryonic brain and spinal cord. We show that most of the known laminins are present in human neurons and glial cells. Importantly, Western analysis demonstrates that the isoforms of laminin present in embryonic human brain differ from those expressed in human spinal cord. Neurons of the brain and spinal cord also express their distinct and characteristic isoforms of laminin compared to the glial cells of the same CNS regions. These results suggest that, in addition to the known laminins, several novel isoforms may exist in the human embryonic CNS. The observed differences between the isoforms of laminin in brain and spinal cord neurons and glial cells may result from primary structural changes or from posttranslational modifications, e.g., variations in glycosylation. Thus, identification of these novel laminins and determination of their function(s) should further our understanding of the mechanisms of aging, disease, and trauma in the human CNS. J. Neurosci. Res. 64:144-167, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Helsinki, Biomedicum Helsinki, Inst Biomed, Dept Anat,Brain Lab, Helsinki 00014, Finland. Karolinska Hosp & Inst, Dept Woman & Child Hlth, Div Obstet & Gynecol, Stockholm, Sweden. NIAAA, Cellular & Mol Neurobiol Lab, Rockville, MD 20852 USA. RP Liesi, P (reprint author), Univ Helsinki, Biomedicum Helsinki, Inst Biomed, Dept Anat,Brain Lab, POB 63,Haartmaninkatu 8, Helsinki 00014, Finland. EM paivi.liesi@helsinki.fi NR 63 TC 34 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR 15 PY 2001 VL 64 IS 2 BP 144 EP 167 DI 10.1002/jnr.1061 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 416UX UT WOS:000167799500005 PM 11288143 ER PT J AU Lipska, BK Kolb, B Halim, N Weinberger, DR AF Lipska, BK Kolb, B Halim, N Weinberger, DR TI Synaptic abnormalities in prefrontal cortex and nucleus accumbens of adult rats with neonatal hippocampal damage SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 47 EP 47 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700155 ER PT J AU Crook, JM Weickert, CS Chaguturu, S Kleinman, JE Hyde, TM AF Crook, JM Weickert, CS Chaguturu, S Kleinman, JE Hyde, TM TI Decreased gene expression of muscarinic M1 and M4 receptors in prefrontal cortex of patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 51 EP 51 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700166 ER PT J AU Weickert, CS Hyde, TM Eisenberg, N Romanczyk, T Kleinman, JE AF Weickert, CS Hyde, TM Eisenberg, N Romanczyk, T Kleinman, JE TI Expression of full-length trkB mRNA in hippocampus of patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 57 EP 57 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700188 ER PT J AU Lenane, M Gogate, N Nicolson, R Gochman, P Brookner, F Rapoport, J AF Lenane, M Gogate, N Nicolson, R Gochman, P Brookner, F Rapoport, J TI Incidence of schizophrenia spectrum disorders in adult siblings of childhood onset schizophrenia patients SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Nicolson, Robert/E-4797-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 73 EP 73 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700240 ER PT J AU Webster, MJ Weickert, CS Herman, MM Hyde, TM Kleinman, JE AF Webster, MJ Weickert, CS Herman, MM Hyde, TM Kleinman, JE TI Synaptophysin and GAP-43 mRNA levels in the hippocampus of subjects with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE GAP-43 mRNA; growth associated protein-43; in situ hybridization; neuroleptic treatment; schizophrenia; synaptophysin ID GROWTH-ASSOCIATED PROTEIN; MEDIAL TEMPORAL-LOBE; GLUTAMATE RECEPTOR GENE; ADULT-RAT BRAIN; MESSENGER-RNA; ENTORHINAL CORTEX; ALZHEIMERS-DISEASE; PARAHIPPOCAMPAL GYRUS; NEURONAL DENSITY; EXPRESSION AB Synaptophysin and growth associated protein-43 (GAP-43) are synaptic proteins colocalized to the presynaptic terminal, and involved in regulating transmitter release and synaptic plasticity. Recent studies have proposed an alteration in the number of synapses in the brains of individuals with schizophrenia. As a corollary, we hypothesized that then may be an alteration in the level of mRNAs that code for synaptic proteins in brains of patients with schizophrenia. Using in situ hybridization, we investigated the levels of synaptophysin and GAP-43 mRNA in the medial temporal lobe of 10 normal subjects, 11 subjects with schizophrenia and 10 psychiatric control subjects. Synaptophysin mRNA levels were significantly reduced in several hippocampal subfields in both the schizophrenic and psychiatric control groups. GAP-43 mRNA levels were not significantly reduced in either group. The implications of these findings are discussed in relation to neuroleptic treatment and the pathophysiology of mental illness. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn, Res Program, Bethesda, MD 20814 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Webster, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn, Res Program, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Shannon Weickert, Cynthia/G-3171-2011 NR 61 TC 35 Z9 38 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 BP 89 EP 98 DI 10.1016/S0920-9964(00)00052-9 PG 10 WC Psychiatry SC Psychiatry GA 440TG UT WOS:000169189900007 PM 11343868 ER PT J AU Elvevag, B Foltz, P Fisher, JE Schwartz, A Bokat, CE Weinberger, DR Goldberg, TE AF Elvevag, B Foltz, P Fisher, JE Schwartz, A Bokat, CE Weinberger, DR Goldberg, TE TI Latent semantic analysis and the semantic coherence of disordered speech in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, NIH, Clin Brain Disorders Branch, Bethesda, 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 105 EP 106 PG 2 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700351 ER PT J AU Weickert, TW Terrazas, A Goldberg, TE AF Weickert, TW Terrazas, A Goldberg, TE TI Probabilistic classification learning in schizophrenia: Dissociation within implicit memory system suggests differential impairment of the basal ganglia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 124 EP 124 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700415 ER PT J AU Bokat, CE Paul, BM Elvevag, B Weinberger, DR Goldberg, TE AF Bokat, CE Paul, BM Elvevag, B Weinberger, DR Goldberg, TE TI Depth of encoding effects on recognition memory in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIH, NIMH, Clin Brain Disorders Branch, 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 129 EP 129 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700432 ER PT J AU Winterer, G Egan, MF Radler, T Hyde, T Coppola, R Weinberger, DR AF Winterer, G Egan, MF Radler, T Hyde, T Coppola, R Weinberger, DR TI An association between reduced interhemispheric EEG coherence in the temporal lobe and genetic risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE coherence; EEG; relative risk; schizophrenia; sib-pair analysis ID HUMAN ELECTROENCEPHALOGRAM EEG; TO-NOISE RATIO; SIBLINGS DISCORDANT; HEALTHY-VOLUNTEERS; LINKAGE STRATEGIES; NEGATIVE SYMPTOMS; ACTIVATION TASKS; COMPLEX TRAITS; BLOOD-FLOW; POWER AB Previous studies have suggested that schizophrenic patients show resting EEG replicate the results on the second data set. power spectrum analysis suggested that schizophrenics are cortically hypoactivated, whereas in unaffected siblings, a tendency for hyperactivation was found. In contrast, spectral coherences (0.5-5 Hz) were reduced in both data sets in the temporal lobe areas in schizophrenics and in their unaffected siblings. Changes were most pronounced for the interhemispheric coherence linking both posterior temporal lobe areas. Relative risk calculations (hs) ranged between 3.7 and 9.8, depending on phenotype definition. Thus, while power spectrum EEG abnormalities may be state-dependent, reduced coherence as a possible measure of neuronal synchronization is familial and potentially a heritable trait related to genetic risk for schizophrenia. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Winterer, G (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 70 TC 48 Z9 52 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 BP 129 EP 143 DI 10.1016/S0920-9964(00)00128-6 PG 15 WC Psychiatry SC Psychiatry GA 440TG UT WOS:000169189900011 PM 11343872 ER PT J AU Kerbs, KM Elvevag, B Malley, JD Seeley, E Weinberger, DR Goldberg, TE AF Kerbs, KM Elvevag, B Malley, JD Seeley, E Weinberger, DR Goldberg, TE TI Autobiographical memory in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIH, NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 137 EP 137 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700458 ER PT J AU Schooler, C Roberts, BR Caplan, LJ AF Schooler, C Roberts, BR Caplan, LJ TI Structural equation modeling of schizophrenic cognitive performance SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIH, NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 144 EP 144 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700485 ER PT J AU Gogate, N Giedd, J Nicolson, R Blumenthal, J Gochman, P Evans, AC Rapoport, J AF Gogate, N Giedd, J Nicolson, R Blumenthal, J Gochman, P Evans, AC Rapoport, J TI Structural brain MRI changes in young healthy siblings of childhood onset schizophrenia patients SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 155 EP 155 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700523 ER PT J AU Meyer-Lindenberg, A Poline, J Kohn, PD Holt, JL Egan, MF Weinberger, DR Berman, KF AF Meyer-Lindenberg, A Poline, J Kohn, PD Holt, JL Egan, MF Weinberger, DR Berman, KF TI Disturbed functional connectivity in schizophrenia: A prospective study using PET SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Unit Integrat Neuroimaging, CBDB, IRP, Bethesda, 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 181 EP 181 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700611 ER PT J AU Raedler, TJ Jones, DW Knable, MB Gorey, JG Lee, KS Egan, MF Weinberger, DR AF Raedler, TJ Jones, DW Knable, MB Gorey, JG Lee, KS Egan, MF Weinberger, DR TI Comparison of the in vivo muscarinic cholinergic receptor availability in patients treated with olanzapine and clozapine SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 184 EP 185 PG 2 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700623 ER PT J AU Case, CJ Strauss, J Nicolson, R Hommer, D Weinberger, DR Egan, MF AF Case, CJ Strauss, J Nicolson, R Hommer, D Weinberger, DR Egan, MF TI Relative risk estimates of eye-tracking dysfunction in siblings of patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 213 EP 213 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700721 ER PT J AU Marenco, S Schreurs, BG Weinberger, DR AF Marenco, S Schreurs, BG Weinberger, DR TI Classical eyeblink conditioning (EC) in schizophrenia (SZ) SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 216 EP 216 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700734 ER PT J AU Fenton, WS Dickerson, FB Boronow, JJ Hibbeln, J Agrawal, R Sims, A Knable, MB AF Fenton, WS Dickerson, FB Boronow, JJ Hibbeln, J Agrawal, R Sims, A Knable, MB TI Placebo-controlled trial of omega-3 fatty acid in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 227 EP 227 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700769 ER PT J AU Apud, JA Wyatt, RJ Egan, MF AF Apud, JA Wyatt, RJ Egan, MF TI Neuroleptic withdrawal studies in treatment-resistent patients with schizophrenia: Tardive dyskinesia is not associated with supersensitivity psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, Intramural Res Program, Neuropsychiat Branch, 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 15 PY 2001 VL 49 IS 1-2 SU S SI SI BP 280 EP 280 PG 1 WC Psychiatry SC Psychiatry GA 427NG UT WOS:000168411700950 ER PT J AU Aeschbach, D Sher, L Postolache, TT Matthews, JR Jackson, MA Wehr, TA AF Aeschbach, D Sher, L Postolache, TT Matthews, JR Jackson, MA Wehr, TA TI A longer biological night in long sleepers than in short sleepers SO SLEEP LA English DT Meeting Abstract C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 8 BP A6 EP A6 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900010 ER PT J AU Larkin, EK Foley, D Masaki, K Romaniuk, J Arnold, J Surovec, S Redline, S AF Larkin, EK Foley, D Masaki, K Romaniuk, J Arnold, J Surovec, S Redline, S TI Variation of sleep architecture with sleep disordered breathing (SDB) in very old Japanese-American men SO SLEEP LA English DT Meeting Abstract C1 Case Western Reserve Univ, Sch Med, Dept Pediat, Div Clin Epidemiol, Cleveland, OH 44106 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Hawaii, Sch Med, Geriatr Med Program, Kuakini Med Ctr,Honolulu Heart Program, Honolulu, HI 96822 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 390 BP A229 EP A229 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900391 ER PT J AU Sanchez-Alavez, M Huitron-Resendiz, S Stobbs, SH Berg, G Gutierrez, T Gallegos, R Chesebro, B Oldstone, MB Criado, JR Henriksen, SJ AF Sanchez-Alavez, M Huitron-Resendiz, S Stobbs, SH Berg, G Gutierrez, T Gallegos, R Chesebro, B Oldstone, MB Criado, JR Henriksen, SJ TI Contributions of neuronal and glial PrP to the sleep/wake cycle SO SLEEP LA English DT Meeting Abstract ID EXPRESSION; MICE C1 Scripps Res Inst, La Jolla, CA 92037 USA. NIH, Rocky Mtn Labs, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 253 BP A152 EP A152 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900255 ER PT J AU Vgontzas, AN Papanicolaou, DA Zoumakis, M Bixler, EO Prolo, P Lin, HM Vela-Bueno, A Kales, A Chrousos, GP AF Vgontzas, AN Papanicolaou, DA Zoumakis, M Bixler, EO Prolo, P Lin, HM Vela-Bueno, A Kales, A Chrousos, GP TI Insomnia is associated with altered circadian interleukin-6 and TNF alpha secretion SO SLEEP LA English DT Meeting Abstract C1 Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, Hershey, PA USA. NIH, Pediat & Reprod Endocrinol Branch, NICHHD, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Penn State Univ, Coll Med, Hershey, PA USA. Autonomous Univ Madrid, Dept Psychiat, E-28049 Madrid, Spain. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD APR 15 PY 2001 VL 24 SU S MA 600 BP A342 EP A342 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424KF UT WOS:000168230900598 ER PT J AU Zheng, G AF Zheng, G TI A characterization of the factorization of hazard function by the Fisher information under Type II censoring with application to the Weibull family SO STATISTICS & PROBABILITY LETTERS LA English DT Article DE asymptotic Fisher information; hazard function; order statistics; Type II censored data; Weibull distribution AB Expressing the asymptotic Fisher information in Type II censored data in terms of the hazard function, we show that the factorization of the hazard function can be characterized by the linear property of the Fisher information under Type II censoring. Applying the result to the class of scale parameter families of lifetime distributions, we characterize the Weibull family by the Fisher information in Type II censored data and by the factorization of the hazard function. Published by Elsevier Science B.V. C1 NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. NR 11 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7152 J9 STAT PROBABIL LETT JI Stat. Probab. Lett. PD APR 15 PY 2001 VL 52 IS 3 BP 249 EP 253 DI 10.1016/S0167-7152(00)00198-X PG 5 WC Statistics & Probability SC Mathematics GA 427JK UT WOS:000168400900004 ER PT J AU Csizmadia, V Gao, W Hancock, SA Rottman, JB Wu, ZH Turka, LA Siebenlist, U Hancock, WW AF Csizmadia, V Gao, W Hancock, SA Rottman, JB Wu, ZH Turka, LA Siebenlist, U Hancock, WW TI Differential NF-kappa B and I kappa B gene expression during development of cardiac allograft rejection versus CD154 monoclonal antibody-induced tolerance SO TRANSPLANTATION LA English DT Article ID GERMINAL CENTER REACTIONS; T-LYMPHOCYTES; CD40 LIGAND; SPLENIC MICROARCHITECTURE; TRANSCRIPTION FACTORS; SIGNALING MOLECULE; IMMUNE-RESPONSES; ACTIVATION; PROTEINS; SUBUNIT AB Background The Rel/NF-kappaB transcription factor pathway, regulated by I kappaB proteins, is considered central to immune responses, although there are surprisingly few in vivo data concerning alloresponses. Methods, We undertook analysis of NF-kappaB and I kappaB mRNA intracardiac allograft expression, and NF-kappaB nuclear translocation, during acute rejection versus CD154 monoclonal antibody (mAb)-induced tolerance induction in fully MHC-disparate mice. Results. Intragraft expression of all nine NF-kappaB and I kappaB genes increased during development of rejection, and nuclear translocation of p50, p52, and p65 was detected. CD154 mAb therapy decreased mRNA levels of all nine NF-kappaB and I kappaB genes, and impaired nuclear translocation of p50, p52, and p65 NF-kappaB proteins. However, prolonged survival could not be induced by CD154 mAb in p50- or p52-deficient allograft recipients, indicating an absolute requirement for expression of these genes in CD154 mAb-induced tolerance. Conclusions, We conclude that, whereas blanket approaches to NF-kappaB suppression are unlikely to be effective strategies for tolerance induction, a better understanding of the roles of individual NF-kappaB and I kappaB genes may allow development of more precise and effective therapies. C1 Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Hancock, WW (reprint author), Millennium Pharmaceut Inc, 75 Sidney St, Cambridge, MA 02139 USA. FU NIAID NIH HHS [AI40152] NR 24 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2001 VL 71 IS 7 BP 835 EP 840 DI 10.1097/00007890-200104150-00003 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 429DN UT WOS:000168500900003 PM 11349713 ER PT J AU McCarron, P Okasha, M McEwen, J Smith, GD AF McCarron, P Okasha, M McEwen, J Smith, GD TI Changes in blood pressure among students attending Glasgow University between 1948 and 1968: analyses of cross sectional surveys SO BRITISH MEDICAL JOURNAL LA English DT Article ID BIRTH-WEIGHT; TRENDS; ADULTHOOD; MORTALITY; DISEASE AB Objectives To examine the changes in blood pressure over time in a cohort of young adults attending university between 1948 and 1968. Design Cross sectional study. Setting Glasgow University. Participants 12 414 students aged 16-25 years-9248 men (mean age 19.9 years) and 3164 women (19.2 years)-who participated in health screening on entering university between 1948 and 1968. Main outcome measures Systolic and diastolic blood pressure. Results in male students mean systolic blood pressure adjusted for age decreased from 134.5 (95% confidence interval 133.8 to 135.2) mm Hg in those born before 1929 to 125.7 (125.0 to 126.3) mm Hg in those born after 1945, and diastolic blood pressure dropped from 80.3 (79.8 to 80.8) mm Hg to 74.7 (74.2 to 75.1) nlm Hg. For female students the corresponding declines were from 129.0 (127.5 to 130.5) mm Hg to 120.6 (119.8 to 121.4) mm Hg and from 79.7 78.7 to 80.6) mm Hg to 77.0 (76.5 to 77.5) mm Hg. Adjustment for potential confounding factors made little difference to these findings. The proportion of students with hypertension declined substantially in both sexes. Conclusions Substantial declines in systolic and diastolic blood pressure over time were occurring up to 50 years ago in young adults who were not taking antihypertensive medication. Since blood pressure tracks into adult life, the results of the cross sectional comparisons suggest that factors acting in early life may be important in determining population risk of cardiovascular disease. Changes in such factors may have made important contributions to the decline in rates of cardiovascular diseases, particularly stroke, seen in developed countries during the past century. C1 NCI, Surveillance Res Program, Div Canc Control & Populat, Bethesda, MD 20892 USA. Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. Univ Glasgow, Dept Publ Hlth, Glasgow G12 8RZ, Lanark, Scotland. RP McCarron, P (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat, 6130 Execut Blvd,Execut Plaza N,Suite 4097, Bethesda, MD 20892 USA. OI Monsalve, Beatriz Elena/0000-0002-5994-866X; Davey Smith, George/0000-0002-1407-8314 NR 26 TC 36 Z9 38 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD APR 14 PY 2001 VL 322 IS 7291 BP 885 EP 888 DI 10.1136/bmj.322.7291.885 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 425VA UT WOS:000168311300015 PM 11302898 ER PT J AU Gray, RH Wawer, MJ Brookmeyer, R Sewankambo, NK Serwadda, D Wabwire-Mangen, F Lutalo, T Li, XB vanCott, T Quinn, TC AF Gray, RH Wawer, MJ Brookmeyer, R Sewankambo, NK Serwadda, D Wabwire-Mangen, F Lutalo, T Li, XB vanCott, T Quinn, TC CA Rakal Project Team TI Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUAL TRANSMISSION; TYPE-1; FEMALE; RELIABILITY; BEHAVIORS; PARTNERS; AFRICA; AIDS AB Background The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various factors thought to influence infectivity. Methods 174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively, HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners. Results The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were 0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-l-positive partner. Interpretation Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Med, Baltimore, MD 21205 USA. Columbia Univ, Heilbrun Ctr Populat & Family Hlth, Joseph L Mailman Sch Publ Hlth, New York, NY USA. Makerere Univ, Dept Med, Kampala, Uganda. Makerere Univ, Clin Epidemiol Unit, Kampala, Uganda. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Uganda Virus Res Inst, Rakai Project, Entebbe, Uganda. Walter Reed Army Inst Res, Rockville, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Suite 4030,615 N Wolfe St, Baltimore, MD 21205 USA. RI Quinn, Thomas/A-2494-2010; OI Sewankambo, Nelson/0000-0001-9362-053X FU FIC NIH HHS [D43 TW001508, 5D43TW00010]; NIAID NIH HHS [R01 AI3426S, R01 AI34826]; NICHD NIH HHS [5P30HD06826] NR 28 TC 800 Z9 820 U1 2 U2 34 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 14 PY 2001 VL 357 IS 9263 BP 1149 EP 1153 DI 10.1016/S0140-6736(00)04331-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 423RX UT WOS:000168192100008 PM 11323041 ER PT J AU Yamashita, TE Phair, JP Munoz, A Margolick, JB Detels, R O'Brien, SJ Mellors, JW Wolinsky, SM Jacobson, LP AF Yamashita, TE Phair, JP Munoz, A Margolick, JB Detels, R O'Brien, SJ Mellors, JW Wolinsky, SM Jacobson, LP TI Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study SO AIDS LA English DT Article DE HIV-1; highly active antiretroviral therapy; prior antiretroviral experience; genetic markers; immunologic response; virologic response ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; HEPATITIS-C VIRUS; DISEASE PROGRESSION; HOMOSEXUAL MEN; CLINICAL PROGRESSION; CELL COUNTS; VIRAL LOAD; CCR5; LYMPHOCYTES AB Objectives: To evaluate prior antiretroviral therapy experience and host characteristics as determinants of immunologic and virologic response to highly active antiretroviral therapy (HAART). Methods: We studied 397 men from the Multicenter AIDS Cohort Study (MACS) who initiated HAART between October 1995 and March 1999. CD4 cell count and HIV-1 RNA responses to HAART were measured at the first visit following HAART (shortterm) and extending from the first visit to approximately 33 months after HAART (longterm). Prior antiretroviral experience was classified into three groups based on antiretroviral therapy use during the 5 years prior to HAART. Age, race and host genetic characteristics also were assessed for their effects on treatment response. Results: Better short- and long-term CD4 cell and HIV-1 RNA responses were observed in the treatment-naive users. Intermittently and consistently experienced users did not significantly differ in response. Whereas race did not independently affect response, among those initiating HAART with > 400 x 10(6) CD4 cells/l, younger age and the Delta 32 CCR5 genotype were associated with a better short-term CD4 cell response. There was a suggestion that having the protective CCR5 genotype also was associated with a better long-term CD4 cell response. Conclusion: Immunologic and virologic response to HAART was stronger in individuals who had no prior experience with the antiretroviral therapy agents subsequently included in their initial HAART regimen. Age, level of immune competence and immunogenetics appeared to play a role in the subsequent immune reconstitution Following use of highly effective HIV therapy. (C) 2001 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Univ Pittsburgh, Pittsburgh, PA USA. Vet Affairs Med Ctr, Pittsburgh, PA USA. RP Jacobson, LP (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E7006, Baltimore, MD 21205 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NCRR NIH HHS [5-MO1-RR-00722]; NIAID NIH HHS [UO1-AI-37984, UO1-AI--35042, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35043, UO1-AI-37613] NR 42 TC 125 Z9 128 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 13 PY 2001 VL 15 IS 6 BP 735 EP 746 DI 10.1097/00002030-200104130-00009 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 428NF UT WOS:000168467200009 PM 11371688 ER PT J AU Lanier, ER Sturge, G McClernon, D Brown, S Halman, M Sacktor, N McArthur, J Atkinson, JH Clifford, D Price, RW Simpson, D Torres, G Catalan, J Marder, K Power, C Hall, C Romero, C Brew, B AF Lanier, ER Sturge, G McClernon, D Brown, S Halman, M Sacktor, N McArthur, J Atkinson, JH Clifford, D Price, RW Simpson, D Torres, G Catalan, J Marder, K Power, C Hall, C Romero, C Brew, B TI HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir SO AIDS LA English DT Article DE HIV-1; reverse transcriptase; genotype; cerebrospinal fluid; HIV-1; RNA; abacavir ID HUMAN-IMMUNODEFICIENCY-VIRUS; CARBOVIR; 1592U89; TYPE-1 AB Objective: To assess HIV-1 RNA levels and the relationship between HIV-1 reverse transcriptase (RT) genotype from plasma and cerebrospinal fluid (CSF) during treat ment with abacavir (Ziagen, ABC) or placebo in combination with stable background therapy (SBG) in subjects with AIDS dementia complex (ADC) (study CNA3001). Design: One-hundred and five HIV-1 infected adults with ADC were randomized to receive either ABC (600 mg twice daily) or ABC-matched placebo (twice daily) in addition to SBG for 12 weeks. Methods: Plasma and CSF were collected for population sequencing at baseline and week 12 (CSF optional). Sequences were analyzed for mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI). Results: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequence data harbored virus with greater than or equal to1 NRTI-associated mutations; 50 out of 67 had the M184V mutation. At week 12, more subjects in the ABC group had plasma HIV-1 RNA less than or equal to 400 copies/ml than the SBG group (46% versus 13%, P= 0.002). Non-response to ABC was associated with multiple baseline zidovudine (ZDV)/stavudine (d4T)-associated mutations. Baseline RT mutation patterns differed in 14 out of 21 (67%) paired samples from plasma and CSF. Four subjects experienced >1 log(10)copies/ml reductions in CSF HIV-1 RNA, two in the absence of reductions in plasma HIV-1 RNA and two With undetectable plasma HIV-1 RNA at baseline. Conclusions: Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appear to be discordant between CSF and plasma in some subjects. (C) 2001 Lippincott Williams & Wilkins. C1 Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NIAID, TRP, DAIDS, NIH, Bethesda, MD 20892 USA. AIDS Res Alliance, W Hollywood, CA USA. St Michaels Hosp, Dept Psychiat, Toronto, ON M5B 1W8, Canada. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. HIV Neurobehav Res Ctr, San Diego, CA USA. Washington Univ, Med Ctr, Dept Neurol, St Louis, MO USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. St Vincents Hosp, New York, NY USA. Univ London Imperial Coll Sci Technol & Med, Psychol Med Unit, London, England. Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. Univ Manitoba, Fac Med, Neurol Sect, Winnipeg, MB, Canada. Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. Glaxo Wellcome, Dept Clin Res, Madrid, Spain. St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia. St Vincents Hosp, Natl Ctr HIV Epidemiol & Clin Res, Ctr Immunol, Sydney, NSW 2010, Australia. RP Lanier, ER (reprint author), Glaxo Wellcome Inc, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. RI Power, Christopher/C-7181-2013; Brew, Bruce/J-6513-2012; OI Power, Christopher/0000-0002-5131-9711 NR 8 TC 40 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 13 PY 2001 VL 15 IS 6 BP 747 EP 751 DI 10.1097/00002030-200104130-00010 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 428NF UT WOS:000168467200010 PM 11371689 ER PT J AU Mziaut, H Korza, G Elkahloun, AG Ozols, J AF Mziaut, H Korza, G Elkahloun, AG Ozols, J TI Induction of stearoyl CoA desaturase is associated with high-level induction of emerin RNA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE desaturase; emerin; microarrays; sterol induction; SREBP; muscular dystrophy; membrane proteins ID DREIFUSS MUSCULAR-DYSTROPHY; ELEMENT-BINDING PROTEINS; MEMBRANE; TRANSCRIPTION; DEGRADATION; IDENTIFICATION; CHOLESTEROL; EXPRESSION; CLEAVAGE; PATHWAY AB The genes encoding enzymes involved in fatty acid metabolism are regulated by sterols. Stearoyl CoA desaturase, a key enzyme in the synthesis of unsaturated fatty acyl-CoAs is transcriptionally regulated by fat-free diet and sterols. To identify other genes that are induced in rat liver by fat-free diet we performed an in vivo gene expression profile analysis using DNA microarrays. Here we report; that among the genes highly expressed is emerin, an integral protein of the inner nuclear membrane. Mutated or nonexpressed emerin occurs in patients with muscular dystrophy. Sterol regulatory element binding proteins activate the transcription of several sterol regulated genes. To investigate whether sterol regulatory element binding proteins or indirectly cholesterol activates the transcription of stearoyl CoA desaturase and emerin, we cultured Chinese hamster ovary (CHO), either in cholesterol-rich or cholesterol-depleted mediums. We also transiently transfected the cell culture with plasmid encoding sterol regulatory element binding proteins in cholesterol-rich medium. Our data show that cholesterol-supplemented media as well, as the transient transfection induced the expression of stearoyl CoA desaturase RNA 3.5- and 7-fold respectively. However, the RNA level of emerin was not altered under these conditions, implying that the parallel induction of emerin is independent of the sterol regulatory element binding regulation pathway. (C) 2001 Academic Press. C1 Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06030 USA. NIH, Bethesda, MD 20892 USA. RP Ozols, J (reprint author), Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06030 USA. FU NIGMS NIH HHS [R01 GM-26351] NR 26 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC 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 APR 13 PY 2001 VL 282 IS 4 BP 910 EP 915 DI 10.1006/bbrc.2001.4658 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 424XC UT WOS:000168258400010 PM 11352637 ER PT J AU Tani, K Murphy, WJ Chertov, O Oppenheim, JJ Wang, JM AF Tani, K Murphy, WJ Chertov, O Oppenheim, JJ Wang, JM TI The neutrophil granule protein cathepsin G activates murine T lymphocytes and upregulates antigen-specific Ig production in mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cathepsin G; T cell; antibody; adjuvant ID DELAYED-TYPE HYPERSENSITIVITY; HUMORAL IMMUNE-RESPONSES; RED-BLOOD-CELLS; MONOCLONAL-ANTIBODY; ESSENTIAL INVOLVEMENT; SELECTIVE DEPLETION; COLORIMETRIC ASSAY; INTERLEUKIN-8 IL-8; RP-3 TREATMENT; IN-VIVO AB Cathepsin G is a neutrophil granule derived antimicrobial chymotrypsin-like enzyme. Our previous study showed that cathepsin G:induces chemotactic migration of human phagocytic leukocytes and increases random migration of T lymphocytes. In this study, we investigated the capacity of cathepsin G to activate T lymphocytes and to modulate antigen-specific humoral responses in mice, We found that cathepsin G is mitogenic for and induces production of IFN-gamma by murine T cells in vitro. Injection of cathepsin G in BALB/c mice immunized with keyhole limpet hemocyanin (KLH) adsorbed to aluminum hydroxide resulted in a significantly increased production of KLH-specific IgG1 and IgG2a antibodies. There was a dose-dependent increase in KLH-specific proliferation of lymphocytes from draining lymph nodes from mice treated with KLH and cathepsin G when compared with those treated with KLH alone. Subsequent analysis of IFN-gamma and IL-4 release following in vitro restimulation of draining lymph node lymphocytes obtained from KLH-immunized mice suggested that cathepsin G augments KLH-specific Ig antibody production via activation of T cells, presumably involving both Th1 and Th2 pathways. Thus, neutrophil granule cathepsin G, in addition to its capacity to kill microbes and to enhance leukocyte motility, activates T lymphocytes and modulates humoral immunity. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Mol Immunoregulat, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Mol Immunoregulat, SAIC Frederick, Bldg 560,Room 21-89A, Frederick, MD 21702 USA. NR 34 TC 20 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC 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 APR 13 PY 2001 VL 282 IS 4 BP 971 EP 976 DI 10.1006/bbrc.2001.4676 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 424XC UT WOS:000168258400020 PM 11352647 ER PT J AU Zhang, T Caffrey, JJ Shears, SB AF Zhang, T Caffrey, JJ Shears, SB TI The transcriptional regulator, Arg82, is a hybrid kinase with both monophosphoinositol and diphosphoinositol polyphosphate synthase activity SO FEBS LETTERS LA English DT Article DE inositol 1.3.4.5-tetrakisphosphate; inositol polyphosphate multikinase; Arg82; inositol pyrophosphate; yeast ID INOSITOL HEXAKISPHOSPHATE KINASE; MESSENGER-RNA EXPORT; SACCHAROMYCES-CEREVISIAE; ARGININE METABOLISM; SCHIZOSACCHAROMYCES-POMBE; FAMILY; YEAST; PHOSPHOHYDROLASE; EXPRESSION; TURNOVER AB The Arg82 gene of Saccharomyces cerevisiae encodes a transcriptional regulator that phosphorylates inositol 1,4,5-trisphosphate [Saiardi et al, (1999) Curr, Biol, 9, 1323-1326]. However, some controversy has surrounded the nature of the reaction products. We now show that Arg82 phosphorylates inositol 1,3,4,5-tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two isomers of diphosphoinositol tetrakisphosphate, one of which has never previously been identified. One of the diphosphoinositol phosphates was further phosphorylated by a yeast cell lysate, We propose that Arg82 is an ancestral precursor of two distinct and specific enzyme families: inositol 1,4,5-trisphosphate kinases and diphosphoinositol polyphosphate synthases, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B,V, ALL rights reserved. C1 NIEHS, Lab Signal Transduct, Inositide Signaling Sect, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, Lab Signal Transduct, Inositide Signaling Sect, Res Triangle Pk, NC 27709 USA. NR 25 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 13 PY 2001 VL 494 IS 3 BP 208 EP 212 DI 10.1016/S0014-5793(01)02351-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 424GE UT WOS:000168223800015 PM 11311242 ER PT J AU Anantharaman, V Koonin, EV Aravind, L AF Anantharaman, V Koonin, EV Aravind, L TI TRAM, a predicted RNA-binding domain, common to tRNA uracil methylation and adenine thiolation enzymes SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE TRAM; TRM2; MiaB; RNA-binding domain; 2-methylthioadenine; biotin/lipoate synthase; sulfur insertion ID ESCHERICHIA-COLI; BIOTIN SYNTHASE; RIBOSOMAL-RNA; PSI-BLAST; PROTEIN; IDENTIFICATION; SEQUENCE; GENE; METHYLTRANSFERASE; 4-THIOURIDINE AB A previously undetected conserved domain is identified in two distinct classes of tRNA-modifying enzymes, namely uridine methylases of the TRM2 family and enzymes of the MiaB family that are involved in 2-methylthioadenine formation. This domain, for which the acronym TRAM is proposed after TRM2 and MiaB, is predicted to bind tRNA and deliver the RNA-modifying enzymatic domains to their targets. In addition to the two families of RNA-modifying enzymes. the TRAM domain is present in several other proteins associated with the translation machinery and in a family of small, uncharacterized archaeal proteins that are predicted to have a role in the regulation of tRNA modification or translation. Secondary structure prediction indicates that the TRAM domain adopts a simple beta -barrel fold. In addition. sequence analysis of the MiaB family enzymes showed that they share the predicted catalytic site with biotin and lipoate synthases and probably employ the same mechanism for sulfur insertion into their respective substrate. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 NR 27 TC 37 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD APR 13 PY 2001 VL 197 IS 2 BP 215 EP 221 DI 10.1111/j.1574-6968.2001.tb10606.x PG 7 WC Microbiology SC Microbiology GA 427GK UT WOS:000168396300013 PM 11313137 ER PT J AU Zanassi, P Paolillo, M Feliciello, A Avvedimento, EV Gallo, V Schinelli, S AF Zanassi, P Paolillo, M Feliciello, A Avvedimento, EV Gallo, V Schinelli, S TI cAMP-dependent protein kinase induces cAMP-response element-binding protein phosphorylation via an intracellular calcium release/ERK-dependent pathway in striatal neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; C-FOS TRANSCRIPTION; MAP KINASE; CYCLIC-AMP; B-RAF; MEMBRANE DEPOLARIZATION; CREB PHOSPHORYLATION; RYANODINE RECEPTOR; GENE-EXPRESSION; ACTIVATION AB Activation of the cAMP dependent protein kinase A (PKA) pathway may induce cAMP-response element-binding protein (CREB) phosphorylation either directly or via cross-talk mechanisms with other signal transduction pathways. In this study, we have investigated in striatal primary cultures the mechanism by which activation of the cAMP/PKA-dependent pathway leads to CREB phosphorylation via the extracellular signal-regulated kinase (ERK) dependent pathway. We have found that PKA-induced CREB phosphorylation and CREB-dependent transcription are mediated by calcium (Ca2+) release from intracellular stores and are blocked by inhibitors of the protein kinase C and ERK pathways. This mechanism appears to be mediated by the small G-protein Rap1, whose activation appears to be primed by PKA-induced Ca2+ release but not further induced by direct or indirect PKA- or protein kinase C-dependent phosphorylation. These results suggest that, in striatal neurons, intracellular Ca2+ release, Rap1, and ERK pathway play a crucial role in the PKA induced CREB phosphorylation and CREB-dependent transcription. C1 Univ Pavia, Fac Farm, Dipartimento Farmacol Sperimentale & Applicata, I-27100 Pavia, Italy. CNR, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy. Univ Catanzaro, Fac Med Catanzaro, Dipartimento Med Sperimentale, I-88100 Catanzaro, Italy. NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Schinelli, S (reprint author), Univ Pavia, Fac Farm, Dipartimento Farmacol Sperimentale & Applicata, 14 Viale Taramelli, I-27100 Pavia, Italy. RI Paolillo, Mayra/N-2615-2015; OI Paolillo, Mayra/0000-0002-7751-3336; Feliciello, Antonio/0000-0002-7932-2170 NR 38 TC 111 Z9 111 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 11487 EP 11495 DI 10.1074/jbc.M007631200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800010 PM 11139572 ER PT J AU Ionescu, AM Schwarz, EM Vinson, C Puzas, JE Rosier, R Reynolds, PR O'Keefe, RJ AF Ionescu, AM Schwarz, EM Vinson, C Puzas, JE Rosier, R Reynolds, PR O'Keefe, RJ TI PTHrP modulates chondrocyte differentiation through AP-1 and CREB signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-RELATED PEPTIDE; GROWTH-PLATE CHONDROCYTES; ENDOCHONDRAL BONE-FORMATION; ELEMENT-BINDING PROTEIN; C-FOS EXPRESSION; PARATHYROID-HORMONE; CYCLIC-AMP; OSTEOBLASTIC CELLS; HYPERTROPHIC CHONDROCYTES; TRANSGENIC MICE AB During the process of differentiation, chondrocytes integrate a complex array of signals from local or systemic factors like parathyroid hormone-related peptide (PTHrP), Indian hedgehog, bone morphogenetic proteins and transforming growth factor beta, While PTHrP is known to be a critical regulator of chondrocyte proliferation and differentiation, the signaling pathways through which this factor acts remain to be elucidated. Here we show that both cAMP response element-binding protein (CREB) and AP-1 activation are critical to PTHrP signaling in chondrocytes. PTHrP treatment leads to rapid CREB phosphorylation and activation, while CREB DNA binding activity is constitutive, In contrast, PTHrP induces AP-1 DNA binding activity through induction of c-Fos protein expression. PTHrP activates CRE and TRE reporter constructs primarily through PKA-mediated signaling events. Both signaling pathways were found to be important mediators of PTHrP effects on chondrocyte phenotype, Alone, PTHrP suppresses maturation and stimulates proliferation of the chondrocyte cultures, However, in the presence of dominant negative inhibitors of CREB and c-Fos, these PTHrP effects were suppressed, and chondrocyte maturation was accelerated. Moreover, in combination, the effects of dominant negative c-Fos and CREB are synergistic, suggesting interaction between these signaling pathways during chondrocyte differentiation. C1 Univ Rochester, Med Ctr, Sch Med & Dent, Dept Orthopaed, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. NCI, NIH, Bethesda, MD 20892 USA. RP O'Keefe, RJ (reprint author), Univ Rochester, Med Ctr, Sch Med & Dent, Dept Orthopaed, Box 665,601 Elmwood Ave, Rochester, NY 14642 USA. FU NIAMS NIH HHS [R01 AR 38945] NR 60 TC 83 Z9 86 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 11639 EP 11647 DI 10.1074/jbc.M006564200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800031 PM 11136722 ER PT J AU Sauna, ZE Ambudkar, SV AF Sauna, ZE Ambudkar, SV TI Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein - The two ATP hydrolysis events in a single catalytic cycle are kinetically similar but affect different functional outcomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE PROTEIN; HAMSTER OVARY CELLS; CRYSTAL-STRUCTURE; TRANSITION-STATE; WALKER-A; NUCLEOTIDE; SITES; BINDING; PURIFICATION; TRANSPORTER AB P-glycoprotein (Pgp) is a plasma membrane protein whose overexpression confers multidrug resistance to tumor cells by extruding amphipathic natural product cytotoxic drugs using the energy of ATP, An elucidation of the catalytic cycle of Pgp would help design rational strategies to combat multidrug resistance and to further our understanding of the mechanism of ATP-binding cassette transporters. We have recently reported (Sauna, Z, E,, and Ambudkar, S, V. (2000) Proc. Natl, Acad Sci, U.S.A. 97, 2515-2520) that there are two independent ATP hydrolysis events in a single catalytic cycle of Pgp, In this study we exploit the vanadate (Vi)induced transition state conformation of Pgp (Pgp ADP Vi) to address the question of what are the effects of ATP hydrolysis on the nucleotide-binding site, We find that at the end of the first hydrolysis event there is a drastic decrease in the affinity of nucleotide for Pgp coincident with decreased substrate binding. Release of occluded dinucleotide is adequate for the next hydrolysis event to occur but is not sufficient for the recovery of substrate binding. Whereas the two hydrolysis events have different functional outcomes vis a vis the substrate, they show comparable t(1/2), for both incorporation and release of nucleotide, and the affinities for [alpha-P-32]8-azido-ATP during Vi induced trapping are identical. In addition, the incorporation of [alpha-P-32]8-azido-ADP in two ATP sites during both hydrolysis events is also similar. These data demonstrate that during individual hydrolysis events, the ATP sites are recruited in a random manner, and only one site is utilized at any given time because of the conformational change in the catalytic site that drastically reduces the affinity of the second ATP site for nucleotide binding. In aggregate, these findings provide an explanation for the alternate catalysis of ATP hydrolysis and offer a mechanistic framework to elucidate events at both the substrate- and nucleotide-binding sites in the catalytic cycle of Pgp. C1 NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Div Basic Sci, NIH, Bldg 37,Rm 1B-22,37 Convent Dr, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 41 TC 128 Z9 129 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 11653 EP 11661 DI 10.1074/jbc.M011294200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800033 PM 11154703 ER PT J AU Dupuy, AJ Morgan, K von Lintig, FC Shen, HF Acar, H Hasz, DE Jenkins, NA Copeland, NG Boss, GR Largaespada, DA AF Dupuy, AJ Morgan, K von Lintig, FC Shen, HF Acar, H Hasz, DE Jenkins, NA Copeland, NG Boss, GR Largaespada, DA TI Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in BXH-2 murine myeloid leukemia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; R-RAS; CELLULAR-TRANSFORMATION; SIGNALING PATHWAY; INTEGRATION SITE; MEMBRANE-PROTEIN; NIH3T3 CELLS; MAP KINASE; PRODUCT; TC21 AB Here we report the recurrent proviral activation of the Rap1-specific guanine nucleotide exchange factor CalDAG-GEF I (Kawasaki, H., Springett, G. M., Toki, S., Canales, J. J., Harlan, P., Blumenstiel, J. P., Chen, E. J., Bany, I. A., Mochizuki, N., Ashbacher, A., Matsuda, M., Housman, D. E., and Graybiel, A. M. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 13288-13283; Correction (1999) Proc. Natl. Acad Sci. U.S.A. 96, 318) gene in BXH-2 acute myeloid leukemia. We also show that CalDAG-GEF I encodes two protein isoforms, a full-length isoform (CalDAG-GEF Ia) and a C-terminally truncated isoform (CalDAG-GEF Ib). Expression of the full-length CalDAG-GEF la isoform in Rat2 fibroblasts enhances growth in low serum, whereas expression in Swiss 3T3 cells causes morphological transformation and increased saturation density. In FDCP1 myeloid cells, CalDAG-GEF Pa expression increases growth and saturation density in the presence of the diacylglycerol analogs phorbol 12-myristate 13-acetate (PMA), which activates CalDAG-GEF Pa exchange activity. Likewise, in 32DcI3 myeloblast cells, CalDAG-GEF Ia expression increases cell adherence to fibronectin in response to PMA and calcium ionophore and allows higher saturation densities and prolonged growth on fibronectin-coated plates. These effects were correlated with increased Rap1, but not Ras, protein activation following PMA. and calcium ionophore treatment. Our results suggest that Rap1-GTP delivers signals that favor progression through the cell cycle and morphological transformation, The identification of CalDAG-GEF I as a proto-oncogene in BXH-2 acute myeloid leukemia is the first evidence implicating Rap1 signaling in myeloid leukemia. C1 Univ Minnesota, Ctr Canc, Inst Human Genet, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Largaespada, DA (reprint author), Univ Minnesota, Ctr Canc, Inst Human Genet, Minneapolis, MN 55455 USA. RI Largaespada, David/C-9832-2014 NR 65 TC 54 Z9 56 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 11804 EP 11811 DI 10.1074/jbc.M008970200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800052 PM 11278453 ER PT J AU Pio, R Martinez, A Unsworth, EJ Kowalak, JA Bengoechea, JA Zipfel, PF Elsasser, TH Cuttitta, F AF Pio, R Martinez, A Unsworth, EJ Kowalak, JA Bengoechea, JA Zipfel, PF Elsasser, TH Cuttitta, F TI Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; IMMUNOREACTIVE ADRENOMEDULLIN; NEISSERIA-GONORRHOEAE; RHEUMATOID-ARTHRITIS; PLASMA-CONCENTRATION; HYPOTENSIVE PEPTIDE; FACTOR-I; IDENTIFICATION; EXPRESSION; RESISTANCE AB Adrenomedullin (AM) is an important regulatory peptide involved in both physiological and pathological states. We have previously demonstrated the existence of a specific AM-binding protein (AMBP-1) in human plasma. In the present study, we developed a nonradioactive ligand blotting assay, which, together with high pressure liquid chromatography/SDS-polyacrylamide gel electrophoresis purification techniques, allowed us to isolate AMBP-1 to homogeneity. The purified protein was identified as human complement factor H. We show that AM/factor H interaction interferes with the established methodology for quantification of circulating AM. Our data suggest that this routine procedure does not take into account the AM bound to its binding protein. In addition, we show that factor H affects AM in vitro functions. It enhances AM-mediated induction of cAMP in fibroblasts, augments the AM-mediated growth of a cancer cell line, and suppresses the bactericidal capability of AM on Escherichia coli. Reciprocally, AM influences the complement regulatory function of factor H by enhancing the cleavage of C3b via factor I. In summary, we report on a potentially new regulatory mechanism of AM biology, the influence of factor H on radioimmunoassay quantification of AM, and the possible involvement of AM as a regulator of the complement cascade. C1 NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Univ Turku, Dept Med Biochem, FIN-20520 Turku, Finland. Hans Knoell Inst Nat Prod Res, Dept Infect Biol, D-07745 Jena, Germany. ARS, Growth Biol Lab, USDA, Beltsville, MD 20705 USA. RP Pio, R (reprint author), NCI, Dept Cell & Canc Biol, NIH, Bldg 10 Rm 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017; OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111; Bengoechea, Jose/0000-0002-9677-8751 NR 56 TC 166 Z9 172 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 12292 EP 12300 DI 10.1074/jbc.M007822200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800114 PM 11116141 ER PT J AU Guan, E Wang, JH Norcross, MA AF Guan, E Wang, JH Norcross, MA TI Identification of human macrophage inflammatory proteins 1 alpha and 1 beta as a native secreted heterodimer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; BETA-CHEMOKINES; H-1-NMR SPECTROSCOPY; PLATELET FACTOR-4; CRYSTAL-STRUCTURE; NMR ASSIGNMENTS; CCR5 EXPRESSION; T-CELLS; RESOLUTION; DIMER AB Chemokines are secreted proteins that function as chemoattractants for leukocytes. The chemokines macrophage inflammatory protein 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) now have been shown to be secreted from activated human monocytes and peripheral blood lymphocytes (PBLs) as a heterodimer. Immunoprecipitation and immunoblot analysis revealed that antibodies to either MIP-1 alpha or MIP-1 beta precipitated a protein complex containing both MIP-1 alpha and MIP-1 beta under normal conditions from culture supernatants and lysates of these cells. Mass spectrometry of the complexes, precipitated from the culture supernatants of monocytes and PBLs, revealed the presence of NH2-terminal truncated MIP-1 alpha (residues 5-70) together with either intact MIP-1 beta or NH2-terminal truncated MIP-1 beta (residues 3-69), respectively. The secreted MIP-1 alpha/beta heterodimers were dissociated into their component monomers under acidic conditions. Exposure of monocytes or PBLs to monensin induced the accumulation of heterodimers composed of NH2-terminal truncated MTP-1 alpha and full-length MIP-1 beta in the Golgi complex. The mixing of recombinant chemokines in vitro demonstrated that heterodimerization of MIP-1 alpha and MIP-1 beta is specific and that it occurs at physiological conditions, pH 7.4, and in the range of nanomolar concentrations. The data presented here provide the first biochemical evidence for the existence of chemokine heterodimers under natural conditions. Formation of heterodimers of MIP-1 alpha/beta may have an impact on intracellular signaling events that contribute to CCR5 and possibly to other chemokine receptor functions. C1 NIH, Lab Gene Regulat, Div Therapeut Prot, Ctr Biol Evaluat & Res,US FDA,HFM 535, Bethesda, MD 20892 USA. RP Guan, E (reprint author), NIH, Lab Gene Regulat, Div Therapeut Prot, Ctr Biol Evaluat & Res,US FDA,HFM 535, Bldg 29B,Rm 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 43 Z9 43 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 12404 EP 12409 DI 10.1074/jbc.M006327200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800128 PM 11278300 ER PT J AU He, JY Cheung, AP Wang, E Fang, KX Liu, P AF He, JY Cheung, AP Wang, E Fang, KX Liu, P TI High-performance liquid chromatographic analysis for a nonchromophore-containing phosphatidyl inositol analog, 1-[(1-O-octadecyl-2-O-methyl-sn-glcero)-phospho]-1D-3-deoxy-myo-inositol , using indirect UV detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 24th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2000) CY JUN 24-30, 2000 CL SEATTLE, WA DE mobile phase composition; detection, LC; indirect detection; ion-pairing reagents; octadecymethylglyderophosphodeoxyinositol; enzyme inhibitors; protriptyline; butylparaben; phospholipids; phosphatidyl inositol ID REVERSED-PHASE CHROMATOGRAPHY; ION-PAIR CHROMATOGRAPHY; HYDROCARBONACEOUS STATIONARY PHASES; MOBILE-PHASE; RESPONSE MODELS; SEPARATION; PHOSPHOLIPIDS; SYSTEMS; RETENTION; CHOLINE AB Phosphatidylinosite-3-kinase (PI3 kinase) is an important constituent of growth factor regulation. It is also involved in oncogene signaling pathways. an ether-containing phosphatidyl inositol(PI) analog, OMDPI, 1-[(1-O-octadecyl-2-O-methyl-sn-glycero)-phospho]-1D-3-deosy-myo-inositol, , is a potent inhibitor of this pathway and may be clinically useful in the treatment of a variety of neoplasms, OMDPI is currently being investigated as an anti-tumor agent by the National Cancer Institute, NIH, OMDPI, a non-chromophore-containing PI analog, is not directly adaptable to the commonly used UV detection of HPLC. This paper reports the development and validation of an HPLC assay for OMDPI based on indirect UV detection, in which a UV-absorbing ion-pair reagent (the probe), protriptyline, is added to the mobile phase to induce a signal for the compound. The method is sensitive (limit of detection <5 l of 1 mug/ml or 5 ng), precise (R.S.D.<2.5%), linear (r(2)=0.9995) and accurate (error<0.07%). It is superior to refractive index detection and evaporative light scattering detection in either sensitivity or linearity and does not require special equipment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 SRI Int, Menlo Pk, CA 94025 USA. NCI, Pharmaceut Resources Branch, DCTD, NIH, Bethesda, MD 20892 USA. RP He, JY (reprint author), SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM jingyi.he@sri.com FU NCI NIH HHS [N01-CM-77104] NR 29 TC 3 Z9 3 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 13 PY 2001 VL 913 IS 1-2 BP 355 EP 363 DI 10.1016/S0021-9673(01)00603-3 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 423BT UT WOS:000168156100036 PM 11355833 ER PT J AU Anantharaman, V Koonin, EV Aravind, L AF Anantharaman, V Koonin, EV Aravind, L TI Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE small-molecule-binding domains; genome comparison; USPA; ATP cone; STAS ID PHOTOACTIVE YELLOW PROTEIN; IRON-MOLYBDENUM COFACTOR; ESCHERICHIA-COLI; RHODOBACTER-CAPSULATUS; STRUCTURAL GENOMICS; ANION TRANSPORTERS; BACILLUS-SUBTILIS; CRYSTAL-STRUCTURE; GAF DOMAIN; PAS DOMAIN AB Central cellular functions such as metabolism, solute transport and signal transduction are regulated, in part, via binding of small. molecules by specialized domains. Using sensitive methods for sequence profile analysis and protein structure comparison, we exhaustively surveyed the protein sets from completely sequenced genomes for all occurrences of 21 intracellular small-molecule-binding domains (SMBDs) that are represented in at least two of the three major divisions of life (bacteria, archaea and eukaryotes). These included previously characterized domains such as PAS, GAF, ACT and ferredoxins, as well as three newly predicted SMBDs, namely the 4-vinyl reductase (4VR) domain, the NIFX domain and the S-histidines (3H) domain. Although there are only a limited number of different superfamilies of these ancient SMBDs, they are present in numerous distinct proteins combined with various enzymatic, transport and signal-transducing domains. Most of the SMBDs show considerable evolutionary mobility and are involved in the generation of many lineage-specific domain architectures. Frequent re-invention of analogous architectures involving functionally related, but not homologous, domains was detected, such as, fusion of different SMBDs to several types of DNA-binding domains to form diverse transcription regulators in prokaryotes and eukaryotes. This is suggestive of similar selective forces affecting the diverse SMBDs and resulting in the formation of multidomain proteins that fit a limited number of functional stereotypes. Using the "guilt by association approach", the identification of SMBDs allowed prediction of functions and mode of regulation for a variety of previously uncharacterized proteins. (C) 2001 Academic Press. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 NR 79 TC 186 Z9 190 U1 1 U2 13 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 13 PY 2001 VL 307 IS 5 BP 1271 EP 1292 DI 10.1006/jmbi.2001.4508 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 427BY UT WOS:000168386000010 PM 11292341 ER PT J AU Jin, JP Perera, L Stafford, D Pedersen, L AF Jin, JP Perera, L Stafford, D Pedersen, L TI Four loops of the catalytic domain of factor VIIa mediate the effect of the first EGF-like domain substitution on factor VIIa catalytic activity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE blood coagulation factor; macromolecular simulation; tissue factor; structure-function study; domain substitution ID COAGULATION-FACTOR-VIIA; HUMAN-TISSUE FACTOR; MESH EWALD METHOD; CRYSTAL-STRUCTURE; BINDING-SITE; BOVINE TRYPSINOGEN; BLOOD-COAGULATION; SERINE PROTEASES; FACTOR-X; IDENTIFICATION AB presence of tissue factor is essential for factor VIIa (FVIIa) to reach its full catalytic potential. The previous work in this laboratory demonstrated that substitution of the EGF1 domain of factor VIIa with that of factor IX (FVII((IXegf1))a) results in a substantial decrease in TF-binding affinity and catalytic activity. Supporting simulations of the solution structures of Ca2+-bound factor VIIa and FVII((IXegf1))a with tissue factor are provided. Mutants are generated, based on the simulation model, to study the effect of EGF1 substitution on catalytic activity. The simulations show larger Gla-EGF1 and EGF1-EGF2 inter-domain motions for FVII((IXegf1))a than for factor VIIa. The catalytic domain of the chimeric factor VIIa has been disturbed and several surface loops in the catalytic domain of FVII((IXegf1))a (Loop 170s (170-182), Loop 1 (185-188) and Loop 2 (221A-225)) manifest larger position fluctuations than wild-type. The position of Loop 140s (142-152) of FVII((IXegf1))a, near the N terminus insertion site of the catalytic domain, shifts relative to factor VIIa, resulting in a slight alteration of the active site. The results suggest that these four loops mediate the effect of the EGF1 domain substitution on the SI site and catalytic residues. To test the model, we prepared mutations of these surface loops, including four FVII mutants, D186A, K188A, L144A and R147A, a FVII mutant with multiple mutations (MM3: L144A + R147A + D186A) and a FVII mutant with Loop 170s partially deleted, Loop 170s(del). The catalytic activities towards a small peptidyl substrate decreased 2.4, 4.5 and 9-fold for Loop 170s(del)a (a, activated), L144Aa and D186Aa, respectively, while MM3a lost almost all catalytic activity. The combined results of the simulations and mutants provide insight into the mechanism by which tissue factor enhances factor VIIa catalytic activity. (C) 2001 Academic Press. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Bioinformat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Pedersen, L (reprint author), Univ N Carolina, Dept Chem, CB 3280, Chapel Hill, NC 27599 USA. RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL 38973, HL 06350] NR 43 TC 12 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 13 PY 2001 VL 307 IS 5 BP 1503 EP 1517 DI 10.1006/jmbi.2001.4556 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 427BY UT WOS:000168386000025 PM 11292356 ER PT J AU Sequeira, E McEntyre, J Lipman, D AF Sequeira, E McEntyre, J Lipman, D TI PubMed central decentralized SO NATURE LA English DT Letter C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sequeira, E (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 1 Z9 3 U1 0 U2 0 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 12 PY 2001 VL 410 IS 6830 BP 740 EP 740 DI 10.1038/35071270 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 420TT UT WOS:000168021900016 PM 11298409 ER PT J AU Di Marzo, V Goparaju, SK Wang, L Liu, J Batkai, S Jarai, Z Fezza, F Miura, GI Palmiter, RD Sugiura, T Kunos, G AF Di Marzo, V Goparaju, SK Wang, L Liu, J Batkai, S Jarai, Z Fezza, F Miura, GI Palmiter, RD Sugiura, T Kunos, G TI Leptin-regulated endocannabinoids are involved in maintaining food intake SO NATURE LA English DT Article ID MELANIN-CONCENTRATING HORMONE; RECEPTOR MESSENGER-RNA; CANNABINOID-RECEPTOR; NEUROPEPTIDE-Y; RAT-BRAIN; MICE; CB1; HYPOTHALAMUS; ANTAGONIST; 2-ARACHIDONOYLGLYCEROL AB Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance(1). Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as a-melanocyte-stimulating hormone(2,3), and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y-4. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors(6), cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y-7. CB1 cannabinoid receptors(8) and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus(9), and marijuana(10) and anandamide(11,12) stimulate food intake. Here we show that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild-type but not knockout mice. Furthermore, defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin. C1 CNR, Ist Chim Mol Interesse Biol, Endocannabinoid Res Grp, I-80072 Arco Felice, Naples, Italy. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Teikyo Univ, Fac Pharmaceut Sci, Kanagawa 1990195, Japan. RP Kunos, G (reprint author), NIAAA, NIH, MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Goparaju, Sravan/H-3422-2011; Batkai, Sandor/H-7983-2014; OI Di Marzo, Vincenzo/0000-0002-1490-3070 NR 29 TC 916 Z9 951 U1 7 U2 39 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 12 PY 2001 VL 410 IS 6830 BP 822 EP 825 DI 10.1038/35071088 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 420TT UT WOS:000168021900057 PM 11298451 ER PT J AU Mork, J Lie, AK Glattre, E Clark, S Hallmans, G Jellum, E Koskela, P Moller, B Pukkala, E Schiller, JT Youngman, L Lehtinen, M Dillner, J AF Mork, J Lie, AK Glattre, E Clark, S Hallmans, G Jellum, E Koskela, P Moller, B Pukkala, E Schiller, JT Youngman, L Lehtinen, M Dillner, J TI Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ORAL-CANCER; TYPE-16; ASSOCIATION; TONSILLAR; WOMEN; HPV; PREVALENCE; PROTEINS; TOBACCO AB Background: Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. Methods: To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. Results: After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. Conclusions: HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck. (N Engl J Med 2001;344:1125-31.) Copyright (C) 2001 Massachusetts Medical Society. C1 Natl Hosp Norway, Dept Otolaryngol, N-0027 Oslo, Norway. Canc Registry Norway, Oslo, Norway. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. No Sweden Hlth & Dis Study, Umea, Sweden. Norwegian Canc Soc, Janus Comm, Oslo, Norway. Natl Publ Hlth Inst, Oulu, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Oxford, Clin Trial Serv Unit, Oxford, England. Univ Oxford, Epidemiol Studies Unit, Oxford, England. Natl Publ Hlth Inst, Helsinki, Finland. Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. RP Mork, J (reprint author), Natl Hosp Norway, Dept Otolaryngol, N-0027 Oslo, Norway. RI Moller, Bjorn/K-7152-2012 NR 42 TC 511 Z9 523 U1 1 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2001 VL 344 IS 15 BP 1125 EP 1131 DI 10.1056/NEJM200104123441503 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 420EC UT WOS:000167990600003 PM 11297703 ER PT J AU Paweletz, CP Charboneau, L Bichsel, VE Simone, NL Chen, T Gillespie, JW Emmert-Buck, MR Roth, MJ Petricoin, EF Liotta, LA AF Paweletz, CP Charboneau, L Bichsel, VE Simone, NL Chen, T Gillespie, JW Emmert-Buck, MR Roth, MJ Petricoin, EF Liotta, LA TI Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front SO ONCOGENE LA English DT Article DE laser capture microdissection; protein microarrays; apoptosis; Akt; mitogen activated protein kinase; tumor progression ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; GLYCOGEN-SYNTHASE KINASE-3; NERVE GROWTH-FACTOR; PROTEOMIC ANALYSIS; GENE-EXPRESSION; APOPTOSIS; AKT; IMMUNOASSAY; SPECIFICITY; ARRAYS AB Protein arrays are described for screening of molecular markers and pathway targets in patient matched human tissue during disease progression. In contrast to previous protein arrays that immobilize the probe, our reverse phase protein array immobilizes the whole repertoire of patient proteins that represent the state of individual tissue cell populations undergoing disease transitions. A high degree of sensitivity, precision and linearity was achieved, making it possible to quantify the phosphorylated status of signal proteins in human tissue cell subpopulations, Using this novel protein microarray we have longitudinally analysed the state of pro-survival checkpoint proteins at the microscopic transition stage from patient matched histologically normal prostate epithelium to prostate intraepithelial neoplasia (PIN) and then to invasive prostate cancer. Cancer progression was associated with increased phosphorylation of Akt (P < 0.04), suppression of apoptosis pathways (P < 0.03), as well as decreased phosphorylation of ERK (P < 0.01), At the transition from histologically normal epithelium to PIN we observed a statistically significant surge in phosphorylated Akt (P < 0.03) and a concomitant suppression of downstream apoptosis pathways which proceeds the transition into invasive carcinoma. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Tissue Prote Unit, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Delehanty, James/F-7454-2012 NR 39 TC 643 Z9 673 U1 5 U2 27 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 12 PY 2001 VL 20 IS 16 BP 1981 EP 1989 DI 10.1038/sj.onc.1204265 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 421CD UT WOS:000168043800006 PM 11360182 ER PT J AU Liu, ML Shibata, MA Von Lintig, FC Wang, WL Cassenaer, S Boss, GR Green, JE AF Liu, ML Shibata, MA Von Lintig, FC Wang, WL Cassenaer, S Boss, GR Green, JE TI Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice SO ONCOGENE LA English DT Article DE Ki-ras; mammary gland tumor; transgenic mice ID CELL-LINE; N-RAS; GENE; CARCINOMA; MOUSE; EXPRESSION; ONCOGENE; ADENOCARCINOMA; IDENTIFICATION; AMPLIFICATION AB We have previously demonstrated that amplification and overexpression of the Ki-ras gene is associated with mammary tumor progression in C3(1)/SV40Tag transgenic mice (Liu Et al,, 1998), To further evaluate the functional significance of the Ki-vas proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-vas gene dosage on tumor progression. The lack of one normal Ki-vas allele C3(1)/SV40Tag transgenic mice resulted in significantly delayed mammary intraepithelial neoplasia (MIN) formation as well as in a decreased number of mammary gland carcinomas, However, despite the retardation of tumor development by reduced Ki-ras gene dosage, overall survival was only modestly affected. This appears to be due to several factors including significant mammary tumor growth associated with Ki-ras gene amplification and over-expression that occurs during the advanced stage of oncogenesis in mice carrying either one or two normal Ki-ras alleles, The retardation of tumor progression due to the haploid loss of Ki-ras did not appear to be related to accelerated apoptosis, or a reduced rate of cell proliferation at the tumor stages examined. These data strongly suggest that the gene dosage of Ki-vas affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis. C1 NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 24 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 12 PY 2001 VL 20 IS 16 BP 2044 EP 2049 DI 10.1038/sj.onc.1204280 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 421CD UT WOS:000168043800012 PM 11360188 ER PT J AU Little, RF Gutierrez, M Jaffe, ES Pau, A Horne, M Wilson, W AF Little, RF Gutierrez, M Jaffe, ES Pau, A Horne, M Wilson, W TI HIV-associated non-Hodgkin lymphoma - Incidence, presentation, and prognosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; EPSTEIN-BARR-VIRUS; LYMPHOPROLIFERATIVE DISORDERS; INTENSIVE CHEMOTHERAPY; DRUG-INTERACTIONS; AIDS; INFECTION; SURVIVAL; CLASSIFICATION AB Patients with acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin lymphoma often present with multiple poor prognostic features, including significant tumor burden, advanced immunosuppression, and other concurrent morbidities, Strategies to manage such complex multiple-disease cases have often incorporated the assumption that prospects for long-term survival are poor and that intensive therapy cannot be tolerated and so is not justified. Since the advent of highly active antiretroviral therapy-for human immunodeficiency virus infection, life expectancy has improved substantially for patients in whom the virus can be successfully suppressed. Thus, for complicated cases involving AIDS-associated malignancy, a reassess ment of treatment strategies and the potential for long-term survival is warranted. Here, we present the case of a patient with poor prognosis due to AIDS-associated lymphoma with leptomeningeal involvement, advanced immunosuppression, and deep venous thrombosis. The management of this case illustrates that a multidisciplinary approach to complex AIDS cases involving malignancy and concurrent morbidity can result in a return to functional health in affected patients. Successful strategies for achieving favorable outcomes currently exist with available therapies. C1 NCI, HIV & AIDS Malignancy Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Little, RF (reprint author), NCI, HIV & AIDS Malignancy Branch, Div Clin Sci, Bldg 10,Room 10S255,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 45 Z9 46 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 11 PY 2001 VL 285 IS 14 BP 1880 EP 1885 DI 10.1001/jama.285.14.1880 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 418DY UT WOS:000167876700029 PM 11308402 ER PT J AU Marini, JC AF Marini, JC TI Genetic risk factors for lumbar disk disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MULTIPLE EPIPHYSEAL DYSPLASIA; COLLAGEN-IX; MUTATIONS; DEGENERATION; CARTILAGE; COL9A2; CHAIN C1 NICHHD, Heritable Disorders Branch, Sect Connect Tissue Disorders, NIH, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHHD, Heritable Disorders Branch, Sect Connect Tissue Disorders, NIH, Bldg 10,Room 9s241,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 8 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 11 PY 2001 VL 285 IS 14 BP 1886 EP 1888 DI 10.1001/jama.285.14.1886 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 418DY UT WOS:000167876700030 PM 11308403 ER PT J AU Robey, FA Robert-Guroff, M AF Robey, FA Robert-Guroff, M TI A defined conformational epitope from the C4 domain of HIV type 1 glycoprotein 120: Anti-cyclic C4 antibodies from HIV-positive donors magnify glycoprotein 120 suppression of interleukin 2 produced by T cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 RECEPTOR; ENVELOPE GLYCOPROTEIN; BINDING-SITE; GP120; ACTIVATION; PEPTIDES; CCR5; IMMUNOGENICITY; INFECTIVITY AB The C4 domain of HIV gp120 plays a functionally vital role in the binding of gp120 to CD4 receptors on target cells. Antibodies to an 11-amino acid cyclic C4 peptide were obtained from immunized rabbits and from the serum of an HIV-positive human and were found to recognize gp120 bound to CD4. Anti-cyclic C4 antibodies magnified gp120-induced suppression of IL-2 produced by T cells in vitro. Rabbit antibodies to the 11-amino acid linear C4 peptide did not recognize gp120 in the free state or when bound to CD4. These results indicate that a conformationally defined, highly conserved epitope in the gp120 C4 region remains exposed on CD4 binding. Naturally occurring antibodies to this epitope can augment gp120-induced immunosuppression and may contribute to disease progression. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Robey, FA (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Res, NIH, NIH Bldg 30,Room 211,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 2 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 2001 VL 17 IS 6 BP 533 EP 541 DI 10.1089/08892220151126625 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 425BY UT WOS:000168269500007 PM 11350667 ER PT J AU Li, DW Levy, LA Gabel, SA Lebetkin, MS DeRose, EF Wall, MJ Howell, EE London, RE AF Li, DW Levy, LA Gabel, SA Lebetkin, MS DeRose, EF Wall, MJ Howell, EE London, RE TI Interligand overhauser effects in type II dihydrofolate reductase SO BIOCHEMISTRY LA English DT Article ID MAPPING STRUCTURAL RELATIONSHIPS; HYDRIDE TRANSFER-REACTIONS; TRANSITION-STATE; MACROMOLECULAR LIGANDS; ESCHERICHIA-COLI; TERNARY COMPLEX; MODEL-SYSTEMS; TRANSFER STEP; TRIMETHOPRIM; NICOTINAMIDE AB R67 dihydrofolate reductase (DHFR) is a type II DHFR produced by bacteria as a resistance mechanism to the increased clinical use of the antibacterial drug trimethoprim. Type II DHFRs are not homologous in either sequence or structure with chromosomal DHFRs. The type II enzymes contain four identical subunits which form a homotetramer containing a single active site pore accessible from either end. Although the crystal structure of the complex of R67 DHFR with folate has been reported [Narayana et al. (1995) Nat. Struct. Biol. 2, 1018], the nature of the ternary complex which must form with substrate and cofactor is unclear. We have performed transferred NOE and interligand NOE (ILOE) studies to analyze the ternary complexes formed from NADP(+) and folate in order to probe the structure of the ternary complex. Consistent with previous studies of the binary complex formed from another type II DHFR, the ribonicotinamide bond of NADP(+) was found to adopt a syn conformation, while the adenosine moiety adopts an anti conformation. Large ILOE peaks connecting NADP(+) H4 and H5 with folate H9 protons are observed, while the absence of a large ILOE connecting NADP(+) H4 and H5 with folate H7 indicates that the relative orientation of the two ligands differs significantly from the orientation in the chromosomal enzyme. To obtain more detailed insight, we prepared and studied the folate analogue 2-deamino-2-methyl-5,8-dideazafolate (DMDDF) which contains additional protons in order to provide additional NOEs. For this analogue, the exchange characteristics of the corresponding ternary complex were considerably poorer, and it was necessary to utilize higher enzyme concentrations and higher temperature in order to obtain ILOE information. The results support a structure in which the NADP(+) and folate/DMDDF molecules extend in opposite directions parallel to the long axis of the pore, with the nicotinamide and pterin ring systems approximately stacked at the center. Such a structure leads to a ternary complex which is in many respects similar to the gas-phase theoretical calculations of the dihydrofolate-NADPH transition state by Andres et al. [(1996) Bioorg. Chem. 24, 10-18]. Analogous NMR studies performed on folate, DMDDF, and R67 DHFR indicate formation of a ternary complex in which two symmetry-related binding sites are occupied by folate and DMDDF. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Penn State Univ, Dept Chem, University Pk, PA 16802 USA. Univ Tennessee, Dept Cell & Mol Biol, Knoxville, TN 37996 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, MR-01,Box 12233, Res Triangle Pk, NC 27709 USA. NR 37 TC 37 Z9 37 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 10 PY 2001 VL 40 IS 14 BP 4242 EP 4252 DI 10.1021/bi0026425 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VL UT WOS:000168198400007 PM 11284680 ER PT J AU Bocharov, AV Vishnyakova, TG Baranova, IN Patterson, AP Eggerman, TL AF Bocharov, AV Vishnyakova, TG Baranova, IN Patterson, AP Eggerman, TL TI Characterization of a 95 kDa high affinity human high density lipoprotein-binding protein SO BIOCHEMISTRY LA English DT Article ID RECEPTOR CLASS-B; SCAVENGER RECEPTOR; SR-BI; CLONING; CELLS; EXPRESSION; SITES; IDENTIFICATION; CHOLESTEROL; MUTATIONS AB A new human 95 kDa high density lipoprotein (HDL)-binding protein (HBP) corresponding to a high affinity HDL-binding site with K-d = 1.67 mug/mL and a capacity of 13.4 ng/mg was identified in human fetal hepatocytes. The HDL binding with the 95 kDa HBP plateaus at 2.5-5 mug/mL under reducing and nonreducing conditions. The association of HDL3 with the 95 kDa HBP plateaued in 15-30 min while dissociation was complete in 30 min. HDL3, apoA-I, and apoA-II were recognized by the 95 kDa HBP while low density lipoproteins (LDL) and tetranitromethane-modified HDL were not. The 95 kDa HBP predominantly resides on the surface of cells since trypsin treatment of HepG2 cells eliminated nearly 70% of HDL binding. All studied human cells and cell lines (HepG2, Caco-2, HeLa, fibroblasts, SKOV-3, PA-I) demonstrated the presence of the 95 kDa protein. Both RT-PCR and Western blotting for HB-2/ALCAM were negative in human fetal hepatocytes while Gp96/GRP94 was clearly differentiated from the 95 kDa HBP by two-dimensional electrophoretic mobility. Moreover, deglycosylation of HepG2 membrane preparations did not affect either HDL binding to the 95 kDa HBP or its size, while in contrast it affected the molecular weights of HB-2/ALCAM and SR-BI/CLA-1. We conclude that the 95 kDa HBP is a new HDL receptor candidate widely expressed in human cells and cell lines. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy, OTRR, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Bocharov, AV (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy, OTRR, 8800 Rockville Pike,NIH Campus Bldg 29B,Room 2NN1, Bethesda, MD 20892 USA. NR 33 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 10 PY 2001 VL 40 IS 14 BP 4407 EP 4416 DI 10.1021/bi001503k PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VL UT WOS:000168198400024 PM 11284697 ER PT J AU Mehta, IK Smith, HRC Wang, J Margulies, DH Yokoyama, WM AF Mehta, IK Smith, HRC Wang, J Margulies, DH Yokoyama, WM TI A "chimeric" C57L-derived Ly49 inhibitory receptor resembling the Ly49D activation receptor SO CELLULAR IMMUNOLOGY LA English DT Article DE NK cells; cell surface molecules; FACS (sorting or staining) ID NATURAL-KILLER-CELLS; CLASS-I MHC; HISTOCOMPATIBILITY COMPLEX-MOLECULES; IL-2-ACTIVATED NK CELLS; LY-49 MULTIGENE FAMILY; NK1.1 ANTIGEN; GENE-COMPLEX; RECOGNITION; CLONING; ASSOCIATION AB Ly49D is a natural killer (NK) cell activation receptor that is responsible for differential mouse inbred strain-determined lysis of Chinese hamster ovary (CHO) cells. Whereas C57BL/6 NK cells kill CHO, BALB/c-derived NK cells cannot kill because they lack expression of Ly49D. Furthermore, the expression of Ly49D, as detected by monoclonal antibody 4E4, correlates well with CHO lysis by NK cells from different inbred strains. However, one discordant mouse strain was identified; C57L NK cells express the mAb 4E4 epitope but fail to lyse CHO cells, Herein we describe a Ly49 molecule isolated from C57L mice that is recognized by mAb 4E4 (anti-Ly49D). Interestingly, this molecule shares extensive similarity to Ly49D(B6) in its extracellular domain, but its cytoplasmic and transmembrane domains are identical to the inhibitory receptor Ly49A(B6), including a cytoplasmic ITIM, This molecule bears substantial overall homology to the previously cloned Ly490 molecule from 129 mice the serologic reactivity and function of which were undefined. Cytotoxicity experiments revealed that 4E4(+) LAK cells from C57L mice failed to lyse CHO cells and inhibited NK cell function in redirected inhibition assays. MHC class I tetramer staining revealed that the Ly490(C57L) bound H-2D(d) and lysis by 4E4+ C57L LAK cells is inhibited by target H-2Dd. The structural basis for ligand binding was also examined in the context of the recent crystallization of a Ly49A-H-2D(d) complex. Therefore, this apparently "chimeric"' Ly49 molecule serologically resembles an NK cell activation receptor but functions as an inhibitory receptor, (C) 2001 Academic Press. C1 Washington Univ, Sch Med, Ctr Arthrit & Related Dis, Dept Med,Immunol Program, St Louis, MO 63110 USA. Washington Univ, Sch Med, Ctr Arthrit & Related Dis, Dept Med,Rheumatol Div, St Louis, MO 63110 USA. Washington Univ, Sch Med, Ctr Arthrit & Related Dis, Dept Pathol, St Louis, MO 63110 USA. Howard Hughes Med Inst, St Louis, MO 63110 USA. NIAID, Immunol Lab, Mol Biol Sect, NIH, Bethesda, MD 20892 USA. RP Mehta, IK (reprint author), Washington Univ, Sch Med, Ctr Arthrit & Related Dis, Dept Med,Immunol Program, St Louis, MO 63110 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NIAID NIH HHS [5T32AI07163] NR 51 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 10 PY 2001 VL 209 IS 1 BP 29 EP 41 DI 10.1006/cimm.2001.1786 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 447ZL UT WOS:000169602300004 PM 11414734 ER PT J AU Bergmann-Leitner, ES Abrams, SI AF Bergmann-Leitner, ES Abrams, SI TI Positive and negative consequences of soluble Fas ligand produced by an antigen-specific CD4(+) T cell response in human carcinoma immune interactions SO CELLULAR IMMUNOLOGY LA English DT Article DE human; CD4(+) T cells; cytotoxicity; tumor immunity; oncogenes ID CANCER VACCINES; PEPTIDE VACCINATION; AUTOLOGOUS TUMOR; LYMPHOCYTES; EXPRESSION; ACTIVATION; MECHANISMS; INDUCTION; RECOGNIZE; EPITOPES AB The influence of a human CD4(+) T cell response in anti-carcinoma immune reactions remains largely uncharacterized. Here, we made use of a major histocompatibility complex (MHC) class-II-restricted, anti-ras oncogene-specific CD4+ T cell line produced previously in vivo from a patient with metastatic carcinoma in a peptide-based phase I trial. Using this patient-derived T cell line as a potentially relevant cell type, we examined the consequences of the anti-carcinoma CD4+ T cell response, with emphasis on specific lymphokines potentially important for the regulation of Fas/Fas ligand (FasL) interactions. Antigen (Ag)-specific CD4+ T cells produced substantial amounts of IFN-gamma following recognition of MHC class-II-matched Ag-presenting cells expressing the cognate peptide. The IFN-gamma promoted significant upregulation of Fas on the surface of colon carcinoma cells and sensitized these targets to Fas-mediated apoptosis and Ag-specific CD8(+) cytotoxic T lymphocyte (CTL)-mediated lysis involving a Fas-based effector mechanism. Moreover, Ag-stimulated CD4(+) T cells secreted soluble Fast (sFasL), which induced the death of TNF-resistant/refractory colon, breast, and ovarian carcinoma cells. Interestingly, although CD4(+)-derived sFasL expressed cytotoxic activity, the recovery of carcinoma cells which resisted Fas-mediated lysis displayed enhanced metastatic ability in vivo, compared with the unselected parental population, in an athymic mouse model. Thus, a tumor-specific CD4+ T cell response may have both positive and negative consequences in human carcinoma via the production of proinflammatory cytokines such as IFN-gamma and/or sFasL that may (1) improve or facilitate CTL-target engagement, contact-independent effector mechanisms, and the overall lytic outcome and (2) potentially select for Fas-resistant tumor cells that escape immune destruction, which may thus impact the metastatic process. C1 NCI, Ctr Canc Res,Div Basic Sci, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Ctr Canc Res,Div Basic Sci, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 31 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 10 PY 2001 VL 209 IS 1 BP 49 EP 62 DI 10.1006/cimm.2001.1781 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 447ZL UT WOS:000169602300006 PM 11414736 ER PT J AU Pharr, V Uttl, B Stark, M Litvan, I Fantie, B Grafman, J AF Pharr, V Uttl, B Stark, M Litvan, I Fantie, B Grafman, J TI Comparison of apraxia in corticobasal degeneration and progressive supranuclear palsy SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE AB Objective: To describe ideomotor apraxia in patients with corticobasal degeneration and those with progressive supranuclear palsy, two parkinsonian disorders that are often misdiagnosed due to the overlap in their clinical features, and to determine whether systematic apraxia testing is useful for differential diagnosis. Method: Fourteen patients fulfilling National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy clinical criteria for progressive supranuclear palsy, 13 patients fulfilling modified Lang criteria for corticobasal degeneration, and 12 normal healthy control subjects were given the Test of Oral and Limb Apraxia, which was scored according to the Florida Apraxia Battery for occurrence of various types of apraxic errors. Results: Both patients with progressive supranuclear palsy and corticobasal degeneration committed a greater number of apraxic errors than normal healthy control subjects on both transitive and intransitive tasks (p < 0.001 in both cases), but apraxia was much more severe in patients with corticobasal degeneration than progressive supranuclear palsy (p < 0.001). The index of apraxia severity, in combination with the assessment of the two key features of progressive supranuclear palsy (falls and vertical gaze palsy), correctly classified all patients. Conclusions: Patients with corticobasal degeneration show more severe ideomotor apraxia than patients with progressive supranuclear palsy, and systematic assessment of ideomotor apraxia facilitates the differential diagnosis between patients with progressive supranuclear palsy and those with corticobasal degeneration. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Def & Vet Head Injury Program, Cognit Neuropharmacol Unit, Rockville, MD USA. Oregon State Univ, Dept Psychol, Corvallis, OR 97331 USA. Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 24 TC 44 Z9 44 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 10 PY 2001 VL 56 IS 7 BP 957 EP 963 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 419RB UT WOS:000167961500022 PM 11294936 ER PT J AU Ishikawa, T Beuron, F Kessel, M Wickner, S Maurizi, MR Steven, AC AF Ishikawa, T Beuron, F Kessel, M Wickner, S Maurizi, MR Steven, AC TI Translocation pathway of protein substrates in ClpAP protease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATP-DEPENDENT PROTEASES; SELF-COMPARTMENTALIZING PROTEASES; ESCHERICHIA-COLI; ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; 20S PROTEASOME; CHAPERONE CLPA; RESOLUTION; BINDING; DEGRADATION AB Intracellular protein degradation, which must be tightly controlled to protect normal proteins, is carried out by ATP-dependent proteases. These multicomponent enzymes have chaperone-like ATPases that recognize and unfold protein substrates and deliver them to the proteinase components for digestion. In ClpAP, hexameric rings of the ClpA ATPase stack axially on either face of the ClpP proteinase, which consists of two apposed heptameric rings. We have used cryoelectron microscopy to characterize interactions of ClpAP with the model substrate, bacteriophage P1 protein, RepA. In complexes stabilized by ATP gammaS, which bind but do not process substrate, RepA dimers are seen at near-axial sites on the distal surface of ClpA. On ATP addition, RepA is translocated through approximate to 150 Angstrom into the digestion chamber inside ClpP. Little change is observed in ClpAP, implying that translocation proceeds without major reorganization of the ClpA hexamer. When translocation is observed in complexes containing a ClpP mutant whose digestion chamber is already occupied by unprocessed propeptides, a small increase in density is observed within ClpP, and RepA-associated density is also seen at other axial sites. These sites appear to represent intermediate points on the translocation pathway, at which segments of unfolded RepA subunits transiently accumulate en route to the digestion chamber. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B09, Bethesda, MD 20892 USA. RI Ishikawa, Takashi/E-5023-2017 OI Ishikawa, Takashi/0000-0002-1976-7477 NR 40 TC 103 Z9 103 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4328 EP 4333 DI 10.1073/pnas.081543698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700015 PM 11287666 ER PT J AU Rai, SK Duh, FM Vigdorovich, V Danilkovitch-Miagkova, A Lerman, MI Miller, AD AF Rai, SK Duh, FM Vigdorovich, V Danilkovitch-Miagkova, A Lerman, MI Miller, AD TI Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID APE LEUKEMIA-VIRUS; GLYCOSYL-PHOSPHATIDYLINOSITOL; CHROMOSOME 3P21.3; MAMMALIAN-CELLS; SARCOMA VIRUS; GENE-TRANSFER; LUNG-CANCER; VECTORS; EXPRESSION; HYALURONIDASE AB Jaagsiekte sheep retrovirus (JSRV) can induce rapid, multifocal lung cancer, but JSRV is a simple retrovirus having no known oncogenes. Here we show that the envelope (env) gene of JSRV has the unusual property that it can induce transformation in rat fibroblasts, and thus is likely to be responsible for oncogenesis in animals. Retrovirus entry into cells is mediated by Env interaction with particular cell-surface receptors, and we have used phenotypic screening of radiation hybrid cell lines to identify the candidate lung cancer tumor suppressor HYAL2/LUCA2 as the receptor for JSRV. HYAL2 was previously described as a lysosomal hyaluronidase, but we show that HYAL2 is actually a glycosylphosphatidylinositol (CPI)-anchored cell-surface protein. Furthermore, we could not detect hyaluronidase activity associated with or secreted by cells expressing HYAL2, whereas we could easily detect such activity from cells expressing the related serum hyaluronidase HYAL1. Although the function of HYAL2 is currently unknown, other GPI-anchored proteins are involved in signal transduction, and some mediate mitogenic responses, suggesting a potential role of HYAL2 in JSRV Env-mediated oncogenesis. Lung cancer induced by JSRV closely resembles human bronchiolo-alveolar carcinoma, a disease that is increasing in frequency and now accounts for approximate to 25% of all lung cancer. The finding that JSRV env is oncogenic and the identification of HYAL2 as the JSRV receptor provide tools for further investigation of the mechanism of JSRV oncogenesis and its relationship to human bronchiolo-alveolar carcinoma. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Miller, AD (reprint author), Fred Hutchinson Canc Res Ctr, Room C2-105,1100 Fairview Ave N, Seattle, WA 98109 USA. OI Miller, Dusty/0000-0002-3736-3660 FU NCI NIH HHS [CO56000]; NHLBI NIH HHS [HL54881, P50 HL054881]; NIDDK NIH HHS [DK47754] NR 27 TC 243 Z9 263 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4443 EP 4448 DI 10.1073/pnas.071572898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700035 PM 11296287 ER PT J AU Zhang, M Dwyer, NK Love, DC Cooney, A Comly, M Neufeld, E Pentchev, PG Blanchette-Mackie, EJ Hanover, JA AF Zhang, M Dwyer, NK Love, DC Cooney, A Comly, M Neufeld, E Pentchev, PG Blanchette-Mackie, EJ Hanover, JA TI Cessation of rapid late endosomal tubulovesicular trafficking in Niemann-Pick type C1 disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STEROL-SENSING DOMAIN; INTRACELLULAR TRAFFICKING; BREFELDIN-A; CHOLESTEROL; PROTEIN; LYSOSOMES; COMPARTMENT; TRANSPORT; PATHWAY AB Niemann-Pick type C1 (NPC1) disease results from a defect in the NPC1 protein and is characterized by a pathological accumulation of cholesterol and glycolipids in endocytic organelles. We followed the biosynthesis and trafficking of NPC1 with the use of a functional green fluorescent protein-fused NPC1, Newly synthesized NPC1 is exported from the endoplasmic reticulum and requires transit through the Golgi before it is targeted to late endosomes. NPC1-containing late endosomes then move by a dynamic process involving tubulation and fission, followed by rapid retrograde and anterograde migration along microtubules. Cell fusion studies with normal and mutant NPC1 cells show that exchange of contents between late endosomes and lysosomes depends upon ongoing tubulovesicular late endocytic trafficking. In turn, rapid endosomal tubular movement requires an intact NPC1 sterol-sensing domain and is retarded by an elevated endosomal cholesterol content. We conclude that the neuropathology and cellular lysosomal lipid accumulation in NPC1 disease results, at least in part, from striking defects in late endosomal tubulovesicular trafficking. C1 NIDDKD, Lipid Cell Biol Sect, Bethesda, MD 20892 USA. NIDDKD, Cell Biochem Sect, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Blanchette-Mackie, EJ (reprint author), NINDK, Lipid Cell Biol Sect, NIH, Bldg 8,Room 427,8 Ctr Dr,MSC 0850, Bethesda, MD 20892 USA. NR 25 TC 99 Z9 101 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4466 EP 4471 DI 10.1073/pnas.081070898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700039 PM 11296289 ER PT J AU Srivastava, M Bubendorf, L Srikantan, V Fossom, L Nolan, L Glasman, M Leighton, X Fehrle, W Pittaluga, S Raffeld, M Koivisto, P Willi, N Gasser, TC Kononen, J Sauter, G Kallioniemi, OP Srivastava, S Pollard, HB AF Srivastava, M Bubendorf, L Srikantan, V Fossom, L Nolan, L Glasman, M Leighton, X Fehrle, W Pittaluga, S Raffeld, M Koivisto, P Willi, N Gasser, TC Kononen, J Sauter, G Kallioniemi, OP Srivastava, S Pollard, HB TI ANX7, a candidate tumor suppressor gene for prostate cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer genetics; chromosome 10q21; loss of heterozygosity ID ANNEXIN-VII SYNEXIN; DICTYOSTELIUM-DISCOIDEUM; CHROMOSOMAL LOCALIZATION; CHROMAFFIN GRANULES; TISSUE MICROARRAYS; RB GENE; EXPRESSION; CARCINOMA; PROTEIN; GROWTH AB The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSC, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression. C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Sch Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Inst Mol Med, Sch Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Sch Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Sch Med, Bethesda, MD 20814 USA. Natl Human Genome Res Inst, Canc Genet Branch, Sect Mol Genet, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. Tampere Univ Hosp, Canc Genet Lab, FIN-33520 Tampere, Finland. Univ Basel, Inst Pathol, CH-4031 Basel, Switzerland. Univ Basel, Urol Clin, CH-4031 Basel, Switzerland. RP Srivastava, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 45 TC 93 Z9 106 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4575 EP 4580 DI 10.1073/pnas.071055798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700057 PM 11287641 ER PT J AU Ernst, M Matochik, JA Heishman, SJ Van Horn, JD Jons, PH Henningfield, JE London, ED AF Ernst, M Matochik, JA Heishman, SJ Van Horn, JD Jons, PH Henningfield, JE London, ED TI Effect of nicotine on brain activation during performance of a working memory task SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BLOOD-FLOW; INTRAVENOUS (H2O)-O-15; ATTENTION; HUMANS; SCALE; PET; VALIDATION; TOLERANCE; INSTITUTE; SMOKERS AB Nicotine influences cognition and behavior, but the mechanisms by which these effects occur are unclear. By using positron emission tomography, we measured cognitive activation (increases in relative regional cerebral blood flow) during a working memory task [2-back task (2BT)] in 11 abstinent smokers and 11 ex-smokers. Assays were performed both after administration of placebo gum and 4-mg nicotine gum. Performance on the 2BT did not differ between groups in either condition, and the pattern of brain activation by the 2BT was consistent with reports in the literature. However, in the placebo condition, activation in ex-smokers predominated in the left hemisphere, whereas in smokers, it occurred in the right hemisphere. When nicotine was administered, activation was reduced in smokers but enhanced in ex-smokers. The lateralization of activation as a function of nicotine dependence suggests that chronic exposure to nicotine or withdrawal from nicotine affects cognitive strategies used to perform the memory task. Furthermore, the lack of enhancement of activation after nicotine administration in smokers likely reflects tolerance. C1 NIDA, Brain Imaging Ctr, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Branch, Baltimore, MD 21224 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Pinney Associates, Bethesda, MD 20814 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 111 Z9 116 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2001 VL 98 IS 8 BP 4728 EP 4733 DI 10.1073/pnas.061369098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421HV UT WOS:000168059700083 PM 11274349 ER PT J AU Chen, D Barros, M Spencer, E Patton, JT AF Chen, D Barros, M Spencer, E Patton, JT TI Features of the 3'-consensus sequence of rotavirus mRNAs critical to minus strand synthesis SO VIROLOGY LA English DT Article ID 3'-TERMINAL CONSENSUS SEQUENCE; MESSENGER-RNA; GENOME REPLICATION; PROTEIN NSP3; POLYMERASE; PARTICLES; REQUIRES; 3'-END AB The last seven nucleotides of the 3 ' -end of rotavirus mRNAs, 5 ' -UGUGACC-3 ', are highly conserved acid form a cis-acting signal that can promote the synthesis of (-) strand RNA to produce the viral dsRNA genome in vitro. Previous studies have shown that the sequence, location, and strandedness (single- versus double-stranded) of the 3 ' -consensus sequence of the mRNA affect the efficiency of (-) strand synthesis. In this study. we have used exhaustive mutagenesis of the SA11 gene 8 mRNA and an in vitro replication system to define the importance of each of the residues in the consensus sequence in (-) strand synthesis. The analysis showed that the CC of the consensus sequence was the most critical for (-) strand synthesis. Furthermore, the data revealed that other, but not all, residues of the consensus sequence contributed to efficient(-) strand synthesis in vitro. Mutant gene 8 RNAs supported an intermediate level of (-) strand synthesis when the 15 nt sequence upstream of the CC was replaced with long tracts of poly(A) or poly(U), but not with poly(G). Predictions of the secondary structure of the mutant RNAs suggested that the poly(G)-RNA could not replicate because its 3 ' -terminus was largely basepaired, instead of extending as a single-stranded tail as is the case for the 3 ' -termini of the poly(A)- and poly(U)-RNAs and wild-type gene 8 RNA. Subsequent experiments performed with complementary oligonucleotides indicated that efficient RNA replication occurs in vitro only when the last four residues of the 3 ' -consensus sequence, and most importantly the two terminal C's, existed in a single-stranded form. A single-stranded CC may be crucial for formation of an initiation complex for (-) strand synthesis consisting of viral RdRP, mRNA, and the dinucleotide pGpG. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Santiago Chile, Fac Quim & Biol, Dept Ciencias Biol, Virol Lab, Santiago, Chile. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 27 TC 24 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2001 VL 282 IS 2 BP 221 EP 229 DI 10.1006/viro.2001.0825 PG 9 WC Virology SC Virology GA 424XW UT WOS:000168260100002 PM 11289804 ER PT J AU Pletnev, AG AF Pletnev, AG TI Infectious cDNA clone of attenuated langat tick-borne flavivirus (strain E5) and a 3 ' deletion mutant constructed from it exhibit decreased neuroinvasiveness in immunodeficient mice SO VIROLOGY LA English DT Article ID DENGUE TYPE-4 VIRUSES; ENCEPHALITIS-VIRUS; JAPANESE ENCEPHALITIS; 3'-NONCODING REGION; GENOMIC RNA; NEUROVIRULENCE AB Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT) strain TP21, was recovered from ticks in Malaysia. subsequently it was tested as a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a large clinical trial its attenuation was confirmed but there was evidence of a low level of residual virulence. Thirty-five years ago further attenuation of LGT TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the genetic determinants of the further attenuation exhibited by E5 and to allow us to manipulate the genome of this virus for the purpose of developing a satisfactory live attenuated tick-borne flavivirus vaccine, we recovered infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus (clone 651) recovered from a full-length infectious cDNA clone was more attenuated in immunodeficient mice than that of its biologically derived E5 parent. Increase in attenuation was associated with three amino acid substitutions, two located in the structural protein E and one in nonstructural protein NS4B. Subsequently an even greater degree of attenuation was achieved by creating a viable 320 nucleotide deletion in the 3 ' -noncoding region of infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian Vero cells and it replicated to lower titer than its E5-651 parent. In addition, the E5 3 ' deletion mutant was less neuroinvasive in SCID mice than its E5-651 parent. Significantly, the deletion mutant proved to be 119.750 times less neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high level of attenuation, the E5 3 ' deletion mutant remained highly immunogenic and intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0740,Bldg 7,Room 236, Bethesda, MD 20892 USA. NR 30 TC 39 Z9 40 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2001 VL 282 IS 2 BP 288 EP 300 DI 10.1006/viro.2001.0846 PG 13 WC Virology SC Virology GA 424XW UT WOS:000168260100009 PM 11289811 ER PT J AU Lloyd-Jones, DM O'Donnell, CJ D'Agostino, RB Massaro, J Silbershatz, H Wilson, PWF AF Lloyd-Jones, DM O'Donnell, CJ D'Agostino, RB Massaro, J Silbershatz, H Wilson, PWF TI Applicability of cholesterol-lowering primary prevention trials to a general population - The Framingham heart study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; COST-EFFECTIVENESS; RISK-FACTORS; DISEASE; MEN; PREVALENCE; ADULTS AB Background: Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD). Methods: To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with. those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not. Results: The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]). Conclusions: In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Stat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Wilson, PWF (reprint author), Framingham Heart Dis Epidemiol Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-38038] NR 27 TC 40 Z9 40 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2001 VL 161 IS 7 BP 949 EP 954 DI 10.1001/archinte.161.7.949 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 419HY UT WOS:000167944300006 PM 11295957 ER PT J AU He, J Ogden, LG Bazzano, LA Vupputuri, S Loria, C Whelton, PK AF He, J Ogden, LG Bazzano, LA Vupputuri, S Loria, C Whelton, PK TI Risk factors for congestive heart failure in US men and women - NHANES I epidemiologic follow-up study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY; UNITED-STATES; DISEASE; HYPERTENSION; INFORMATION; PREVALENCE; MORTALITY; PRESSURE; EXERCISE; WALKING AB Background: The incidence of congestive heart failure (CHF) has been increasing steadily in the United States during the past 2 decades. We studied risk factors for CHF and their corresponding attributable risk in the First National Health and Nutrition Examination Sun ey Epidemiologic Follow-up Study. Participants and Methods: A total of 13643 men and women without a history of CHF at baseline examination were included in this prospective cohort study. Risk factors were measured using standard methods between 1971 and 1975. Incidence of CHF was assessed using medical records and death certificates obtained between 1982 and 1984 and in 1986, 1987, and 1992. Results: During average follow-up of 19 years, 1382 CHF cases were documented. Incidence of CHF was positively and significantly associated with male sex (relative risk [RR], 1.24; 95% confidence interval [CI], 1.10-1.39; P<.001; population attributable risk [PAR], 8.9%), less than a high school education (RR, 1.22; 95% CI, 1.04-1.42; P=.01; PAR, 8.9%), low physical activity (RR, 1.23; 95% CI, 1.09-1.38; P<.001; PAR, 9.2%), cigarette smoking (RR, 1.59; 95% CI, 1.39-1.83; P<.001; PAR, 17.1%), overweight (RR, 1.30; 95% CI, 1.12-1.52; P=.001; PAR, 8.0%), hypertension (RR, 1.40; 95% CI, 1.24-1.59; P<.001; PAR, 10.1%), diabetes (RR, 1.85; 95% CI, 1.51-2.28; P<.001; PAR, 3.1%), valvular heart disease (RR, 1.46; 95% CI, 1.17-1.82; P=.001; PAR, 2.2%), and corollary heart disease (RR, 8.11; 95% CI, 6.95-9.46; P<.001; PAR, 61.6%). Conclusions: Male sex, less education, physical inactivity, cigarette smoking, overweight, diabetes, hypertension, valvular heart disease, and coronary heart disease are all independent risk factors for CHF. More than 60% of the CHF that occurs in the US general population might be attributable to coronary heart disease. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA 70112 USA. NHLBI, Bethesda, MD 20892 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave,SL18, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [R01HL60300, R03 HL61954] NR 32 TC 512 Z9 530 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2001 VL 161 IS 7 BP 996 EP 1002 DI 10.1001/archinte.161.7.996 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 419HY UT WOS:000167944300012 PM 11295963 ER PT J AU Philibert, RA Cheung, D Welsh, N Damschroder-Williams, P Thiel, B Ginns, EI Gershenfeld, HK AF Philibert, RA Cheung, D Welsh, N Damschroder-Williams, P Thiel, B Ginns, EI Gershenfeld, HK TI Absence of a significant linkage between Na+,K+-ATPase suburmit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE bipolar affective disorder; linkage; association; genetics; Na+; K+-ATPase; Amish ID GENOME-WIDE SEARCH; COMPLEX TRAITS; SUBUNIT GENE; NA,K-ATPASE; SCAN; POLYMORPHISM; ASSOCIATION; EXPRESSION; PEDIGREES; ISOZYMES AB Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na+,K+-ATPase may be a candidate gene for BPAD, This study examines the relationship between BPAD in the old-order Amish cohort and the Na+,K+-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods, Suggestive levels of statistical significance were not reached in any stratification model for affective illness, Overall, the results do not support linkage of bipolar disorder to the Na+,K+-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na+,K+-ATPase subunit genes are not major effect genes (greater than or equal to fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na+,K+-ATPase hypothesis for BPAD, whereby other loci may modifying Na+,K+-ATPase activity, (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Med Ctr, Brudnick Inst, Worcester, MA USA. Case Western Reserve Sch Med, Dept Epidemiol & Biostat, Cleveland, OH USA. RP Gershenfeld, HK (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. FU NCRR NIH HHS [1 P41 RR03655]; NIMH NIH HHS [R01-MH58882] NR 28 TC 6 Z9 7 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 8 PY 2001 VL 105 IS 3 BP 291 EP 294 DI 10.1002/ajmg.1322 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 429AT UT WOS:000168494400015 PM 11353452 ER PT J AU Moroni, M Garland, D AF Moroni, M Garland, D TI In vitro dephosphorylation of alpha-crystallin is dependent on the state of oligomerization SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE alpha A-crystallin; alpha B-crystallin; phosphorylation; protein phosphatase; deoxycholate; alkaline phosphatase; acid phosphatase; protein phosphatase-1; protein phosphatase-2A; protein phosphatase-2B ID HEAT-SHOCK-PROTEIN; B-CRYSTALLIN; A-CRYSTALLIN; PHOSPHORYLATION; DISSOCIATION; HSP27; SUBUNITS AB alphaA- and alphaB-crystallin, members of the small heat shock protein family, are present in lens cell extracts as large aggregates. Both alpha -crystallins are found partially phosphorylated. This study tests the ability of five phosphatases (protein phosphatase PP1, PP2A, PP2B, alkaline and acid phosphatases) to dephosphorylate aA- and alphaB-crystallin in vitro. Activity of a phosphatase was dependent on the size of the aggregate. Each of the phosphatases tested showed different specificity and efficiency towards alphaA- and alphaB-crystallins, which depended on the oligomeric state of the alpha -crystallin aggregate. Alkaline phosphatase dephosphorylated both alphaA- and alphaB-crystallin. The reaction was faster when alpha -crystallin was in a tetrameric form. PP2A dephosphorylated primarily alphaA-crystallin but only after the conversion of alpha -crystallin to tetramers. PPI and PP2B did not dephosphorylate either alphaA- or alphaB-crystallins present as large aggregates but could not be tested on the lower molecular weight form of alphaA-crystallin. Acid phosphatase dephosphorylated both alphaA- and alphaB-crystallin. The results suggest that an important relationship exists between the structure of alpha -crystallin and its level of phosphorylation in the cell. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Garland, D (reprint author), NEI, Lab Mechanisms Ocular Dis, NIH, 9000 Rockville Pike,Bldg 6,Rm 235, Bethesda, MD 20892 USA. NR 25 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD APR 7 PY 2001 VL 1546 IS 2 BP 282 EP 290 DI 10.1016/S0167-4838(01)00154-6 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 424AQ UT WOS:000168210300003 PM 11295434 ER PT J AU Brown, P AF Brown, P TI Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease SO BRITISH MEDICAL JOURNAL LA English DT Review ID GREAT-BRITAIN; BSE; MICE; SCRAPIE; RISK; CJD C1 Natl Inst Neurol Disorders & Blindness, Lab Cent Nervous Syst Dis, NIH, Bethesda, MD 20892 USA. RP Brown, P (reprint author), Natl Inst Neurol Disorders & Blindness, Lab Cent Nervous Syst Dis, NIH, Bethesda, MD 20892 USA. NR 19 TC 42 Z9 44 U1 0 U2 8 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD APR 7 PY 2001 VL 322 IS 7290 BP 841 EP 844 DI 10.1136/bmj.322.7290.841 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 421KF UT WOS:000168063000027 PM 11290640 ER PT J AU Tisdale, JF Young, NS AF Tisdale, JF Young, NS TI High-dose cyclophosphamide in aplastic anaemia - Reply SO LANCET LA English DT Letter C1 NIDDKD, Mol & Clin Haematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Haematol Branch, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDKD, Mol & Clin Haematol Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 7 PY 2001 VL 357 IS 9262 BP 1129 EP 1129 DI 10.1016/S0140-6736(00)04279-3 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 420GA UT WOS:000167996200046 ER PT J AU Puertollano, R Randazzo, PA Presley, JF Hartnell, LM Bonifacino, JS AF Puertollano, R Randazzo, PA Presley, JF Hartnell, LM Bonifacino, JS TI The GGAs promote ARF-dependent recruitment of clathrin to the TGN SO CELL LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING PROTEIN; AP-3 ADAPTER COMPLEX; GOLGI MEMBRANES; GAMMA-ADAPTIN; MEDIATED ENDOCYTOSIS; SYNTHETIC LIPOSOMES; BINDING PROTEIN; TRANS-GOLGI; FACTOR-I AB The GGAs constitute a family of modular adaptor-related proteins that bind ADP-ribosylation factors (ARFs) and localize to the trans-Golgi network (TGN) via their GAT domains. Here, we show that binding of the GAT domain stabilizes membrane-bound ARF1 . GTP due to interference with the action of GTPase-activating proteins. We also show that the hinge and ear domains of the GGAs interact with clathrin in vitro, and that the GGAs promote recruitment of clathrin to liposomes in vitro and to TGN membranes in vivo. These observations suggest that the GGAs could function to link clathrin to membrane-bound ARF GTP. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 46 TC 183 Z9 189 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 6 PY 2001 VL 105 IS 1 BP 93 EP 102 DI 10.1016/S0092-8674(01)00299-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 421KJ UT WOS:000168063300010 PM 11301005 ER PT J AU Choi, HJ Kim, SJ Mukhopadhyay, P Cho, S Woo, JR Storz, G Ryu, SE AF Choi, HJ Kim, SJ Mukhopadhyay, P Cho, S Woo, JR Storz, G Ryu, SE TI Structural basis of the redox switch in the OxyR transcription factor SO CELL LA English DT Article ID CRYSTAL-STRUCTURE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; ESCHERICHIA-COLI; REVERSIBLE INACTIVATION; SALMONELLA-TYPHIMURIUM; SIGNAL-TRANSDUCTION; MUTATIONAL ANALYSIS; REGIONS IMPORTANT; INDUCIBLE GENES AB The Escherichia coli OxyR transcription factor senses H2O2 and is activated through the formation of an intramolecular disulfide bond. Here we present the crystal structures of the regulatory domain of OxyR in its reduced and oxidized forms, determined at 2.7 Angstrom and 2.3 Angstrom resolutions, respectively. In the reduced form, the two redox-active cysteines are separated by approximately 17 Angstrom. Disulfide bond formation in the oxidized form results in a significant structural change in the regulatory domain. The structural remodeling, which leads to different oligomeric associations, accounts for the redox-dependent switch in OxyR and provides a novel example of protein regulation by "fold editing" through a reversible disulfide bond formation within a folded domain. C1 Korea Res Inst Biosci & Biotechnol, Ctr Cellular Switch Prot Struct, Taejon 305600, South Korea. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ryu, SE (reprint author), Korea Res Inst Biosci & Biotechnol, Ctr Cellular Switch Prot Struct, POB 115, Taejon 305600, South Korea. RI MUKHOPADHYAY, PARTHA/G-3890-2010; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Storz, Gisela/0000-0001-6698-1241 NR 39 TC 309 Z9 318 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 6 PY 2001 VL 105 IS 1 BP 103 EP 113 DI 10.1016/S0092-8674(01)00300-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 421KJ UT WOS:000168063300011 PM 11301006 ER PT J AU Campbell, VC Welch, SP AF Campbell, VC Welch, SP TI The role of minoxidil on endogenous opioid peptides in the spinal cord: a putative co-agonist relationship between K-ATP openers and opioids SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE K+ channel; minoxidil; opioid; (rat); antinociception; ATP-gated ID POTASSIUM CHANNEL OPENERS; BETA-ENDORPHIN; MORPHINE ANALGESIA; RECEPTORS; ANTINOCICEPTION; RAT; MODULATION; DISINHIBITION; RELEASE; NEURONS AB ATP-gated K+ channel openers produce antinociception that is attenuated by opioid receptor antagonists, indicating K-ATP openers produce antinociception, in part, via the release of endogenous opioid peptides. Utilizing the spinal perfusion method, male Sprague-Dawley rats were administered minoxidil intrathecally (i.t.) at doses ranging from 12.5 to 200 mug/rat for 3 min, tested for antinociception using the tail-flick test, and perfused with artificial cerebrospinal fluid (aCSF) to collect endogenous opioid peptides. Endogenous opioid peptide levels were measured by radioimmunoassay. Naltrindole, a delta -opioid receptor antagonist, at 4 mg/kg, subcutaneously (s.c.), blocked minoxidil-induced antinociception. beta -Funaltrexamine, a mu -opioid receptor antagonist, at 100 mug/rat, partially blocked minoxidil, whereas the kappa -opioid receptor antagonist nor-binaltorphimine, at a dose of 100 mug/rat, did not attenuate minoxidil. Although antagonists of the mu- and delta -opioid receptor attenuated minoxidil-induced antinociception, there was no increase in beta -endorphin, an endogenous ligand with affinity for both mu- and delta -opioid receptors or [Leu(5)]enkephalin, an endogenous ligand with affinity for delta -opioid receptors. (C) 2001 Published by Elsevier Science B.V. C1 NIDA, Baltimore, MD 21224 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. RP Campbell, VC (reprint author), NIDA, 5500 Nathan Shock Dr Bldg C, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA01647, KO2DA00186, T32DA07027] NR 36 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 6 PY 2001 VL 417 IS 1-2 BP 91 EP 98 DI 10.1016/S0014-2999(01)00885-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 424FA UT WOS:000168220400011 PM 11301063 ER PT J AU Minton, AP AF Minton, AP TI The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID CONCENTRATED HEMOGLOBIN-SOLUTIONS; SELF-ASSOCIATION; ESCHERICHIA-COLI; EXCLUDED-VOLUME; PROTEIN SOLUTIONS; HUMAN SPECTRIN; DNA; CELL; DETERMINANT; REACTIVITY C1 NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bldg 8,Rm 226, Bethesda, MD 20892 USA. NR 48 TC 790 Z9 806 U1 7 U2 89 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 10577 EP 10580 DI 10.1074/jbc.R100005200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900001 PM 11279227 ER PT J AU Dong, F Gutkind, JS Larner, AC AF Dong, F Gutkind, JS Larner, AC TI Granulocyte colony-stimulating factor induces Erk5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C - Regulation of cell proliferation and survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID G-CSF RECEPTOR; DISTINCT CYTOPLASMIC REGIONS; SIGNALING PATHWAY; PROTEIN-KINASE-1 BMK1; TRANSCRIPTION FACTOR; RAPID ACTIVATION; MYELOID CELLS; JUN PROMOTER; MAP KINASE; INHIBITOR AB Granulocyte colony-stimulating factor (G-CSF) plays a major role in the regulation of granulopoiesis. Treatment of cells with G-CSF has been shown to activate multiple signal transduction pathways. We show here that Erk5, a novel member of the MAPK family, and its specific upstream activator MEK5 were activated in response to incubation of cells with G-CSF. Different from other members of the MAPK family including Erk1/2, JNK, and p38, maximal activation of Erk5 by G-CSF required the C-terminal region of the G-CSF receptor. Genistein, a specific inhibitor of protein-tyrosine kinases, blocked G-CSF-induced Erk5 activation. In contrast, inhibition of protein kinase C activity increased G-CSF-mediated activation of Erk5 and MEK5, whereas stimulation of protein kinase C activity inhibited activation of the two kinases by G-CSF, The proliferation of BAF3 cells in response to G-CSF was inhibited by expression of a dominant-negative MEK5 but potentiated by expression of a constitutively active MEK5. Expression of the constitutively active MEK5 also increased the survival of BAF3 cells cultured in the absence of or in low concentrations of G-CSF. Together, these data implicate Erk5 as an important signaling component in the biological actions of G-CSF. C1 Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, Cleveland, OH 44195 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Dong, F (reprint author), Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [CA77741, CA77736] NR 56 TC 39 Z9 41 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 10811 EP 10816 DI 10.1074/jbc.M008748200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900035 PM 11278431 ER PT J AU Nielsen, PK Yamada, Y AF Nielsen, PK Yamada, Y TI Identification of cell-binding sites on the laminin alpha(5) N-terminal domain by site-directed mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-2-BETA-1 INTEGRINS; SULFATE PROTEOGLYCANS; SHORT ARM; CHAIN; ADHESION; HEPARIN; ALPHA-1-BETA-1; DYSTROGLYCAN; ALPHA-3-BETA-1; SPECIFICITY AB The newly discovered laminin alpha (5) chain is a multidomain, extracellular matrix protein implicated in various biological functions such as the development of blood vessels and nerves. The N-terminal globular domain of the laminin a chains has an important role for biological activities through interactions with cell surface receptors. In this study, we identified residues that are critical for cell binding within the laminin alpha (5) N-terminal globular domain VI (similar to 270 residues) using site-directed mutagenesis and synthetic peptides. A recombinant protein of domain VI and the first four epidermal growth factor-like repeats of domain V, generated in a mammalian expression system, was highly active for HT-1080 cell binding, while a recombinant protein consisting of only the epidermal growth factor-like repeats showed no cell binding. By competition analysis with synthetic peptides for cell binding, we identified two sequences: S2, (123)GQVFHVAYVLIKF(135) and S6, (225)RDFTKATNIRLRFLR(239), within domain VI that inhibited cell binding to domain VI. Alanine substitution mutagenesis indicated that four residues (Tyr(130), Arg(225), Lys(229), and Arg(239)) within these two sequences are crucial for cell binding. Real-time heparin-binding kinetics of the domain VI mutants analyzed by surface plasmon resonance indicated that Arg(239) of S6 was critical for both heparin and cell binding. In addition, cell binding to domain VI was inhibited by heparin/heparan sulfate, which suggests an overlap of cell and heparin-binding sites. Furthermore, inhibition studies using integrin subunit monoclonal antibodies showed that integrin alpha (3)beta (1) was a major receptor for domain VI binding. Our results provide evidence that two sites spaced about 90 residues apart within the laminin alpha (5) chain N-terminal globular domain VI are critical for cell surface receptor binding. C1 NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, Y (reprint author), NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Rm 405,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. NR 26 TC 41 Z9 41 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 10906 EP 10912 DI 10.1074/jbc.M008743200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900047 PM 11098055 ER PT J AU Thyagarajan, T Sreenath, T Cho, A Wright, JT Kulkarni, AB AF Thyagarajan, T Sreenath, T Cho, A Wright, JT Kulkarni, AB TI Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-beta 1 in teeth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOGENESIS IMPERFECTA; TGF-BETA; ODONTOBLAST DIFFERENTIATION; DENTINOGENESIS IMPERFECTA; PULP COMPLEX; IN-VITRO; GENE; MUTATION; COLLAGEN; GROWTH-FACTOR-BETA-1 AB Transforming growth factor (TGF)-beta1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of TGF-beta1 in the tooth continues throughout life; however, the precise biological functions of this growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active TGF-beta1 predominantly in the odontoblasts, Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules, Dentin extracellular matrix components such as type I and III collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as dentin dysplasia and dentinogenesis imperfecta, Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of dentin sialophosphoprotein (dspp), a candidate gene implicated in dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that TGF-beta1 mediated expression of dspp is crucial for dentin mineralization, These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420). C1 NIDCR, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. NIDCR, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), NIDCR, Funct Genom Unit, NIH, Bldg 30,Rm 529,30 Convent Dr, Bethesda, MD 20892 USA. NR 29 TC 58 Z9 63 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 11016 EP 11020 DI 10.1074/jbc.M010502200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900061 PM 11116156 ER PT J AU Olah, Z Szabo, T Karai, L Hough, C Fields, RD Caudle, RM Blumberg, PM Iadarola, MJ AF Olah, Z Szabo, T Karai, L Hough, C Fields, RD Caudle, RM Blumberg, PM Iadarola, MJ TI Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DORSAL-ROOT GANGLION; ACTIVATED ION-CHANNEL; CAPSAICIN RECEPTOR; SUBSTANCE-P; SENSORY NEURONS; SPINAL-CORD; RAT; CALCIUM; DESENSITIZATION; RESINIFERATOXIN AB The real time dynamics of vanilloid-induced cytotoxicity and the specific deletion of nociceptive neurons expressing the wild-type vanilloid receptor (VR1) were investigated. VR1 was C-terminally tagged with either the 27-kDa enhanced green fluorescent protein (eGFP) or a 12-amino acid epsilon -epitope. Upon exposure to resiniferatoxin, VR1eGFP- or VR1 epsilon -expressing cells exhibited pharmacological responses similar to those of cells expressing the untagged VR1. Within seconds of vanilloid exposure, the intracellular free calcium ([Ca2+](i)) was elevated in cells expressing VR1, A functional pool of VR1 also was localized to the endoplasmic reticulum that, in the absence of extracellular calcium, also was capable of releasing calcium upon agonist treatment. Confocal imaging disclosed that resiniferatoxin treatment: induced vesiculation of the mitochondria and the endoplasmic reticulum (similar to1 min), nuclear membrane disruption (5-10 min), and cell lysis (1-2 h), Nociceptive primary sensory neurons endogenously express VR1, and resiniferatoxin treatment induced a sudden increase in [Ca2+](i) and mitochondrial disruption which was cell-selective, as glia and non-VR1-expressing neurons were unaffected. Early hallmarks of cytotoxicity were followed by specific deletion of VR1-expressing cells. These data demonstrate that vanilloids disrupt vital organelles within the cell body and, if administered to sensory ganglia, may be employed to rapidly and selectively delete nociceptive neurons. C1 NIDCR, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. NINDS, Neuroanl Excitabil Sect, Epilepsy Branch, Bethesda, MD 20892 USA. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Olah, Z (reprint author), NIDCR, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bldg 49,Rm 1A19,49 Convent Dr,MSC-4410, Bethesda, MD 20892 USA. NR 40 TC 136 Z9 140 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 11021 EP 11030 DI 10.1074/jbc.M008392200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900062 PM 11124944 ER PT J AU Baumann, CT Maruvada, P Hager, GL Yen, PM AF Baumann, CT Maruvada, P Hager, GL Yen, PM TI Nuclear cytoplasmic shuttling by thyroid hormone receptors - Multiple protein interactions are required for nuclear retention SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEASOME-DEPENDENT DEGRADATION; HUMAN ESTROGEN-RECEPTOR; RETINOIC ACID RECEPTOR; GLUCOCORTICOID-RECEPTOR; PROGESTERONE-RECEPTOR; LIVING CELLS; HISTONE ACETYLTRANSFERASE; MEDIATED PROTEOLYSIS; ANDROGEN RECEPTOR; BINDING DOMAIN AB In this report, we have studied the intracellular dynamics and distribution of the thyroid hormone receptor-beta (TR beta) in living cells, utilizing fusions to the green fluorescent protein. Wild-type TB beta was mostly nuclear in both the absence and presence of triiodothyronine; however, triiodothyronine induced a nuclear reorganization of TR beta. By mutating defined regions of TR beta, we found that both nuclear corepressor and retinoid X receptor are involved in maintaining the unliganded receptor within the nucleus. A TR beta mutant defective in DNA binding had only a slightly altered nuclear/cytoplasmic distribution compared with wild-type TR beta; thus, site-specific DNA binding is not essential for maintaining TR beta within the nucleus. Both AT beta depletion studies and heterokaryon analysis demonstrated that TR beta rapidly shuttles between the nuclear and the cytoplasmic compartments. Cotransfection of nuclear corepressor and retinoid X receptor markedly decreased the shuttling by maintaining unliganded TR beta within the nucleus. In summary, our findings demonstrate that TR beta rapidly shuttles between the nucleus and the cytoplasm and that protein-protein interactions of TR beta with various cofactors, rather than specific DNA interactions, play the predominant role in determining the intracellular distribution of the receptor. C1 NCI, Lab Recept Biol & Gene Express, Bethesda, MD 20892 USA. NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Recept Biol & Gene Express, 41 Lib Dr,Bldg 41,Rm B602, Bethesda, MD 20892 USA. NR 57 TC 98 Z9 101 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2001 VL 276 IS 14 BP 11237 EP 11245 DI 10.1074/jbc.M011112200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 420AC UT WOS:000167980900089 PM 11152480 ER PT J AU Hosohata, Y Varga, EV Stropova, D Li, XP Knapp, RJ Hruby, VJ Rice, KC Nagase, H Roeske, WR Yamamura, HI AF Hosohata, Y Varga, EV Stropova, D Li, XP Knapp, RJ Hruby, VJ Rice, KC Nagase, H Roeske, WR Yamamura, HI TI Mutation W284L of the human delta opioid receptor reveals agonist specific receptor conformations for G protein activation SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on Membrane Receptors, Signal Transduction and Drug Action CY MAR 25-26, 2000 CL YOKOHAMA, JAPAN SP Nagai Fdn, Naito Fdn, Novartis Fdn Promot Sci, Res Fdn Pharmaceut Sci, Uehara Mem Fdn, Souyaku Yakuri Forum, Univ Tokyo, Univ Arizona DE human delta opioid receptor; W284L point mutation; [S-35]GTP gamma S binding; intrinsic activity; SNC 80; DPDPE; (-)TAN 67; SB 219825 ID MESSAGE-ADDRESS CONCEPT; 3RD EXTRACELLULAR LOOP; SITE-DIRECTED MUTAGENESIS; BETA(2)-ADRENERGIC RECEPTOR; BINDING RESIDUES; SEGMENT-VI; IDENTIFICATION; PHARMACOLOGY; DELINEATION; ANTAGONISTS AB Intrinsic activities of different delta opioid agonists were determined in a [S-35]GTP gammaS binding assay using cell membranes from Chinese hamster ovary (CHO) cells stably expressing the wild type (hDOR/CHO) or W284L mutant human delta opioid receptor (W284L/CHO). Agonist binding affinities were regulated more robustly by sodium and guanine nucleotide in W284L/CHO than in hDOR/CHO cell membranes. The W284L mutation selectively reduced the affinity of SNC 80 while having moderate effect ((-) TAN 67) or no effect (DPDPE) on the affinities of other delta selective agonists. The mutation had opposite effects on the intrinsic activities of agonists belonging to different chemical classes. The effects of the mutation on agonist affinities and potencies were independent from its effects on the intrinsic activities of the agonists. Maximal stimulation of [S-35]GTP gammaS binding by SNC 80 was 2-fold higher in W284L mutant cell membranes than in wild type hDOR/CHO cell membranes, despite lower receptor expression levels in the W284L/CHO cells. The binding affinity of SNC 80 however, was significantly reduced (15-fold and 30-fold in the absence or presence of sodium+GDP respectively) in W284L/CHO cell membranes relative to wild type hDOR/CHO membranes. Conversely, the E-max of (-)TAN 67 in the [S-35]GTP gammaS binding assay was markedly reduced (0.6-fold of that of the wild type) with only a slight (6-fold) reduction in its binding affinity. The affinity and intrinsic activity of DPDPE on the other hand remained unchanged at the W284L mutant hDOR. The mutation had similar effects on the affinities potencies and intrinsic activities of (-)TAN 67 and SB 219825. The results indicate that delta opioid agonists of different chemical classes use specific conformations for G protein activation. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85724 USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. Univ Arizona, Dept Med, Tucson, AZ 85724 USA. Univ Arizona, Program Neurosci, Tucson, AZ 85724 USA. Univ Arizona, Dept Chem, Tucson, AZ 85724 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Toray Ind, Kamakura, Kanagawa, Japan. RP Yamamura, HI (reprint author), Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. NR 27 TC 10 Z9 12 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 6 PY 2001 VL 68 IS 19-20 BP 2233 EP 2242 DI 10.1016/S0024-3205(01)01011-6 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 421WW UT WOS:000168087400009 PM 11358332 ER PT J AU Amara, RR Villinger, F Altman, JD Lydy, SL O'Neil, SP Staprans, SI Montefiori, DC Xu, Y Herndon, JG Wyatt, LS Candido, MA Kozyr, NL Earl, PL Smith, JM Ma, HL Grimm, BD Hulsey, ML Miller, J McClure, HM McNicholl, JM Moss, B Robinson, HL AF Amara, RR Villinger, F Altman, JD Lydy, SL O'Neil, SP Staprans, SI Montefiori, DC Xu, Y Herndon, JG Wyatt, LS Candido, MA Kozyr, NL Earl, PL Smith, JM Ma, HL Grimm, BD Hulsey, ML Miller, J McClure, HM McNicholl, JM Moss, B Robinson, HL TI Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RHESUS-MONKEYS; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEINS; PATHOGENIC SIV; INFECTION; REPLICATION; RESPONSES; TYPE-1; ASSAY AB Heterologous prime/boost regimens have the potential for raising high Levels of immune responses. Here we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model. Both the DNA and rMVA components of the vaccine expressed multiple immunodeficiency virus proteins. Two DNA inoculations at 0 and 8 weeks and a single rMVA booster at 24 weeks effectively controlled an intrarectal challenge administered 7 months after the booster. These findings provide hope that a relatively simple multiprotein DNA/MVA vaccine can help to control the acquired immune deficiency syndrome epidemic. C1 Emory Univ, Vaccine Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Sch Med, Vaccine Res Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30330 USA. RP Robinson, HL (reprint author), Emory Univ, Vaccine Res Ctr, Atlanta, GA 30329 USA. EM hrobins@rmy.emory.edu FU NCRR NIH HHS [P51 RR000165]; NIAID NIH HHS [P01 AI 43045]; NIDA NIH HHS [P30 DA 12121] NR 19 TC 925 Z9 952 U1 1 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 6 PY 2001 VL 292 IS 5514 BP 69 EP 74 DI 10.1126/science.1058915 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 420FU UT WOS:000167995200037 PM 11393868 ER PT J AU Kabrane-Lazizi, Y Emerson, SU Herzog, C Purcell, RH AF Kabrane-Lazizi, Y Emerson, SU Herzog, C Purcell, RH TI Detection of antibodies to HAV 3C proteinase in experimentally infected chimpanzees and in naturally infected children SO VACCINE LA English DT Article DE hepatitis A virus; 3C proteinase; vaccine ID HEPATITIS-A VIRUS; VACCINE; LIVE; STRAIN AB Commercial assays for the diagnosis of hepatitis A detect antibody to hepatitis A virus (anti-HAV), but they cannot discriminate between antibody resulting from infection and antibody induced by inactivated vaccine. With the licensing and increasing use of inactivated hepatitis A vaccines, there is a need for a test to distinguish between infection and vaccination. Since antibodies to viral non-structural proteins are elicited by infection but not by vaccination with inactivated vaccine, we developed and evaluated a test for such antibodies. The antibody response to the non-structural 3C proteinase (anti-3C) of virus HAV was studied by ELISA in chimpanzees experimentally infected with virulent (wild type) or with attenuated HAV strains and in children who received inactivated HAV vaccine or placebo during a vaccination trial in Nicaragua. Anti-3C was detected in 89% of 18 chimpanzees infected with wild-type HAV strains and 27% of 26 chimpanzees infected with attenuated HAV strains. There was a direct correlation between severity of hepatitis and magnitude of the anti-3C response. In the vaccine trial, anti-3C was detected only in children who were infected with HAV during the study; IgG anti-3C persisted for at least 15 months after infection in one child. Vaccinated and uninfected children remained negative for anti-3C. The anti-3C response can be regarded as an indicator of viral replication. Its detection should be useful for distinguishing between antibody acquired in response to HAV infection and antibody induced by immunization with inactivated vaccine. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Mol Hepatitis Sec, NIH, Bethesda, MD 20892 USA. Swiss Serum & Vaccine Inst, CH-3001 Bern, Switzerland. RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NR 16 TC 9 Z9 11 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 6 PY 2001 VL 19 IS 20-22 BP 2878 EP 2883 DI 10.1016/S0264-410X(00)00560-0 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 416VB UT WOS:000167799900014 PM 11282198 ER PT J AU Hilfiker, MA Mysak, ER Samet, C Maynard, A AF Hilfiker, MA Mysak, ER Samet, C Maynard, A TI Matrix isolation infrared and ab initio study of the 1 : 1 complexes of cyclopentadiene with nitrogen and oxygen bases: C-H center dot center dot center dot(NO) hydrogen bonding involving an sp(3)-hbridized carbon SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID C-H BONDS; AMMONIA; SPECTRA; ALKYNES; ROTATION; SYSTEM; FTIR AB Hydrogen-bonded complexes of cyclopentadiene with the strong bases ammonia, trimethylamine, and dimethyl ether have been isolated and characterized for the first time in argon matrices at 16. K. Coordination of the acidic alkyl hydrogen to the electron donor was evidenced by distinct red shifts of the CH2 stretching modes of cyclopentadiene in the infrared spectrum. An additional NH . . . pi interaction was evidenced by the red shift of an olefinic C-H stretching mode. Ab initio calculations yield a complex with NH3 located above the ring, oriented by both of these hydrogen-bonding interactions. The calculated interaction energy of the complex is 2.40 kcal/mol, with the energy being divided equally between these two interactions. This study represents the first example of an sp(3)-hybridized carbon on a hydrocarbon taking part in a C-H . . .N(O) hydrogen bond. C1 Dickinson Coll, Dept Chem, Carlisle, PA 17013 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, IRSP,Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Samet, C (reprint author), Dickinson Coll, Dept Chem, Carlisle, PA 17013 USA. NR 45 TC 11 Z9 11 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD APR 5 PY 2001 VL 105 IS 13 BP 3087 EP 3095 DI 10.1021/jp004464v PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 419AV UT WOS:000167927900024 ER PT J AU Putney, JW AF Putney, JW TI Cell biology - Channelling calcium SO NATURE LA English DT Editorial Material ID ENTRY; INFLUX C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 14 TC 27 Z9 27 U1 0 U2 1 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 5 PY 2001 VL 410 IS 6829 BP 648 EP 649 DI 10.1038/35070704 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 418DJ UT WOS:000167875400031 PM 11287938 ER PT J AU Orlic, D Kajstura, J Chimenti, S Jakoniuk, I Anderson, SM Li, BS Pickel, J McKay, R Nadal-Ginard, B Bodine, DM Leri, A Anversa, P AF Orlic, D Kajstura, J Chimenti, S Jakoniuk, I Anderson, SM Li, BS Pickel, J McKay, R Nadal-Ginard, B Bodine, DM Leri, A Anversa, P TI Bone marrow cells regenerate infarcted myocardium SO NATURE LA English DT Article ID GROWTH-FACTOR-I; STEM-CELLS; ADULT MICE; C-KIT; EXPRESSION; HEART; VIVO; DIFFERENTIATE; PROLIFERATION; HYPERTROPHY AB Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time(1). Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation(2-5); these events promote structural and functional repair(6-8). This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin(-)) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein(9) by fluorescence-activated cell sorting on the basis of c-kit expression(10). Shortly after coronary ligation, Lin(-) c-kit(POS) cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease. C1 New York Med Coll, Dept Med, Valhalla, NY 10595 USA. NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Anversa, P (reprint author), New York Med Coll, Dept Med, Valhalla, NY 10595 USA. NR 30 TC 3453 Z9 3955 U1 38 U2 350 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 5 PY 2001 VL 410 IS 6829 BP 701 EP 705 DI 10.1038/35070587 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 418DJ UT WOS:000167875400050 PM 11287958 ER PT J AU Shao, RG Cao, CX Nieves-Neira, W Dimanche-Boitrel, MT Solary, E Pommier, Y AF Shao, RG Cao, CX Nieves-Neira, W Dimanche-Boitrel, MT Solary, E Pommier, Y TI Activation of the Fas pathway independently of Fas ligand during apoptosis induced by camptothecin in p53 mutant human colon carcinoma cells SO ONCOGENE LA English DT Article DE Bar; caspase; FADD; z-VAD; nuclease; programmed cell death ID DRUG-INDUCED APOPTOSIS; CANCER-CELLS; TOPOISOMERASE-I; LEUKEMIA-CELLS; DNA-DAMAGE; CUTTING EDGE; WILD-TYPE; DEATH; CD95; CYTOTOXICITY AB The present study explored the role of the cell surface receptor Fas (CD95/APO-1) in apoptosis induced by camptothecin (CPT) in the HT29 colon carcinoma cell line. CPT-induced apoptosis was associated with high molecular weight DNA fragmentation as measured by filter elution, This fragmentation was inhibited by the caspase inhibitor, z-VAD-fmk and by cycloheximide, which also prevented proteolytic activation of caspase-3 and poly(ADP-ribose)polymerase cleavage. Under such conditions, Fas, Fas ligand, Bar, and p21 expression were increased and Fas recruited the FADD adaptor. Fas expression increase was blocked by cycloheximide but not by z-VAD-fmk, consistent with caspase activation downstream from Fas, Treatment of HT29 cells with Fast or with the CH-11 agonistic anti-Fas antibody potentiated the apoptotic response of cells treated with CPT, The anti-Fas blocking antibody ZB4 and the Fas-ligand inhibitor failed to protect HT29 cells from CPT-induced apoptosis, Such a protection was obtained by transient expression of constructs encoding a dominant-negative mutant of FADD, FADD in an antisense orientation and E8 or MC159 viral proteins that inhibit Fas-induced apoptosis at the level of FADD and procaspase-8, respectively. Together, these data show that topoisomerase I-mediated DNA damage-induced apoptosis involves activation of the Fas pathway without detectable Fas-ligand requirement in CPT-treated cells. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Fac Med & Pharm Dijon, INSERM U517, Dept Biol & Therapy Canc, Dijon, France. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 4E28, Bethesda, MD 20892 USA. RI Dimanche-Boitrel, Marie-Therese/I-4642-2015 NR 44 TC 61 Z9 69 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 5 PY 2001 VL 20 IS 15 BP 1852 EP 1859 DI 10.1038/sj.onc.1204264 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 418TX UT WOS:000167908400006 PM 11313933 ER PT J AU Charlab, R Valenzuela, JG Andersen, J Ribeiro, JMC AF Charlab, R Valenzuela, JG Andersen, J Ribeiro, JMC TI The invertebrate growth factor/CECR1 subfamily of adenosine deaminase proteins SO GENE LA English DT Article DE gene family; pfam domain; sand fly; salivary gland ID FLY LUTZOMYIA-LONGIPALPIS; MOSQUITO ANOPHELES-ALBIMANUS; SALIVARY-GLANDS; MAST-CELLS; PURIFICATION; CLONING; NOCICEPTION; RECEPTORS; MOLSCRIPT; DATABASE AB Adenosine deaminase (ADA) catalyzes the hydrolysis of adenosine to inosine. Its lack determines severe combined immunodeficiency in mammals, possibly due to accumulation of extracellular adenosine, which induces apoptosis in lymphocytes (Franco et al., 1998). Thus, presence of normal levels of ADA leads to normal growth and proliferation of lymphocytes. Several vertebrate and microbial ADA aminoacid sequences are known, with substantial similarity to each other. On the other hand, there are invertebrate growth factors as well as a candidate gene for the human cat eye syndrome (CECR1) (Riazi et al., 2000. Genomics 64, 277-285), which share substantial similarity to each other, and also to ADA. In this study, we report the expression and ADA enzymatic activity of a cDNA from the salivary glands of Lutzomyia longipalpis, a blood-sucking insect, with substantial similarity to insect growth factors and to human CECR1. We also demonstrate the existence of a subfamily of the adenosine deaminase family characterized by their unique amino-terminal region. Both Drosophila melanogaster and humans have both types of adenosine deaminases. Results indicate that these invertebrate proteins previously annotated as growth factors, as well as the human CECR1 gene product, may exert their actions through adenosine depletion. The different roles played by each type of adenosine deaminase in humans and Drosophila remains to be fully investigated. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 4-126, Bethesda, MD 20892 USA. EM jribeiro@nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 NR 40 TC 24 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 4 PY 2001 VL 267 IS 1 BP 13 EP 22 DI 10.1016/S0378-1119(01)00393-6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 424FU UT WOS:000168222300002 PM 11311551 ER PT J AU McDevitt, AL Deming, MS Rosenberg, HF Dyer, KD AF McDevitt, AL Deming, MS Rosenberg, HF Dyer, KD TI Gene structure and enzymatic activity of mouse eosinophil-associated ribonuclease 2 SO GENE LA English DT Article DE genome; transcription; rodent; nucleic acid enzymology ID CATIONIC PROTEIN; MOLECULAR-CLONING; INTRONIC ENHANCER; NEUROTOXIN RNS2; RAPID EVOLUTION; A SUPERFAMILY; FAMILY; TRANSCRIPTION; LOCALIZATION; EXPRESSION AB Mouse eosinophil-associated ribonuclease-2 (mEAR-2) is one of a cluster of genes identified in the genome of the mouse Mus musculus that are highly divergent orthologs of the primate ribonucleases, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP). Northern analysis revealed expression of genes hybridizing to mEAR-2 in mouse lung, liver and spleen tissues. We obtained full-length cDNA by hybridization screening of mouse eosinophil and lung cDNA libraries and by rapid amplification of cDNA ends (RACE) from liver, spleen and lung RNA. Using these methods we have isolated the 195 base pair (bp) 3' untranslated region (UTR) that includes a typical polyadenylation signal preceding a poly A tail and the 5' UTR which includes 63-71 bp and three distinct transcriptional start sites. Using unidirectional PCR we isolated a 361-bp 5' promoter region and delineated the intronic / exonic boundaries which include a non-coding exon 1, a single intron, and a coding exon 2, a structure that is typical of genes of the RNase A superfamily. Consensus sites for PU.1 and EoTF, both active as intronic enhancer elements of the gene encoding EDN, are also present in the intron of the gene encoding mEAR-2. The catalytic activity of recombinant baculovirus-derived mEAR-2 is similar to that of rhEDN from this source, with catalytic constants k(cat)/K-m = 5.6 x 10(6) M-1 s(-1) and 10.5 x 10(6) M-1 s(-1), respectively, against a standard yeast tRNA substrate. Sequence analysis of the non-coding regions and enzymatic characterization of the gene product provide further evidence indicating that mEAR-2 is a structural and functional ortholog of primate EDNs and ECPs. Published by Elsevier Science B.V. C1 NIAID, Eosinophil Biol Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Eosinophil Biol Unit, Host Def Lab, NIH, 10-11N104,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 14 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 4 PY 2001 VL 267 IS 1 BP 23 EP 30 DI 10.1016/S0378-1119(01)00392-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 424FU UT WOS:000168222300003 PM 11311552 ER PT J AU Blackshear, PJ Lai, WS Thorn, JM Kennington, EA Staffa, NG Moore, DT Bouffard, GG Beckstrom-Sternberg, SM Touchman, JW Bonaldo, MD Soares, MB AF Blackshear, PJ Lai, WS Thorn, JM Kennington, EA Staffa, NG Moore, DT Bouffard, GG Beckstrom-Sternberg, SM Touchman, JW Bonaldo, MD Soares, MB TI The NIEHS Xenopus maternal EST project: interim analysis of the first 13,879 ESTs from unfertilized eggs SO GENE LA English DT Article DE genomics; allelic variants; gene duplication; sequence tags ID INTERLABORATORY VALIDATION; GENUS XENOPUS; PHASE-III; TROPICALIS; ACTIVATION; PROTEINS; EMBRYOS; FETAX; BETA AB The sequencing of expressed sequence tags (ESTs) from Xenopus laevis has lagged behind efforts on many other common experimental organisms and man, partly because of the pseudotetraploid nature of the Xenopus genome. Nonetheless, large collections of Xenopus ESTs would be useful in gene discovery, oligonucleotide-based knockout studies, gene chip analyses of normal and perturbed development, mapping studies in the related diploid frog X. tropicalis, and for other reasons. We have created a normalized library of cDNAs from unfertilized Xenopus eggs. These cells contain all of the information necessary for the first several cell divisions in the early embryo, as well as much of the information needed for embryonic pattern formation and cell fate determination. To date, we have successfully sequenced 13,879 ESTs out of 16,607 attempts (83.6% success rate), with an average sequence read length of 508 bp. Using a fragment assembly program, these ESTs were assembled into 8,985 'contigs' comprised of up to 11 ESTs each. When these contigs were used to search publicly available databases, 46.2% bore no relationship to protein or DNA sequences in the database at the significance level of 1e-6. Examination of a sample of 100 of the assembled contigs revealed that most (similar to 87%) were comprised of two apparent allelic variants. Expression profiles of 16 of the most prominent contigs showed that 12 exhibited some degree of zygotic expression. These findings have implications for sequence-specific applications for Xenopus ESTs, particularly the use of allele-specific oligonucleotides for knockout studies, differential hybridization techniques such as gene chip analysis, and the establishment of accurate nomenclature and databases for this species. (C) 2001 Published by Elsevier Science B.V. All rights reserved. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NIEHS, Informat Technol Support Serv, Res Triangle Pk, NC 27709 USA. Res Genet Inc, Huntsville, AL 35801 USA. NIH Intramural Sequencing Ctr, Gaithersburg, MD 20877 USA. NHGRI, Gaithersburg, MD 20877 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 18 TC 21 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 4 PY 2001 VL 267 IS 1 BP 71 EP 87 DI 10.1016/S0378-1119(01)00383-3 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 424FU UT WOS:000168222300008 PM 11311557 ER PT J AU Gravitt, PE Castle, PE AF Gravitt, PE Castle, PE TI Chlamydia trachomatis and cervical squamous cell carcinoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Gravitt, PE (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 5 TC 12 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2001 VL 285 IS 13 BP 1703 EP 1704 DI 10.1001/jama.285.13.1703 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 415FR UT WOS:000167710600018 PM 11277819 ER PT J AU Frisch, M Biggar, RJ Engels, EA Goedert, JJ AF Frisch, M Biggar, RJ Engels, EA Goedert, JJ CA AIDS-Canc Match Registry Study Grp TI Association of cancer with AIDS-related immunosuppression in adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NON-HODGKINS-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SQUAMOUS-CELL CARCINOMA; EPSTEIN-BARR-VIRUS; HUMAN PAPILLOMAVIRUS; KAPOSIS-SARCOMA; HOMOSEXUAL MEN; TESTICULAR-CANCER; SAN-FRANCISCO; RISK-FACTORS AB nContext Large-scale studies are needed to determine if cancers other than Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer occur in excess in persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), Objectives To examine the general cancer pattern among adults with HIV/AIDS and to distinguish immunosuppression-associated cancers from other cancers that may occur in excess among persons with HIV/AIDS, Design, Setting, and Subjects Analysis of linked population-based AIDS and cancer registry data from 11 geographically diverse areas in the United States, including 302834 adults aged 15 to 69 years with HIV/AIDS, The period of study varied by registry between 1978 and 1996, Main Outcome Measure Relative risks (RRs) of cancers, calculated by dividing the number of observed cancer cases by the number expected based on contemporaneous population-based incidence rates. We defined cancers potentially influenced by immunosuppression by 3 criteria: (1) elevated overall RR in the period from 60 months before to 27 months after AIDS; (2) elevated RR in the 4- to 27-month post-AIDS period; and (3) increasing trend in RR from before to after AIDS onset, Results Expected excesses were observed for the AIDS-defining cancers, but non-AIDS-defining cancers also occurred in statistically significant excess (n =4422; overall RR, 2.7; 95% confidence interval [CI], 2,7-2,8), Of individual cancers, only Hodgkin disease (n=612; RR, 11.5; 95% CI, 10.6-12,5), particularly of the mixed cellularity (n=217; RR, 18.3; 95% CI, 15.9-20.9) and lymphocytic depletion (n=36; RR, 35.3; 95% CI, 24.7-48.8) subtypes; lung cancer (n=808; RR, 4.5; 95% CI, 4.2-4.8); penile cancer (n=14; RR, 3.9; 95% CI, 2.1-6.5); soft tissue malignancies (n=78; RR, 3.3; 95% CI, 2.6-4.1); lip cancer (n=20; RR, 3,1; 95% CI, 1.9-4.8); and testicular seminoma (n=115; RR, 2.0; 95% CI, 1.7-2.4) met all 3 criteria for potential association with immunosuppression, Conclusion Although occurring in overall excess, most non-AIDS-defining cancers do not appear to be influenced by the advancing immunosuppression associated with HIV disease progression. Some cancers that met our criteria for potential association with immunosuppression may have occurred in excess in persons with HIV/AIDS because of heavy smoking (lung cancer), frequent exposure to human papillomavirus (penile cancer), or inaccurately recorded cases of Kaposi sarcoma (soft tissue malignancies) in these persons. However, Hodgkin disease, notably of the mixed cellularity and lymphocytic depletion subtypes, and possibly lip cancer and testicular seminoma may be genuinely influenced by immunosuppression. C1 Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. RP Frisch, M (reprint author), Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 FU NCI NIH HHS [Y1-CP-8040-02] NR 45 TC 491 Z9 497 U1 2 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 4 PY 2001 VL 285 IS 13 BP 1736 EP 1745 DI 10.1001/jama.285.13.1736 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 415FR UT WOS:000167710600027 PM 11277828 ER PT J AU Strohsnitter, WC Noller, KL Hoover, RN Robboy, SJ Palmer, JR Titus-Ernstoff, L Kaufman, RH Adam, E Herbst, AL Hatch, EE AF Strohsnitter, WC Noller, KL Hoover, RN Robboy, SJ Palmer, JR Titus-Ernstoff, L Kaufman, RH Adam, E Herbst, AL Hatch, EE TI Cancer risk in men exposed in utero to diethylstilbestrol SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TESTICULAR CANCER; BREAST-CANCER; FOLLOW-UP; STILBESTROL THERAPY; ESTROGEN-RECEPTOR; YOUNG-ADULTS; PREGNANCY; MOTHERS; PROGESTERONE; INUTERO AB Background: An association between prenatal diethylstilbestrol (DES) exposure and cancer in men, especially testicular cancer, has been suspected, but findings from case-control studies have been inconsistent. This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospective follow-up. Methods: A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994, The overall and site-specific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population-based rates. The relative rate (RR) was used to assess the strength of the association between prenatal DES exposure and cancer development. All statistical tests were two-sided. Results: Overall cancer rates among DES-exposed men were similar to those among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be elevated among DES-exposed men, since the RRs for testicular cancer were 3.05 (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95% CI = 0.82 to 4.20) times those of males in the population-based rates. The higher rate of testicular cancer in the DES-exposed men is, however, also compatible with a chance observation. Conclusions: To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer. C1 Tufts Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02111 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Slone Epidemiol Unit, Brookline, MA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Baylor Coll Med, Dept Epidemiol, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Strohsnitter, WC (reprint author), New England Med Ctr, Dept Obstet & Gynecol, 750 Washington St,N Bldg, Boston, MA 02111 USA. FU NCI NIH HHS [N01CP21167] NR 45 TC 115 Z9 118 U1 0 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2001 VL 93 IS 7 BP 545 EP 551 DI 10.1093/jnci/93.7.545 PG 7 WC Oncology SC Oncology GA 416UT UT WOS:000167799100016 PM 11287449 ER PT J AU Roberts, AB Piek, E De Caestecker, MP AF Roberts, AB Piek, E De Caestecker, MP TI Re: Role of transforming growth factor-beta signaling in cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bldg 41,Rm C629,41 Lib Dr,MSC 505, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2001 VL 93 IS 7 BP 556 EP 557 DI 10.1093/jnci/93.7.556 PG 2 WC Oncology SC Oncology GA 416UT UT WOS:000167799100020 ER PT J AU Gail, MH Brown, LM You, WC AF Gail, MH Brown, LM You, WC TI Re: Chemoprevention of gastric dysplasia: Randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS-8032, Bethesda, MD 20892 USA. NR 1 TC 5 Z9 6 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2001 VL 93 IS 7 BP 559 EP 559 DI 10.1093/jnci/93.7.559 PG 1 WC Oncology SC Oncology GA 416UT UT WOS:000167799100023 PM 11287457 ER PT J AU Torigoe, C Metzger, H AF Torigoe, C Metzger, H TI Spontaneous phosphorylation of the receptor with high affinity for IgE in transfected fibroblasts SO BIOCHEMISTRY LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; BASOPHILIC LEUKEMIA-CELLS; RESONANCE ENERGY-TRANSFER; FC-EPSILON-RI; IMMUNOGLOBULIN-E; MEMBRANE GLYCOPROTEIN; SIGNAL-TRANSDUCTION; BETA-SUBUNIT; MAST-CELLS; RAT AB Receptors with high affinity for IgE, Fc epsilon RI, which had been transfected into Chinese hamster ovary fibroblasts exhibit an over 20-fold greater spontaneous phosphorylation at physiological temperatures than the same receptors on the widely studied rat mucosal mast cell line, RBL-2H3. This enhanced phosphorylation was not accounted for either by changes in the src-family kinase responsible for the phosphorylation, by reduced activity of phosphatases, or by spontaneous association of the receptors with microdomains. A variety of approaches failed to detect evidence for stable spontaneous aggregates of the receptor. Whereas the altered posttranslational glycosylation of the receptor's principal ectodomain we detected could promote transient spontaneous aggregation and explain the observed effect, other changes in the membrane milieu cannot be excluded. The functional consequences of such spontaneous phosphorylation are considered. C1 NIAMS, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIAMS, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 56 TC 12 Z9 12 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2001 VL 40 IS 13 BP 4016 EP 4025 DI 10.1021/bi0027534 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 416UM UT WOS:000167798600028 PM 11300782 ER PT J AU Merrick, BA Zhou, W Martin, KJ Jeyarajah, S Parker, CE Selkirk, JK Tomer, KB Borchers, CH AF Merrick, BA Zhou, W Martin, KJ Jeyarajah, S Parker, CE Selkirk, JK Tomer, KB Borchers, CH TI Site-specific phosphorylation of human p53 protein determined by mass spectrometry SO BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Meeting of the American-Association-of-Mass-Spectrometry CY JUN 08-11, 1999 CL DALLAS, TEXAS SP Amer Assoc Mass Spectrometry ID WILD-TYPE P53; DAMAGE-INDUCED PHOSPHORYLATION; DNA-BINDING FUNCTION; OKADAIC ACID; GROWTH ARREST; IN-VITRO; DEPENDENT PHOSPHORYLATION; IONIZING-RADIATION; CARBOXY-TERMINUS; KINASE AB Human recombinant p53 (r-p53) protein was studied by mass spectrometry (MS) to determine site-specific posttranslational differences between basal and hyperphosphorylated r-p53. Wild-type p53 was basally expressed after baculovirus infection while a parallel preparation was treated with the phosphatase inhibitor okadaic acid during the terminal stages of expression to create a hyperphosphorylated form of p53 known for its higher DNA binding and transcriptional activation. After immunoaffinity and HPLC purification, MALDI/MS measured a higher molecular mass for r-p53 from okadaic acid treatment relative to control, suggesting a higher phosphorylation state. This was supported by an acidic shift of r-p53 isoforms separated by gel isoelectric focusing. Employing a variety of mass spectrometric analyses combined with separation and affinity techniques, six specific phosphorylation sites of p53 were identified. The MS data indicated that hyperphosphorylated p53 showed a higher degree of phosphorylation than basal p53 at specific amino- and carboxy-terminal sites. In particular, ESI-MS demonstrated that Ser(315) was entirely phosphorylated after okadaic acid treatment, as confirmed biochemically by CDK2 kinase assay and by isoelectric focusing. In summary, MS analysis uniquely revealed increased, site-specific phosphorylations on p53 after phosphatase inhibition, particularly at Ser(315), which may be critical molecular events in defining p53 activity. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Borchers, CH (reprint author), NIEHS, Struct Biol Lab, MD-F0-04,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 65 TC 28 Z9 28 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2001 VL 40 IS 13 BP 4053 EP 4066 DI 10.1021/bi002045i PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 416UM UT WOS:000167798600032 PM 11300786 ER PT J AU Paniagua, OA Bryant, MB Panza, JA AF Paniagua, OA Bryant, MB Panza, JA TI Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature - Diminished activity in hypertensive and hypercholesterolemic patients SO CIRCULATION LA English DT Article DE microcirculation; endothelium; nitric oxide; hypertension; hypercholesterolemia ID DEPENDENT VASCULAR RELAXATION; FOREARM RESISTANCE VESSELS; MUSCLE ARTERIOLES; INDUCED DILATION; BLOOD-FLOW; DILATATION; MICROCIRCULATION; ATHEROSCLEROSIS; PATHWAY; RATS AB Background-It has been proposed that flow-mediated shear stress regulates vascular tone; however, whether this operates in the human microcirculation is unknown. This study was designed to investigate the effect of shear stress on human microvascular tone, to assess the contribution of nitric oxide (NO), and to determine whether this mechanism is defective in hypertension and in hypercholesterolemia. Methods and Results-In 9 normal controls (NC), 1 1 hypertensive patients (HT), and 12 hypercholesterolemic patients (HChol), arteries (internal diameter 201 +/- 26 mum) isolated from gluteal fat biopsies were cannulated and perfused in chambers. Shear stress was induced by increasing the flow rate from 1 to 50 muL/min after preconstriction with norepinephrine (NE). Arterial internal diameter was expressed as percent of NE-induced constriction. In NC, shear stress induced flow-dependent vasodilation from 23 +/-9% at 1 muL/min to 53 +/- 14% at 50 muL/min (P<0.0001), which was abolished by endothelial removal, The NO synthase inhibitor Nw-nitro-L-arginine (L-NNA) significantly blunted this response (mean vasodilation decreased from 276% to 6 +/-9%; P=0.04). HT had significant impairment of flow-mediated dilation (mean vasodilation 5 +/-6%; P=0.01 versus NC), which was not affected by L-NNA. HChol had preserved now-mediated vasodilation (mean vasodilation 24 +/-7%; P=0.56 versus NC), but this was not significantly modified by L-NNA. Conclusions-In the human microvasculature, shear stress induces endothelium-dependent, NO-mediated vasodilation. This phenomenon is blunted in HT patients because of reduced activity of NO. Tn contrast, the HChol microvasculature has preserved shear stress-induced dilation despite diminished NO activity. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, 10 Ctr Dr,MSC 1650,Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 28 TC 90 Z9 100 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 3 PY 2001 VL 103 IS 13 BP 1752 EP 1758 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 420FT UT WOS:000167994900008 PM 11282906 ER PT J AU Lichten, M AF Lichten, M TI Meiotic recombination: Breaking the genome to save it SO CURRENT BIOLOGY LA English DT Article ID CHROMOSOME SYNAPSIS; MOUSE SPERMATOCYTES; GENETIC-CONTROL; YEAST MEIOSIS; SPO11; PROGRESSION; PROTEINS AB Recombination ensures the correct segregation of chromosomes to gametes during meiosis. Recent studies point to a universal mechanism for initiating meiotic recombination: the formation of double-strand DNA breaks by Spo11p. C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Lichten, M (reprint author), NCI, Biochem Lab, Bldg 37 Room 6124, Bethesda, MD 20892 USA. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 24 TC 52 Z9 53 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 3 PY 2001 VL 11 IS 7 BP R253 EP R256 DI 10.1016/S0960-9822(01)00131-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 438WF UT WOS:000169076700006 PM 11413012 ER PT J AU Mal, A Sturniolo, M Schiltz, RL Ghosh, MK Harter, ML AF Mal, A Sturniolo, M Schiltz, RL Ghosh, MK Harter, ML TI A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program SO EMBO JOURNAL LA English DT Article DE HDAC1; MyoD; myogenic conversion; skeletal muscle cells ID CELL-CYCLE WITHDRAWAL; DNA-BINDING PROTEINS; SKELETAL-MUSCLE DIFFERENTIATION; RETINOBLASTOMA PROTEIN; TERMINAL DIFFERENTIATION; REPRESS TRANSCRIPTION; KINASE-ACTIVITY; GENE-TRANSCRIPTION; EPITHELIAL-CELLS; SODIUM-BUTYRATE AB The molecular mechanism(s) that are responsible for suppressing MyoD's transcriptional activities in undifferentiated skeletal muscle cells have not yet been determined. We now show that MyoD associates with a histone deacetylase-1 (HDAC1) in these cells and that this interaction is responsible for silencing MyoD-dependent transcription of endogenous p21 as well as muscle-specific genes. Specifically, we present evidence that HDAC1 can bind directly to MyoD and use an acetylated MyoD as a substrate in vitro, whereas a mutant version of HDAC1 (H141A) can not. Furthermore, this mutant also fails to repress MyoD-mediated transcription in vivo, and unlike wild-type HDAC1 it can not inhibit myogenic conversion, as judged by confocal microscopy. Finally, we show that an endogenous MyoD can be acetylated upon its conversion to a hypophosphorylated state and only when the cells have been induced to differentiate. These results provide for a model which postulates that MyoD may be co-dependent on HDAC1 and P/CAF for temporally controlling its transcriptional activity before and after the differentiation of muscle cells. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Biol, Cleveland, OH 44195 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Harter, ML (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NIGMS NIH HHS [GM54014] NR 77 TC 167 Z9 170 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 2 PY 2001 VL 20 IS 7 BP 1739 EP 1753 DI 10.1093/emboj/20.7.1739 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 420AH UT WOS:000167981400025 PM 11285237 ER PT J AU Shumaker, DK Lee, KK Tanhehco, YC Craigie, R Wilson, KL AF Shumaker, DK Lee, KK Tanhehco, YC Craigie, R Wilson, KL TI LAP2 binds to BAF center dot DNA complexes: requirement for the LEM domain and modulation by variable regions SO EMBO JOURNAL LA English DT Article DE barrier-to-autointegration factor; emerin; Emery-Dreifuss muscular dystrophy; lamin-associated polypeptide 2 (LAP2); nuclear envelope ID LAMINA-ASSOCIATED POLYPEPTIDE-2; DREIFUSS MUSCULAR-DYSTROPHY; NUCLEAR-MEMBRANE PROTEIN; TO-AUTOINTEGRATION FACTOR; ENVELOPE INNER MEMBRANE; CELL-CYCLE; STRUCTURE DYNAMICS; TARGETING DOMAIN; INTEGRAL PROTEIN; RETROVIRAL DNA AB LAP2 belongs to a family of nuclear membrane proteins sharing a 43 residue LEM domain. All LAP2 isoforms have the same N-terminal 'constant' region (LAP2-c), which includes the LEM domain, plus a C-terminal 'variable' region. LAP2-c polypeptide inhibits nuclear assembly in Xenopus extracts, and binds in vitro to barrier-to-autointegration factor (BAF), a DNA-bridging protein. We tested 17 Xenopus LAP2-c mutants for nuclear assembly inhibition, and binding to BAF and BAB DNA complexes. LEM domain mutations disrupted all activities tested. Some mutations outside the LEM domain had no effect on binding to BAF, but disrupted activity in Xenopus extracts, suggesting that LAP2-c has an additional unknown function required to inhibit nuclear assembly. Mutagenesis results suggest that BAF changes conformation when complexed with DNA. The binding affinity of LAP2 was higher for BAF DNA complexes than for BAF, suggesting that these interactions are physiologically relevant. Nucleoplasmic domains of Xenopus LAP2 isoforms varied 9-fold in their affinities for BAF, but all isoforms supershifted BAP DNA complexes. We propose that the LEM domain is a core BAF-binding domain that can be modulated by the variable regions of LAP2 isoforms. C1 Johns Hopkins Univ, Sch Med, Dept Cell Biol & Anat, Baltimore, MD 21205 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wilson, KL (reprint author), Johns Hopkins Univ, Sch Med, Dept Cell Biol & Anat, 725 N Wolfe St, Baltimore, MD 21205 USA. FU NIGMS NIH HHS [R01 GM048646, R01 GM48646] NR 43 TC 135 Z9 141 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 2 PY 2001 VL 20 IS 7 BP 1754 EP 1764 DI 10.1093/emboj/20.7.1754 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 420AH UT WOS:000167981400026 PM 11285238 ER PT J AU Yang, X Chen, L Xu, XL Li, CL Huang, CF Deng, CX AF Yang, X Chen, L Xu, XL Li, CL Huang, CF Deng, CX TI TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage SO JOURNAL OF CELL BIOLOGY LA English DT Article DE TGF-beta/SMad3; mouse model; osteoarthritis; synovium; growth plate ID GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEINS; MURINE KNEE-JOINT; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; RHEUMATOID-ARTHRITIS; TARGETED DISRUPTION; PROTEOGLYCAN LOSS; GENE-EXPRESSION; SKELETAL TISSUE AB Endochondral ossification begins from the condensation and differentiation of mesenchymal cells into cartilage. The cartilage then goes through a program of cell proliferation, hypertrophic differentiation, calcification, apoptosis, and eventually is replaced by bone. Unlike most cartilage. articular cartilage is arrested before terminal hypertrophic differentiation. In this study, we showed that TGF-beta /Smad3 signals inhibit terminal hypertrophic differentiation of chondrocyte and are essential for maintaining articular cartilage. Mutant mice homozygous for a targeted disruption of Smad3 exon 8 (Smad3(ex8/ex8)) developed degenerative joint disease resembling human osteoarthritis, as characterized by progressive loss of articular cartilage, formation of large osteophytes, decreased production of proteoglycans, and abnormally increased number of type X collagen-expressing chondrocytes in synovial joints. Enhanced terminal differentiation of epiphyseal growth plate chondrocytes was also observed in mutant mice shortly after weaning. In an in vitro embryonic metatarsal rudiment culture system, we found that TGF-beta1 significantly inhibits chondrocyte differentiation of wild-type metatarsal rudiments. However, this inhibition is diminished in metatarsal bones isolated from Smad3(ex8/ex8) mice. These data suggest that TGF-beta /Smad3 signals are essential for repressing articular chondrocyte differentiation, Without these inhibition signals, chondrocytes break quiescent state and undergo abnormal terminal differentiation, ultimately leading to osteoarthritis. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Inst Biotechnol, Beijing 100071, Peoples R China. RP Deng, CX (reprint author), NIDDK, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 77 TC 330 Z9 364 U1 2 U2 18 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 2 PY 2001 VL 153 IS 1 BP 35 EP 46 DI 10.1083/jcb.153.1.35 PG 12 WC Cell Biology SC Cell Biology GA 419BP UT WOS:000167929700004 PM 11285272 ER PT J AU Mousa, SA Zhang, Q Sitte, N Ji, RR Stein, C AF Mousa, SA Zhang, Q Sitte, N Ji, RR Stein, C TI beta-endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE pain; narcotic; neuro-immune interactions; sensory neurons; memory cells ID DORSAL-ROOT GANGLIA; CAPSAICIN-SENSITIVE NEURONS; ENHANCES AXONAL-TRANSPORT; SPINAL-CORD; OPIATE RECEPTORS; GENE-EXPRESSION; HIGH-AFFINITY; IMMUNE CELLS; RAT-BRAIN; INFLAMMATION AB Immunocyte-derived beta -endorphin can activate peripheral opioid receptors on sensory neurons to inhibit pain within inflamed tissue. This study examined mu -opioid receptors (MOR) on sensory nerves and beta -endorphin (END) in activated/memory CD4(+) cells (the predominant population homing to inflamed tissue). We found an upregulation of MOR in dorsal root ganglia, an increased axonal transport of MOR in the sciatic nerve and an accumulation of MOR in peripheral nerve terminals in Freund's adjuvant-induced hindpaw inflammation. A large number of CD4(+) cells containing beta -endorphin, but very few naive cells (CD45RC(+)), were observed in inflamed tissue, suggesting that this opioid is mainly present in activated/memory cells (CD4(+)/CD45RC(-)). Taken together, our results indicate an enhanced transport of both MOR and of the endogenous ligand beta -endorphin to injured tissue. This unique simultaneous upregulation of both receptors and ligands may serve to prevent excessive and/or chronic inflammatory pain. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Free Univ Berlin, Klin Anaesthesiol & Operat Intens Med, D-12200 Berlin, Germany. Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NIDA, Behav Pharmacol & Genet Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. RP Mousa, SA (reprint author), Free Univ Berlin, Klin Anaesthesiol & Operat Intens Med, Hindenburgdamm 30, D-12200 Berlin, Germany. FU NINDS NIH HHS [R01NS32466] NR 41 TC 130 Z9 139 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 2 PY 2001 VL 115 IS 1-2 BP 71 EP 78 DI 10.1016/S0165-5728(01)00271-5 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 419JW UT WOS:000167946400008 PM 11282156 ER PT J AU Bonifant, CL Buzard, GS Ji, XH Singh, SV Shami, PJ Saavedra, JE Keefer, LK AF Bonifant, CL Buzard, GS Ji, XH Singh, SV Shami, PJ Saavedra, JE Keefer, LK TI Design and synthesis of arylated diazeniumdiolates with anti-leukemic activity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, SAIC, IRSP, Frederick, MD 21702 USA. NCI, Struct Biol Program, Frederick, MD 21702 USA. Mercy Hosp, Canc Res Lab, Pittsburgh, PA USA. Univ Utah, Div Oncol, Salt Lake City, UT 84112 USA. VA Med Ctr, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 292-MEDI BP U51 EP U51 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800287 ER PT J AU Brooks, BR Steinbach, PJ AF Brooks, BR Steinbach, PJ TI Temperature and hydration dependence of protein dynamics examined by macromolecular simulation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, CIT, Ctr Mol Modeling, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 386-PHYS BP U292 EP U292 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801708 ER PT J AU Byrd, RA AF Byrd, RA TI Modern multi-dimensional NMR spectroscopy of biopolymers - New techniques, new labeling, new parameters, new dynamics. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 206-POLY BP U325 EP U325 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801927 ER PT J AU Cantoni, G Bonner, RF Sehgal, A Douglas, JF Karim, A AF Cantoni, G Bonner, RF Sehgal, A Douglas, JF Karim, A TI High-throughput polymer microwell arrays for Laser Capture Microdissection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. NIST, Div Polymers, MSEL, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 72-BTEC BP U465 EP U465 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824802815 ER PT J AU Cao, JJ Husbands, SM Kopajtic, T Katz, JL Newman, AH AF Cao, JJ Husbands, SM Kopajtic, T Katz, JL Newman, AH TI [3-cis-3,5-dimethyl-1-piperazinyl)alkyl]-bis-(4 '-fluorophenyl)amine analogs as novel probes for the dopamine transporter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA, Med Chem Sect, IRP, Baltimore, MD 21224 USA. NIDA, Psychol Sect, IRP, Baltimore, MD 21224 USA. RI Husbands, Stephen/D-5926-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 96-MEDI BP U17 EP U17 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800096 ER PT J AU Chong, HS Garmestani, K Bryant, LH Brechbiel, MW AF Chong, HS Garmestani, K Bryant, LH Brechbiel, MW TI Synthesis of DTPA analogs derived from piperidine and azepine: Potential contrast enhancement agents for magnetic resonance imaging. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Diagnost Radiol Res Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 155-ORGN BP U120 EP U120 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800713 ER PT J AU Chong, HS Garmestani, K Brechbiel, MW AF Chong, HS Garmestani, K Brechbiel, MW TI Design, synthesis, and evaluation of novel NOTA-like macrocycles with pendant donor groups as potential radioimmunotherapy agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Radiat Oncol Branch, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 46-MEDI BP U8 EP U8 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800046 ER PT J AU Coxon, B Pozsgay, V AF Coxon, B Pozsgay, V TI Applications of NMR spectroscopy in vaccine research. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD 20892 USA. EM coxonb@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 71-CARB BP U166 EP U166 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700807 ER PT J AU Doak, DL Phillips, JA AF Doak, DL Phillips, JA TI Closed-loop control of a fed-batch E-coli fermentation using on-line mid-IR spectroscopy. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Biopharmaceut Dev Program, Ft Detrick, MD 21702 USA. Centocor Inc, Malvern, PA 19355 USA. EM denisedoak@netscape.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 58-BIOT BP U117 EP U117 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700535 ER PT J AU Fan, H Scheffel, U Finley, PA Dannals, RF Wong, DF Fitch, R Xiao, YX Kellar, KJ Musachio, JL AF Fan, H Scheffel, U Finley, PA Dannals, RF Wong, DF Fitch, R Xiao, YX Kellar, KJ Musachio, JL TI C-11 labeled 5-propargyl-O-methyl and 5-propyl-O-methyl analogs of A-85380 as in vivo markers of central nicotinic acetylcholine receptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Pharmacol, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 81-MEDI BP U14 EP U15 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800081 ER PT J AU Frankel, SL Maglott, DR AF Frankel, SL Maglott, DR TI LocusLink and RefSeq: Developing tools for genomic annotation and analysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Yeshiva Univ, Stern Coll Women, Dept Biol, New York, NY 10016 USA. Yeshiva Univ, Stern Coll Women, Dept Comp Sci, New York, NY 10016 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA. EM slfranke@ymail.yu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 448-CHED BP U169 EP U169 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824701416 ER PT J AU Gabrielsen, B Boyd, M Cragg, G Hamel, E Harris, C Johnson, J Le Grice, S Pommier, Y Roberts, A Schneider, T Shoemaker, R Sybert, K AF Gabrielsen, B Boyd, M Cragg, G Hamel, E Harris, C Johnson, J Le Grice, S Pommier, Y Roberts, A Schneider, T Shoemaker, R Sybert, K TI National Cancer Institute initiatives, resources, and opportunities for collaboration in the development of therapeutics. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Technol Dev & Commercializat Branch, Fairview Ctr, Frederick, MD 21701 USA. NCI, Div Basic Sci, Frederick, MD USA. NCI, Dev Therapeut Program, Frederick, MD USA. NCI, Div Basic Sci, Bethesda, MD USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Technol Dev & Commercializat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 221-MEDI BP U39 EP U39 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800218 ER PT J AU Garcia, AE Hummer, G AF Garcia, AE Hummer, G TI Water penetration and escape in proteins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA. NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 88-PHYS BP U240 EP U240 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801413 ER PT J AU Gilbert, E AF Gilbert, E TI Cancer studies in radiation worker populations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 27-NUCL BP U68 EP U68 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800387 ER PT J AU Haley, MA Chuang, EJ Panyutin, IV Panyutin, IG Neumann, RD AF Haley, MA Chuang, EJ Panyutin, IV Panyutin, IG Neumann, RD TI In vitro sequence specific gene targeting by triplex forming oligonucleotides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Carroll Coll, Dept Biol, Waukesha, WI 53186 USA. Carroll Coll, Dept Chem, Waukesha, WI 53186 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. EM mhaley@cc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 604-CHED BP U192 EP U192 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824701571 ER PT J AU Harms, GS Cognet, L Lommerse, PHM Blab, GA Kahr, H Soldatov, N Romanin, C Schmidt, T AF Harms, GS Cognet, L Lommerse, PHM Blab, GA Kahr, H Soldatov, N Romanin, C Schmidt, T TI Aggregation of individual eYFP-labeled human cardiac L-type calcium channels in living cell membranes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Pacific NW Natl Lab, EMSL, Richland, WA 99352 USA. Univ Bordeaux, Bordeaux, France. Leiden Univ, Leiden, Netherlands. Univ Linz, A-4040 Linz, Austria. NIH, Bethesda, MD 20892 USA. RI Blab, Gerhard/D-2275-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 343-PHYS BP U285 EP U285 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801665 ER PT J AU Hernandez, S Ford, H Marquez, VE AF Hernandez, S Ford, H Marquez, VE TI Chirospecific synthesis of a conformationally restricted analog of 2 '-deoxycoformycin containing a bicyclo[3.1.0]hexane pseudosugar. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 325-MEDI BP U57 EP U57 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800319 ER PT J AU Horkay, F McKenna, GB Geissler, E AF Horkay, F McKenna, GB Geissler, E TI Structural hierarchy in polyisoprene/toluene gels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Texas Tech Univ, Dept Chem Engn, Lubbock, TX 79409 USA. Univ Grenoble 1, CNRS UMR 5588, Spectrometrie Phys Lab, Grenoble, France. RI McKenna, Gregory/O-1134-2013 OI McKenna, Gregory/0000-0002-5676-9930 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 139-POLY BP U314 EP U314 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801861 ER PT J AU Horkay, F Basser, PJ Geissler, E AF Horkay, F Basser, PJ Geissler, E TI Ion-induced volume transition in synthetic and biopolymer gels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NICHD, Lab Integrated & Med Biophys, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, F-38041 Grenoble, France. RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 17-POLY BP U297 EP U297 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801739 ER PT J AU Hummer, G Siebert, X AF Hummer, G Siebert, X TI Mapping protein surfaces: Results for the coiled coil of HIV-1 gp41. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 155-PHYS BP U250 EP U251 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801479 ER PT J AU Lapidus, LJ Eaton, WA Hofrichter, J AF Lapidus, LJ Eaton, WA Hofrichter, J TI Dynamics of contact formation in polypeptides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Chem Phys Lab, Bethesda, MD 20892 USA. EM jim@sunder.niddk.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 204-COMP BP U431 EP U431 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824702968 ER PT J AU Lubin, J AF Lubin, J TI Exposure to residential radon. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 24-NUCL BP U68 EP U68 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800384 ER PT J AU McAfee, JG AF McAfee, JG TI Recent advances in immunology are influencing nuclear medicine. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 153-NUCL BP U86 EP U86 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800513 ER PT J AU Mu, FR Cushman, M Riese, DJ Geahlen, RL Verdier-Pinard, P Hamel, E Johnson, J AF Mu, FR Cushman, M Riese, DJ Geahlen, RL Verdier-Pinard, P Hamel, E Johnson, J TI Synthesis and biological evaluation of new lavendustin A analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 146-MEDI BP U26 EP U26 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800144 ER PT J AU Ohrui, H Mitsuya, H AF Ohrui, H Mitsuya, H TI Development structurally new nucleosides highly active against multi-drug-resistant HIV. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Tohoku Univ, Dept Agr Chem, Sendai, Miyagi 9818555, Japan. NCI, Expt Retrovirol Sect, Bethesda, MD 20892 USA. EM ohrui@biochem.tohoku.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 97-CARB BP U170 EP U170 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700833 ER PT J AU Rhoden, JB Lomenzo, SA Izenwasser, S Wade, D Katz, JL Kopajtic, T Trudell, ML AF Rhoden, JB Lomenzo, SA Izenwasser, S Wade, D Katz, JL Kopajtic, T Trudell, ML TI Synthesis and structure-activity relationship studies of meperidine analogs at the dopamine transporter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA. Univ Miami, Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. NIDA, Div Intramural Res, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 93-MEDI BP U16 EP U16 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800093 ER PT J AU Shapiro, CA Camerini-Otero, C Daly, JW Ma, JY Ziffer, H AF Shapiro, CA Camerini-Otero, C Daly, JW Ma, JY Ziffer, H TI Loperamide analogs as positive modulators of calcium influx in leukemic HL-60 cells. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Colgate Univ, Dept Chem, Hamilton, NY 13346 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 124-MEDI BP U22 EP U22 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800122 ER PT J AU Szu, SC Kossaczka, Z Lin, K Schneerson, R Robbins, JB AF Szu, SC Kossaczka, Z Lin, K Schneerson, R Robbins, JB TI Advances in conjugate vaccines: Development of Vi-rEPA for typhoid fever. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NICHHD, Bethesda, MD 20892 USA. EM szus@dir6.nichd.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 39-BIOT BP U113 EP U113 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700516 ER PT J AU Tang, Y Nicklaus, MC AF Tang, Y Nicklaus, MC TI Molecular modeling of full-length HIV-1 integrase and its complexes with viral and human DNAs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Canc Inst, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM yuntang@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 174-COMP BP U427 EP U427 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824702938 ER PT J AU Tomer, KB Borchers, CH Dial, JM Walker, NJ Hartis, JE Wetmore, BA Barrett, JC Merrick, BA AF Tomer, KB Borchers, CH Dial, JM Walker, NJ Hartis, JE Wetmore, BA Barrett, JC Merrick, BA TI Role of mass spectrometry in a molecular approach to the investigation of the physiological effects of environmental toxins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC USA. EM tomer@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 91-ENVR BP U458 EP U458 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824703109 ER PT J AU Valdez, CA Saavedra, JE Keefer, LK Barchi, JJ AF Valdez, CA Saavedra, JE Keefer, LK Barchi, JJ TI Carbohydrates as novel diazeniumdiolate protecting groups. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, SAIC, IRSP, Frederick, MD 21702 USA. NCI, Med Chem Lab, Frederick, MD 21702 USA. EM valdezc@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 43-CARB BP U161 EP U162 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700780 ER PT J AU Venkateswarlu, D Perera, L Darden, T Pedersen, LG AF Venkateswarlu, D Perera, L Darden, T Pedersen, LG TI Structure and dynamics of zymogenic form of blood coagulation factor X: Molecular dynamics investigation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27519 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. EM divi@email.unc.edu RI Pedersen, Lee/E-3405-2013; Venkateswarlu, Divi/K-1815-2014 OI Pedersen, Lee/0000-0003-1262-9861; Venkateswarlu, Divi/0000-0003-2481-7480 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 218-COMP BP U433 EP U434 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824702982 ER PT J AU Webb, TR Lvovskiy, D Melman, N Ji, X Linden, J Jacobson, KA AF Webb, TR Lvovskiy, D Melman, N Ji, X Linden, J Jacobson, KA TI Discovery of new antagonists of the adenosine A2B receptor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ChemBridge Corp, San Diego, CA 92127 USA. NIH, NIDDK, Mol Recognit Sect, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA 22903 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 30-MEDI BP U6 EP U6 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800030 ER PT J AU Weber, HA Zart, MK White, KD Harris, RK Clark, AP Greaves, JG Overstreet, D Smith, C AF Weber, HA Zart, MK White, KD Harris, RK Clark, AP Greaves, JG Overstreet, D Smith, C TI Characterization of the herbal product goldenseal (Hydrastis canadensis L.): A practical approach. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Midwest Res Inst, Kansas City, MO 64110 USA. NIEHS, Res Triangle Pk, NC 27709 USA. EM hweber@mriresearch.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 90-ENVR BP U458 EP U458 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824703108 ER PT J AU Yan, SQ Sigano, DM Tang, Y Voigt, JH Nicklaus, MC Marquez, VE AF Yan, SQ Sigano, DM Tang, Y Voigt, JH Nicklaus, MC Marquez, VE TI Docking and molecular dynamic studies of diacylglycerols binding to protein kinase C. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NCI, Med Chem Lab, Frederick, MD 21702 USA. EM yshunqi@helix.nih.gov RI Sigano, Dina/M-6144-2014 OI Sigano, Dina/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 179-COMP BP U428 EP U428 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824702943 ER PT J AU Zhu, XX Greig, NH Mattson, MP Culmsee, C Yu, QS AF Zhu, XX Greig, NH Mattson, MP Culmsee, C Yu, QS TI Design and synthesis of novel p53 inhibitors for neuroprotection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, LNS, GRC, Baltimore, MD 21224 USA. Univ Marburg, Inst Pharmakol & Toxikol, D-3550 Marburg, Germany. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 107-MEDI BP U19 EP U19 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800107 ER PT J AU Zou, MF Belov, Y Agoston, G Kopajtic, T Katz, JL Newman, AH AF Zou, MF Belov, Y Agoston, G Kopajtic, T Katz, JL Newman, AH TI Synthesis of (S)-2-beta-carboalkoxy-3-alpha-[bis(4-fluorophenyl)methoxy]tropanes and binding at the dopamine transporter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA, IRP, Med Chem Sect, Baltimore, MD 21224 USA. NIDA, IRP, Psychobiol Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 89-MEDI BP U16 EP U16 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800089 ER PT J AU Straus, SE AF Straus, SE TI Dancing with a dream: The folly of pursuing alternative medicine - Reply SO ACADEMIC MEDICINE LA English DT Letter C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2001 VL 76 IS 4 BP 303 EP 303 DI 10.1097/00001888-200104000-00002 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 422RF UT WOS:000168132500002 ER PT J AU Croft, BY Hoffman, JM AF Croft, BY Hoffman, JM TI NCI-funded small animal imaging programs SO ACADEMIC RADIOLOGY LA English DT Article C1 NCI, Biomed Imaging Program, Bethesda, MD 20892 USA. RP Croft, BY (reprint author), NCI, Biomed Imaging Program, 6130 Execut Blvd,EPN 6064, Bethesda, MD 20892 USA. RI Croft, Barbara/D-1248-2013 OI Croft, Barbara/0000-0003-2544-150X NR 0 TC 2 Z9 2 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 APR PY 2001 VL 8 IS 4 BP 372 EP 374 DI 10.1016/S1076-6332(03)80511-1 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 433QG UT WOS:000168770800012 PM 11293784 ER PT J AU Evdokimov, A Gilboa, AJ Koetzle, TF Klooster, WT Schultz, AJ Mason, SA Albinati, A Frolow, F AF Evdokimov, A Gilboa, AJ Koetzle, TF Klooster, WT Schultz, AJ Mason, SA Albinati, A Frolow, F TI Structures of furanosides: geometrical analysis of low-temperature X-ray and neutron crystal structures of five crystalline methyl pentofuranosides SO ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE LA English DT Article ID RING; DIFFRACTION; HYDROGEN; PSEUDOROTATION AB Crystal structures of all five crystalline methyl D-pentofuranosides, methyl alpha -D-arabinofuranoside (1), methyl beta -D-arabinofuranoside (2), methyl alpha -D-lyxofuranoside (3), methyl beta -D-ribofuranoside (4) and methyl alpha -D-xylofuranoside (5) have been determined by means of cryogenic X-ray and neutron crystallography. The neutron diffraction experiments provide accurate. unbiased H-atom positions which are especially important because of the critical role of hydrogen bonding in these systems. This paper summarizes the geometrical and conformational parameters of the structures of all five crystalline methyl pentofuranosides, several of them reported here for the first time. The methyl pentofuranoside structures are compared with the structures of the five crystalline methyl hexopyranosides for which accurate X-ray and neutron structures have been determined. Unlike the methyl hexopyranosides, which crystallize exclusively in the C-1 chair conformation, the five crystalline methyl pentofuranosides represent a very wide range of ring conformations. C1 NCI, Prot Engn Sect, Program Struct Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Argonne Natl Lab, Div Intense Pulsed Neutron Source, Argonne, IL 60439 USA. Inst Max Von Laue Paul Langevin, F-38042 Grenoble 9, France. Univ Milan, Ist Chim Farmaceut, I-20131 Milan, Italy. Tel Aviv Univ, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. RP Evdokimov, A (reprint author), NCI, Prot Engn Sect, Program Struct Biol, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. RI mason, sax /E-6738-2011; Frolow, Felix/A-1760-2013; Albinati, Alberto/I-1262-2015 OI Albinati, Alberto/0000-0002-8779-3327 NR 36 TC 16 Z9 16 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7681 J9 ACTA CRYSTALLOGR B JI Acta Crystallogr. Sect. B-Struct. Sci. PD APR PY 2001 VL 57 BP 213 EP 220 DI 10.1107/S010876810001661X PN 2 PG 8 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA 422MN UT WOS:000168122700013 PM 11262436 ER PT J AU Mascarucci, P Taub, D Saccani, S Paloma, MA Dawson, H Roth, GS Ingram, DK Lane, MA AF Mascarucci, P Taub, D Saccani, S Paloma, MA Dawson, H Roth, GS Ingram, DK Lane, MA TI Age-related changes in cytokine production by leukocytes in rhesus monkeys SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE IL-1; IL-6; IL-10; IFN gamma; TNF alpha; rhesus monkey; PBMCs ID BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; IMMUNE-SYSTEM; DIETARY RESTRICTION; NONHUMAN-PRIMATES; INTERFERON-GAMMA; WHOLE-BLOOD; IFN-GAMMA; EXPRESSION; IMMUNOSENESCENCE AB Using a variety of experimental rodent and human models, age-related alterations in cytokine production by immune cells have been described extensively. While the precise mechanism(s) responsible for such age-related changes in cytokine responses remain unclear, it seems likely that these changes may have a significant effect on immune cell function. In an attempt to clarify such changes in aging primates, we examined cytokine production by white cells derived from a controlled colony of rhesus monkeys (Macaca mulatta). Non-fractionated whole blood and peripheral blood mononuclear cells (PBMCs) were obtained from male monkeys of different ages (6-28 years), and were subsequently evaluated for their ability to express mRNA and protein for the cytokines, IL-10, IL-6, IFN gamma, IL-1 beta, and TNF alpha, following in vitro stimulation with polyclonal mitogens. Our results suggest that white blood cells derived from aged rhesus monkeys exhibit a significant increase in their ability to produce the Th2-associated cytokine, IL-10, upon stimulation with lipopolysaccharide (LPS when compared to white cells derived from younger counterparts Similarly, a significant age-related decrease in the expression of the Thlassociated cytokine, IFN gamma, was also observed using phytohemagglutinin (PHA)-stimulated PBMCs. No significant age-related differences in the production of IL-1 beta or TNF alpha were observed in response to any stimulation, but there was limited evidence of an age-related increase in IL-6 production. Overall, our results suggest that a possible systemic change from a Th0/Th1 to a Th2-like cytokine profile occurs in circulating leukocytes derived from aging primates. We believe that such age-related alterations in cytokine production may play a role in the reduced immune responses observed in elderly human populations. (C) 2001, Editrice Kurtis. C1 NIA, Gerontol Res Ctr, Lab Neurosci, NIH, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Gerontol Res Ctr, Lab Neurosci, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Dawson, Harry/H-8242-2013 NR 37 TC 24 Z9 26 U1 2 U2 3 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 2001 VL 13 IS 2 BP 85 EP 94 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 437HU UT WOS:000168986900004 PM 11405390 ER PT J AU Scuteri, A Lakatta, EG Bos, AJG Fleg, JL AF Scuteri, A Lakatta, EG Bos, AJG Fleg, JL TI Effect of estrogen and progestin replacement on arterial stiffness indices in postmenopausal women SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE arterial stiffness; blood pressure; estrogen replacement; menopause; progestin ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; HYPERTENSIVE WOMEN; CONNECTIVE-TISSUE; PULSE PRESSURE; RISK FACTOR; THERAPY; MENOPAUSE; AGE AB Our objectives were to investigate whether long-term estrogen replacement therapy (ERT) is associated with a reduction in age-associated increases in arterial stiffness and blood pressure (BP) and whether the addition of progestin modifies the effects of estrogen. ERT has been found to have beneficial effects on cardiovascular risk. There are few data, however, delineating the effects of ERT on BP and arterial stiffness, and their age-associated changes. BP and aorto-femoral pulse wave velocity (PWV) were measured in 134 postmenopausal volunteers, aged 51 to 90 years, from the Baltimore Longitudinal Study of Aging, screened to exclude clinical and occult cardiovascular disease, and classified as ERT non-users (N=57) or ERT users (N=77). The latter group was further substratified according to the use of estrogen alone (N=32) or a combination of estrogen and progestins (N=45). ERT users showed similar body habitus, physical activity, and plasma lipids compared to non-ERT users. ERT was associated with an average 9.8 mmHg lower systolic BP (p <0.001), and a 6.3 mmHg lower pulse pressure (p <0.01) than in nonusers. Multiple regression analysis showed that ERT was an independent predictor of lower SEP and PP (p <0.05). By analysis of covariance, ERT predicted a reduced age-associated increase in SEP, PP, and PWV (p <0.05). When systolic BP was > 130 mmHg, the combination of ERT and progestins predicted a higher PWV than ERT alone. In conclusion, ERT in postmenopausal women can beneficially affect the vascular system, by reducing BP and the age-associated increase in arterial stiffness. The addition of progestins to ERT may reduce these beneficial effects. (C) 2001, Editrice Kurtis. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Fleg, JL (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 17 Z9 17 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 2001 VL 13 IS 2 BP 122 EP 130 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 437HU UT WOS:000168986900008 PM 11405385 ER PT J AU Ghys, PD Jenkins, C Pisani, E AF Ghys, PD Jenkins, C Pisani, E TI HIV surveillance among female sex workers SO AIDS LA English DT Article DE female sex workers; surveillance; sexually transmitted infections; behavior; mapping ID IVORY-COAST; RISK; PREVALENCE; PREVENTION; INFECTION; ABIDJAN; PROSTITUTES; EPIDEMIC; THAILAND; CLIENTS AB Female sex workers are at high risk for infection with HIV, and their clients may act as a bridging population by spreading HIV to the general population. Comprehensive HIV surveillance among sex workers includes surveillance of HIV infection, of sexually transmitted infections and of risk behavior. Surveillance of HIV infection among sex workers is critical for countries with low-level or concentrated HIV epidemics, and can help in monitoring the response to the HIV epidemic in countries with a generalized epidemic. Sex workers are a vulnerable population, and particular attention needs to be paid to human rights issues including consent, confidentiality and stigma. Collaborations with key players in the local sex work scene - sex workers themselves in the first place - and alliances with salient institutions and groups are key to the success of surveillance among sex workers. Surveillance activities should have a strong link to interventions targeted at sex workers. Surveillance for HIV infection among sex workers can be institution- or community-based. Institutional settings include screening programs for registered sex workers, of sexually transmitted diseases clinics, and re-education camps. Specific sources of bias need to be considered in different settings, and must be measured - through the collection of socio-demographic and behavioral data - to allow a correct interpretation of prevalence data and time trends. Community-based HIV infection surveillance can be conducted in a probability sample of the sex worker population, thereby reducing selection bias. This requires the mapping of sex workers' contact venues, and drawing a random sample from the resulting sampling frame. (C) 2001 Lippincott Williams & Wilkins. C1 UNAIDS, Strategy & Res, CH-1211 Geneva 27, Switzerland. NIH, Bethesda, MD 20892 USA. RP Ghys, PD (reprint author), UNAIDS, Strategy & Res, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. NR 36 TC 57 Z9 59 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2001 VL 15 SU 3 BP S33 EP S40 DI 10.1097/00002030-200104003-00005 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 437NK UT WOS:000168997600005 PM 11421180 ER PT J AU Saif, MW AF Saif, MW TI HIV-associated autoimmune hemolytic anemia: An update SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INFECTION; AIDS; PATIENT; VIRUS; RETICULOCYTOPENIA AB In addition to developing immunosuppression, opportunistic infections, and malignancies, patients infected with human immunodeficiency virus (HIV) also develop many hematologic disorders. Although cytopenias including thrombocytopenia, anemia, and leukopenia, and bone marrow dysplasia are the most common hematologic complications encountered in such patients, hemostatic abnormalities that predispose patients to thromboembolism have also been recognized. Anemia in HIV patients can be multifactorial but an increased incidence of autoimmune hemolytic anemia has been manifested by the increased incidence of positive Coombs' test reported in patients with acquired immune deficiency syndrome (AIDS). Overt hemolysis is a rare complication. This review article discusses the etiology, pathophysiology, clinical features, diagnosis, treatment, and complications of autoimmune hemolytic anemia (AIHA) associated with HIV infection. C1 NCI, Natl Naval Med Ctr, NIH, Bethesda, MD 20889 USA. RP Saif, MW (reprint author), NCI, Natl Naval Med Ctr, NIH, Bldg 8,Room 5101,8902 Wisconsin Ave, Bethesda, MD 20889 USA. NR 35 TC 15 Z9 16 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD APR PY 2001 VL 15 IS 4 BP 217 EP 224 DI 10.1089/10872910151133783 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 426ZV UT WOS:000168381000007 PM 11359664 ER PT J AU Gordis, E AF Gordis, E TI The living legacy of science: In memory of Markku Linnoila, MD, PhD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Gordis, E (reprint author), NIAAA, NIH, Willco Bldg,Suite 400,6000 Execut Blvd, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2001 VL 25 IS 4 BP 485 EP 486 PG 2 WC Substance Abuse SC Substance Abuse GA 422GU UT WOS:000168110800001 PM 11329485 ER PT J AU Heinz, A Mann, K Weinberger, DR Goldman, D AF Heinz, A Mann, K Weinberger, DR Goldman, D TI Serotonergic dysfunction, negative mood states, and response to alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE serotonin transporters; SLC6A4-level of response to alcohol; impulsivity; negative mood states ID OBSESSIVE-COMPULSIVE DISORDER; FLUID MONOAMINE METABOLITES; ANXIETY-RELATED TRAITS; FREELY MOVING RATS; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; TRANSPORTER GENE; RHESUS-MONKEYS; AGGRESSIVE-BEHAVIOR; MICE LACKING AB Background: Dysfunction of central serotonergic neurotransmission has been implicated in the pathogenesis and maintenance of alcoholism. Serotonergic dysfunction may be associated with three behavior patterns relevant for alcoholism: impulsive aggression, negative mood states, and a low response to alcohol intake. Methods: We reviewed the literature on the psychopathological correlates of serotonergic dysfunction and focused on studies that assess the interaction between negative mood states and alcohol response. Results: Prospective studies in nonhuman primates that underwent early separation stress found an association between a low serotonin turnover rate and the disposition to excessive alcohol intake and impulsive aggression. These findings seem to be relevant for a subgroup of alcoholics with a low serotonin turnover rate and antisocial personality traits. Cross-sectional data in humans also support a relationship between reduced serotonergic neurotransmission and aggressive behavior and indicate that the association of serotonergic dysfunction and aggression may be mediated by negative mood states. This hypothesis is in accordance with a large body of data linking anxiety and depression to serotonergic dysfunction. In human alcoholics, brain imaging has detected a reduction in serotonin transporter availability in association with depression. Serotonin transporter availability seems to be related to reduced GABA-ergic sedation and the acute response to alcohol intake, an important predictor of subsequent development of alcohol dependence. Conclusions: Several lines of evidence point to a relationship between serotonergic dysfunction, negative mood states, and excessive alcohol intake, which may be mediated in part by reduced alcohol-induced sedation. C1 Univ Heidelberg, Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, D-68159 Mannheim, Germany. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. NIAAA, Intramural Res Program, NIH, Bethesda, MD USA. RP Heinz, A (reprint author), Univ Heidelberg, Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, J5, D-68159 Mannheim, Germany. EM heinza@as200.zi-mannheim.de RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 104 TC 123 Z9 124 U1 6 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2001 VL 25 IS 4 BP 487 EP 495 PG 9 WC Substance Abuse SC Substance Abuse GA 422GU UT WOS:000168110800002 PM 11329486 ER PT J AU Shah, MR O'Connor, CM Sopko, G Hasselblad, V Califf, RM Stevenson, LW AF Shah, MR O'Connor, CM Sopko, G Hasselblad, V Califf, RM Stevenson, LW CA ESCAPE Investigators TI Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE): Design and rationale SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; FILLING PRESSURES; THERAPY; CARE; DOBUTAMINE; MANAGEMENT; INCLUSION; MORTALITY; KNOWLEDGE AB Background There is little information about how to adjust pharmacologic agents in the treatment of patients with advanced congestive heart failure (CHF). Some studies have suggested that use of pulmonary artery catheterization to guide reductions in filling pressures may improve outcomes for patients with heart failure who are hospitalized with evidence of elevated filling pressures. However, there is no consensus regarding the true utility of this strategy. A randomized clinical trial is needed to test the safety, efficacy, and treatment benefit of pulmonary artery catheterization in patients with advanced CHF. Study Design The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial is a multicenter, randomized trial designed to test the long-term safety and efficacy of treatment guided by hemodynamic monitoring and clinical assessment versus that guided by clinical assessment alone in patients hospitalized with New York Heart Association class IV CHF. Five hundred patients will be randomly assigned to receive either medical therapy guided by a combination of clinical assessment and hemodynamic monitoring (PAC arm) or medical therapy guided by clinical assessment alone (CLIN arm). The primary end point of ESCAPE will be the number of days that patients are hospitalized or die during the 6-month period after randomization. Secondary end points will include changes in mitral regurgitation, peak oxygen consumption, and natriuretic peptide levels. Other secondary end points will be pulmonary artery catheter-associated complications, resource utilization, quality of life measures, and patient preferences regarding survival. Implications The primary goal of ESCAPE will be to provide information about the utility of the pulmonary artery catheter in patients with advanced heart failure, independent of various treatment approaches used by individual physicians. In addition, this study will define current outcomes for this severely compromised population. C1 Duke Clin Res Inst, Durham, NC 27715 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shah, MR (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. OI Sopko, George/0000-0002-5482-8992 NR 38 TC 61 Z9 63 U1 1 U2 3 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 APR PY 2001 VL 141 IS 4 BP 528 EP 535 DI 10.1067/mhj.2001.113995 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419JK UT WOS:000167945400003 PM 11275915 ER PT J AU Gaertner, EM Tsokos, M Derringer, GA Neuhauser, RS Arciero, C Andriko, JW AF Gaertner, EM Tsokos, M Derringer, GA Neuhauser, RS Arciero, C Andriko, JW TI Interdigitating dendritic cell sarcoma - A report of four cases and review of the literature SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE interdigitating dendritic sarcoma; accessory cells; neoplasm; lymph node; tonsil ID LYMPH-NODE; RETICULUM CELLS; MALIGNANT HISTIOCYTOSIS; TUMOR; EXPRESSION; INTESTINE; PHENOTYPE; FEATURES; ENTITY; FASCIN AB To better define the clinical and pathologic features of interdigitating dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites of tumor included I case each in the right cervical lymph node, left axillary lymph node, right tonsil, and right inguinal lymph node. Histologically, all showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled cells with convoluted nuclei and abundant eosinophilic cytoplasm. All were immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3 cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains, including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative. Ultrastructurally the tumor cells were elongated and showed indented nuclei, variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow-up was available for all cases. One patient died of widespread disease 2 months after diagnosis. One was alive with metastatic lung disease at 12 months. Two patients were disease free at 5 and 9 months. C1 Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Gen Surg, Washington, DC 20307 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Hematopathol, Washington, DC 20306 USA. RP Gaertner, EM (reprint author), Armed Forces Inst Pathol, Dept Dermatopathol, 14th St & Alaska Ave NW,Bldg 54, Washington, DC 20307 USA. NR 40 TC 68 Z9 78 U1 1 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2001 VL 115 IS 4 BP 589 EP 597 PG 9 WC Pathology SC Pathology GA 416RM UT WOS:000167794000015 PM 11293908 ER PT J AU Seage, GR Holte, SE Metzger, D Koblin, BA Gross, M Celum, C Marmor, M Woody, G Mayer, KH Stevens, C Judson, FN McKirnan, D Sheon, A Self, S Buchbinder, SP AF Seage, GR Holte, SE Metzger, D Koblin, BA Gross, M Celum, C Marmor, M Woody, G Mayer, KH Stevens, C Judson, FN McKirnan, D Sheon, A Self, S Buchbinder, SP TI Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; HIV infections; incidence; vaccination; vaccines ID INJECTION-DRUG USERS; NEW-YORK-CITY; EFFICACY TRIALS; BISEXUAL MEN; COMMUNITY CONCERNS; UNITED-STATES; RISK BEHAVIOR; SOCIAL-ISSUES; INFECTION; SEROCONVERSION AB Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-I seroincidence rates varied significantly by baseline eligibility criteria-1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained. C1 Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. ABT Associates Inc, Cambridge, MA 02138 USA. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent SCHARP, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Penn, VA Ctr Studies Addict, Philadelphia, PA 19104 USA. Univ Penn, VA Ctr Studies Addict, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. New York Blood Ctr, Lab Epidemiol, New York, NY 10021 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. NYU, Sch Med, Dept Environm Med, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Fenway Community Hlth Ctr, Dept Res, Providence, RI USA. Brown Univ, Denver, CO USA. Denver Dept Publ Hlth, Denver, CO USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. Howard Brown Hlth Ctr, Chicago, IL USA. Univ Michigan, Ann Arbor, MI 48109 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. RP Seage, GR (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. OI Marmor, Michael/0000-0001-6605-2661 FU NCRR NIH HHS [M01RR00096]; NIAID NIH HHS [AI 27742, N01-AI-35176, N01-AI-45200] NR 49 TC 84 Z9 85 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2001 VL 153 IS 7 BP 619 EP 627 DI 10.1093/aje/153.7.619 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 419CD UT WOS:000167931000001 PM 11282787 ER PT J AU Zhang, J Klebanoff, MA AF Zhang, J Klebanoff, MA TI Low blood pressure during pregnancy and poor perinatal outcomes: An obstetric paradox SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE blood pressure; fetal growth; pregnancy ID BIRTH-WEIGHT; HYPOTENSION AB Low blood pressure during pregnancy has been associated with poor perinatal outcomes. However, whether this association is causal or is due to confounding has never been carefully assessed. The authors used data from the Collaborative Perinatal Project, a large prospective cohort study in 12 hospitals in the United States from 1959 to 1966. A total of 28.095 subjects were included. At first glance, it appeared that the lower the baseline blood pressure during pregnancy, the higher the incidence of very premature birth (<34 weeks) and severe small for gestational age (<5th percentile) in a consistent dose-response pattern. However, women with low blood pressure were generally younger, shorter, lighter, leaner, poorer, and more often a minority, and they gained less weight. After the authors controlled for these factors, low blood pressure was not associated with preterm birth (adjusted relative risks ranging from 0.86 to 0,93, p > 0.05) or small for gestational age (relative risks ranging from 0.45 to 2.0). Therefore, the association between low blood pressure during pregnancy and poor perinatal outcomes is largely due to confounding by other risk factors. Low blood pressure by itself does not increase risk of poor perinatal outcomes at a population level. However, this conclusion may not apply to individual patients who also have a compromised plasma volume expansion or pathologic homeostasis. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 10 TC 12 Z9 12 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2001 VL 153 IS 7 BP 642 EP 646 DI 10.1093/aje/153.7.642 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 419CD UT WOS:000167931000004 PM 11282790 ER PT J AU Stolzenberg-Solomon, RZ Pietinen, P Barrett, MJ Taylor, PR Virtamo, J Albanes, D AF Stolzenberg-Solomon, RZ Pietinen, P Barrett, MJ Taylor, PR Virtamo, J Albanes, D TI Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; folic acid; methionine; pancreatic neoplasms; pyridoxine; smoking; vitamin B 12 ID HEREDITARY PANCREATITIS; CIGARETTE-SMOKING; COLON-CANCER; FOLATE; DNA; ALCOHOL; TOBACCO; HEALTH; MEN; 5'-PHOSPHATE AB The authors examined prospectively whether dietary folate and other factors known to influence methyl-group availability were associated with the development of exocrine pancreatic cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Of the 27,101 healthy male smokers aged 50-69 years who completed a self-administered dietary questionnaire at baseline, 157 developed pancreatic cancer during up to 13 years of follow-up from 1985 to 1997. Cox proportional hazards models were used to estimate the hazards ratios and 95% confidence intervals. The adjusted hazards ratio comparing the highest with the lowest quintile of dietary folate intake was 0.52 (95% confidence interval: 0,31, 0.871 p-trend = 0.05). Dietary methionine, alcohol intake, and smoking history did not modify this relation. No significant associations were observed between dietary methionine, vitamins B-6 and B-12, or alcohol intake and pancreatic cancer risk. Consistent with prior studies, this study shows that cigarette smoking was associated with an increased risk (highest compared with lowest quintile, cigarettes per day: hazards ratio = 1.82; 95% confidence interval: 1.10, 3.03; p-trend = 0.05). These results support the hypothesis that dietary folate intake is inversely associated with the risk of pancreatic cancer and confirm the risk associated with greater cigarette smoking. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. Informat Management Serv, Silver Spring, MD USA. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,6120 Execut Blvd,Suite 7036,MSC 70, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01CN45035, N01CN45165] NR 51 TC 77 Z9 89 U1 0 U2 4 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 APR 1 PY 2001 VL 153 IS 7 BP 680 EP 687 DI 10.1093/aje/153.7.680 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 419CD UT WOS:000167931000010 PM 11282796 ER PT J AU Hartman, TJ Woodson, K Stolzenberg-Solomon, R Virtamo, J Selhub, J Barrett, MJ Albanes, D AF Hartman, TJ Woodson, K Stolzenberg-Solomon, R Virtamo, J Selhub, J Barrett, MJ Albanes, D TI Association of the B-vitamins pyridoxal 5 '-phosphate (B-6), B-12, and folate with lung cancer risk in older men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE folic acid; homocysteine; lung neoplasms; methylation; pyridoxine; vitamin B 12 ID NESTED CASE-CONTROL; DIETARY QUESTIONNAIRE; ALCOHOL-CONSUMPTION; TOTAL HOMOCYSTEINE; CIGARETTE-SMOKING; COLORECTAL-CANCER; MALE SMOKERS; DEFICIENCY; PLASMA; CHROMATOGRAPHY AB A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B,, vitamin B,,) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B-12, or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B-6 levels. Compared with men with the lowest vitamin B-6 concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B-12, and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B-6 in lung cancer. C1 Informat Management Serv, Silver Spring, MD USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Natl Publ Hlth Inst, Helsinki, Finland. NCI, Div Clin Sci, Bethesda, MD 20892 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. RP Albanes, D (reprint author), Execut Blvd 2120,EPS 7016, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 50 TC 49 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2001 VL 153 IS 7 BP 688 EP 694 DI 10.1093/aje/153.7.688 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 419CD UT WOS:000167931000011 PM 11282797 ER PT J AU Yuan, P Grimes, GJ Shankman, SE Daniels, CE Goldspiel, BR Potti, CK AF Yuan, P Grimes, GJ Shankman, SE Daniels, CE Goldspiel, BR Potti, CK TI Compatibility and stability of vincristine sulfate, doxorubicin hydrochloride, and etoposide phosphate in 0.9% sodium chloride injection SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NIH, Pharmaceut Dev Sect, Dept Pharm, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Summer Res Student Program, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Qual Control & Analyt Lab, Bethesda, MD USA. RP Yuan, P (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1D51,10 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 2 U2 4 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 1 PY 2001 VL 58 IS 7 BP 594 EP 598 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 417YJ UT WOS:000167862800014 PM 11296609 ER PT J AU Xu, JF Zheng, SQL Carpten, JD Nupponen, NN Robbins, CM Mestre, J Moses, TY Faith, DA Kelly, BD Isaacs, SD Wiley, KE Ewing, DM Bujnowszky, P Chang, BI Bailey-Wilson, J Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB AF Xu, JF Zheng, SQL Carpten, JD Nupponen, NN Robbins, CM Mestre, J Moses, TY Faith, DA Kelly, BD Isaacs, SD Wiley, KE Ewing, DM Bujnowszky, P Chang, BI Bailey-Wilson, J Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB TI Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY LOCUS; CHROMOSOME 1Q42.2-43; HIGH-RISK; DOMINANT INHERITANCE; HISTORY; TESTS; 1Q; 1Q24-25; SUPPORT; COHORT AB To investigate the relationship between HPC2/ELAC2 and prostate cancer risk, we performed the following analyses: (1) a linkage study of six markers in and around the HPC2/ELAC2 gene at 17p11 in 159 pedigrees with hereditary prostate cancer (HPC); (2) a mutation-screening analysis of all coding exons of the gene in 93 probands with HPC; (3) family-based and population-based association study of common HPC2/ELAC2 missense variants in 159 probands with HPC, 249 patients with sporadic prostate cancer, and 222 unaffected male control subjects. No evidence for linkage was found in the total sample, nor in any subset of pedigrees based on characteristics that included age at onset, number of affected members, male-to-male disease transmission, or race. Furthermore, only the two previously reported missense changes (Ser217Leu and Ala541Thr) were identified by mutational analysis of all HPC2/ELAC exons in 93 probands with HPC. In association analyses, family-based tests did not reveal excess transmission of the Leu217 and/or Thr541 alleles to affected offspring, and population-based tests failed to reveal any statistically significant difference in the allele frequencies of the two polymorphisms between patients with prostate cancer and control subjects. The results of this study lead us to reject the three alternative hypotheses of (1) a highly penetrant, major prostate cancer-susceptibility gene at 17p11, (2) the allelic variants Leu217 or Thr541 of HPC2/ELAC2 as high-penetrance mutations, and (3) the variants Leu217 or Thr541 as low-penetrance, risk-modifying alleles. However, we did observe a trend of higher Leu217 homozygous carrier rates in patients than in control subjects. Considering the impact of genetic heterogeneity, phenocopies, and incomplete penetrance on the linkage and association studies of prostate cancer and on the power to detect linkage and association in our study sample, our results cannot rule out the possibility of a highly penetrant prostate cancer gene at this locus that only segregates in a small number of pedigrees. Nor can we rule out a prostate cancer-modifier gene that confers a lower-than-reported risk. Additional larger studies are needed to more fully evaluate the role of this gene in prostate cancer risk. C1 Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Isaacs, WB (reprint author), Johns Hopkins Hosp, Marburg 115,600 N Wolfe St, Baltimore, MD 21287 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [P50 CA058236, CA58236] NR 38 TC 81 Z9 84 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 APR PY 2001 VL 68 IS 4 BP 901 EP 911 DI 10.1086/319513 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 414KQ UT WOS:000167666000012 PM 11254448 ER PT J AU Jawaheer, D Seldin, MF Amos, CI Chen, WV Shigeta, R Monteiro, J Kern, M Criswell, LA Albani, S Nelson, JL Clegg, DO Pope, R Schroeder, HW Bridges, SL Pisetsky, DS Ward, R Kastner, DL Wilder, RL Pincus, T Callahan, LF Flemming, D Wener, MH Gregersen, PK AF Jawaheer, D Seldin, MF Amos, CI Chen, WV Shigeta, R Monteiro, J Kern, M Criswell, LA Albani, S Nelson, JL Clegg, DO Pope, R Schroeder, HW Bridges, SL Pisetsky, DS Ward, R Kastner, DL Wilder, RL Pincus, T Callahan, LF Flemming, D Wener, MH Gregersen, PK TI A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COMPLEX TRAITS; SUSCEPTIBILITY LOCI; LINKAGE STRATEGIES; AMERICAN PATIENTS; IDENTIFICATION; EPITOPE; 1Q AB Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P<.00005), with (HLA) = HLA. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P<.05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk. C1 N Shore Univ Hosp, Div Biol & Human Genet, Manhasset, NY 11030 USA. Univ Calif Davis, Dept Biol Chem, Davis, CA 95616 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA USA. Univ Calif San Diego, Ctr Pediat Rheumatol, La Jolla, CA 92093 USA. Fred Hutchinson Canc Res Ctr, Program Immunogenet, Seattle, WA 98104 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Med Res Serv,Div Rheumatol Allergy & Clin Immunol, Durham VA Hosp, Durham, NC USA. Univ Oxford, Inst Biol Anthropol, Oxford, England. NIAMS, NIH, Bethesda, MD USA. USN, CDR, MC, Dept Radiol,Natl Naval Med Ctr, Bethesda, MD 20084 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Univ N Carolina, Thurston Arthrit Res Ctr, Dept Orthoped & Med, Chapel Hill, NC USA. RP Gregersen, PK (reprint author), N Shore Univ Hosp, Div Biol & Human Genet, 350 Community Dr, Manhasset, NY 11030 USA. FU NCRR NIH HHS [5 M01 RR-00079, M01 RR000079, P41 RR003655, 1 P41 RR03655]; NIAMS NIH HHS [N01-AR-7-2232, R01 AR044422, R01 AR44222] NR 34 TC 272 Z9 284 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2001 VL 68 IS 4 BP 927 EP 936 DI 10.1086/319518 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 414KQ UT WOS:000167666000015 PM 11254450 ER PT J AU Hanson, RL Kobes, S Lindsay, RS Knowler, WC AF Hanson, RL Kobes, S Lindsay, RS Knowler, WC TI Assessment of parent-of-origin effects in linkage analysis of quantitative traits SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ASSESSING GENETIC-LINKAGE; VARIANCE-COMPONENTS; DIABETES-MELLITUS; PEDIGREE ANALYSIS; SIB-PAIR; CHROMOSOME-18; ASSOCIATION; DISORDER; LOCI; RECOMBINATION AB Methods are presented for incorporation of parent-of-origin effects into linkage analysis of quantitative traits. The estimated proportion of marker alleles shared identical by descent is first partitioned into a component derived from the mother and a component derived from the father. These parent-specific estimates of allele sharing are used in variance-components or Haseman-Elston methods of linkage analysis so that the effect of the quantitative-trait locus carried on the maternally derived chromosome is potentially different from the effect of the locus on the paternally derived chromosome. Statistics for linkage between trait and marker loci derived from either or both parents are then calculated, as are statistics for testing whether the effect of the maternally derived locus is equal to that of the paternally derived locus. Analyses of data simulated for 956 siblings from 263 nuclear families who had participated in a linkage study revealed that type I error rates for these statistics were generally similar to nominal values. Power to detect an imprinted locus was substantially increased when analyzed with a model allowing for parent-of-origin effects, compared with analyses that assumed equal effects; for example, for an imprinted locus accounting for 30% of the phenotypic variance, the expected LOD score was 4.5 when parent-of-origin effects were incorporated into the analysis, compared with 3.1 when these effects were ignored. The ability to include parent-of-origin effects within linkage analysis of quantitative traits will facilitate genetic dissection of complex traits. C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 43 TC 51 Z9 51 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2001 VL 68 IS 4 BP 951 EP 962 DI 10.1086/319508 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 414KQ UT WOS:000167666000017 PM 11254452 ER PT J AU Martin, ER Bass, MP Kaplan, NL AF Martin, ER Bass, MP Kaplan, NL TI Correcting for a potential bias in the pedigree disequilibrium test SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID ASSOCIATION; LINKAGE C1 Duke Univ, Med Ctr, Ctr Human Genet, Dept Med, Durham, NC 27710 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Martin, ER (reprint author), Duke Univ, Med Ctr, Ctr Human Genet, Dept Med, Box 3468, Durham, NC 27710 USA. FU NIMH NIH HHS [R01 MH-98-017]; NINDS NIH HHS [NS-99-004] NR 5 TC 132 Z9 135 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 APR PY 2001 VL 68 IS 4 BP 1065 EP 1067 DI 10.1086/319525 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 414KQ UT WOS:000167666000028 PM 11254459 ER PT J AU Hypolite, IO Bucci, J Yuan, CM Taylor, A Hshieh, P Cruess, D Agodoa, LYC Abbott, KC AF Hypolite, IO Bucci, J Yuan, CM Taylor, A Hshieh, P Cruess, D Agodoa, LYC Abbott, KC TI Hospitalizations resulting from congestive heart failure in patients with end stage renal disease resulting from diabetes after renal transplantation compared with patients on the renal transplant waiting list SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC USA. NIDDK, NIH, Off Minority Hlth Res Coordinat, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2001 VL 37 IS 4 MA 36 BP A19 EP A19 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 453FG UT WOS:000169905400069 ER PT J AU Hypolite, IO Bucci, J Yuan, CM Taylor, A Hshieh, P Cruess, D Agodoa, LYC Abbott, KC AF Hypolite, IO Bucci, J Yuan, CM Taylor, A Hshieh, P Cruess, D Agodoa, LYC Abbott, KC TI Acute coronary syndromes in patients with end stage renal disease resulting from diabetes after renal transplantation compared with patients on the renal transplant waiting list SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 NIDDK, NIH, Off Minority Hlth Res Coordinat, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2001 VL 37 IS 4 MA 35 BP A19 EP A19 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 453FG UT WOS:000169905400068 ER PT J AU Hypolite, IO Bucci, J Yuan, CM Raylor, A Hshieh, P Cruess, D Agodoa, LYC Abbott, KC AF Hypolite, IO Bucci, J Yuan, CM Raylor, A Hshieh, P Cruess, D Agodoa, LYC Abbott, KC TI Hospitalizations resulting from valvular heart disease in patients with end stage renal disease after renal transplantation compared with patients on the renal transplant waiting list SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 NIDDK, NIH, Off Minority Hlth Res Coordinat, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2001 VL 37 IS 4 MA 37 BP A20 EP A20 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 453FG UT WOS:000169905400070 ER PT J AU Stryker, VL Kreps, C AF Stryker, VL Kreps, C TI Fabry disease SO AMERICAN JOURNAL OF NURSING LA English DT Article ID FABRYS-DISEASE; TRANSPLANTATION; INVOLVEMENT; DYSFUNCTION C1 NIH, Outpatient Canc Ctr, Crit & Acute Care Patient Serv, Clin Ctr,Nursing Dept, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Stryker, VL (reprint author), NIH, Outpatient Canc Ctr, Crit & Acute Care Patient Serv, Clin Ctr,Nursing Dept, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2001 VL 101 IS 4 BP 39 EP 44 PG 6 WC Nursing SC Nursing GA 442EX UT WOS:000169273200033 PM 11301683 ER PT J AU Branch, DW Porter, TF Rittenhouse, L Caritis, S Sibai, B Hogg, B Lindheimer, MD Klebanoff, M MacPherson, C VanDorsten, JP Landon, M Paul, R Miodovnik, M Meis, P Thurnau, G AF Branch, DW Porter, TF Rittenhouse, L Caritis, S Sibai, B Hogg, B Lindheimer, MD Klebanoff, M MacPherson, C VanDorsten, JP Landon, M Paul, R Miodovnik, M Meis, P Thurnau, G CA Natl Inst Child Hlth Human Dev Mat TI Antiphospholipid antibodies in women at risk for preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 07-09, 2000 CL WILLIAMSBURG, VIRGINIA SP Amer Gynecol & Obstetr Soc DE anticardiolipin antibodies; antiphospholipid antibodies; intrauterine growth restriction; preeclampsia ID LOW-DOSE ASPIRIN; HEALTHY PREGNANT-WOMEN; ANTICARDIOLIPIN ANTIBODIES; FETAL GROWTH; ASSOCIATION; PREVALENCE; HEPARIN; RETARDATION; ECLAMPSIA; WORKSHOP AB OBJECTIVE: The aim of this study was to determine whether positive results of tests for any of 5 antiphospholipid antibodies are associated with recurrent preeclampsia among women with a history of preeclampsia in a previous pregnancy. STUDY DESIGN: Second-trimester serum samples were obtained from 317 women with preeclampsia in a previous pregnancy who were being followed up in a prospective treatment trial. The serum samples were measured by enzyme-linked immunoassay for immunoglobulin G and immunoglobulin M antibodies against 5 phospholipids. Positive results were analyzed with regard to preeclampsia, severe preeclampsia, intrauterine growth restriction, and preterm delivery. RESULTS: Sixty-two of the 317 women (20%) had recurrent preeclampsia develop, 19 (6%) had severe preeclampsia, and 18 (5.8%) were delivered of infants with growth restriction. Positive results of tests for immunoglobulin G or immunoglobulin M antiphospholipid antibodies were not associated with recurrent preeclampsia. Positive results for immunoglobulin G or immunoglobulin M antibodies at the 99th percentile were also not associated with preterm delivery. Positive results at the 99th percentile for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results at the 99th percentile for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. The positive predictive values for these outcomes all were approximately 30%. CONCLUSION: Positive results of testing for antiphospholipid antibodies in the second trimester were not associated with recurrent preeclampsia among women at risk because of a history of preeclampsia. Positive results for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. However, the positive predictive values for all these associations were modest. Testing for antiphospholipid antibodies during pregnancy is of little prognostic value in the assessment of the risk for recurrent preeclampsia among women with a history of preeclampsia. C1 Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. RP Branch, DW (reprint author), Room 2B200 Med Ctr,50 N Med Dr, Salt Lake City, UT 84132 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21410, HD19897, HD21414, HD21434, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917] NR 25 TC 52 Z9 55 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 APR PY 2001 VL 184 IS 5 BP 825 EP 832 DI 10.1067/mob.2001.113846 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 426FA UT WOS:000168338100010 PM 11303189 ER PT J AU Guedez, L McMarlin, AJ Kingma, DW Bennett, TA Stetler-Stevenson, M Stetler-Stevenson, WG AF Guedez, L McMarlin, AJ Kingma, DW Bennett, TA Stetler-Stevenson, M Stetler-Stevenson, WG TI Tissue inhibitor of metalloproteinase-1 alters the tumorigenicity of Burkitt's lymphoma via divergent effects on tumor growth and angiogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID B-CELLS; IN-VITRO; BREAST-CANCER; TIMP-1; METASTASIS; REGRESSION; EXPRESSION; CARCINOMA; INVASION; CARCINOGENESIS AB Epstein-Barr virus (EBV)-postive Burkitt's lymphoma cells and EBV-infected B cells elicit humoral factors that inhibit tumor-induced angiogenesis, resulting in tumor necrosis and regression, Of the chemokine factors identified in association with this growth behavior, none have induced complete tumor regression, We have previously identified tissue inhibitors of metalloptoteinase (TIMP)-1 in various B cell lymphoma cell lines. Here we show that Induction of TEMP-1 expression in an EBV-negative Burkitt's lymphoma cell line results in a biphasic, in vivo tumor growth pattern in the nude mouse that is essentially identical to EBV-positive Burkitt's lymphoma cell lines, The initial effect of TIMP-1 is to enhance tumor growth, consistent with the reported anti-apoptotic effect of TIMP-1 on B cell growth. Tumor necrosis and regression then follow the initial period of rapid, increased tumor growth. Only microscopic foci of residual, proliferating tumor cells are observed on biopsy of the tumor site. This latter effect is mediated by TEMP-1 inhibition of an angiogenic response within the developing tumor mass, as demonstrated by immunostaining and microvessel counts. These findings suggest that TIMP-1 is an important mediator of the in vivo growth properties of EBV-positive Burkitt's lymphoma. C1 NCI, Pathol Lab, Div Clin Sci, Extracellular Matrix Sect,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, Flow Cytometry Unit,NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, WG (reprint author), NCI, Pathol Lab, Div Clin Sci, Extracellular Matrix Sect,NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012; Guedez, Liliana/H-4951-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808; NR 43 TC 79 Z9 82 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2001 VL 158 IS 4 BP 1207 EP 1215 DI 10.1016/S0002-9440(10)64070-9 PG 9 WC Pathology SC Pathology GA 422RX UT WOS:000168134000005 PM 11290537 ER PT J AU Paku, S Schnur, J Nagy, P Thorgeirsson, SS AF Paku, S Schnur, J Nagy, P Thorgeirsson, SS TI Origin and structural evolution of the early proliferating oval cells in rat liver SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BILE-DUCT LIGATION; STEM-CELLS; CHEMICAL HEPATOCARCINOGENESIS; HEPATOCELLULAR-CARCINOMA; FUNCTIONAL-HETEROGENEITY; BONE-MARROW; HEPATOCYTES; CARCINOGENESIS; LINEAGES; DIFFERENTIATION AB We have analyzed the histological changes in rat liver after 2-acetylaminofluorene (AAF) administration. The data demonstrate that AAF-induced oval cells were preferentially generated by proliferation of the terminal biliary ductules that we suggest constitute the primary hepatic stem cell niche. The oval cells formed ductular structures, representing an extension of the canals of Hering. This histological organization provides continuous bile drainage of the hepatocytes and uninterrupted blood flow in the sinusoids. The oval cell ductules are surrounded by a continuous basement membrane that is intermittently disrupted by processes of stellate cells that form direct cell-cell contact with the oval cells. Although both AAF treatment and bile duct Ligation results In proliferation of biliary epithelial cells, the mechanism(s) responsible for the proliferation of the biliary epithelium seems to differ in the two models. in contrast to the biliary proliferation stimulated by bile ligation, AAF-induced oval cell proliferation as well as the capacity of these cells to differentiate into hepatocytes, bile epithelial cells and possibly other cell lineages can be blocked by administration of dexamethasone. C1 Natl Canc Inst, NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Joint Res Org Hungarian Acad Sci & Semmelweis Uni, H-1085 Budapest, Hungary. Semmelweis Univ, Inst Pathol 1 & Expt Canc Res, H-1085 Budapest, Hungary. RP Nagy, P (reprint author), Natl Canc Inst, NIH, Expt Carcinogenesis Lab, 37 Convent Dr MSC 4255,Bldg 37,Room 3C28, Bethesda, MD 20892 USA. NR 53 TC 203 Z9 219 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2001 VL 158 IS 4 BP 1313 EP 1323 DI 10.1016/S0002-9440(10)64082-5 PG 11 WC Pathology SC Pathology GA 422RX UT WOS:000168134000017 PM 11290549 ER PT J AU Meinhold-Heerlein, I Stenner-Liewen, F Liewen, H Kitada, S Krajewska, M Krajewski, S Zapata, JM Monks, A Scudiero, DA Bauknecht, T Reed, JC AF Meinhold-Heerlein, I Stenner-Liewen, F Liewen, H Kitada, S Krajewska, M Krajewski, S Zapata, JM Monks, A Scudiero, DA Bauknecht, T Reed, JC TI Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTEIN-TYROSINE-PHOSPHATASE; COLON-CARCINOMA CELLS; IN-VIVO PATTERNS; MEDIATED APOPTOSIS; IMMUNOHISTOCHEMICAL ANALYSIS; FACTOR RECEPTORS; DIVERSE PANEL; FAP-1; LINES AB Fas-associated phosphatase-1 (FAP-1) is a protein-tyrosine phosphatase that binds the cytosolic tail of Fas (Apo1, CD95), presumably regulating Fas-induced apoptosis, Elevations of FAP-1 protein levels in some tumor cell lines have been correlated with resistance to Fas-induced apoptosis. To explore the expression of FAP-1 in ovarian cancer cell lines and archival tumor specimens, mouse monoclonal and rabbit polyclonal antibodies were generated against a FAP-1 peptide and recombinant FAP-1 protein. These antibodies were used for immunoblotting, Immunohistochemistry, and now-cytometry analysis of FAP-1 expression in the Fas-sensitive ovarian cancer lines HEY and BG-1, and In the Fas-resistant lines OVCAR-3 FR and SK-OV-3. All methods demonstrated high levels of FAP-1 in the resistant lines OVCAR-3 FR and SK-OV-3, but not in the Fas-sensitive lines HEY and BG-1. Furthermore, levels of FAP-1 protein also correlated with the amounts of FAP-1 mRNA, as determined by reverse transcriptase-polymerase chain reaction analysis. FAP-1 protein levels were Investigated by immunoblotting in the National Cancer Institute's panel of 60 human tumor cell lines. Although FAP-1 failed to correlate with Fas-resistance across the entire tumor panel, Fas-resistance correlated significantly with FAP-1 expression (P less than or equal to 0.05) and a low Fas/FAP-1 ratio (P less than or equal to 0.028) in ovarian cancer cell lines, FAP-1 expression was also evaluated in 95 archival ovarian cancer specimens using tissue-microarray technology, FAP-1 was expressed in neatly all tumors, regardless of histological type or grade, stage, patient age, response to chemotherapy, or patient survival We conclude that FAP-1 correlates significantly with Fas resistance in ovarian cancer cell lines and is commonly expressed in ovarian cancers. C1 Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA. Natl Canc Inst, Dev Therapeut Program, Div Canc Treatment & Diagnost, Bethesda, MD USA. Univ Bonn, Dept Gynecol & Obstet, Bonn, Germany. RP Reed, JC (reprint author), Burnham Inst, Program Apoptosis & Cell Death Res, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Zapata, Juan/J-6304-2014 OI Zapata, Juan/0000-0002-0110-0009 FU NCI NIH HHS [CA-72994] NR 40 TC 50 Z9 51 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2001 VL 158 IS 4 BP 1335 EP 1344 DI 10.1016/S0002-9440(10)64084-9 PG 10 WC Pathology SC Pathology GA 422RX UT WOS:000168134000019 PM 11290551 ER PT J AU Aliberti, JCS Souto, JT Marino, APMP Lannes-Vieira, J Teixeira, MM Farber, J Gazzinelli, RT Silva, JS AF Aliberti, JCS Souto, JT Marino, APMP Lannes-Vieira, J Teixeira, MM Farber, J Gazzinelli, RT Silva, JS TI Modulation of chemokine production and inflammatory responses in interferon-gamma- and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOGENOUS IFN-GAMMA; GROWTH-FACTOR-BETA; NITRIC-OXIDE; MEDIATES RESISTANCE; GENE-EXPRESSION; IN-SITU; MACROPHAGES; INTERLEUKIN-10; CYTOKINES; CELLS AB Infection with Trypanosoma cruzi causes a strong inflammatory reaction at the inoculation site and, later, in the myocardium, The present study investigates the role of cytokines as modulators of T. cruzi-induced chemokine expression in vivo and in vitro, In macrophage cultures, although the stimulation with interferon (IFN)-gamma increases the expression of IP-10, it blocks KC expression, Tumor necrosis factor (TNF)-alpha, on the other hand, potentiates KC, IP-10, macrophage inflammatory protein-1 alpha, and JE/monocyte chemotatic protein-1 expression. Interleukin-10 and transforming growth factor-beta inhibited almost all chemokines tested. The role of IFN-gamma and TNF-alpha in chemokine modulation during infection was investigated in T, cruzi-infected IFN-gamma -deficient (GKO) or TNF-R1/p55-deficient (p55-/-) mice. The expression of chemokines detected in the inoculation site correlated with the infiltrating cell type observed. Although GKO mice had a delayed and intense neutrophilic infiltrate correlating with the expression of KC and macrophage inflammatory protein-2, none of the above was observed in p55-/- mice, The detection of infiltrating T cells, Mig, and IP-10 in the myocardium was observed in wild-type and p55-/-, but not in GKO mice. Together, these results suggest that the regulatory roles of IFN-gamma and TNF-alpha on chemokine expression may play a crucial role in the modulation of the inflammatory response during T, cruzi infection and mediate resistance to infection. C1 USP, Sch Med Ribeirao Preto, Dept Biochem, BR-14049900 Ribeirao Preto, SP, Brazil. USP, Sch Med Ribeirao Preto, Dept Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. Fundacao Osvaldo Cruz, Dept Immunol, Rio De Janeiro, Brazil. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Silva, JS (reprint author), USP, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. RI Teixeira, Mauro/A-4587-2008; Silva, Joao/A-4484-2008; Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Teixeira, Mauro/0000-0002-6944-3008; Aliberti, Julio/0000-0003-3420-8478 NR 25 TC 93 Z9 95 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2001 VL 158 IS 4 BP 1433 EP 1440 DI 10.1016/S0002-9440(10)64094-1 PG 8 WC Pathology SC Pathology GA 422RX UT WOS:000168134000029 PM 11290561 ER PT J AU Gusenoff, JA Harman, SM Veldhuis, JD Jayme, JJ St Clair, C Munzer, T Christmas, C O'Connor, KG Stevens, TE Bellantoni, MF Pabst, K Blackman, MR AF Gusenoff, JA Harman, SM Veldhuis, JD Jayme, JJ St Clair, C Munzer, T Christmas, C O'Connor, KG Stevens, TE Bellantoni, MF Pabst, K Blackman, MR TI Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE aging; hormone secretion; approximate entropy ID GROWTH-HORMONE SECRETION; ULTRASENSITIVE CHEMILUMINESCENCE ASSAY; CUSHINGS-DISEASE; LUTEINIZING-HORMONE; PREMENOPAUSAL WOMEN; BODY-COMPOSITION; PLASMA-CORTISOL; PULSATILE MODE; OLDER-PEOPLE; RELEASE AB We studied 130 healthy aged women (n = 57) and men (n = 73), age 65-88 yr, with age-related reductions in insulin-like growth factor I and gonadal steroid levels to assess the interrelationships between cortisol and growth hormone (GH) secretion and whether these relationships differ by sex. Blood was sampled every 20 min from 8:00 PM to 8:00 AM; cortisol was measured by RIA and GH by immunoradiometric assay, followed by deconvolution analyses of hormone secretory parameters and assessment of approximate entropy (ApEn) and cross-ApEn. Cortisol mass/burst, cortisol production rate, and mean and integrated serum cortisol concentrations (P < 0.0005), and overnight basal GH secretion (P < 0.05), were elevated in women vs. men. Integrated cortisol concentrations were directly related to most measures of GH secretion in women (P < 0.01) and with mean and integrated GH concentrations in men (P, 0.05). Integrated GH concentrations were directly related to mean and integrated cortisol levels in women (P < 0.005) and men (P, 0.05), with no sex differences. There were no sex differences in cortisol or GH ApEn values; however, the cross-ApEn score was greater in women (P, 0.05), indicating reduced GH-cortisol pattern synchrony in aged women vs. men. There were no significant relationships of integrated cortisol secretion with GH ApEn, or vice versa, in either sex. Thus postmenopausal women appear to maintain elevated cortisol production in patterns that are relatively uncoupled from those of GH, whereas mean hormone outputs remain correlated. C1 Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Med, Div Gerontol & Geriatr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. NIA, Endocrinol Sect, Clin Invest Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Univ Virginia Hlth Syst, Dept Med, Div Endocrinol & Metab, Charlottesville, VA 22908 USA. RP Blackman, MR (reprint author), Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol & Metab, 4940 Eastern Ave, Baltimore, MD 21224 USA. FU NCRR NIH HHS [MO1-RR-02719, RR-00847]; NIA NIH HHS [R01-AG-11005, AG-14799] NR 70 TC 28 Z9 29 U1 0 U2 1 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 APR PY 2001 VL 280 IS 4 BP E616 EP E625 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 413QG UT WOS:000167622800010 PM 11254469 ER PT J AU Nejsum, LN Kwon, TH Marples, D Flyvbjerg, A Knepper, MA Frokiaer, J Nielsen, S AF Nejsum, LN Kwon, TH Marples, D Flyvbjerg, A Knepper, MA Frokiaer, J Nielsen, S TI Compensatory increase in AQP2, p-AQP2, and AQP3 expression in rats with diabetes mellitus SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporins; polyuria; sodium transport; urinary concentrating mechanism ID THICK ASCENDING LIMB; AQUAPORIN-2 WATER CHANNEL; IMMUNOELECTRON MICROSCOPIC LOCALIZATION; INDUCED DOWN-REGULATION; ACUTE-RENAL-FAILURE; COLLECTING DUCT; ALTERED EXPRESSION; NA+ TRANSPORTERS; CONCENTRATING DEFECT; KIDNEY MEDULLA AB Diabetes mellitus (DM) is associated with osmotic diuresis and natriuresis. At day 15, rats with DM induced by streptozotocin (n = 13) had severe hyperglycemia (27.1 +/- 0.4 vs. 4.7 +/- 0.1 mM in controls) and had a fivefold increase in water intake (123 +/- 5 vs. 25 +/- 2 ml/ day) and urine output. Semiquantitative immunoblotting revealed a significant increase in inner medullary AQP2 (201 +/- 12% of control rats, P < 0.05) and phosphorylated (Ser(256)) AQP2 (p- AQP2) abundance (299 +/- 32%) in DM rats. Also, the abundance of inner medullary AQP3 was markedly increased to 171 +/- 19% of control levels (100 +/- 4%, n = 7, P < 0.05). In contrast, the abundance of whole kidney AQP1 (90 +/- 3%) and inner medullary AQP4 (121 +/- 16%) was unchanged in rats with DM. Immunoelectron microscopy further revealed an increased labeling of AQP2 in the apical plasma membrane of collecting duct principal cells (with less labeling in the intracellular vesicles) of DM rats, indicating enhanced trafficking of AQP2 to the apical plasma membrane. There was a marked increase in urinary sodium excretion in DM. Only Na(+)/H(+) exchanger NHE3 was downregulated (67 +/- 10 vs. 100 +/- 11%) whereas there were no significant changes in abundance of type 2 Na- phosphate cotransporter (128 +/- 6 vs. 100 +/- 10%); the Na- K- 2Cl cotransporter (125 +/- 19 vs. 100 +/- 10%); the thiazide- sensitive Na- Cl cotransporter (121 +/- 9 vs. 100 +/- 10%); the alpha (1)-subunit of the Na- K- ATPase (106 +/- 7 vs. 100 +/- 5%); and the proximal tubule Na-HCO(3) cotransporter (98 +/- 16 vs. 100 +/- 7%). In conclusion, DM rats had an increased AQP2, p- AQP2, and AQP3 abundance as well as high AQP2 labeling of the apical plasma membrane, which is likely to represent a vasopressin- mediated compensatory increase in response to the severe polyuria. In contrast, there were no major changes in the abundance of AQP1, AQP4, and several major proximal and distal tubule Na(+) transporters except NHE3 downregulation, which may participate in the increased sodium excretion. C1 Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungju 780714, South Korea. Univ Leeds, Sch Biomed Sci, Leeds LS2 9NQ, W Yorkshire, England. Aarhus Univ Hosp, Lab Diabet & Endocrinol M, DK-8000 Aarhus C, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Aarhus Univ Hosp, Inst Expt Clin Res, Dept Clin Physiol, DK-8200 Aarhus N, Denmark. RP Nielsen, S (reprint author), Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 53 TC 50 Z9 50 U1 1 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 APR PY 2001 VL 280 IS 4 BP F715 EP F726 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 410VK UT WOS:000167461600018 PM 11249863 ER PT J AU Helfand, WH Lazarus, J Theerman, P AF Helfand, WH Lazarus, J Theerman, P TI Donora, Pennsylvania: An environmental disaster of the 20th century SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 1 TC 20 Z9 21 U1 0 U2 26 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2001 VL 91 IS 4 BP 553 EP 553 DI 10.2105/AJPH.91.4.553 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BM UT WOS:000170345100002 PM 11291362 ER PT J AU Freedman, DM Stewart, P Kleinerman, RA Wacholder, S Hatch, EE Tarone, RE Robison, LL Linet, MS AF Freedman, DM Stewart, P Kleinerman, RA Wacholder, S Hatch, EE Tarone, RE Robison, LL Linet, MS TI Household solvent exposures and childhood acute lymphoblastic leukemia SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PARENTAL OCCUPATION; CANCER; RISK; CHILDREN AB Objectives. This study explored the risk of childhood acute lymphoblastic leukemia (ALL) associated with participation by household members in hobbies or other home projects involving organic solvents. Methods. Participants in this case-control study were 640 subjects with ALL and 640 matched controls. Results. Childhood ALL was associated with frequent (>4 times/month) exposure to model building (odds ratio [OR]=1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes painted extensively (>4 rooms) in the year before the children's birth. Conclusions. In this exploratory study, substantial participation by household members in some common household activities that involve organic solvents was associated with elevated risks of childhood ALL. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pediat, Div Pediat Epidemiol & Clin Res, Minneapolis, MN 55455 USA. RP Freedman, DM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7087,6120 Execut Blvd, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [R01 CA 48051, U01 CA 13539] NR 24 TC 36 Z9 41 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2001 VL 91 IS 4 BP 564 EP 567 DI 10.2105/AJPH.91.4.564 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BM UT WOS:000170345100006 PM 11291366 ER PT J AU Snyder, SK Wessner, DH Wessells, JL Waterhouse, RM Wahl, LM Zimmermann, W Dveksler, GS AF Snyder, SK Wessner, DH Wessells, JL Waterhouse, RM Wahl, LM Zimmermann, W Dveksler, GS TI Pregnancy-specific glycoproteins function as immunomodulators by inducing secretion of IL-10, IL-6 and TGF-beta 1 by human monocytes SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE cytokines; immunoregulation; reproduction ID TRANSFORMING GROWTH-FACTOR; GENE-EXPRESSION; FACTOR-BETA; HUMAN TROPHOBLASTS; MONONUCLEAR-CELLS; FETAL RESORPTIONS; NITRIC-OXIDE; TGF-BETA; CYTOKINE; MACROPHAGE AB PROBLEM: Low levels of pregnancy-specific glycoproteins (PSGs) in maternal serum have been correlated with complications of pregnancy. We investigated the ability of human PSGs to regulate in vitro production of cytokines. METHOD OF STUDY: Human monocytes and murine RAW 264.7 cells were treated with recombinant PSG1, PSG6, PSG11, or a truncated PSG6 consisting of only the N-terminal domain (PSG6N). Cytokine production in response to PSG-treatment was measured by ELISA and/or reverse transcriptase-PCR. RESULTS: All PSGs tested induced secretion of interleukin (IL)-10, IL-6 and transforming growth factor (TGF)-beta1 by both human and murine cells, but not IL-1 beta, tumor necrosis factor (TNF)-alpha or IL-12. The N-terminal domain of PSG6 was sufficient for induction of monocyte cytokine secretion. Induction of IL-10 and IL-6 was preceded by an increase in the specific mRNAs. CONCLUSIONS: PSG1, PSG6, PSG6N, and PSG11 induce dose-dependent secretion of anti-inflammatory cytokines by human monocytes. Human and murine PSGs exhibit cross-species activity. Our results are consistent with a role for PSGs in modulation of the innate immune system. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Davidson Coll, Dept Biol, Davidson, NC 28036 USA. NIDR, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Inst Mol Med & Cell Res, D-79104 Freiburg, Germany. RP Dveksler, GS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Zimmermann, Wolfgang/L-9277-2013 FU NICHD NIH HHS [HD35832] NR 51 TC 77 Z9 77 U1 0 U2 8 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD APR PY 2001 VL 45 IS 4 BP 205 EP 216 DI 10.1111/j.8755-8920.2001.450403.x PG 12 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 421QG UT WOS:000168074600003 PM 11327547 ER PT J AU Deem, S Gladwin, MT Berg, JT Kerr, ME Swenson, ER AF Deem, S Gladwin, MT Berg, JT Kerr, ME Swenson, ER TI Effects of S-nitrosation of hemoglobin on hypoxic pulmonary vasoconstriction and nitric oxide flux SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ISOLATED RAT LUNGS; BIOCHEMICAL-CHARACTERIZATION; VASCULAR REACTIVITY; OXYGEN-BINDING; NITROSOHEMOGLOBIN; MECHANISMS; CIRCULATION; METABOLISM; TRANSPORT AB Free hemoglobin (Hb) augments hypoxic pulmonary vasoconstriction (HPV), ostensibly by scavenging nitric oxide (NO). However, recent evidence suggests that Hb that is S-nitrosated may act as an NO donor and vasodilator. We studied the effects of oxyHb, Hb that is chemically modified to prevent heme binding or oxidation of NO (cyanometHb), and Hb that is S-nitrosated (SNO-Hb and SNO-cyanometHb) on HPV, expired NO (eNO), and perfusate S-nitrosothiol (SNO) concentration in isolated, perfused rabbit lungs. Perfusate containing either 4 muM oxyHb or SNO-Hb increased normoxic pulmonary artery pressure (Ppa), augmented HPV dramatically, and resulted in an 80% fall in eNO in comparison to perfusion with buffer, whereas 4 muM cyanometHb or SNO-cynanometHb had no effect on these variables. Excess glutathione (GSH) added to perfusate containing SNO-Hb resulted in a 20 to 40% fall in the perfusate SNO concentration, with a concomitant increase in metHb content, without affecting Ppa, HPV, or eNO. In conclusion, free Hb augments HPV by scavenging NO, an effect that is not prevented by S-nitrosation. NO released from SNO-Hb in the presence of GSH does not produce measurable vascular effects in the lung or changes in eNO because of immediate oxidation and metHb formation. C1 Univ Washington, Harborview Med Ctr, Dept Anesthesiol, Seattle, WA 98104 USA. Univ Washington, Dept Med Pulm & Crit Care, Seattle, WA 98104 USA. Puget Sound Vet Affairs Hlth Care Syst, Seattle, WA USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Deem, S (reprint author), Univ Washington, Harborview Med Ctr, Dept Anesthesiol, Box 359724, Seattle, WA 98104 USA. FU NHLBI NIH HHS [HL-03796, HL-45571] NR 29 TC 25 Z9 25 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2001 VL 163 IS 5 BP 1164 EP 1170 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 426QJ UT WOS:000168359600029 PM 11316654 ER PT J AU Kraft, M Hamid, Q Chrousos, GP Martin, RJ Leung, DYM AF Kraft, M Hamid, Q Chrousos, GP Martin, RJ Leung, DYM TI Decreased steroid responsiveness at night in nocturnal asthma - Is the macrophage responsible? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HUMAN GLUCOCORTICOID RECEPTOR; NF-KAPPA-B; BETA-ISOFORM; BINDING AFFINITY; RESISTANT ASTHMA; BRONCHIAL-ASTHMA; MESSENGER-RNA; CELL-FUNCTION; EXPRESSION; INTERLEUKIN-13 AB As peripheral blood mononuclear cells from patients with nocturnal asthma (NA) exhibit reduced steroid responsiveness at 4:00 A.M. as compared with 4:00 P.M,, We hypothesized that NA is-associated with increased nocturnal airway cell expression of GRP, an endogenous inhibitor of steroid action. Ten subjects with NA and seven subjects with nonnocturnal asthma (NNA) underwent bronchoscopy with bronchoalveolar lavage (BAL) at 4:00 P.M. and 4:00 A.M. BAL lymphocytes and macrophages were incubated with dexamethasone (DEX) at 10(-5) to 10(-8) M. DEX suppressed proliferation of BAL lymphocytes similarly at 4:00 P.M. and 4:00 A,M. in both groups. However, BAL macrophages from NA exhibited less suppression of IL-8 and TNF-c( production by DEX at 4:00 A.M. as compared with 4:00 P.M. (P = 0.0001), whereas in the NNA group DEX suppressed IL-8 and TNF-alpha production equally at both time points. GRP expression was increased at night only in NA, primarily due to significantly increased expression by BAL macrophages (p = 0.008). IL-13 mRNA expression was increased at night but only in the NA group and addition of neutralizing antibodies to IL-13 reduced GRP expression by BAL macrophages. We conclude that the airway macrophage may be the airway inflammatory cell driving the reduction in steroid responsiveness at night in NA, and this function is modulated by IL-13. C1 Univ Colorado, Hlth Sci Ctr, Natl Jewish Med & Res Ctr, Div Pulm Sci & Crit Care Med,Dept Med, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Natl Jewish Med & Res Ctr, Div Pulm Sci & Crit Care Med,Dept Pediat, Denver, CO 80206 USA. McGill Univ, Meakins Christie Labs, Montreal, PQ, Canada. NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Kraft, M (reprint author), Univ Colorado, Hlth Sci Ctr, Natl Jewish Med & Res Ctr, Div Pulm Sci & Crit Care Med,Dept Med, 1400 Jackson St,Room J107, Denver, CO 80206 USA. FU NCRR NIH HHS [RR-00051]; NHLBI NIH HHS [HL36577, HL03343]; NIAMS NIH HHS [AR-41256] NR 56 TC 43 Z9 45 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2001 VL 163 IS 5 BP 1219 EP 1225 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 426QJ UT WOS:000168359600037 PM 11316662 ER PT J AU Matsui, K Beasley, MB Nelson, WK Barnes, PM Bechtle, J Falk, R Ferrans, VJ Moss, J Travis, WD AF Matsui, K Beasley, MB Nelson, WK Barnes, PM Bechtle, J Falk, R Ferrans, VJ Moss, J Travis, WD TI Prognostic significance of pulmonary lymphangioleiomyomatosis histologic score SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphangioleiomyomatosis; lung; prognosis; smooth muscle; HMB-45 ID MATRIX METALLOPROTEINASES; TRANSBRONCHIAL BIOPSY; LYMPHANGIOMYOMATOSIS; DIAGNOSIS AB Correlations were made between clinical and follow-up data and histopathologic findings in 105 women (mean age +/- standard deviation, 38.3 +/- 9.0 years) with pulmonary lymphangioleiomyomatosis (LAM). The actuarial survival (to pulmonary transplantation or death) of the patients from the time of lung biopsy was 85.1% and 71.0% after 5 and 10 years respectively. The histologic severity of LAM, graded as a LAM histologic score (LHS), was determined on the basis of semiquantitative estimation of the percentage of tissue involvement by the two major features of LAM: the cystic lesions and the infiltration by abnormal smooth muscle cells (LAM cells) in each case: LHS-1, < 25%; LHS-2, 25% to 50%; and LHS-3, > 50%. Analysis using the Kaplan-Meier method revealed significant differences in survival for patients with LHS-1, -2, and -3 (p = 0.01), The 5- and 10-year survivals were 100% and 100% for LHS-1, 81.2% and 74.4% for LHS-2, and 62.8% and 52.4% for LHS-3. Increased degrees of accumulation of hemosiderin in macrophages also were associated with higher LHS scores (p = 0.029) and a worse prognosis (p = 0.0012), Thus, the current study suggests that the LHS may provide a basis for determining the prognosis of LAM. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. NCI, Environm Epidemiol Branch, NIH, Rockville, MD USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Travis, WD (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 NW 16th St,Bldg 54,Room M003B, Washington, DC 20306 USA. NR 14 TC 54 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2001 VL 25 IS 4 BP 479 EP 484 DI 10.1097/00000478-200104000-00007 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 415GC UT WOS:000167711700007 PM 11257622 ER PT J AU Stratakis, CA AF Stratakis, CA TI Genetics of adrenocortical tumors: Carney complex SO ANNALES D ENDOCRINOLOGIE LA English DT Article; Proceedings Paper CT 43th International Congress of Clinic Endocrinology CY 2000 CL PARIS, FRANCE DE adrenal cortex; genetics; tumor; primary pigmented adrenocortical disease (PPNAD); Carney complex ID ENDOCRINE OVERACTIVITY; MYXOMAS; DISEASE; PIGMENTATION; LOCUS AB Adrenal cancer is a rare neoplasm; however, up to 1 in 1500 adrenal incidentalomas may hide a carcinoma, which, if diagnosed late or left untreated, is associated with significant morbidity and mortality. Despite extensive investigation of the molecular mechanisms involved in adrenal carcinogenesis and significant improvements in diagnostic imaging, efforts to cure advanced adrenal cancer remain largely unsuccessful. Thus, the investigation of the genetics of adrenocortical cancer by the candidate or positional cloning gene approach is essential in the development of new therapies for this disease. We propose that adrenocortical tumorigenesis follows a pattern similar to that in other organs : As the pathology of the adrenocortical tumor increases towards malignancy, the genetic changes that are observed also increase. Known genetic associations, like TP53 gene changes, occur during the latest stages of adrenocortical tumorigenesis. Thus, it is essential to study the relatively few genes that are affected at the beginning of this process, at the stages of benign tumorigenesis in the cortex. We have studied primary pigmented adrenocortical disease (PPNAD), a benign, bilateral, adrenocortical hyperplasia, which either in its isolated form or as part of Carney complex (CNC), is inherited in an autosomal dominant manner and, therefore, the gene(s) responsible for this disorder could be identified by positional cloning approaches. Indeed, we have identified two genetic loci harboring genes for PPNAD and/or CNC on chromosomal loci 2p16 and 17q22-24. The chromosome 17 gene, PRKAR1A, was recently cloned and the identification of other responsible genes is currently under way in our, and collaborating laboratories. The present report reviews the genetics of adrenocortical cancer first, followed by what is known today about the genetics of PPNAD and/or CNC. C1 NICHD, Unit Genet & Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD APR PY 2001 VL 62 IS 3 BP 180 EP 184 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 439HP UT WOS:000169106100005 PM 11353891 ER PT J AU Cadet, JL Thiriet, N Jayanthi, S AF Cadet, JL Thiriet, N Jayanthi, S TI Involvement of free radicals in MDMA-induced neurotoxicity in mice SO ANNALES DE MEDECINE INTERNE LA English DT Article DE MDMA; drug abuse; toxicity ID METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; ECSTASY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; HUMANS; BRAIN AB 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a substituted amphetamine with stimulating and hallucinogenic properties, Administration of MDMA leads to the formation of metabolites responsible for its toxic effects on serotonergic neurons in rats and non-human primates and on dopaminergic neurons in mice. Our findings indicate that overexpression of the human superoxide dismutase gene (Cu/Zn-SOD) abolishes certain effects of MDMA such as the decreased level of dopamine, DOPAC and 5-HT in the striatum, inactivation of certain antioxidant enzymes (Cu/Zn-SPD, catalase or glutathione peroxidase) or peroxidation of lipids. These data are in agreement with the implication of free radicals and consequently of oxidative stress in the mode of action of MDMA. C1 NIDA, Mol Neuropsychait Sect, NIH, Div Intramural Res, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychait Sect, NIH, Div Intramural Res, Baltimore, MD 21224 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0003-410X J9 ANN MED INTERNE JI Ann. Med. Interne PD APR PY 2001 VL 152 SU 3 BP S57 EP S59 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 450ZV UT WOS:000169775500010 ER PT J AU Praxmarer, M Sung, C Bungay, PM van Osdol, WW AF Praxmarer, M Sung, C Bungay, PM van Osdol, WW TI Computational models of antibody-based tumor imaging and treatment protocols SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE pretargeting; monoclonal antibody antibodies; streptavidin; biotin; pharmacokinetics; diffusion; permeability ID BINDING-SITE BARRIER; BIOTINYLATED MONOCLONAL-ANTIBODIES; RADIOLABELED BIOTIN; NEOPLASTIC TISSUES; STREPTAVIDIN; DIFFUSION; PHARMACOLOGY; XENOGRAFT; HAPTENS; AVIDIN AB We present improved computational models for investigating monoclonal antibody-based protocols for diagnostic imaging and therapy of solid tumors. Our earlier models used a boundary condition (Dirichlet) that specified concentrations of diffusing molecular species at the interface between a prevascular tumor nodule and surrounding normal tissue. Here we introduce a concentration-dependent Bur boundary condition with finite rates of diffusion in the normal tissue. WP then study the effects of this new condition on the tumor's temporal uptake and spatial distribution of radiolabeled targeting agents. We compare these results to ones obtained with the Dirichlet boundary condition and also conduct parameter sensitivity analyses. Introducing finite diffusivity for any molecular species in normal tissue retards its delivery to and removal from the tumor nodule. Effects are protocol- and dose regimen-dependent. generally, however? mean radionuclide concentration and tumor-to-blood ratio declined, whereas relative exposure and mean residence time increased, Finite diffusivity exacerbates the negative effects of antigen internalization, Also, the sensitivity analyses show that mean concentration and tumor-to-blond ratio are quite sensitive to transcapillary permeability and limphatic efflux values, yet relatively insensitive to precise values of diffusion coefficients. Our analysis underscores that knowledge of antigen internalization rates and doses required to saturate antigen in the tumor will be important for exploiting antibody-based imaging and treatment approaches. (C) 2001 Biomedical Engineering Society. C1 NIH, DBEPS, Off Res Serv, Bethesda, MD 20892 USA. Alza Corp, Mt View, CA USA. RP Bungay, PM (reprint author), NIH, DBEPS, Off Res Serv, Bldg 13-3N17,MSC 5766, Bethesda, MD 20892 USA. NR 30 TC 8 Z9 8 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2001 VL 29 IS 4 BP 340 EP 358 DI 10.1114/1.1359453 PG 19 WC Engineering, Biomedical SC Engineering GA 425KC UT WOS:000168288900007 PM 11339331 ER PT J AU Kothari, RU Hacke, W Brott, T Dykstra, EH Furlan, A Koroshetz, W Marler, J Sayre, MR AF Kothari, RU Hacke, W Brott, T Dykstra, EH Furlan, A Koroshetz, W Marler, J Sayre, MR TI Stroke SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE ISCHEMIC STROKE; THROMBOLYTIC THERAPY; PLASMINOGEN-ACTIVATOR; CONTROLLED TRIAL; PERFUSION; ALTEPLASE; EMERGENCY; ACCURACY; ECASS; SCALE C1 Borges Hosp, Borges Res Inst, Kalamazoo, MI 49001 USA. Univ Heidelberg, Heidelberg, Germany. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. PECEMMS Fdn, Apeldoom, Netherlands. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. RP Kothari, RU (reprint author), Borges Hosp, Borges Res Inst, 1521 Gull Rd, Kalamazoo, MI 49001 USA. RI Sayre, Michael/E-8383-2017 OI Sayre, Michael/0000-0003-0322-3181 NR 27 TC 9 Z9 9 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 APR PY 2001 VL 37 IS 4 SU S BP S137 EP S144 DI 10.1067/mem.2001.114171 PG 8 WC Emergency Medicine SC Emergency Medicine GA 425ED UT WOS:000168274600015 PM 11290977 ER PT J AU Duell, EJ Millikan, RC Savitz, DA Schell, MJ Newman, B Tse, CKJ Sandler, DP AF Duell, EJ Millikan, RC Savitz, DA Schell, MJ Newman, B Tse, CKJ Sandler, DP TI Reproducibility of reported farming activities and pesticide use among breast cancer cases and controls: A comparison of two modes of data collection SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE agriculture; data collection; epidemiologic methods; pesticides; recall; reproducibility of results ID FOOD FREQUENCY QUESTIONNAIRE; PHYSICAL-ACTIVITY; EPIDEMIOLOGIC RESEARCH; SURROGATE RESPONDENTS; RELIABILITY; KAPPA; VALIDITY; AGREEMENT; COEFFICIENT; REAPPRAISAL AB PURPOSE: Farming is associated with exposure to many potential hazards including pesticides and other agents, but the quality of self-reported data on farm exposures has not been well studied. METHODS: The reproducibility of self-reported farming history was evaluated among women in a population-based, case-control study of breast: cancer in North Carolina. Thirty cases and 31 controls were randomly re-interviewed by telephone an average of 13.8 months after the initial interview. The initial interview was based on a farm-by-farm questionnaire, while the repeat interview was based on a shorter ever/never questionnaire. Agreement was estimated using proportions in exact agreement, kappa (kappa), and intraclass correlation coefficients (ICC). RESULTS: In general, group prevalences and means were higher on re-interview. Kappa estimates ranged from 0.15 to 0.84 among cases, and 0.26 to 0.87 among controls, with most estimates falling between 0.5 and 0.8. Moderate to almost perfect agreement (kappa) was observed for questions on crop work (0.47-0.70), crop type (0.56-0.82), pesticide application to tobacco (0.77), and farm residence (0.84). ICC estimates for continuous variables showed fair to substantial agreement (0.30 to 0.69 among cases, 0.38 to 0.69 among controls). Cider cases, less educated cases, cases who lived on more than one farm, and cases with longer time intervals between interviews gave lower total agreement than similar groups of controls. CONCLUSIONS: Agreement estimates in this study are similar to those for other types of exposure information typically collected in epidemiologic studies. Nevertheless, a farm-by-farm method of exposure assessment may he preferable to an ever/never determination.,Ann Epidemiol 2001;11:178-185. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Millikan, RC (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CB 7400, Chapel Hill, NC 27599 USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA58223, CA09330]; NIEHS NIH HHS [ES07128] NR 30 TC 9 Z9 9 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 2001 VL 11 IS 3 BP 178 EP 185 DI 10.1016/S1047-2797(00)00208-8 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 409DG UT WOS:000167368800004 PM 11248581 ER PT J AU Muntaner, C Sorlie, P O'Campo, P Johnson, N Backlund, E AF Muntaner, C Sorlie, P O'Campo, P Johnson, N Backlund, E TI Occupational hierarchy, economic sector, and mortality from cardiovascular disease among men and women: Findings from the National Longitudinal Mortality Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cardiovascular disease; mortality; occupational exposures; socioeconomic status; social inequalities; social class; women's health ID PSYCHOSOCIAL WORK-ENVIRONMENT; SOCIOECONOMIC-STATUS; HEART-DISEASE; UNITED-STATES; RISK; EPIDEMIOLOGY; HEALTH AB PURPOSE: Although socioeconomic position has been identified as a determinant of cardiovascular disease among employed men and women in the U.S., the role of economic sector in shaping this relationship has yet to be examined. We sought to estimate the combined effects of economic sector-one of the three major sectors of the economy: finance, government and production-and socioeconomic position on cardiovascular mortality among employed men and women. METHODS: Approximately 375,000 men and women 25 years of age or more were identified from selected Current Population Surveys between 1979 and 1985. These persons were followed for cardiovascular mortality through use of the National Death Index for the years 1979 through 1989. RESULTS: In men, the lowest cardiovascular mortality was found for professionals in the finance sector (76/100,000 person/years). The highest cardiovascular mortality was found among male nonprofessional workers in the production sector (192/100,000 person years). A different pattern war observed among women. Professional women in the finance sector had the highest rates of cardiovascular mortality (133/100,000 person years). For both men and women, the professional/non-professional gap in cardiovascular mortality was lower in the government sector than in the production and finance sectors. These associations were strong even after adjustment for age, race and income. CONCLUSIONS: Characteristics of government, finance and production work differentially influence the risk of cardiovascular disease mortality. Men, women, professionals and non-professionals experience this risk differently.,Ann Epidemiol 2001;Il:194-201. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Maryland, Dept Behav & Community Hlth Nursing, Baltimore, MD USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Bur Census, Demog & Stat Methods Div, Suitland, MD USA. RP O'Campo, P (reprint author), Johns Hopkins Univ, 624 N Broadway 390, Baltimore, MD 21205 USA. RI Muntaner, C/A-5043-2010 NR 41 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 2001 VL 11 IS 3 BP 194 EP 201 DI 10.1016/S1047-2797(00)00210-6 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 409DG UT WOS:000167368800006 PM 11248583 ER PT J AU Li, M Dalakas, MC AF Li, M Dalakas, MC TI Abnormal desmin protein in myofibrillar myopathies caused by desmin gene mutations SO ANNALS OF NEUROLOGY LA English DT Article ID SKELETAL MYOPATHY; MISSENSE MUTATION; DISTAL MYOPATHY; CARDIOMYOPATHY; DISEASE; FAMILY; DOMAIN AB Muscle proteins were extracted in various sodium dodecyl sulfate buffers from 6 patients with myofibrillar myopathy (MFM) and previously identified with mutations in the desmin gene (desmin myopathy, DesM), 6 with MFM without mutations, and 14 disease controls to search for alterations in biochemistry and solubility of mutated desmin filaments. In the 1% posthigh-speed pellet fraction, desmin was detected with immunoblots only in DesM and not the other MFM. We conclude that mutant desmin forms insoluble aggregates that are specific for the DesM and can be detected with Western blots. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. NR 20 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2001 VL 49 IS 4 BP 532 EP 536 DI 10.1002/ana.106 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 418FJ UT WOS:000167880000018 PM 11310634 ER PT J AU Bushara, KO Goebel, SU Shill, H Goldfarb, LG Hallett, M AF Bushara, KO Goebel, SU Shill, H Goldfarb, LG Hallett, M TI Gluten sensitivity in sporadic and hereditary cerebellar ataxia SO ANNALS OF NEUROLOGY LA English DT Article ID CELIAC-DISEASE; DEGENERATION; ANTIBODIES; ATROPHY AB Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC1428, Bethesda, MD 20892 USA. NR 17 TC 67 Z9 69 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2001 VL 49 IS 4 BP 540 EP 543 DI 10.1002/ana.108 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 418FJ UT WOS:000167880000020 PM 11310636 ER PT J AU Hampel, H Buerger, K Kohnken, R Teipel, SJ Zinkowski, R Moeller, HJ Rapoport, SI Davies, P AF Hampel, H Buerger, K Kohnken, R Teipel, SJ Zinkowski, R Moeller, HJ Rapoport, SI Davies, P TI Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231 SO ANNALS OF NEUROLOGY LA English DT Letter ID CSF-TAU; STABILITY C1 Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Univ Munich, Dementia Res Sect, Munich, Germany. Univ Munich, Memory Clin, Munich, Germany. Mol Geriatr Corp, Vernon Hills, IL USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. RP Hampel, H (reprint author), Univ Munich, Dept Psychiat, D-8000 Munich, Germany. NR 5 TC 67 Z9 68 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2001 VL 49 IS 4 BP 545 EP 546 DI 10.1002/ana.111 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 418FJ UT WOS:000167880000023 PM 11310639 ER PT J AU Okin, PM Devereux, RB Kors, JA van Herpen, G Crow, RS Fabsitz, RR Howard, BV AF Okin, PM Devereux, RB Kors, JA van Herpen, G Crow, RS Fabsitz, RR Howard, BV TI Computerized ST depression analysis improves prediction of all-cause and cardiovascular mortality: The strong heart study SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE electrocardiogram; computerized; Minnesota code; ST depression ID AMERICAN-INDIANS; DISEASE MORTALITY; T ABNORMALITIES; MINNESOTA CODE; RISK; DEATH; ELECTROCARDIOGRAMS; ASSOCIATION; POPULATION; PROGRAMS AB Background: Nonspecific ST depression assessed by standard visual Minnesota coding (MC) has been demonstrated to predict risk. Although computer analysis has been applied to digital ECGs for MC, the prognostic value of computerized MC and computerized ST depression analyses have not been examined in relation to standard visual MC, Methods: The predictive value of nonspecific ST depression as determined by visual and computerized MC codes 4.2 or 4.3 was compared with computer-measured ST depression greater than or equal to 50 muV in 2,127 American Indian participants in the first Strong Heart Study examination. Computerized MC and ST depression were determined using separate computerized-ECG analysis programs and visual MC was performed by an experienced ECG core laboratory. Results: The prevalence of MC 4.2 or 4.3 by computer was higher than by visual analysis (6.4 vs 4.4%, P < 0.001). After mean follow-up of 3.7 +/- 0.9 years, there were 73 cardiovascular deaths and 227 deaths from al I causes. in univariate Cox analyses, visual MC (relative risk [RR] 4.8, 95% confidence interval [CI] 2.6-9.1), computerized MC (RR 6.0, 95% Cl 3.5-10.3), and computer-measured ST depression (RR 7.6, 95% CI 4.5-12.9) were all significant predictors of cardiovascular death. In separate multivariate Cox regression analyses that included age, sex, diabetes, HDL and LDL cholesterol, body mass index, systolic and diastolic blood pressure, microalbuminuria, smoking, and the presence of coronary heart disease, computerized MC (RR 3.0, 95% Cl 1.6-5.6) and computer-measured ST depression (RR 3.1, 95% Cl 1.7-5.7), but not visual MC, remained significant predictors of cardiovascular mortality. When both computerized MC and computer-measured ST depression were entered into the multivariate Cox regression, each variable provided independent risk stratification (RR 2.1, 95% Cl 1.0-4.4, and RR 2.1, 95% Cl 1.0-4.4, respectively). Similarly, computerized MC and computer-measured ST depression, but not visual MC, were independent predictors of all-cause mortality after controlling for standard risk factors. Conclusions: Computer analysis of the ECG, using computerized MC and computer-measured ST depression, provides independent and additive risk stratification for cardiovascular and all-cause mortality, and improves risk stratification compared with visual MC. These findings support the use of routine computer analysis of ST depression on the rest ECG for assessment of risk and suggest that computerized MC can replace visual MC for this purpose. C1 Cornell Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10021 USA. Erasmus Univ, Sch Med, Rotterdam, Netherlands. Univ Minnesota, Sch Epidemiol, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. Medstar Res Inst, Washington, DC USA. RP Okin, PM (reprint author), Cornell Univ, Med Ctr, Dept Med, Div Cardiol, 525 E 68th St, New York, NY 10021 USA. FU NHLBI NIH HHS [U01-HL41652, U01-HL41642, U01-HL41654] NR 36 TC 15 Z9 15 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD APR PY 2001 VL 6 IS 2 BP 107 EP 116 DI 10.1111/j.1542-474X.2001.tb00094.x PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 485RH UT WOS:000171770500006 PM 11333167 ER PT J AU Liu, XZ Xu, LR Hu, Y Nance, WE Sismanis, A Zhang, SL Xu, Y AF Liu, XZ Xu, LR Hu, Y Nance, WE Sismanis, A Zhang, SL Xu, Y TI Epidemiological studies on hearing impairment with preference to genetic factors in Sichuan, China SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE Chinese; epidemiology; etiology; genetic deafness; hearing loss ID GENERAL-POPULATION; PROFOUND DEAFNESS; PREVALENCE; DISABILITY AB Hearing impairment is the most common disorder of sensorineural function and is an economically and socially important cause of human morbidity. A large-scale epidemiological survey of hearing loss was conducted with 126,876 unselected subjects (63,741 male and 63,135 female) from Sichuan, China. The overall prevalence of hearing loss was 3.28% (4,164 of 126,876), and the prevalence increased with age, reaching 12.8% (1,465 of 11.421) at 60 years of age. In 73.03% of all cases (3,041 of 4,164), the hearing loss was sensorineural, and in 20.39% (849 of 4,164), it was conductive; the remaining cases (6%) were mixed hearing loss. Bilateral loss was found in 74.5% of cases 13,103 of 4,164). In 63.79% of cases (2,656 of 4,164). the degree of hearing loss was less than 55 dB hearing level (HL), and in 5.67% of cases (236 of 4.164), it was greater than 90 dB HL. The prevalence of hearing loss in childhood (<15 years of age) was 0.67% (227 of 34,157), of which 57.7% of cases were conductive and 38.8% were sensorineural. The prevalence of genetic hearing loss was 0.28% (349 of 126,876). Persons who lived in the flatlands appeared to have a higher prevalence than those who lived in the hills. Several ethnic groups, including Tibetans, the Yi, and the Lisu, had a higher prevalence of hearing loss. Presbycusis, otitis media, and genetic factors were the most commonly recognized causes of hearing impairment overall, but otitis media and genetic factors were the main causes of hearing loss in children. Causes for the observed differences in prevalence and etiologic factors between China and industrialized countries will be discussed. In China, infections and genetic factors appear to be of major importance as causes of hearing loss. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, NIH, Washington, DC USA. W China Univ Med Sci, Dept Otolaryngol, Chengdu 610041, Peoples R China. Sichuan Family Planning Res Inst, Dept Epidemiol Survey, Chengdu, Peoples R China. RP Liu, XZ (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Sanger Hall,1101 E Marshall St,POB 980033, Richmond, VA 23298 USA. FU NIDCD NIH HHS [DC02530, R03 DC04530] NR 27 TC 24 Z9 25 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 2001 VL 110 IS 4 BP 356 EP 363 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 420QD UT WOS:000168014900012 PM 11307913 ER PT J AU Wink, DA Miranda, KM Espey, MG Pluta, RM Hewett, SJ Colton, C Vitek, M Feelisch, M Grisham, MB AF Wink, DA Miranda, KM Espey, MG Pluta, RM Hewett, SJ Colton, C Vitek, M Feelisch, M Grisham, MB TI Mechanisms of the antioxidant effects of nitric oxide SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; OXIDIZED LIPID DERIVATIVES; OXIDATIVE-STRESS; ENDOTHELIAL-CELLS; HYDROGEN-PEROXIDE; MYOCARDIAL-ISCHEMIA; ESCHERICHIA-COLI; SUPEROXIDE; PEROXYNITRITE; REPERFUSION AB The Janus face of nitric oxide (NO) has prompted a debate as to whether NO plays a deleterious or protective role in tissue injury. There are a number of reactive nitrogen oxide species, such as N2O3 and ONOO-, that can alter critical cellular components under high local concentrations of NO. However, NO can also abate the oxidation chemistry mediated by reactive oxygen species such as H2O2 and O-2(-) that occurs at physiological levels of NO. In addition to the antioxidant chemistry, NO protects against cell death mediated by H2O2, alkylhydroperoxides, and xanthine oxidase. The attenuation of metal/peroxide oxidative chemistry, as well as lipid peroxidation, appears to be the major chemical mechanisms by which NO may limit oxidative injury to mammalian cells. In addition to these chemical and biochemical properties, NO can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. This review will address these aspects of the chemical biology of this multifaceted free radical and explore the beneficial effect of NO against oxidative stress. C1 NCI, Radiat Biol Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Surg Branch, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA USA. RP NCI, Radiat Biol Branch, Tumor Biol Sect, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM Wink@mail.nih.com RI Miranda, Katrina/B-7823-2009; Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; Hewett, Sandra/0000-0002-2987-3791 NR 62 TC 160 Z9 167 U1 0 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2001 VL 3 IS 2 BP 203 EP 213 DI 10.1089/152308601300185179 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 532WW UT WOS:000174498900004 PM 11396476 ER PT J AU Alayash, AI Patel, RP Cashon, RE AF Alayash, AI Patel, RP Cashon, RE TI Redox reactions of hemoglobin and myoglobin: Biological and toxicological implications SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVE CROSS-LINKING; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; NITRIC-OXIDE; FERRYL INTERMEDIATE; MYOCARDIAL ISCHEMIA; SIGNAL-TRANSDUCTION; HUMAN METHEMOGLOBIN; CEREBRAL VASOSPASM AB Direct cytotoxic effects associated with hemoglobin (Hb) or myoglobin (Mb) have been ascribed to redox reactions (involving either one- or two-electron steps) between the heme group and peroxides. These interactions are the basis of the pseudoperoxidase activity of these hemoproteins and can be cytotoxic when reactive species are formed at relatively high concentrations during inflammation and typically lead to cell death. Peroxides relevant to biological systems include hydrogen peroxide, lipid hydroperoxides, and peroxynitrite. Reactions between Hb/Mb and peroxides form the ferryl oxidation state of the protein, analogous to compounds I and II formed in the catalytic cycle of many peroxidase enzymes. This higher oxidation state of the protein is a potent oxidant capable of promoting oxidative damage to most classes of biological molecules. Free iron, released from Hb, also has the potential to promote oxidative damage via classical "Fenton" chemistry. It has become increasingly evident that Hb/Mb redox reactions or their by-products play a critical role in the pathophysiology of some disease states. This review briefly discusses the reactions of Hb/Mb with biological peroxides, potential cytotoxicity and the impact of these interactions on modulation of cell signaling pathways regulated by these reactive species. Also discussed in this article is the role of heme-protein chemistry in relation to the toxicity of hemoproteins. C1 US FDA, CBER, Bethesda, MD 20892 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. Univ Maine, Dept Biochem Microbiol & Mol Biol, Orono, ME 04469 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP US FDA, CBER, NIH Campus,Bldg 29,Rm 112, Bethesda, MD 20892 USA. EM Alayash@cber.fda.gov OI Patel, Rakesh/0000-0002-1526-4303 NR 98 TC 138 Z9 144 U1 1 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2001 VL 3 IS 2 BP 313 EP 327 DI 10.1089/152308601300185250 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 532WW UT WOS:000174498900012 PM 11396484 ER PT J AU McLachlan, JA Newbold, RR Burow, ME Li, SF AF McLachlan, JA Newbold, RR Burow, ME Li, SF TI From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters SO APMIS LA English DT Review DE malformations; male; estrogens; reproductive system; molecular mechanisms ID DIETHYLSTILBESTROL EXPOSURE INUTERO; MOUSE SEMINAL-VESICLE; PRENATAL EXPOSURE; MALE-MICE; LACTOTRANSFERRIN GENE; GENITAL-TRACT; EXPRESSION; CRYPTORCHIDISM; ADENOCARCINOMA; ABNORMALITIES AB For three decades, we have known that estrogens alter the development of the mammalian reproductive system in predictable ways. In mice exposed prenatally to diethylstilbestrol (DES) or other estrogens, the male offspring exhibit structural malformations including cryptorchidism, epididymal cysts and retained Mullerian ducts. The estrogen-associated alterations in the genital tract phenotype can be usefully considered as a model called Developmental Estrogenization Syndrome. While estrogen treatment during critical periods of morphogenesis of the male reproductive system has been associated with these changes, the mechanisms at the molecular level are still being discovered. Parallel findings on the hormones involved in Mullerian duct regression and testicular descent have helped guide research on the mechanisms of developmental estrogenization of the male. Cellular localization of molecular signals associated with key steps in genital tract development, use of mice with gene disruption, and knowledge of the mechanisms underlying persistent changes in gene expression are beginning to provide a blue print for both the physiological role and pathological effects of estrogens in reproductive tract development. Since many of the same biological principles underlie genital tract morphogenesis in mammals, one may expect some of the same changes in males of other species exposed to estrogen during the appropriate developmental periods. C1 Tulane Univ, Ctr Bioenvironm Res, Environm Endocrinol Lab, New Orleans, LA 70118 USA. Xavier Univ, New Orleans, LA 70125 USA. Tulane Univ, Ctr Hlth Sci, Dept Pharmacol, New Orleans, LA 70118 USA. Natl Inst Environm Hlth Sci, Toxicol Lab, Res Triangle Pk, NC USA. RP McLachlan, JA (reprint author), Tulane Univ, Ctr Bioenvironm Res, Environm Endocrinol Lab, New Orleans, LA 70118 USA. RI Burow, Matthew/D-6351-2013 OI Burow, Matthew/0000-0002-0642-6630 NR 44 TC 68 Z9 69 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD APR PY 2001 VL 109 IS 4 BP 263 EP 272 DI 10.1034/j.1600-0463.2001.d01-119.x PG 10 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 449JP UT WOS:000169681700002 PM 11469497 ER PT J AU Ghate, JV Turner, ML Rudek, MA Figg, WD Dahut, W Dyer, V Pluda, JM Reed, E AF Ghate, JV Turner, ML Rudek, MA Figg, WD Dahut, W Dyer, V Pluda, JM Reed, E TI Drug-induced lupus associated with COL-3 - Report of 3 cases SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ERYTHEMATOSUS; MINOCYCLINE AB Background: Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduce of a phase 1 clinical trial for refractory metastatic cancer at the National institutes of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus. Observations: Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer within 8 to 29 days of starting treatment. Two of: 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up. Conclusions: COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed. C1 NCI, Dermatol Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Investigat Drug Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Turner, ML (reprint author), NCI, Clin Pharmacokinet Sect, Med Branch, Bldg 10,Room 5A-01, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 9 TC 20 Z9 20 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2001 VL 137 IS 4 BP 471 EP 474 PG 4 WC Dermatology SC Dermatology GA 421YL UT WOS:000168091100009 PM 11295928 ER PT J AU Huestis, MA Gorelick, DA Heishman, SJ Preston, KL Nelson, RA Moolchan, ET Frank, RA AF Huestis, MA Gorelick, DA Heishman, SJ Preston, KL Nelson, RA Moolchan, ET Frank, RA TI Blockade of effects of smoked marijuana by the CBl-selective cannabinoid receptor antagonist SR141716 SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SR 141716A; MOLECULAR-CLONING; RHESUS-MONKEYS; BRAIN; HUMANS; MEMORY; RATS; DELTA-9-TETRAHYDROCANNABINOL; SCHIZOPHRENIA; PERFORMANCE AB Background: SR141716, a recently developed CB1 cannabinoid receptor antagonist, blocks acute effects of Delta -9-tetrahydrocannabinol (THC) and other CB1 cannabinoid agonists invitro and in animals. These findings suggest that CB1 receptors mediate many of the effects of marijuana, but this has not been evaluated in humans. Methods: Sixty-three healthy men with a history of marijuana use were randomly assigned to receive oral SR141716 or a placebo in an escalating dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64%; THC) or placebo marijuana cigarette 2 hours later. Psychological effects associated with marijuana intoxication and heart rate were measured before and after antagonist and marijuana administration. Results: Single oral doses of SR141716 produced a significant dose-dependent blockade of marijuana-induced subjective intoxication and tachycardia. The 90-mg dose produced 38% to 43%; reductions in visual analog scale ratings of "How high do you feel now?" "How stoned on marijuana are you now?" and "How strong. is the drug effect you feel now?" and produced a 59% reduction in heart rate. SR141716 alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or the area under the time x concentration curve. SR141716 was well tolerated by all subjects. Conclusions: SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana. C1 Sanofi Synthelabo Inc, Malvern, PA USA. NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Branch, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 43 TC 246 Z9 253 U1 3 U2 14 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 APR PY 2001 VL 58 IS 4 BP 322 EP 328 DI 10.1001/archpsyc.58.4.322 PG 7 WC Psychiatry SC Psychiatry GA 419ZF UT WOS:000167978900001 PM 11296091 ER PT J AU Daly, RC Schmidt, PJ Roca, CA Rubinow, DR AF Daly, RC Schmidt, PJ Roca, CA Rubinow, DR TI Testosterone's effects not limited to mood SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID CONTROLLED TRIAL; MEN C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Daly, RC (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3 N242,10 Ctr Dr,MSC 1277, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH52037] NR 5 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2001 VL 58 IS 4 BP 403 EP 403 DI 10.1001/archpsyc.58.4.403 PG 1 WC Psychiatry SC Psychiatry GA 419ZF UT WOS:000167978900014 PM 11296104 ER PT J AU Linfante, I Llinas, RH Schlaug, G Chaves, C Warach, S Caplan, LR AF Linfante, I Llinas, RH Schlaug, G Chaves, C Warach, S Caplan, LR TI Diffusion-weighted imaging and National Institutes of Health Stroke Scale in the acute phase of posterior-circulation stroke SO ARCHIVES OF NEUROLOGY LA English DT Article ID ACUTE CEREBRAL INFARCTION; ACUTE ISCHEMIC STROKE; HUMAN BRAIN; MRI; PERFUSION; THERAPY; TENSOR; CT AB Background: Occlusive disease of the posterior circulation represents a heterogeneous group of strokes that differ in etiology, clinical presentation, and prognosis. Computed tomography provides suboptimal visualization of posterior-circulation infarcts. Anatomic definition of traditional magnetic resonance imaging sequences has been used for clinicoradiologic correlation in patients with posterior-circulation disease. These studies focused on the subacute rather than the acute phase of ischemia. Lesion volumes on diffusion-weighted imaging (DWI) and perfusion imaging were found to have a good correlation with 24-hour National Institutes of Health stroke scale (NIHSS) score in ischemia of the anterior circulation. Correlation between NIHSS score and lesion volume in posterior-circulation infarcts is unknown. Objectives: To investigate whether DWI is useful for clinicoradiologic correlation of posterior-circulation ischemia within 24 hours after symptom onset and whether NIHSS score correlates with lesion volumes in patients with posterior-circulation stroke. Patients and Methods: In a database analysis of 631 patients with stroke from June 26, 1996, to July 30, 1999, 115 patients (18%) had symptoms of posterior-circulation ischemia by imaging and clinical criteria. Among these 115, we included all patients (n=40) who underwent DWI within 24 hours from symptom onset (mean, 9.7 +/-7.1 hours). All 40 patients also underwent magnetic resonance angiography and T2-weighted imaging. Seventy-five did not meet inclusion criteria: in 45, magnetic resonance imaging was performed more than 24 hours after symptom onset; 12 did not have DWI; in 11 patients, symptoms resolved within 24 hours; 6 had hemorrhages; and 1 had a border zone infarct. Results: An acute lesion on DWI corresponding to the patient's symptoms was detected in all 40 patients, 16 (40%) of whom had detectable acute lesions on T2-weighted images. The lesions on DWI were larger in 11 of the 16 patients with positive T2-weighted images. Acute lesion volume did not correlate with NIHSS score (n=40; p=0.30; P=.06, Spearman rank) also when DWI lesion volumes were divided by cause and territory. Conclusions: Diffusion-weighted imaging is more effective than T2-weighted imaging in patients with acute posterior-circulation strokes. The DWI lesion volume did not significantly correlate with NIHSS score, suggesting that NIHSS is more weighted toward anterior-circulation stroke symptoms. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Div Cerebrovasc Dis, Boston, MA 02115 USA. NINDS, Stroke Branch, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. RP Linfante, I (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Div Cerebrovasc Dis, E Campus DA 779,330 Brookline Ave, Boston, MA 02115 USA. NR 30 TC 58 Z9 61 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2001 VL 58 IS 4 BP 621 EP 628 DI 10.1001/archneur.58.4.621 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 419EG UT WOS:000167935900012 PM 11295993 ER PT J AU Longstreth, WT Diehr, P Manolio, TA Beauchamp, NJ Jungreis, CA Lefkowitz, D AF Longstreth, WT Diehr, P Manolio, TA Beauchamp, NJ Jungreis, CA Lefkowitz, D CA Cardiovas Hlth Study Collaborative TI Cluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly - The cardiovascular health study SO ARCHIVES OF NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; WHITE-MATTER FINDINGS; OLDER ADULTS; MRI FINDINGS; BRAIN; ABNORMALITIES; PEOPLE; PREVALENCE; INFARCTION; DISEASE AB Objective: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis. Subjects and Methods: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations. Results: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected. Conclusions: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly. C1 Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Neuroradiol Div, Baltimore, MD 21205 USA. Univ Pittsburgh, Med Ctr, Dept Radiol & Neurol Surg, Neuroradiol Div, Pittsburgh, PA USA. Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA. RP Longstreth, WT (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, Box 359775,325 9Th Ave, Seattle, WA 98104 USA. FU NHLBI NIH HHS [N01-HC-85056, N01-HC-85079, N01 HC-95100] NR 24 TC 48 Z9 48 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2001 VL 58 IS 4 BP 635 EP 640 DI 10.1001/archneur.58.4.635 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 419EG UT WOS:000167935900014 PM 11295995 ER PT J AU del Zoppo, GJ Becker, KJ Hallenbeck, JM AF del Zoppo, GJ Becker, KJ Hallenbeck, JM TI Inflammation after stroke - Is it harmful? SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID FOCAL CEREBRAL-ISCHEMIA; TUMOR-NECROSIS-FACTOR; PLATELET-ACTIVATING-FACTOR; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-BETA; TRANSGENIC MICE; FACTOR-ALPHA; GENE-EXPRESSION; BRAIN INJURY; HIPPOCAMPAL-NEURONS C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. Scripps Clin, Div Hematol Med Oncol, La Jolla, CA USA. RP del Zoppo, GJ (reprint author), Scripps Res Inst, Dept Mol & Expt Med, Room MEM 132,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NINDS NIH HHS [R01 NS 26945, K02 NS02160] NR 66 TC 100 Z9 103 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2001 VL 58 IS 4 BP 669 EP 672 DI 10.1001/archneur.58.4.669 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 419EG UT WOS:000167935900021 PM 11296002 ER PT J AU Fong, DS Ferris, FL AF Fong, DS Ferris, FL TI Evidence-guided ophthalmology SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETINITIS-PIGMENTOSA; VITAMIN-A C1 So Calif Permanente Med Grp, Dept Ophthalmol, Baldwin Pk, CA 91706 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NEI, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. RP Fong, DS (reprint author), 1011 Baldwin Pk Blvd, Baldwin Pk, CA 91706 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2001 VL 119 IS 4 BP 585 EP 589 PG 5 WC Ophthalmology SC Ophthalmology GA 422QL UT WOS:000168130700016 PM 11296026 ER PT J AU Bradley, RH AF Bradley, RH TI Child Care and Common Communicable Illnesses - Results from the National Institute of Child Health and Human Development Study of Early Child Care SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID ACUTE OTITIS-MEDIA; 1ST 2 YEARS; YOUNG-CHILDREN; RISK-FACTORS; RESPIRATORY ILLNESS; CENTER ATTENDANCE; FAMILIAL FACTORS; SMOKE EXPOSURE; INFECTIONS; CENTERS AB Objectives: To examine the relationship between experiences in child care and communicable illnesses (gastrointestinal tract illness, upper respiratory tract infection, and ear infections or otitis media) throughout the first 3 years of life and to investigate whether increased frequency of these illnesses is related to language development, school readiness, and behavior problems. Design: Health, child care, family, and child developmental data were obtained from more than 1200 participants in the National Institute of Child Health and Human Development Study of Early Child Care, a 10-site prospective study that began at the participants' birth. Longitudinal logistic regression analyses were performed using each type of communicable illness as the outcome variable, with family, child, and child care variables as predictors in the model, and followed by a series of regression analyses with developmental measures as the outcome variables. Results: Rates of illness were higher in children in child care than for children reared exclusively at home during the first 2 years of life, but the differences were nonsignificant by age 3 years. Number of hours in child care per week during the first year and number of other children in the child care arrangement were related to the rates of illness. There was no evidence that increased rates of illness have a negative effect on school readiness or language competence. However, there was some evidence that increased illness was associated with behavior problems as reported by mothers, but not by child care providers. Conclusions: Children in child care experience more bouts of illness in the first 2 years of life, but differences are negligible by age 3 years. The increased rates of illness bear little relation to other aspects of children's development, except, perhaps, for a small increase in behavior problems. C1 Univ Arkansas, Ctr Appl Studies Educ, Little Rock, AR 72204 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ London, London WC1E 7HU, England. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Calif Irvine, Irvine, CA 92717 USA. NICHD, Bethesda, MD USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Texas, Austin, TX 78712 USA. Res Triangle Inst, Cary, NC USA. Wellesley Coll, Wellesley, MA 02181 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ Texas, Dallas, TX 75230 USA. Univ Virginia, Charlottesville, VA 22903 USA. Georgetown Univ, Washington, DC 20057 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Bradley, RH (reprint author), Univ Arkansas, Ctr Appl Studies Educ, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM rhbradley@ualr.edu NR 39 TC 28 Z9 29 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 1072-4710 EI 1538-3628 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 2001 VL 155 IS 4 BP 481 EP 488 PG 8 WC Pediatrics SC Pediatrics GA 419VH UT WOS:000167969100009 ER PT J AU Huang, W Zhang, WY Ishii, I Kruth, HS AF Huang, W Zhang, WY Ishii, I Kruth, HS TI PMA inhibits plasmin-mediated release of aggregated LDL macrophages. SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2001 VL 21 IS 4 MA 103 BP 663 EP 663 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 424WZ UT WOS:000168258100126 ER PT J AU Letterman, J van der Westhuyzen, DR Ruderman, NB Liscum, L Sipe, JD Schreiber, BM AF Letterman, J van der Westhuyzen, DR Ruderman, NB Liscum, L Sipe, JD Schreiber, BM TI Serum amyloid A induces cholesterol movement to the endoplasmic reticulum and regulates SREBP-responsive genes. SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Kentucky, Med Ctr, Lexington, KY USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2001 VL 21 IS 4 MA 137 BP 672 EP 672 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 424WZ UT WOS:000168258100158 ER PT J AU Nallamshetty, S Boehm, M Yoshimoto, T Nabel, EG AF Nallamshetty, S Boehm, M Yoshimoto, T Nabel, EG TI MCM7,a replication licensing factor, interacts with the cell cycle regulator p27(kip1) SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 NIH, NHLBI, Vasc Biol Branch, 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2001 VL 21 IS 4 MA 223 BP 693 EP 693 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 424WZ UT WOS:000168258100240 ER PT J AU True, AL San, H Xu, YH Kesselheim, JA Qu, X Boehm, M Westrick, RJ Eitzman, DT Nabel, EG AF True, AL San, H Xu, YH Kesselheim, JA Qu, X Boehm, M Westrick, RJ Eitzman, DT Nabel, EG TI Deletion of heme oxygenase-1 accelerates arterial thrombus formation. SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 NHLBI, Vasc Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2001 VL 21 IS 4 MA 265 BP 704 EP 704 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 424WZ UT WOS:000168258100282 ER PT J AU Vogel, AM Lawson, ND Pham, VN Scheer, N Kim, CH Chitnis, AB Campos-Ortega, JA Weinstein, BM AF Vogel, AM Lawson, ND Pham, VN Scheer, N Kim, CH Chitnis, AB Campos-Ortega, JA Weinstein, BM TI Formation and arterial-venous differentiation of embryonic blood vessels requires the Hedgehog and Notch signaling pathways SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. Univ Cologne, Inst Entwicklungsbiol, D-50923 Cologne, Germany. 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2001 VL 21 IS 4 MA 270 BP 706 EP 706 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 424WZ UT WOS:000168258100287 ER PT J AU Potter, K Kidder, LH Levin, IW Lewis, EN Spencer, RGS AF Potter, K Kidder, LH Levin, IW Lewis, EN Spencer, RGS TI Imaging of collagen and proteoglycan in cartilage sections using Fourier transform infrared spectral imaging SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MAGNETIC-RESONANCE MICROSCOPY; CHONDROCYTES; TISSUES; MICROSPECTROSCOPY; ULTRASTRUCTURE; SPECTROSCOPY; BIOREACTOR; OXYGEN AB Objective. To test the hypothesis that Fourier transform infrared (FTIR) spectral imaging, coupled with multivariate data processing techniques, can image the spatial distribution of matrix constituents in native and engineered cartilage samples. Methods. Tissue sections from native and trypsin-digested bovine nasal cartilage (BNC) and from engineered cartilage, generated by chick sternal chondrocytes grown in a hollow fiber bioreactor, were placed either on calcium fluoride windows for FTIR analysis or gelatinized microscope slides for histologic analysis. Based on the assumption that cartilage is predominantly chondroitin sulfate (CS) and type H collagen, chemical images were extracted from FTIR spectral imaging data sets using 2 multivariate methods: the Euclidean distance algorithm and a least-squares approach. Results. Least-squares analysis of the FTIR data of native BNC yielded a collagen content of 54 +/- 13% and a CS content of 37 +/- 16% (mean +/- SD). Euclidean distance analysis of measurements made on trypsin-digested BNC demonstrated only trace amounts of CS. For engineered cartilage, the CS content was significantly lower (15 +/- 5%), while the collagen content (73 +/- 6%) was significantly higher than biochemically determined values (CS 34%, collagen 5%, protein 61%). These differences are due to the fact that the dimethylmethylene blue assay overestimated the CS content of the tissue because it is not specific for CS, while the FTIR spectral imaging technique overestimated the collagen content because it lacks specificity for different proteins. Conclusion. FTIR spectral imaging combines histology-like spatial localization with the quantitative capability of bulk chemical analysis. For molecules with a unique spectral signature, such as CS, the FTIR technique coupled with multivariate analysis can define a unique spatial distribution. However, for some applications, the lack of specificity of this technique for different types of proteins may be a limitation. C1 NIA, Nucl Magnet Resonance Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Spectral Dimens Inc, Olney, MD 20832 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Spencer, RGS (reprint author), NIA, Nucl Magnet Resonance Unit, Intramural Res Program, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 109 Z9 113 U1 1 U2 14 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2001 VL 44 IS 4 BP 846 EP 855 DI 10.1002/1529-0131(200104)44:4<846::AID-ANR141>3.0.CO;2-E PG 10 WC Rheumatology SC Rheumatology GA 485JG UT WOS:000171750800013 PM 11315924 ER PT J AU Goulet, S Murray, EA AF Goulet, S Murray, EA TI Neural substrates of crossmodal association memory in monkeys: The amygdala versus the anterior rhinal cortex SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID PERIRHINAL CORTEX; RHESUS-MONKEYS; PARAHIPPOCAMPAL CORTICES; INFEROTEMPORAL CORTEX; PREFRONTAL CORTEX; MACAQUE MONKEY; AREA TE; LESIONS; CONNECTIONS; ABLATION AB Nine rhesus monkeys were trained on visual, tactual, and crossmodal (tactual-visual) versions of delayed nonmatching-to-sample (DNMS). They then received bilateral aspiration lesions of the anterior rhinal cortex or bilateral excitotoxic lesions of the amygdala or were retained as unoperated controls. Monkeys with anterior rhinal cortex lesions displayed a persistent deficit on crossmodal DNMS as well as a deficit on tactual DNMS, In contrast, monkeys with amygdala lesions exhibited only a transient impairment on crossmodal DNMS, and their difficulty appeared to be related to inadvertent damage to the anterior rhinal cortex. The present findings support the idea that the rhinal cortex is important for the formation and retrieval of stimulus-stimulus associations across sensory modalities. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Laval, Ecole Psychol, Laval, PQ, Canada. RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 41 TC 49 Z9 49 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2001 VL 115 IS 2 BP 271 EP 284 DI 10.1037//0735-7044.115.2.271 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 471DB UT WOS:000170911400002 PM 11345954 ER PT J AU Abu-Asab, MS Peterson, PM Shetler, SG Orli, SS AF Abu-Asab, MS Peterson, PM Shetler, SG Orli, SS TI Earlier plant flowering in spring as a response to global warming in the Washington, DC, area SO BIODIVERSITY AND CONSERVATION LA English DT Article DE first-flowering; global warming; minimum temperature; spring-flowering; Washington DC ID CLIMATE AB Evidence for global warming is inferred from spring advances in first-flowering in plants. The trend of average first-flowering times per year for the study group shows a significant advance of 2.4 days over a 30-year period. When 11 species that exhibit later first-flowering times are excluded from the data set, the remaining 89 show a significant advance of 4.5 days. Significant trends for earlier-flowering species range from -3.2 to -46 days, while those for later-flowering species range from +3.1 to +10.4 days. Advances of first-flowering in these 89 species are directly correlated with local increase in minimum temperature (T-min). C1 NCI, Sect Ultrastruct Pathol, Pathol Lab, Bethesda, MD 20892 USA. Smithsonian Inst, Natl Museum Nat Hist, Dept Bot, Washington, DC 20560 USA. RP Abu-Asab, MS (reprint author), NCI, Sect Ultrastruct Pathol, Pathol Lab, Bethesda, MD 20892 USA. OI Abu-Asab, Mones/0000-0002-4047-1232 NR 10 TC 137 Z9 162 U1 5 U2 52 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0960-3115 J9 BIODIVERS CONSERV JI Biodivers. Conserv. PD APR PY 2001 VL 10 IS 4 BP 597 EP 612 DI 10.1023/A:1016667125469 PG 16 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 426AR UT WOS:000168327400008 ER PT J AU Mullins, C Bonifacino, JS AF Mullins, C Bonifacino, JS TI The molecular machinery for lysosome biogenesis SO BIOESSAYS LA English DT Review ID AP-3 ADAPTER COMPLEX; MANNOSE 6-PHOSPHATE RECEPTOR; TRANS-GOLGI NETWORK; PIGMENT GRANULE BIOGENESIS; CLATHRIN-COATED VESICLES; SACCHAROMYCES-CEREVISIAE; PROTEIN COMPLEX; YEAST VACUOLE; PHOSPHATIDYLINOSITOL 3-KINASE; DROSOPHILA-MELANOGASTER AB The lysosome serves as a site for delivery of materials targeted for removal from the eukaryotic cell. The mechanisms underlying the biogenesis of this organelle are currently the subject of renewed interest due to advances in our understanding of the protein sorting machinery. Genetic model systems such as yeast and Drosophila have been instrumental in identifying both protein and lipid components of this machinery. Importantly, many of these components, as well as the processes in which they are involved, are proving conserved in mammals. Other recently identified components, however, appear to be unique to higher eukaryotes. Published 2001 John Wiley & Sons, Inc.dagger C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Mullins, C (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 98 TC 144 Z9 145 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD APR PY 2001 VL 23 IS 4 BP 333 EP 343 DI 10.1002/bies.1048 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 414BA UT WOS:000167645000007 PM 11268039 ER PT J AU Flaws, JA Hirshfield, AN Hewitt, JA Babus, JK Furth, PA AF Flaws, JA Hirshfield, AN Hewitt, JA Babus, JK Furth, PA TI Effect of bcl-2 on the primordial follicle endowment in the mouse ovary SO BIOLOGY OF REPRODUCTION LA English DT Article DE apoptosis; follicle; gene regulation; oocyte development; ovary ID PROGRAMMED CELL-DEATH; MESSENGER-RIBONUCLEIC-ACID; C-KIT RECEPTOR; GERM-CELLS; RAT OVARY; W LOCUS; EXPRESSION; APOPTOSIS; GROWTH; LIGAND AB Little is known about the embryonic factors that regulate the size of the primordial follicle endowment at birth. A few studies suggest that members of the B-cell lymphoma/leukemia-2 (bcl-2) family of protooncogenes may be important determinants. Thus, the purpose of this study was to test whether bcl-2 regulates the size of the primordial follicle pool at birth. To test this hypothesis, three lines of transgenic mice (c-kit/bcl-2 mice) were generated that overexpress human bcl-2 in an effort to reduce prenatal oocyte loss. The overexpression was targeted to the ovary and appropriate embryonic time period with the use of a 4.8-kilobase c-kit promoter. This promoter provided two to three times more expression of bcl-2 in the ovaries with minimal or no overexpression in most nongonadal tissues. On Postnatal Days 8-60, ovaries were collected from homozygous c-kit/bcl-2 and nontransgenic littermates (controls) and processed for histological evaluation of follicle numbers. All lines of c-kit/bcl-2 mice were born with significantly more primordial follicles than control mice (P less than or equal to 0.05). By Postnatal Days 30-60, however, there were no significant differences in follicle numbers between c-kit/bcl-2 and control mice. These results indicate that bcl-2 overexpression increases the number of primordial follicles at birth, but that the surfeit of primordial follicles is not maintained in postnatal life. These data suggest that it is possible that the ovary may contain a census mechanism by which excess numbers of primordial follicles at birth are detected and removed from the ovary by adulthood. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Anat Neurobiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. NIAID, Frederick, MD 21702 USA. RP Flaws, JA (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 660 W Redwood St, Baltimore, MD 21201 USA. FU NCI NIH HHS [CA68033]; NIA NIH HHS [AG13844]; NICHD NIH HHS [HD38955] NR 45 TC 95 Z9 105 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 2001 VL 64 IS 4 BP 1153 EP 1159 DI 10.1095/biolreprod64.4.1153 PG 7 WC Reproductive Biology SC Reproductive Biology GA 414RQ UT WOS:000167680300017 PM 11259262 ER PT J AU Minton, AP AF Minton, AP TI Effects of excluded surface area and adsorbate clustering on surface adsorption of proteins. II. Kinetic models SO BIOPHYSICAL JOURNAL LA English DT Article ID LOCALLY PLANAR SURFACES; LARGE-LIGAND ADSORPTION; GLOBULAR-PROTEINS; BINDING; MEMBRANES; AGGREGATION; EQUILIBRIA; EXCLUSION; LYSOZYME; FERRITIN AB Models for equilibrium surface adsorption of proteins have been recently proposed (Minton, A. P., 2000. Biophys. Chem. 86:239-247) in which negative cooperativity due to area exclusion by adsorbate molecules is compensated to a variable extent by the formation of a heterogeneous population of monolayer surface clusters of adsorbed protein molecules. In the present work this concept is extended to treat the kinetics of protein adsorption. It is postulated that clusters may grow via two distinct kinetic pathways. The first pathway is the diffusion of adsorbed monomer to the edge of a preexisting cluster and subsequent accretion. The second pathway consists of direct deposition of a monomer in solution onto the upper (solution-facing) surface of a preexisting cluster ("piggyback" deposition) and subsequent incorporation into the cluster, Results of calculations of the time course of adsorption, carried out for two different limiting models of cluster structure and energetics, shaw that in the absence of piggyback deposition, enhancement of the tendency of adsorbate to cluster can reduce, but not eliminate, the negative kinetic cooperativity due to surface area exclusion by adsorbate, Apparently noncooperative (Langmuir-like) and positively cooperative adsorption progress curves, qualitatively similar to those reported in several published experimental studies, require a significant fraction of total adsorption flux through the piggyback deposition pathway. According to the model developed here and in the above-mentioned reference, the formation of surface clusters should be a common concomitant of non-site-specific surface adsorption of proteins, and may provide an important mechanism for assembly of organized "protein machines" in vivo. C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bldg 8,Rm 226, Bethesda, MD 20892 USA. EM minton@helix.nih.gov NR 31 TC 61 Z9 61 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2001 VL 80 IS 4 BP 1641 EP 1648 PG 8 WC Biophysics SC Biophysics GA 416UD UT WOS:000167797800003 PM 11259279 ER PT J AU Melikov, KC Frolov, VA Shcherbakov, A Samsonov, AV Chizmadzhev, YA Chernomordik, LV AF Melikov, KC Frolov, VA Shcherbakov, A Samsonov, AV Chizmadzhev, YA Chernomordik, LV TI Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer SO BIOPHYSICAL JOURNAL LA English DT Article ID REVERSIBLE ELECTRICAL BREAKDOWN; MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; STABILIZED PORES; ELECTROPORATION; VESICLES; TENSION; CELL; TRANSITION; HEMIFUSION AB Electric fields promote pore formation in both biological and model membranes. We clamped unmodified planar bilayers at 150-550 mV to monitor transient single pores for a long period of time. We observed fast transitions between different conductance levels reflecting opening and closing of metastable lipid pores. Although mean lifetime of the pores was 3 +/- 0.8 ms (250 mV), some pores remained open for up to similar to1 s. The mean amplitude of conductance fluctuations (similar to 500 pS) was independent of voltage and close for bilayers of different area (40,000 and 10 mum(2)), indicating the local nature of the conductive defects. The distribution of pore conductance was rather broad (dispersion of similar to 250 pS). Based on the conductance value and its dependence of the ion size, the radius of the average pore was estimated as similar to1 nm. Short bursts of conductance spikes (opening and closing of pores) were often separated by periods of background conductance. Within the same burst the conductance between spikes was indistinguishable from the background. The mean time interval between spikes in the burst was much smaller than that between adjacent bursts. These data indicate that opening and closing of lipidic pores proceed through some electrically invisible (silent) pre-pores. Similar pre-pore defects and metastable conductive pores might be involved in remodeling of cell membranes in different biologically relevant processes. C1 NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, AN Frumkin Electrochem Inst, Moscow 117071, Russia. RP Chernomordik, LV (reprint author), NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 10D-04,10 Ctr Dr, Bethesda, MD 20892 USA. RI Melikov, Kamran/A-6604-2009; Chizmadzhev, Yuri/L-1984-2013; OI Frolov, Vadim/0000-0002-0653-5669 NR 38 TC 141 Z9 147 U1 1 U2 20 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2001 VL 80 IS 4 BP 1829 EP 1836 PG 8 WC Biophysics SC Biophysics GA 416UD UT WOS:000167797800020 PM 11259296 ER PT J AU Combs, CA Balaban, RS AF Combs, CA Balaban, RS TI Direct imaging of dehydrogenase activity within living cells using enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) SO BIOPHYSICAL JOURNAL LA English DT Article ID MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION; PERFUSED RAT-HEART; CARDIAC MYOCYTES; METABOLISM; FLAVOPROTEIN; SPECTROSCOPY; RESPIRATION; KINETICS; ISCHEMIA; TISSUES AB Reduced nicotine adenine dinucleotide (NADH) is a key metabolite involved in cellular energy conversion and many redox reactions. We describe the use of confocal microscopy in conjunction with enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) of NADH as a topological assay of NADH generation capacity within living cardiac myocytes. Quantitative validation of this approach was performed using a dehydrogenase system, in vitro. In intact cells the NADH ED-FRAP was sensitive to temperature (Q(10) of 2.5) and to dehydrogenase activation by dichloroacetate or cAMP (twofold increase for each). In addition, NADH ED-FRAP was correlated with flavin adenine dinucleotide (FAD(+)) fluorescence. These data, coupled with the cellular patterns of NADH ED-FRAP changes with dehydrogenase stimulation, suggest that NADH ED-FRAP is localized to the mitochondria. These results suggest that ED-FRAP enables measurement of regional dynamics of mitochondrial NADH production in intact cells, thus providing information regarding region-specific intracellular redox reactions and energy metabolism. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Combs, CA (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D-416, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 39 TC 31 Z9 31 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2001 VL 80 IS 4 BP 2018 EP 2028 PG 11 WC Biophysics SC Biophysics GA 416UD UT WOS:000167797800039 PM 11259315 ER PT J AU Moatti, D Faure, S Fumeron, F Amara, ME Seknadji, P McDermott, DH Debre, P Aumont, MC Murphy, PM de Prost, D Combadiere, C AF Moatti, D Faure, S Fumeron, F Amara, ME Seknadji, P McDermott, DH Debre, P Aumont, MC Murphy, PM de Prost, D Combadiere, C TI Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease SO BLOOD LA English DT Article ID TISSUE FACTOR; CX(3)CR1; CHEMOKINE; MONOCYTE; TFPI AB Coronary atherosclerosis is a major cause of death in industrialized countries, Monocytes, which play a key role in atherosclerosis, migrate into the vessel wall, presumably guided by specific chemoattractant and adhesion molecules. A compelling candidate for this role is the chemokine receptor CX3CR1,which is expressed on monocytes and acts as either a chemotactic receptor or an adhesion molecule, depending on whether its ligand, fractalkine, is presented free or membrane bound. A common variant of CX3CR1 was recently identified, encoded by the alleles I249 and M280, which form a common I249M280 haplotype, When CX3CR1 genotypes were analyzed in 151 patients with acute coronary syndromes and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated with a markedly reduced risk of acute coronary events, independent of established acquired coronary risk factors leg, smoking, diabetes). The adjusted odds ratio for this allele was 0.43 (95% confidence interval, 0.26-0.72; P =.001). Consistent with this, functional analysis of peripheral blood mononuclear cells showed that CX3CR1 I249 heterozygosity was associated with a significant decrease in the number of fractalkine binding sites per cell. The results show that CX3CR1 I249 is an independent genetic risk factor for coronary artery disease and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease. (Blood, 2001;97: 1925-1928) (C) 2001 by The American Society of Hematology. C1 AP HP, Hop Louis Mourier, Serv Hematol Biol & Immunol, F-92701 Colombes, France. Fac Bichat, INSERM, U479, Paris, France. Hop La Pitie Salpetriere, Lab Immunol Cellulaire & Tissulaire, CNRS, UMR 7627, Paris, France. Fac Bichat, Serv Nutr Humaine, Paris, France. CHU Bichat, Serv Cardiol, Paris, France. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Moatti, D (reprint author), AP HP, Hop Louis Mourier, Serv Hematol Biol & Immunol, 178 Rue Renouillers, F-92701 Colombes, France. RI Combadiere, Christophe/I-5639-2013; OI Combadiere, Christophe/0000-0002-1755-4531; McDermott, David/0000-0001-6978-0867 NR 11 TC 249 Z9 266 U1 1 U2 7 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 APR 1 PY 2001 VL 97 IS 7 BP 1925 EP 1928 DI 10.1182/blood.V97.7.1925 PG 4 WC Hematology SC Hematology GA 429KM UT WOS:000168516000004 PM 11264153 ER PT J AU Janik, JE Miller, LL Korn, EL Stevens, D Curti, BD Smith, JW Sznol, M Conlon, KC Sharfman, W Urba, WJ Gause, BL Longo, DL AF Janik, JE Miller, LL Korn, EL Stevens, D Curti, BD Smith, JW Sznol, M Conlon, KC Sharfman, W Urba, WJ Gause, BL Longo, DL TI A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BREAST-CANCER; GRANULOCYTE; MYELOSUPPRESSION; KINETICS AB We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GMCSF after topotecan at a dose of 250 mug/m(2) daily for at least 8 days, Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 mug/m(2) twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P =.0074). The mean duration of neutropenia was reduced by GMCSF priming: grade 3 neutropenia from 5.2 +/- 0.7 to 2.8 +/- 0.7 days (P =.0232) and grade 4 neutropenia from 2.7 +/- 0.6 to 1.1 +/- 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy. (Blood, 2001;97: 1942-1946) (C) 2001 by The American Society of Hematology. C1 NCI, Frederick Canc Res & Dev Ctr, Biol Response Modifiers Program, Frederick, MD 21702 USA. NCI, Clin Serv Program, SAIC Frederick, FCRDC, Frederick, MD 21701 USA. NCI, Biometr Res Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA. RP Janik, JE (reprint author), NCI, Metab Branch, Div Clin Sci, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. NR 23 TC 9 Z9 9 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 APR 1 PY 2001 VL 97 IS 7 BP 1942 EP 1946 DI 10.1182/blood.V97.7.1942 PG 5 WC Hematology SC Hematology GA 429KM UT WOS:000168516000007 PM 11264156 ER PT J AU Aoki, Y Yarchoan, R Wyvill, K Okamoto, S Little, RF Tosato, G AF Aoki, Y Yarchoan, R Wyvill, K Okamoto, S Little, RF Tosato, G TI Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders SO BLOOD LA English DT Article ID MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; HUMAN-HERPESVIRUS-8; CELLS; VIRUS; EXPRESSION; GROWTH; LOAD; INVOLVEMENT; PROTEINS AB Expression of a viral interleukin-6 (vIL-6) has been detected in certain Kaposi sarcoma (KS)-associated herpesvirus positive (KSHV+) lesions. The release of vIL-6 systemically and its contribution to the pathogenesis of HIV-related malignancies was studied. Serum vIL-6 was detected in 13 (38.2%) of 34 HIV+ patients with KS, in 6 (85.7%) of 7 HIV+ patients with primary effusion lymphoma (PEL) and/or multicentric Castleman disease (MCD), and in 18 (60.0%) of 30 HIV+, mostly homosexual, individuals without KS, MCD, or PEL. By contrast, serum vIL-6 was detected in only 3 (23.1%) of 13 patients with classic KS, 1 (2.5%) of 40 blood donors from the United States, and 4 (19.0%) of 21 blood donors from Italy. Circulating vIL-6 levels were associated with HIV+ status (P < .0001). However, within the HIV+ cohort, serum vIL-6 levels were not associated with the occurrence of KSHV-associated malignancies (P = .43). (Blood, 2001;97:2173-2176) (C) 2001 by The American Society of Hematology. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Aoki, Y (reprint author), NCI, Med Branch, NIH, Bldg 10 Rm 12C207,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 59 Z9 60 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 APR 1 PY 2001 VL 97 IS 7 BP 2173 EP 2176 DI 10.1182/blood.V97.7.2173 PG 4 WC Hematology SC Hematology GA 429KM UT WOS:000168516000040 PM 11264189 ER PT J AU Graber, C de Almeida, KNF Childs, R Barrett, AJ Gill, VJ Bennett, JE AF Graber, C de Almeida, KNF Childs, R Barrett, AJ Gill, VJ Bennett, JE TI CMV reactivation in nonmyeloablative HSCT SO BONE MARROW TRANSPLANTATION LA English DT Letter C1 NIAID, Clin Invest Lab, Clin Mycol Sect, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Stem Cell Allotransplant Unit, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Clin Pathol, Microbiol Serv, Bethesda, MD 20892 USA. RP Graber, C (reprint author), NIAID, Clin Invest Lab, Clin Mycol Sect, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2001 VL 27 IS 7 BP 775 EP 775 DI 10.1038/sj.bmt.1702871 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 426VW UT WOS:000168369900019 PM 11360122 ER PT J AU Grady, CL Furey, ML Pietrini, P Horwitz, B Rapoport, SI AF Grady, CL Furey, ML Pietrini, P Horwitz, B Rapoport, SI TI Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease SO BRAIN LA English DT Article DE neuroimaging; dementia; face recognition; PET; memory ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; EMOTIONAL FACIAL EXPRESSIONS; CORTICAL GLUCOSE-UTILIZATION; FACE PROCESSING IMPAIRMENTS; HUMAN EXTRASTRIATE CORTEX; PARTIAL LEAST-SQUARES; HUMAN WORKING-MEMORY; AGE-RELATED-CHANGES; RECOGNITION MEMORY AB To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls, We used a delayed match to sample paradigm with delays from 1 to 16 s, There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala, Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients, Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions, In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions, Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula, Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas, These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls, Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion-related network of regions. C1 Univ Toronto, Baycrest Ctr Geriat Care, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Voice Speech & Language Branch, Language Sect, Bethesda, MD USA. NIA, Sect Brain Physiol & Metab, Bethesda, MD USA. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. RP Grady, CL (reprint author), Univ Toronto, Baycrest Ctr Geriat Care, Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. RI Furey, Maura/H-5273-2013 NR 74 TC 212 Z9 220 U1 3 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 2001 VL 124 BP 739 EP 756 DI 10.1093/brain/124.4.739 PN 4 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 427PN UT WOS:000168414900009 PM 11287374 ER PT J AU Burke, RE AF Burke, RE TI Comment on "The significance of supraspinal control of reflex actions" - Dr Burke replies SO BRAIN RESEARCH BULLETIN LA English DT Letter ID INTERNEURONS C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Burke, RE (reprint author), NINDS, Neural Control Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR PY 2001 VL 54 IS 6 BP 586 EP 586 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 441GC UT WOS:000169221800002 ER PT J AU Qu, Y Arckens, L Vandesande, F Vandenbussche, E AF Qu, Y Arckens, L Vandesande, F Vandenbussche, E TI In vivo microdialysis in the visual cortex of awake cat I: Surgery, animal training and sampling SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE in vivo microdialysis; visual cortex; awake cat; surgery technique; animal training ID GAMMA-AMINOBUTYRIC-ACID; STRIATE CORTEX; ASPARTATE; GLUTAMATE; RELEASE; RATS AB Sampling and monitoring release of excitatory and inhibitory amino acids in the striate cortex of mammals will provide important information for visual system research. A method allowing repeated microdialysis in the cortical layers of area 17 of the awake cat is described, Under visual control through a surgical microscope and using a stereotactic instrument, four probe guides are permanently implanted in area 17 of one hemisphere of the anesthetized animal and two fixation bars are mounted on the skull to allow fixation of the cat in a stereotactic frame. The implantation of four probe guides in the same hemisphere allows simultaneous sampling from different cortical regions subserving different parts of the visual field, A removable transparent cover protects the probe guides. After recovery from surgery the awake cats are trained to adapt to a fixation in a stereotaxic apparatus. Once adapted to that situation, the cats are used for 5 h in vivo microdialysis experiments without anesthesia. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Katholieke Univ Leuven, Inst Zool, Lab Neuroendocrinol & Immunol Biotechnol, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Sch Med, Neuropsychol Lab, B-3000 Louvain, Belgium. RP Qu, Y (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Bldg 10, Bethesda, MD 20892 USA. RI Arckens, Lutgarde/C-3822-2016 NR 14 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2001 VL 7 IS 1 BP 38 EP 44 DI 10.1016/S1385-299X(00)00060-X PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 421XF UT WOS:000168088300005 PM 11275522 ER PT J AU Qu, Y Li, YM Vandenbussche, E Vandesande, F Arckens, L AF Qu, Y Li, YM Vandenbussche, E Vandesande, F Arckens, L TI In vivo microdialysis in the visual cortex of awake cat II: Sample analysis by microbore HPLC-electrochemical detection and capillary electrophoresis-laser-induced fluorescence detection SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE in vivo microdialysis; HPLC; electrochemical detection; capillary electrophoresis laser-induced fluorescence; amino acid ID AMINO-ACID NEUROTRANSMITTERS; GAMMA-AMINOBUTYRIC-ACID; LIQUID-CHROMATOGRAPHY; GLUTAMATE; BRAIN; SEPARATION; ASPARTATE; PATHWAYS; RAT AB Sampling and monitoring release of excitatory and inhibitory amino acids in the striate cortex of mammals will provide important information for visual system research. Two microbore high performance liquid chromatography-electrochemical detection methods and a capillary electrophoresis-laser induced fluorescence detection were developed to determine the inhibitory amino acid, gamma -aminobutyric acid and the excitatory amino acids, glutamate and aspartate in microdialysates of cat striate cortex. In the liquid chromatography method, samples were derivatized using OPA-TBT. Ten microliters of derivatized product was injected onto the microbore column (100x1 mm i.d., C8) for quantitative analysis. Electrochemical detection was employed. In the capillary electrophoresis method, samples were derivatized using fluorescein isothiocyanate and separated in berate buffer within 15 min, then detected by a laser-induced fluorescence detector. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Katholieke Univ Leuven, Sch Med, Neuropsychol Lab, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Sch Med, Lab Neuroendocrinol & Immunol Biotechnol, B-3000 Louvain, Belgium. RP Qu, Y (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. RI Arckens, Lutgarde/C-3822-2016 NR 15 TC 9 Z9 10 U1 0 U2 3 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 APR PY 2001 VL 7 IS 1 BP 45 EP 51 DI 10.1016/S1385-299X(00)00061-1 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 421XF UT WOS:000168088300006 PM 11275523 ER PT J AU Qu, Y Van der Gucht, E Massie, A Vandenbussche, E Vandesande, F Arckens, L AF Qu, Y Van der Gucht, E Massie, A Vandenbussche, E Vandesande, F Arckens, L TI In vivo microdialysis in the visual cortex of awake cat III: Histological verification SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE in vivo microdialysis; visual cortex; GFAP; Fos immunocytochemistry; sensory deprivation; glutamate ID FIBRILLARY ACIDIC PROTEIN; C-FOS; GENE-EXPRESSION; RETINAL LESIONS; NERVOUS-SYSTEM; BRAIN; INJURY; RATS AB In vivo microdialysis sampling extracellular excitatory and inhibitory amino acids from the striate cortex of mammals will provide important information for visual system research. To facilitate the interpretation of microdialysis results, this protocol critically examines: (1) the location of probe implantation in the visual cortex using Nissl staining. (2) the morphological changes after probe implantation by visualization of neurons containing glutamate; (3) the morphological changes after probe implantation by visualization of gliosis using glial fibrillary acidic protein (GFAP) immunocytochemistry; (4) the implantation of the probe in sensory-deprived versus non-deprived cortical regions by visualization of neurons containing c-Fos protein after limited retinal lesion. The histochemical and immunocytochemical methods of Glu, GFAP and c-Fos used are described. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Katholieke Univ Leuven, Sch Med, Neuropsychol Lab, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Inst Zool, Lab Neuroendocrinol & Immunol Biotechnol, B-3000 Louvain, Belgium. RP Qu, Y (reprint author), NIA, Sect Brain Psychol & Metab, NIH, Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. RI Massie, Ann/F-1039-2013; Arckens, Lutgarde/C-3822-2016 NR 19 TC 5 Z9 5 U1 0 U2 0 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 APR PY 2001 VL 7 IS 1 BP 52 EP 60 DI 10.1016/S1385-299X(00)00062-3 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 421XF UT WOS:000168088300007 PM 11275524 ER PT J AU Galdzicki, Z Siarey, R Pearce, R Stoll, J Rapoport, SI AF Galdzicki, Z Siarey, R Pearce, R Stoll, J Rapoport, SI TI On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models SO BRAIN RESEARCH REVIEWS LA English DT Review DE dorsal root ganglion; brain; hippocampus; patch clamp; action potential; Down syndrome; trisomy 21; mouse; trisomy 16; nerve growth factor; mental retardation; electrical properties; conduction; neurodevelopment; long-term potentiation; long-term depression ID NERVE GROWTH-FACTOR; DORSAL-ROOT GANGLION; LONG-TERM POTENTIATION; PROTEIN-KINASE-C; CULTURED HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE NEUROPATHOLOGY; ELECTRICAL MEMBRANE-PROPERTIES; TRANSCRANIAL MAGNETIC STIMULATION; CAMP-DEPENDENT PHOSPHORYLATION; FOREBRAIN CHOLINERGIC NEURONS AB Down syndrome (DS, trisomy 21, Ts21) is the most common known cause of mental retardation. In vivo structural brain imaging in young DS adults, and post-mortem studies, indicate a normal brain size after correction for height, and the absence of neuropathology. Functional imaging with positron emission tomography (PET) shows normal brain glucose metabolism, but fewer significant correlations between metabolic rates in different brain regions than in controls, suggesting reduced functional connections between brain circuit elements. Cultured neurons from Ts21 fetuses and from fetuses of an animal model for DS, the trisomy 16 (Ts16) mouse, do not differ from controls with regard to passive electrical membrane properties, including resting potential and membrane resistance. On the other hand, the trisomic neurons demonstrate abnormal active electrical and biochemical properties (duration of action potential and its rates of depolarization and repolarization, altered kinetics of active Na+, Ca2+ and K+ currents, altered membrane densities of Na+ and Ca2+ channels). Another animal model, the adult segmental trisomy 16 mouse (Ts65Dn), demonstrates reduced long-term potentiation and increased long-term depression (models for learning and memory related to synaptic plasticity) in the CA1 region of the hippocampus. Evidence suggests that the abnormalities in the trisomy mouse models are related to defective signal transduction pathways involving the phosphoinositide cycle, protein kinase A and protein kinase C. The phenotypes of DS and its mouse models do not involve abnormal gene products due to mutations or deletions, but result from altered expression of genes on human chromosome 21 or mouse chromosome 16, respectively. To the extent that the defects in signal transduction and in active electrical properties, including synaptic plasticity, that are found in the Ts16 and Ts65Dn mouse models, are found in the brain of DS subjects, we postulate that mental retardation in DS results from such abnormalities. Changes in timing and synaptic interaction between neurons during development can lead to less than optimal functioning of neural circuitry and signaling then and in later life. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM zgaldzicki@usuhs.mil FU NICHD NIH HHS [HD38417] NR 261 TC 53 Z9 54 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD APR PY 2001 VL 35 IS 2 BP 115 EP 145 DI 10.1016/S0926-6410(00)00074-4 PG 31 WC Neurosciences SC Neurosciences & Neurology GA 436NB UT WOS:000168941000002 PM 11336779 ER PT J AU Zhou, J Allred, DC Avis, I Martinez, A Vos, MD Smith, L Treston, AM Mulshine, JL AF Zhou, J Allred, DC Avis, I Martinez, A Vos, MD Smith, L Treston, AM Mulshine, JL TI Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast carcinogenesis; early detection marker; immunohistochemistry; intermediate endpoint marker ID MESSENGER-RNA; CELLS; PROTEINS; A2/B1; EPITHELIUM; ANTIGEN; GROWTH; ACID AB Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical stages of lung development and carcinogenesis. To determine if the expression of hnRNP-A2/B1 is an informative biomarker in breast carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in archived specimens. Expression was detected in 48/85 (56.5%) primary invasive breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1 expression compared to normal or transformed breast cells. Expression of hnRNP-A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately with decreased cell growth. These results warrant further evaluation of hnRNP-A2/B1 as a marker of breast carcinogenesis. C1 NCI, Intervent Sect, Dept Cell & Canc Biol, Med Branch,Div Clin Sci,NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Dept Cell & Canc Biol, Med Branch,Div Clin Sci,NIH, 10-12N226 MSC 1906,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 20 TC 62 Z9 68 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2001 VL 66 IS 3 BP 217 EP 224 DI 10.1023/A:1010631915831 PG 8 WC Oncology SC Oncology GA 448FL UT WOS:000169616200006 PM 11510693 ER PT J AU Milenic, DE Roselli, M Mirzadeh, S Pippin, CG Gansow, OA Colcher, D Brechbiel, MW Schlom, J AF Milenic, DE Roselli, M Mirzadeh, S Pippin, CG Gansow, OA Colcher, D Brechbiel, MW Schlom, J TI In vivo evaluation of bismuth-labeled monoclonal antibody comparing DTPA-derived bifunctional chelates SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE monoclonal antibody; radioimmunotherapy; a-emitters; bismuth; chelates ID SINGLE-CHAIN-FV; COLON CARCINOMA XENOGRAFTS; ALPHA-PARTICLE-EMITTER; MICE BEARING; IN-VIVO; INTRAPERITONEAL RADIOIMMUNOTHERAPY; COMPARATIVE BIODISTRIBUTION; IMPROVED GENERATOR; OVARIAN-CANCER; CHX-DTPA AB Among the radionuclides considered for radioimmunotherapy, alpha -emitters such as the bismuth isotopes, Bi-212 and Bi-213, are of particular interest. The macrocyclic ligand, DOTA, has been shown to form stable complexes with bismuth isotopes. The kinetics of the complexation of bismuth with the DOTA chelate, however, are slow and impractical for use with Bi-212 and Bi-213 that have half-lilies of 60.6 and 45.6 min. The study described herein compares six DTPA derived bifunctional chelates with the goal of identifying an alternative to the DOTA ligand for radiolabeling with bismuth. Radioimmunoconjugates comprised of MAb B72.3, each of the six DTPA chelates, and radiolabeled with Bi-206, which facilitated the evaluation due to its readily detectable gamma -emission. In vitro studies showed that each of rite radioimmunoconjugates retained immunoreactivity that was comparable to its I-125-labeled counterpart. The Bi-206- and I-125-labeled immunoconjugates were then co-injected i.p. into normal athymic mice. injection of Afree@ Bi-206 demonstrated that the kidneys were the critical organ to evaluate for retention of bismuth in the chelate complex. Major differences were identified among the six preparations. The CHX-A and -B immunoconjugates were found to hale 1) the lowest %ID/gm in the kidney; 2) a level of Bi-206 in the kidney that was comparable to that of I-125-B72.3; and 3) Ilo significant uptake of Bi-206 evident In other organs such as bone, lung and spleen. The results described her-ein suggest that either of the cyclohexyl derivatives of DTPA may be suitable candidates for the labeling of immunoconjugates with alpha -emitting bismuth isotopes for radioimmunotherapeutic applications. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, NIH, 9000 Rockville Pike,Bld 10,Room B3B69, Bethesda, MD 20892 USA. NR 47 TC 33 Z9 33 U1 4 U2 11 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD APR PY 2001 VL 16 IS 2 BP 133 EP 146 DI 10.1089/108497801300189227 PG 14 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 433CQ UT WOS:000168738100004 PM 11385960 ER PT J AU Guemei, AA Cottrell, J Band, R Hehman, H Prudhomme, M Pavlov, MV Grem, JL Ismail, AS Bowen, D Taylor, RE Takimoto, CH AF Guemei, AA Cottrell, J Band, R Hehman, H Prudhomme, M Pavlov, MV Grem, JL Ismail, AS Bowen, D Taylor, RE Takimoto, CH TI Human plasma carboxylesterase and butyrylcholinesterase enzyme activity: correlations with SN-38 pharmacokinetics during a prolonged infusion of irinotecan SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE irinotecan; SN-38; carboxylesterase; butyrylcholinesterase ID HUMAN LIVER-MICROSOMES; PHASE-I; METABOLITE SN-38; CPT-11; GLUCURONIDATION; SERUM; MODULATION; TISSUE; CANCER; TUMOR AB Purpose: To characterize the relationships between human plasma irinotecan carboxylesterase-converting enzyme activity, caboxylesterase-mediated hydrolysis of p-nitrophenyl acetate (pNPA), and the butyrylcholinesterase-mediated hydrolysis of butyrylthiocholine in human plasma and to test the ability of these in vitro tests to predict the variability in SN-38 pharmacokinetics in adult patients during a prolonged infusion of irinotecan. Methods: Individual plasma-converting enzyme activity was measured in 20 adult cancer patients participating in a pharmacokinetic and phase I clinical trial of a prolonged 96-h intravenous infusion of irinotecan. The pNPA and butyrylthiocholine hydrolysis in patient plasma was also assayed. Results: The irinotecan carboxylesterase-converting enzyme in human plasma had a V-max of 89.9 +/- 22.7 pmol/h per ml plasma and a Km of 207 +/- 56 muM (mean +/- SD, n = 3). The mean value of the specific activity of this enzyme in 20 adult cancer patients was 10.08 +/- 2.96 pmol/h per mi plasma ranging from 5.43 to 15.39 pmol/h per mi. The area-under-the-concentration-versus time curve (AUC) ratio of SN-38 to irinotecan (AUC(SN-38)/AUC(CPT-11)) was used to assess the relative SN-38 exposure to the active metabolite in individual patients. Pharmacokinetic variations in the relative exposure to SN-38 did not correlate with the measured carboxylesterase-converting enzyme activity nor with plasma butyrylcholinesterase activity in our patient population. However, it did correlate with the measured pNPA hydrolysis activity in patient plasma (r(2) = 0.350, P = 0.0124, n = 18). Conclusions: Determination of patient plasma pNPA hydrolysis activity may have utility in predicting SN-38 pharmacokinetics during prolonged infusions of irinotecan. C1 NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci, Bethesda, MD 20889 USA. Howard Univ, Sch Med, Dept Pharmacol, Washington, DC 20059 USA. RP Takimoto, CH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Med Oncol, 7703 Floyd Curl Dr,MSC 7884, San Antonio, TX 78229 USA. NR 28 TC 32 Z9 32 U1 1 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2001 VL 47 IS 4 BP 283 EP 290 DI 10.1007/s002800000258 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 427BB UT WOS:000168384000001 PM 11345644 ER PT J AU Egorin, MJ Zuhowski, EG Rosen, DM Sentz, DL Covey, JM Eiseman, JL AF Egorin, MJ Zuhowski, EG Rosen, DM Sentz, DL Covey, JM Eiseman, JL TI Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1 SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE geldanamycin; ansamycin; HSP90; pharmacokinetics ID ANTICANCER DRUG TARGETS; GENE-PRODUCT P185; CELL-CYCLE; GELDANAMYCIN DERIVATIVES; BENZOQUINOID ANSAMYCINS; ANTITUMOR AGENT; CYCLOSPORINE-A; BIOAVAILABILITY; INHIBITION; PACLITAXEL AB Purpose: 17-(Allylamino)-17-demethoxygeldanamycin (17AAG) is a benzoquinone ansamycin compound agent that has entered clinical trials. Studies were performed in mice to: (1) define the plasma pharmacokinetics, tissue distribution, and urinary excretion of 17AAG after i.v. delivery; (2) to define the bioavailability of 17AAG after i.p. and oral delivery; and (3) to characterize the concentrations of 17AAG metabolites in plasma and tissue. Materials and Methods: All studies were performed in female CD2F1 mice. Preliminary toxicity studies used 17AAG i.v. bolus doses of 20, 40 and 60 mg/kg. Pharmacokinetic studies used i.v. 17AAG doses of 60, 40, and 26.67 mg/kg and i.p. and oral doses of 40 mg/kg. The plasma concentration versus time data were analyzed by compartmental and noncompartmental methods. The concentrations of 17AAG were also determined in brain, heart, lung, liver, kidney, spleen. skeletal muscle, and fat. Urinary drug excretion was calculated until 24 h after treatment. Results: A 60 mg/ kg dose of 17AAG, in its initial, microdispersed formulation, caused no changes in appearance, appetite: waste elimination, or survival of treated animals as compared to vehicle-treated controls. Bolus i.v. delivery of 60 mg/kg microdispersed 17AAG produced "peak" plasma 17AAG concentrations between 5.8 and 19.3 mug/ mi in mice killed 5 min after injection. Sequential reduction of the 17AAG dose to 40 and 26.67 mg/kg resulted in "peak" plasma 17AAG concentrations between 8.9 and 19.0 mug/ml, and 4.8 and 6.1 mug/ml, respectively. Noncompartmental analysis of the plasma 17AAG concentration versus time data showed an increase in AUC from 402 to 625 and 1738 mug/ml min when the 17AAG dose increased from 26.67 to 40 and 60 mg/kg, respectively. Across the range of doses studied, 17AAG total body clearance varied from 34 to 66 ml/min per kg. Compartmental modeling of the plasma 17AAG concentration versus time data showed that the data were fitted best by a two-compartment, open, linear model. In each study, substantial concentrations of a material, subsequently identified as 17-(amino)-17-demethoxygeldanamycin (17AG), were measured in plasma. A subsequent, lyophilized formulation of 17AAG proved excessively toxic when delivered i.v. at 60 mg/kg. A repeat i.v. study using a 40 mg/kg dose of this new formulation produced peak plasma 17AAG concentrations of 20.2-38.4 mug/ml, and a 17AAG AUC of 912 mug/ml min, which was approximately 50% greater than the AUC produced by a 40 mg/kg dose of microdispersed 17AAG. The bioavailabilities of 17AAG after i.p. and oral delivery were 99% and 24%, respectively. Minimal amounts of 17AAG and 17AG were detected in the urine. After i.v. bolus delivery to mice, 17AAG distributed rapidly to all tissues, except the brain. Substantial concentrations of 17AG were measured in each tissue. Conclusions: 17AAG has excellent bioavailability when given i.p. but only modest bioavailability when given orally and is metabolized to 17AG and other metabolites when given i.v., i.p., or orally. 17AAG is widely distributed to tissues. These pharmacokinetic data generated have proven relevant to the design of recently initiated clinical trials of 17AAG and could be useful in their interpretation. C1 Univ Maryland, Ctr Canc, Div Hematol Oncol, Dept Med, Baltimore, MD 21201 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, E1040 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [2P30 CA47904, N01-CM57199] NR 45 TC 104 Z9 109 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2001 VL 47 IS 4 BP 291 EP 302 DI 10.1007/s002800000242 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 427BB UT WOS:000168384000002 PM 11345645 ER PT J AU Clifford, JL Sabichi, AL Zou, CC Yang, XL Steele, VE Kelloff, GJ Lotan, R Lippman, SM AF Clifford, JL Sabichi, AL Zou, CC Yang, XL Steele, VE Kelloff, GJ Lotan, R Lippman, SM TI Effects of novel phenylretinamides on cell growth and apoptosis in bladder cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANS-RETINOIC ACID; EPITHELIAL-CELLS; BREAST-CANCER; RECEPTOR-BETA; N-(4-HYDROXYPHENYL)RETINAMIDE; LINES; CHEMOPREVENTION; CARCINOMA; FENRETINIDE; INHIBITION AB Superficial bladder cancer is a major target for chemoprevention. Retinoids are important modulators of epithelial differentiation and proliferation and are effective in the treatment and prevention of several epithelial cancers. One class of compounds, the retinamides, is structurally similar to other retinoids but have the added feature of being potent apoptosis inducers. Among these, fenretinide (N-[4-hydroxyphenyl]retinamide), or 4HPR, has promise for bladder cancer chemoprevention and is currently under Phase III study in this setting. In addition to 4HPR, there are several new structurally related phenylretinamides bearing hydroxyl, carboxyl, or methoxyl residues on carbons 2, 3, and 4 of the terminal phenylamine ring [designated N-(2-hydroxyphenyl)retinamide, N-(3-hydroxyphenyl)retinamide, N-(2-carboxyphenyl)retinamide, N-(3-carboxyphenyl)retinamide, N-(4-carboxyphenyl)retinamide, and N-(4-methoxyphenyl) retinamide, respectively], The objective of this study was to compare the growth inhibitory and apoptotic effects of these phenylretinamides with 4HPR in human bladder transitional cell cancer-derived cell lines of varying histological grade (RT4, grade 1; UM-UC9 and UM-UC10, grade 3; and UM-UC14, grade 4) by cell counting, cell cycle fluorescence-activated cell sorter analysis and a dual stain apoptosis assay. All of the seven phenylretinamides reduced cell number, altered the cell cycle distribution, and induced apoptosis when administered at a concentration of 10 muM, which is within the pharmacologically achievable range. Although the relative potencies of the phenylretinamides varied depending on the cell line, N-(3-hydroxy phenyl)retinamide was the most active with significantly greater growth inhibition than 4HPR in all of the four cell lines. These in vitro findings warrant further study of these novel phenylretinamides, which may have potential as preventive or therapeutic agents in transitional cell cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. RP Clifford, JL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Box 236,1515 Holcombe Blvd, Houston, TX 77030 USA. EM jclifford@mdanderson.org FU NCI NIH HHS [CA16672, CA45809, CA77150] NR 29 TC 37 Z9 39 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 APR PY 2001 VL 10 IS 4 BP 391 EP 395 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 427BH UT WOS:000168384600015 PM 11319181 ER PT J AU Dorgan, JF Boudou, P Stanczyk, FZ Longcope, C Tejpar, AA Falk, RT Schussler, N Stephenson, HE AF Dorgan, JF Boudou, P Stanczyk, FZ Longcope, C Tejpar, AA Falk, RT Schussler, N Stephenson, HE TI Sources of elevated serum androgens in postmenopausal women who develop breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DEHYDROEPIANDROSTERONE SULFATE; ADRENAL STIMULATION; POLYCYSTIC OVARIES; 11-BETA-HYDROXYANDROSTENEDIONE; RISK; MARKER; EXCESS; ANDROSTENEDIONE; TESTOSTERONE; HIRSUTISM AB Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in these women suggest increased adrenal secretion. Both the adrenals and ovaries could contribute to elevated concentrations of androstenedione (Delta (4)A). 11 beta -Hydroxyandrostenedione (11 beta OHA) is elevated, and the Delta (4)A:11 beta OHA ratio is depressed when the adrenals are the primary source of elevated Delta (4)A in women. Conversely, Delta (4)A:11 beta OHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11 beta OHA and Delta (4)A:11 beta OHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated Delta (4)A related to risk. Fifty-three postmenopausal women who were not taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two controls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum Delta (4)A concentration was significantly (trend P = 0.02) positively associated with breast cancer risk. Adjusted risk ratios for women in the lowest to highest tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. However, neither 11 beta OHA concentration nor Delta (4)A:11 beta OHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11 beta OHA and 1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta (4)A:11 beta OHA, Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Delta (4)A in postmenopausal women who develop breast cancer, but rather both may contribute. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Ctr Hosp Univ St Louis, Lab Biol Hormonale, F-75010 Paris, France. Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Salomon Smith Barney, New York, NY 10013 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. Univ Missouri, Hlth Sci Ctr, Dept Surg, Columbia, MO 65212 USA. RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2001 VL 10 IS 4 BP 407 EP 410 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 427BH UT WOS:000168384600018 PM 11319184 ER PT J AU Zheng, TZ Cantor, KP Zhang, YW Chiu, BCH Lynch, CF AF Zheng, TZ Cantor, KP Zhang, YW Chiu, BCH Lynch, CF TI Risk of brain glioma not associated with cigarette smoking or use of other tobacco products in Iowa SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PREVALENCE C1 Yale Univ, Sch Publ Hlth, New Haven, CT 06501 USA. NCI, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. RP Zheng, TZ (reprint author), 129 Church St,Suite 700-704, New Haven, CT 06510 USA. NR 7 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2001 VL 10 IS 4 BP 413 EP 414 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 427BH UT WOS:000168384600020 PM 11319186 ER PT J AU Hawk, E Graubard, BI Breslow, RA AF Hawk, E Graubard, BI Breslow, RA TI Correspondence re: E.!Hawk, et al., Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the First National Health and Nutrition Examination Survey. Cancer Epidemiol. Biomark. Prev., 9 : 523-527, 2000 - Reply SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter C1 NCI, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. RP Hawk, E (reprint author), NCI, Gastrointestinal & Other Canc Res Grp, Execut Plaza N,Suite 201,MSC-7322,6130 Execut Blv, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2001 VL 10 IS 4 BP 415 EP 416 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 427BH UT WOS:000168384600022 ER PT J AU Renner, C Stehle, I Lee, FT Hall, C Catimel, B Nice, EC Mountain, A Rigopoulos, A Brechbiel, MW Pfreundschuh, M Scott, AM AF Renner, C Stehle, I Lee, FT Hall, C Catimel, B Nice, EC Mountain, A Rigopoulos, A Brechbiel, MW Pfreundschuh, M Scott, AM TI Targeting properties of an anti-CD16/anti-CD30 bispecific: antibody in an in vivo system SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE bispecific antibodies; Hodgkin's lymphoma; tumor targeting ID REFRACTORY HODGKINS-DISEASE; BINDING-SITE BARRIER; CELLS IN-VITRO; HUMAN T-CELLS; MONOCLONAL-ANTIBODIES; TUMORS; THERAPY; CANCER; LYSIS; FRAGMENTS AB Bispecific antibodies are currently being used in clinical trials in increasing numbers in the areas of breast cancer, prostate cancer, non-Hodgkin's lymphoma and Hodgkin's lymphoma. We have previously performed two clinical trials in patients with Hodgkin's disease with an anti-CD30/anti-CD16 bispecific antibody and demonstrated a 30% response rate in a cohort of patients otherwise resistant to standard therapeutic modalities. However, no surrogate marker could be defined in these trials indicative of optimal antibody dosing/scheduling or predictive for favorable response. In order to evaluate accurately the potential biodistribution properties of bispecific antibody in patients, we have performed a detailed analysis of the binding properties and animal model in vivo characteristics of these constructs. For this purpose, the parental antibodies (anti-CD30 and anti-CD16) and the bispecific antibody (anti-CD30/anti-CD16) were radiolabeled with either I-125 or In-111. Antibody integrity and binding properties after labeling were confirmed by Scatchard plot and Lindmo analysis. In-111-labeled antibodies revealed superior targeting properties in a standard SCID mouse tumor model. Both the bivalent parental anti-CD30 monoclonal antibody and the monovalent anti-CD30/anti-CD16 bispecific antibody showed excellent uptake in CD30(+) tumors which did not differ significantly between the two (maximum uptake 16.5% +/- 4.2% vs. 18.4% +/- 3.8% injected dose/gram tissue). The equivalent targeting properties of the bispecific antibody compared with the parental anti-CD30 antibody encourages the further clinical development of this bispecific antibody, and might help to explain the clinical responses seen with this antibody so far in patients suffering from Hodgkin's disease. C1 Univ Saarland, Med Dept 1, D-66424 Homburg, Germany. Austin & Repatriat Med Ctr, Ludwig Inst Canc Res, Heidelberg, Vic, Australia. NCI, Radioimmune & Inorgan Chem Sect, ROB, DCS,NIH, Bethesda, MD 20892 USA. RP Renner, C (reprint author), Univ Saarland, Med Dept 1, Kirrberger Str, D-66424 Homburg, Germany. RI Nice, Edouard/B-1026-2011 NR 38 TC 11 Z9 11 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2001 VL 50 IS 2 BP 102 EP 108 DI 10.1007/s002620100172 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 434AY UT WOS:000168794000007 PM 11401024 ER PT J AU Butkiewicz, D Rusin, M Enewold, L Shields, PG Chorazy, M Harris, CC AF Butkiewicz, D Rusin, M Enewold, L Shields, PG Chorazy, M Harris, CC TI Genetic polymorphisms in DNA repair genes and risk of lung cancer SO CARCINOGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; ENVIRONMENTALLY POLLUTED REGION; BASAL-CELL CARCINOMA; MOLECULAR EPIDEMIOLOGY; MISMATCH REPAIR; SUSCEPTIBILITY; ADDUCTS; XPD; PREDISPOSITION; LYMPHOCYTES AB Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of lung cancer. The frequencies of several amino acid substitutions in XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XRCC3 (Thr241Met), XPD (Ilel99Met, Hisa201Tyr, Asp312Asn and Lys751Gln) and XPF (Pro379Ser) genes were studied in 96 non-small-cell lung cancer (NSCLC) cases and in 96 healthy controls matched for age, gender and cigarette smoking. The XPD codon 312 Asp/Asp genotype was found to have almost twice the risk of lung cancer when the Asp/Asn + Asn/Asn combined genotype served as reference [odds ratio (OR) 1.86, 95% confidence interval (CI), 1.02-3.40]. In light cigarette smokers (less than the median of 34.5 pack-years), the XPD codon 312 Asp/Asp genotype was more frequent among cases than in controls and was associated with an increased risk of NSCLC, Compared with the Asn/ Asn carriers, the OR in light smokers with the Asp/Asn genotype was 1.70 (CI0.35 0.43-6.74) and the OR in those with the Asp/Asp genotype was 5.32 (CI0.35-21.02) (P trend = 0.01), The 312 Asp/Asp genotype was not associated with lung cancer risk in never-smokers or heavy smokers (>34.5 pack-years). The XPD-312Asp and -751Lys polymorphisms were in linkage disequilibrium in the group studied; this finding was further supported by pedigree analysis of four families from Utah. The XPD 312Asp amino acid is evolutionarily conserved and is located in the seven-moth helicase domain of the RecQ family of DNA helicases, Our results indicate that these polymorphisms in the XPD gene should be investigated further for the possible attenuation of DNA repair and apoptotic functions and that additional molecular epidemiological studies are warranted to extend these findings. C1 NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. M Sklodowska Curie Mem Inst, Ctr Oncol, Dept Tumor Biol, PL-44101 Gliwice, Poland. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, 37 Convent Dr,Bldg 37,Room 2C05, Bethesda, MD 20892 USA. RI Shields, Peter/I-1644-2012 NR 35 TC 263 Z9 294 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2001 VL 22 IS 4 BP 593 EP 597 DI 10.1093/carcin/22.4.593 PG 5 WC Oncology SC Oncology GA 421LR UT WOS:000168066300009 PM 11285194 ER PT J AU Battalora, MS Spalding, JW Szczesniak, CJ Cape, JE Morris, RJ Trempus, CS Bortner, CD Lee, BM Tennant, RW AF Battalora, MS Spalding, JW Szczesniak, CJ Cape, JE Morris, RJ Trempus, CS Bortner, CD Lee, BM Tennant, RW TI Age-dependent skin tumorigenesis and transgene expression in the Tg.AC (v-Ha-ras) transgenic mouse SO CARCINOGENESIS LA English DT Article ID LABEL-RETAINING CELLS; TUMOR PROMOTION; 2-STAGE CARCINOGENESIS; PAPILLOMA DEVELOPMENT; SENCAR MICE; STEM-CELLS; INITIATION; INDUCTION; EPIDERMIS; BIOASSAYS AB Transgenic Tg,AC (v-Ha-ras)mice develop skin tumors in response to specific carcinogens and tumor promoters. The Tg,AC mouse carries the coding sequence of v-Ha ras, linked to a zeta -globin promoter and an SV40 polyadenylation signal sequence, The transgene confers on these mice the property of genetically initiated skin. This study examines the age-dependent sensitivity of the incidence of skin papillomas in Tg,AC mice exposed to topically applied 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, full thickness skin wounding or UV radiation. Skin tumor incidence and multiplicity were strongly age-dependent, increasing with increasing age of the animal when first treated at 5, 10, 21 or 32 weeks of age. Furthermore, the temporal induction of transgene expression in keratinocytes isolated from TPA-treated mouse skin was also influenced by the age of the mice. Transgene expression was seen as early as 14 days after the start of TPA treatment in mice that were 10-32 weeks of age, but was not detected in similarly treated 5-week old mice. When isolated keratinocytes were fractionated by density gradient centrifugation the highest transgene expression was found in the denser basal keratinocytes, Transgene expression could be detected in the denser keratinocyte fraction as early as 9 days from start of TPA treatment in 32-week old mice. Using flow cytometry, a positive correlation was observed between expression of the v-sa-ras transgene and enriched expression of the cell surface protein pl-integrin, a putative marker of epidermal stem cells, This result suggests that, in the Tg,AC mouse, an age-dependent sensitivity to tumor promotion and the correlated induction of transgene expression are related to changes in cellular development in the follicular compartment of the skin. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Lankenau med Res Ctr, Wynnewood, PA 19096 USA. BASF AG, Dept Toxicol Z470, D-67056 Ludwigshafen, Germany. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, Kyunggi Do, South Korea. RP Spalding, JW (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. EM spalding@niehs.nih.gov FU NCI NIH HHS [CA54293] NR 44 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2001 VL 22 IS 4 BP 651 EP 659 DI 10.1093/carcin/22.4.651 PG 9 WC Oncology SC Oncology GA 421LR UT WOS:000168066300017 PM 11285202 ER PT J AU Avkiran, M Gross, G Karmazyn, M Klein, H Murphy, E Ytrehus, K AF Avkiran, M Gross, G Karmazyn, M Klein, H Murphy, E Ytrehus, K TI Na+/H+ exchange in ischemia, reperfusion and preconditioning SO CARDIOVASCULAR RESEARCH LA English DT Letter ID ISOLATED RAT-HEART; RESIDUAL BLOOD-FLOW; H+ EXCHANGE; MYOCARDIAL-ISCHEMIA; PORCINE HEARTS; INFARCT SIZE; INHIBITION; PROTECTION; OVERLOAD; INJURY C1 Univ London Kings Coll, St Thomas Hosp, Rayne Inst, Ctr Cardiovasc Biol & Med, London SE1 7EH, England. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Western Ontario, London, ON, Canada. Stadt Krankenanstalten Idar Oberstein GmbH, Idar Oberstein, Germany. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Tromso, Tromso, Norway. RP Avkiran, M (reprint author), Univ London Kings Coll, St Thomas Hosp, Rayne Inst, Ctr Cardiovasc Biol & Med, London SE1 7EH, England. NR 21 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD APR PY 2001 VL 50 IS 1 BP 162 EP 163 DI 10.1016/S0008-6363(01)00228-0 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 420XX UT WOS:000168031500019 PM 11345942 ER PT J AU Mather, IH Jack, LJW Madara, PJ Johnson, VG AF Mather, IH Jack, LJW Madara, PJ Johnson, VG TI The distribution of MUC1, an apical membrane glycoprotein, in mammary epithelial cells at the resolution of the electron microscope: implications for the mechanism of milk secretion SO CELL AND TISSUE RESEARCH LA English DT Article DE apical glycoprotein; milk-fat globule membrane immunocytochemistry of MUC1; exocytosis; milk-fat secretion; epithelial cell polarity; membrane protein targeting; guinea-pig ID FAT-GLOBULE-MEMBRANE; GUINEA-PIG MILK; CARCINOMA-ASSOCIATED MUCIN; BREAST-CANCER CELLS; TRANS-GOLGI NETWORK; ENDOPLASMIC-RETICULUM; O-GLYCOSYLATION; DIFFERENTIATION ANTIGENS; MONOCLONAL-ANTIBODIES; MOLECULAR-CLONING AB The distribution of the glycoprotein, mucin 1 (MUC1), was determined in lactating guinea-pig mammary tissue at the resolution of the electron microscope. MUC1 was detected on the apical plasma membrane of secretory epithelial cells, the surface of secreted milk-fat globules, the limiting membranes of secretory vesicles containing casein micelles and in small vesicles and tubules in the apical cytoplasm. Some of the small MUC1-containing vesicles were associated with the surfaces of secretory vesicles and fat droplets in the cytoplasm, MUC1 was detected in much lower amounts on basal and lateral plasma membranes. By quantitative immunocytochemistry, the ratio of MUC1 on apical membranes and milk-fat globules to that on secretory vesicle membranes was estimated to be 9.2:1 (density of colloidal gold particles/mum membrane length). The ratio of MUC1 on apical membranes compared with basal/lateral membranes was approximately 99.1. The data are consistent with a mechanism for milk-fat secretion in which lipid globules acquire an envelope of membrane from the apical surface and possibly from small vesicles containing MUC1 in the cytoplasm. During established lactation, secretory vesicle membrane does not appear to contribute substantially to the milk-fat globule membrane, or to gi give rise in toro to the apical plasma membrane. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. DynPort, Frederick, MD 21702 USA. RP Mather, IH (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NR 80 TC 22 Z9 22 U1 0 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 2001 VL 304 IS 1 BP 91 EP 101 DI 10.1007/s004410100351 PG 11 WC Cell Biology SC Cell Biology GA 431JW UT WOS:000168628900010 PM 11383890 ER PT J AU Du, C MacGowan, GA Farkas, DL Koretsky, AP AF Du, C MacGowan, GA Farkas, DL Koretsky, AP TI Calibration of the calcium dissociation constant of Rhod(2) in the perfused mouse heart using manganese quenching SO CELL CALCIUM LA English DT Article ID FLUORESCENT CALCIUM; INTRACELLULAR CALIBRATION; INDICATOR INDO-1; CYTOSOLIC CA2+; BUFFER SYSTEMS; FURA-2; CHANNELS; BINDING; MUSCLE; QUANTITATION AB Both theoretical and experimental results are presented for in vivo calibration of the dissociation constant K-d(Ca) of the calcium-sensitive fluorescent dye Rhod(2) in the perfused mouse heart, using manganese quenching of fluorescence transients. An analytical model is derived, based on the biochemical equilibrium of manganese competition with calcium for Rhod(2) binding. Expressing the differential of the changes between systole and diastole in fluorescence transient (delta DeltaF(sys-dia)). delta DeltaF(sys-dia) in a beating heart as a function of the perfusate manganese concentration [Mn2+](p) allows correlation of the measured differential transient changes delta DeltaF(sys-dia) with the calcium dissociation constant K-d(Ca) Of Rhod(2) and the calcium concentration in the heart. Numerical modeling indicates that the K-d(Ca) predominantly affects the asymptotic slope of the delta DeltaF(sys-dia) versus [Mn2+](p) curve at certain manganese concentrations, which suggests that the K-d(Ca) can be inversely calculated by partially fitting the delta DeltaF(sys-dia) distribution as a function of the perfusate manganese concentration. The feasibility of this approach is confirmed by quenching of calcium transients by manganese infusion into isolated perfused beating mouse hearts. The resulting calculated dissociation constant K-d(Ca) Of Rhod(2) is 720 nM. Using the same approach, we are able to also estimate intracellular calcium concentrations of 700 nM at peak systole and 300 nM in diastole. This is in good agreement with values obtained by calibration of fluorescence values with a calcium saturation tetanization procedure in the same perfused mouse heart model. (C) 2001 Harcourt Publishers Ltd. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Carnegie Mellon Univ, NSF, Ctr Light Microscope Imaging & Biotechnol, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Pittsburgh NMR Ctr Biomed Res, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bldg 10,B1D-69B,MSC 1060,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NHLBI NIH HHS [HL-40354, HL-03826, HL-02847] NR 28 TC 27 Z9 27 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 APR PY 2001 VL 29 IS 4 BP 217 EP 227 DI 10.1054/ceca.2000.0186 PG 11 WC Cell Biology SC Cell Biology GA 417DL UT WOS:000167820100001 PM 11243930 ER PT J AU Sakaue, M Adachi, H Dawson, M Jetten, AM AF Sakaue, M Adachi, H Dawson, M Jetten, AM TI Induction of Egr-l expression by the retinoid AHPN in human lung carcinoma cells is dependent on activated ERK1/2 SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE retinoids; lung carcinoma; apoptosis; proliferation; MAPK ID RECEPTOR-SELECTIVE RETINOIDS; BRONCHIAL EPITHELIAL-CELLS; EARLY GROWTH RESPONSE-1; MUCIN GENE-EXPRESSION; IMMEDIATE-EARLY GENE; CANCER CELLS; POSTTRANSCRIPTIONAL REGULATION; INDUCED APOPTOSIS; CARBOXYLIC-ACID; TRANSCRIPTION FACTORS AB The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) inhibits cell proliferation and is a very effective inducer of apoptosis in a variety of carcinoma cell lines, In order to obtain greater insight into the mechanism of AHPN-induced growth arrest and apoptosis, we began to examine AHPN-induced changes in gene expression by cDNA array screening using human lung carcinoma H460 cells. This analysis identified several AHPN-inducible genes, including the immediate-early genes Egr-1 and Nur77, AHPN was able to increase Egr-1 and Nur77 mRNA expression and protein in a variety of carcinoma cell lines. This induction appeared to be regulated at the transcriptional level and was specific for AHPN since an RAR- and an RXR-selective retinoid were inactive, These results suggest that the induction of Egr-1 and Nur77 by AHPN is independent of nuclear retinoid receptors and involves a novel mechanism. Overexpression of Bcl-2, which inhibits AHPN-induced apoptosis but not growth arrest in human T cell lymphoma Molt-4 cells, did not block the induction of immediate early gene expression, Treatment of H460 cells with AHPN induced activation of the p38 MAP-kinase but not the ERK1/2 signaling pathway. However, inhibition of the ERK1/2 signaling pathway by PD98059 blocked the induction of Egr-1 and Nur77 mRNA while the p38 MAPK inhibitor PD169316 had little effect, Expression of a dominant-negative ERK1 completely abolished the increase in Egr-1 mRNA, Treatment with MAPK inhibitors or expression of dnERK1 reduced but did not block AHPN-induced apoptosis, Our results suggest that the induction of Egr-1 in H460 by AHPN requires active ERK1/2 and is independent of p38 activation. Egr-1, in cooperation with several other growth suppressor proteins, is likely involved in AHPN-induced inhibition of cell growth and cell death. C1 NIEHS, Pulm Pathobiol Lab, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. Mol Med Res Inst, Mt View, CA 94043 USA. RP Jetten, AM (reprint author), NIEHS, Pulm Pathobiol Lab, Cell Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 81 TC 28 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2001 VL 8 IS 4 BP 411 EP 424 DI 10.1038/sj.cdd.4400818 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 423DP UT WOS:000168160400012 PM 11550093 ER PT J AU Sacks, DL AF Sacks, DL TI Leishmania-sand fly interactions controlling species-specific vector competence SO CELLULAR MICROBIOLOGY LA English DT Review ID PHLEBOTOMUS-PAPATASI DIPTERA; ANTHROPONOTIC CUTANEOUS LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS DIPTERA; SURFACE LIPOPHOSPHOGLYCAN; MAJOR LIPOPHOSPHOGLYCAN; LIFE-CYCLE; PSYCHODIDAE; MIDGUT; DONOVANI; INFECTION AB Leishmaniasis is caused by a wide range of parasites that are transmitted by an even wider range of sand fly vectors. The phlebotomine vectors of Leishmaniasis are in some cases only permissive to the complete development of the species of Leishmania that they transmit in nature. The parasite-sand fly interactions that control this specificity are related to differences in the ability of the parasite to inhibit or to resist killing by proteolytic enzymes released into the midgut soon after blood feeding, and/or to maintain infection in the mid-gut during excretion of the digested blood meal. In each case, surface expressed or released phosphoglycan-containing molecules appear to promote parasite survival. The evidence that the surface lipophosphoglycan (LPG) mediates promastigote attachment to the mid-gut epithelium so as to prevent their loss during blood-meal excretion is especially strong based on the comparison of development in sand flies using LPG-deficient mutants. LPG displays interspecies polymorphisms in their phosphoglycan domains that in most cases can fully account for species-specific vector competence. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 48 TC 77 Z9 78 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2001 VL 3 IS 4 BP 189 EP 196 DI 10.1046/j.1462-5822.2001.00115.x PG 8 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 427AF UT WOS:000168382100001 PM 11298643 ER PT J AU Bourdi, M Amouzadeh, HR Rushmore, TH Martin, JL Pohl, LR AF Bourdi, M Amouzadeh, HR Rushmore, TH Martin, JL Pohl, LR TI Halothane-induced liver injury in outbred guinea pigs: Role of trifluoroacetylated protein adducts in animal susceptibility SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM CHAPERONES; INHALATION ANESTHETIC HALOTHANE; CYTOCHROME-P450 2E1; OXIDATIVE BIOTRANSFORMATION; DISULFIDE-ISOMERASE; SPECIES-DIFFERENCES; HEPATITIS PATIENTS; COVALENT BINDING; ENZYME-INDUCTION; SERUM ANTIBODIES AB Halothane causes a mild form of liver injury in guinea pigs that appears to model the hepatotoxicity seen in approximately 20% of patients treated with this drug. In previous studies, it was concluded that the increased susceptibility of some outbred guinea pigs to halothane-induced liver injury is not caused by their inherent ability to metabolize halothane to form toxic levels of trifluoroacetylated protein adducts in the liver. In this study, we reevaluated the role of trifluoroacetylated protein adducts in halothane-induced liver injury in guinea pigs. Male outbred Hartley guinea pigs were treated with halothane intraperitoneally. On the basis of serum alanine aminotransferase levels and liver histology, treated animals were designated as being susceptible, mildly susceptible, or resistant to halothane, Immunoblot studies with the use of anti-trifluoroacetylated antibodies showed that susceptible guinea pigs for the most part had higher levels of trifluoroacetylated protein adducts in the liver 48 h after treatment with halothane than did less susceptible animals. In support of this finding, the level of trifluoroacetylated protein adducts detected immunochemically in the sera of treated guinea pigs correlated with sera levels of alanine aminotransferase activity. In addition, the levels of cytochrome P450 2A-related protein but not those of other cytochrome P450 isoforms, measured by immunoblot analysis with isoform-specific antibodies, correlated with the amount of trifluoroacetylated protein adducts detected in the livers of guinea pigs 8 h after halothane administration. The results of this study indicate that the susceptibility of outbred guinea pigs to halothane-induced liver injury is related to an enhanced ability to metabolize halothane in the liver to form relatively high levels of trifluoroacetylated protein adducts, They also suggest that cytochrome P450 BA-related protein might have a major role in catalyzing the formation of trifluoroacetylated protein adducts in the liver of susceptible guinea pigs. Similar mechanisms may be important in humans. C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. RP Bourdi, M (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bldg 10,Room 8N110, Bethesda, MD 20892 USA. NR 69 TC 29 Z9 29 U1 1 U2 1 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 APR PY 2001 VL 14 IS 4 BP 362 EP 370 DI 10.1021/tx000244x PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 424XZ UT WOS:000168260400006 PM 11304124 ER PT J AU Lans, TE Bartlett, DL Libutti, SK Gnant, MFX Liewehr, DJ Venzon, DJ Turner, EM Alexander, HR AF Lans, TE Bartlett, DL Libutti, SK Gnant, MFX Liewehr, DJ Venzon, DJ Turner, EM Alexander, HR TI Role of tumor necrosis factor on toxicity and cytokine production after isolated hepatic perfusion SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-of-Surgical-Oncology CY MAR 16-19, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Surg Oncol ID ISOLATED LIMB PERFUSION; FACTOR-ALPHA; INTERFERON-GAMMA; PLASMA-LEVELS; MELPHALAN; LIVER; SHOCK; ENDOTOXIN; SEPSIS; INTERLEUKIN-8 AB Purpose: Isolated limb or liver perfusion with tumor necrosis factor (TNF) and melphalan results in regression of advanced cancers in the majority of treated patients. However, the contribution of TNF to the efficacy of isolation perfusion with melphalan has net been demonstrated conclusively in random assignment trials. Furthermore, TNF is an inflammatory cytokine and may be associated with significant systemic and regional toxicity. This study was conducted to characterize the toxicity and secondary cytokine production attributable to TNF by comparing these parameters in patients undergoing isolated hepatic perfusion (IHP) using melphalan with or without TNF. Experimental Design: Thirty-two patients with unresectable colorectal cancer confined to the liver underwent a 60-min hyperthermic IHP using 15 mg/kg melphalan alone (n = 17) or with 1.0 mg of TNF (rr = 15) with inflow via the gastroduodenal artery and outflow via an isolated segment of inferior vena cava, Complete vascular isolation was confirmed using the I-131 radiolabeled albumin-monitoring technique. Post-TBP parameters of hepatic and systemic toxicity and cytokine levels [TNF, interleukin (IL)-6 and IL-8] in perfusate and serum mere measured. Results: Levels of IL-6 and IL-8 in perfusate at the end of the 60-min IHP were significantly higher in TNF-treated patients (P less than or equal to 0.001). Peak systemic IL-6 and IL-8 levels post-IHP mere also significantly higher in TNF-treated compared with non-TNF-treated patients (P < 0.0001) by 28- and 268-fold, respectively, The peak levels of these cytokines were associated with significantly lower systolic blood pressure and higher heart rate and mean pulmonary artery blood pressure in TNP-treated patients during the first 48 h post-IHP (P 0.03). Serum bilirubin levels were significantly higher (P = 0.017) and platelets lower (P = 0.03) in TNF-treated compared with non-TNF treated patients. However, elevations in aspartate aminotransferase, alanine aminotransfefase, and alkaline phosphatase were not significantly different between groups and returned toward baseline within 1 week after IHP, Conclusions: Addition of TNF to melphalan during MP results in significant differences in post-IHP production of IL-6 and IL-8 with associated changes in mean arterial blood pressure and greater regional toxicity, as reflected in higher levels of serum bilirubin, However, these measurable differences were transient and did not appear to be of major clinical consequence. Prior to its routine use, the benefit of TNF in isolation perfusion should be demonstrated in random assignment trials. C1 NCI, Surg Branch, NIH, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, NIH, Div Clin Sci, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; OI Gnant, Michael/0000-0003-1002-2118 NR 31 TC 40 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 784 EP 790 PG 7 WC Oncology SC Oncology GA 425NR UT WOS:000168297800004 PM 11309322 ER PT J AU Rodrigues, RG Panizo-Santos, A Cashel, JA Krutzsch, HC Merino, MJ Roberts, DD AF Rodrigues, RG Panizo-Santos, A Cashel, JA Krutzsch, HC Merino, MJ Roberts, DD TI Semenogelins are ectopically expressed in small cell lung carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN SEMINAL-VESICLE; CIRCULATING TUMOR-MARKERS; HUMAN-SEMEN; MONOCLONAL-ANTIBODY; PROTEINS; IDENTIFICATION; ANTIGEN; CANCER; THROMBOSPONDIN-1; DIFFERENTIATION AB Two proteins recovered from cell surface adhesion complexes in a small cell lung carcinoma (SCLC) cell line were identified as fragments of the seminal plasma proteins semenogelin I and semenogelin II. Association of both proteins with the adhesion complexes was induced by epidermal growth factor. Expression of semenogelins was previously thought to be highly specific to seminal vesicles, but Western blot analysis demonstrated that semenogelin II is widely expressed in SCLC cell lines and occasionally in other malignant cell lines. Although semenogelin expression is normally restricted to males, two SCLC cell lines from female patients were also positive for semenogelin ZI expression. Immunohistochemical analysis demonstrated diffuse expression of semenogelins in 12 of 13 SCLC tumors and focal expression in a minority of lung squamous and adenocarcinomas, Semenogelins were secreted into the medium by cultured SCLC cells, which suggested that these proteins mag. be useful markers for detecting residual tumor burden or recurrence of SCLC after treatment. C1 NCI, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 34 TC 21 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 854 EP 860 PG 7 WC Oncology SC Oncology GA 425NR UT WOS:000168297800015 PM 11309333 ER PT J AU Hu, N Huang, J Emmert-Buck, MR Tang, ZZ Roth, MJ Wang, CY Dawsey, SM Li, G Li, WJ Wang, QH Han, XY Ding, T Giffen, C Goldstein, AM Taylor, PR AF Hu, N Huang, J Emmert-Buck, MR Tang, ZZ Roth, MJ Wang, CY Dawsey, SM Li, G Li, WJ Wang, QH Han, XY Ding, T Giffen, C Goldstein, AM Taylor, PR TI Frequent inactivation of the TP53 gene in esophageal squamous cell carcinoma from a high-risk population in China SO CLINICAL CANCER RESEARCH LA English DT Article ID LASER CAPTURE MICRODISSECTION; SHANXI-PROVINCE; FAMILY HISTORY; P53 MUTATIONS; ALLELIC LOSS; CANCER; TUMORS; ACCUMULATION; VARIANTS; SPECTRUM AB Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers worldwide, and north central China has some of the highest rates in the world, Previous studies from tumors in this area of China have shown high frequencies of allelic loss on chromosome 17p13-11, which includes the region where the TP53 gene is found. We examined 56 ESCC patients using single-strand conformation polymorphism and DNA sequencing to assess the frequency and spectrum of TP53 mutation and the association between allelic loss at microsatellite marker TP53 and TP53 mutations. Ninety-six % of cases were found to have at least one genetic alteration, including TP53 mutation (77%), allelic loss within the TP53 gene (73%), and/or loss of heterozygosity at the TP53 microsatellite marker (80%); 75% had two or more such alterations, including 59% with both a point mutation and an intragenic allelic loss ("two hits"). The majority of mutations observed were in exon 5, where the most common type of nucleotide substitution was a G:C -->A:T or C:G -->T:A transition, including half that occurred at CpG sites, Allelic loss was most commonly found in exon 4 but was very common in exon 5 as well. Taken together, the multiple genetic alterations of TP53 in this population at high risk for ESCC indicate that there is a very high degree of genetic instability in these tumors, that TP53 is a primary target for inactivation, and that this tumor suppressor gene plays a critical role in the carcinogenesis process for ESCC. C1 Informat Management Serv Inc, Silver Spring, MD 20904 USA. Shanxi Canc Hosp & Inst, Taiyuan 030013, Shanxi, Peoples R China. Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100021, Peoples R China. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Taylor, PR (reprint author), NCI, Div Clin Sci, 6006 Execut Plaza,Room 321, Bethesda, MD 20892 USA. NR 37 TC 46 Z9 48 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 883 EP 891 PG 9 WC Oncology SC Oncology GA 425NR UT WOS:000168297800019 PM 11309337 ER PT J AU Grem, JL Danenberg, KD Behan, K Parr, A Young, L Danenberg, PV Nguyen, D Drake, J Monks, A Allegra, CJ AF Grem, JL Danenberg, KD Behan, K Parr, A Young, L Danenberg, PV Nguyen, D Drake, J Monks, A Allegra, CJ TI Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the national cancer institute's anticancer drug screen SO CLINICAL CANCER RESEARCH LA English DT Article ID DISSEMINATED COLORECTAL-CANCER; 48-HOUR CONTINUOUS-INFUSION; MESSENGER-RNA LEVEL; COLON-CANCER; DISCOVERY SCREEN; DOSE LEUCOVORIN; GENE-EXPRESSION; PHASE-I; 5-FLUOROURACIL; RESISTANCE AB Purpose: To determine the expression of three targets of 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) in human tumor cell lines and to compare these with the 50% growth inhibition concentrations (GI(50)) from the National Cancer Institute database. Experimental Design: Thymidine kinase (TK) activity was assessed by conversion of [H-3]thymidine to [H-3]TMP. Thymidylate synthase (TS) protein expression was determined by Western analysis. TS and dihydropyrimidine dehydrogenase (DPD) mRNA expression were measured by quantitative reverse transcription-PCR, Results: The median (range) for the targets were as follows: 5-FU GI(50), 20.8 muM (0.8-536); FdUrd GI(50), 0.75 muM (0.25-237); TK, 0.93 nmol/min/mg (0.16-5.7); in arbitrary units: TS protein, 0.41 (0.05-2.95); TS mRNA, 1.05 (0.12-6.41); and DPD mRNA, 1.09 (0.00-24.4). A moderately strong correlation was noted between 5-FU and FdUrd GI(50)s (r = 0.60), whereas a week-moderate correlation was seen between TS mRNA and protein expression (r = 0.45). Neither TS expression nor TK activity correlated with 5-FU or FdUrd GI(50)s, whereas lines with lower DPD expression tended to be more sensitive to 5-FU, Cell lines with faster doubling times and wild-type p53 were significantly more sensitive to 5-FU and FdUrd, Conclusions: The lack of correlation may in part be attributable to the influence of downstream factors such as p53, the observation that the more sensitive cell lines with faster doubling times also had higher TS levels, and the standard procedure of the screen that uses a relatively short (48-h) drug exposure. C1 NCI, Med Branch, Natl Naval Med Ctr, Dev Therapeut Dept,Div Clin Sci, Bethesda, MD 20889 USA. Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90033 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Rockville, MD 20852 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. RP Grem, JL (reprint author), NCI, Med Branch, Natl Naval Med Ctr, Dev Therapeut Dept,Div Clin Sci, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 51 TC 56 Z9 56 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 999 EP 1009 PG 11 WC Oncology SC Oncology GA 425NR UT WOS:000168297800033 PM 11309351 ER PT J AU Tahtis, K Lee, FT Smyth, FE Power, BE Renner, C Brechbiel, MW Old, LJ Hudson, PJ Scott, AM AF Tahtis, K Lee, FT Smyth, FE Power, BE Renner, C Brechbiel, MW Old, LJ Hudson, PJ Scott, AM TI Biodistribution properties of (111)Indium-labeled C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and F(ab ')(2) constructs in a breast carcinoma xenograft model SO CLINICAL CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN FV; RECOMBINANT ANTIBODY FRAGMENTS; ANTICARCINOEMBRYONIC ANTIGEN-ANTIBODY; COLON-CANCER XENOGRAFTS; BLOOD-GROUP ANTIGENS; NUDE-MICE; IN-VIVO; MONOCLONAL-ANTIBODIES; SCFV MULTIMERS; SOLID TUMORS AB The humanized complementarity determining region-grafted anti-le,vis Y (Le(y)) monoclonal antibody [humanized 3S193 (hu3S193)] was developed for targeting Le(y)-expressing epithelial tumors such as breast, colon, lung, prostate, and ovarian carcinoma. We are exploring the potential use of smaller molecular size, bivalent analogues of hu3S193, because the faster blood clearance of M-r similar to 54,000 diabody and M-r similar to 110,000 F(ab')(2) molecules may be advantageous in achieving optimal and rapid tumor uptake for diagnostic and potential therapeutic applications, The single-chain variable fragment-5 residue linker construct (diabody) was expressed using the bacterial secretion vector pPOW3, and soluble product was purified without refolding processes. The F(ab'), fragment was obtained by pepsin digest of parental hu3S193. To facilitate evaluations, the radiometal In-111 was used to label C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid chelated diabody and F(ab')(2), The immunoreactivity of the radiolabeled constructs was 41.3 and 58.6%, and the K-a was 1.68 x 10(6) M-1 and 5.33 x 10(6) M-1 for the diabody and F(ab')(2), respectively. Radioconjugates were injected into mice bearing Le(y)-positive MCF-7 tumors, and biodistribution properties were determined at various time points after injection. The uptake of radiolabeled diabody in xenografts was maximal at 1 h after injection (4.7 +/- 0.6% injected dose/g), whereas the F(ab')(2) peaked at 8 h after injection (14.2 +/- 2.4% injected dose/g), The tumor:blood ratio at 4 h for the diabody and F(ab')(2) was 5:1 and 2:1, which increased to 20:1 and 5:1, respectively, at 8 h and increased further to 40:1 and 130:1, respectively, at 48 h, These results demonstrate that the diabody construct may have applications as a diagnostic imaging reagent, whereas F(ab'), displayed effective tumor targeting and may have potential as a therapeutic molecule in patients with Le(y)-expressing tumors. C1 Ludwig Inst Canc Res, Austin & Repatriat Med Ctr, Melbourne Branch, Tumor Target Program, Heidelberg, Vic 3084, Australia. CSIRO, Div Hlth Sci & Nutr, Parkville, Vic 3052, Australia. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, DCS,NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York, NY 10021 USA. RP Scott, AM (reprint author), Ludwig Inst Canc Res, Austin & Repatriat Med Ctr, Melbourne Branch, Tumor Target Program, Heidelberg, Vic 3084, Australia. OI Power, Barbara/0000-0002-4182-3375 NR 52 TC 38 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2001 VL 7 IS 4 BP 1061 EP 1072 PG 12 WC Oncology SC Oncology GA 425NR UT WOS:000168297800040 PM 11309358 ER PT J AU Lipsky, RH Mazzanti, CM Rudolph, JG Xu, K Vyas, G Bozak, D Radel, MQ Goldman, D AF Lipsky, RH Mazzanti, CM Rudolph, JG Xu, K Vyas, G Bozak, D Radel, MQ Goldman, D TI DNA melting analysis for detection of single nucleotide polymorphisms SO CLINICAL CHEMISTRY LA English DT Article ID NEAREST-NEIGHBOR THERMODYNAMICS; GEL-ELECTROPHORESIS; NUCLEIC-ACIDS; MISMATCHES; HYBRIDIZATION; PARAMETERS; STABILITY; ASSAY; NMR AB Background: Several methods for detection of single nucleotide polymorphisms (SNPs; e.g., denaturing gradient gel electrophoresis and denaturing HPLC) are indirectly based on the principle of differential melting of heteroduplex DNA. We present a method for detecting SNPs that is directly based on this principle. Methods: We used a double-stranded DNA-specific fluorescent dye, SYBR Green I (SYBR) in an efficient system (PE 7700 Sequence Detector) in which DNA melting was controlled and monitored in a 96-well plate format. We measured the decrease in fluorescence intensity that accompanied DNA duplex denaturation, evaluating the effects of fragment length, dye concentration, DNA concentration, and sequence context using four naturally occurring polymorphisms (three SNPs and a single-base deletion/insertion). Results: DNA melting analysis (DM) was used successfully for variant detection, and we also discovered two previously unknown SNPs by this approach. Concentrations of DNA amplicons were readily monitored by SYBR fluorescence, and DNA amplicon concentrations were highly reproducible, with a CV of 2.6%. We readily detected differences in the melting temperature between homoduplex and heteroduplex fragments 15-167 bp in length and differing by only a single nucleotide substitution. Conclusions: The efficiency and sensitivity of DMA make it highly suitable for the large-scale detection of sequence variants. (C) 2001 American Association for Clinical Chemistry. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Lipsky, RH (reprint author), 12420 Parklawn Dr,Suite 451,MSC 8110, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 21 TC 68 Z9 76 U1 0 U2 12 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 APR PY 2001 VL 47 IS 4 BP 635 EP 644 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 417QZ UT WOS:000167846800004 PM 11274012 ER PT J AU Zhang, J Kumar, A Stalker, HJ Virdi, G Ferrans, VJ Horiba, K Fricker, FJ Wallace, MR AF Zhang, J Kumar, A Stalker, HJ Virdi, G Ferrans, VJ Horiba, K Fricker, FJ Wallace, MR TI Clinical and molecular studies of a large family with desmin-associated restrictive cardiomyopathy SO CLINICAL GENETICS LA English DT Article DE autosomal dominant; CRYAB; desmin; desminopathy; genetic; linkage analysis; polymorphism; restrictive cardiomyopathy ID HYPERTROPHIC CARDIOMYOPATHY; INTERMEDIATE FILAMENTS; DILATED CARDIOMYOPATHY; SKELETAL MYOPATHY; ATRIOVENTRICULAR-BLOCK; MISSENSE MUTATION; ACTIN GENE; EXCLUSION; DISEASE; IDENTIFICATION AB Patients with restrictive cardiomyopathy (RC) have impaired diastolic function, but intact systolic function until later stages of the disease, ultimately leading to heart failure. Primary RC is often sporadic, but also may be inherited in an autosomal dominant fashion, particularly the idiopathic forms. Recently there has been great interest in inherited cardiomyopathy associated with myocyte desmin deposition ('desminopathies'). In some such families, desmin or alpha-B crystallin gene mutation is the underlying cause, and the desmin accumulation affects skeletal muscle as well, usually causing skeletal myopathy. We describe a large family with apparent autosomal dominant inheritance of desmin-associated RC spanning four generations, with the age of onset and severity/rate of progression being highly variable. This family is relatively unique in that there is no symptom-based evidence of skeletal muscle involvement, and the known desminopathy and cardiomyopathy genes/loci have been ruled out. These data support literature suggesting that desmin deposition may be associated with different underlying gene defects, and that a novel desminopathy gene is responsible for the condition in this family. C1 Univ Florida, Coll Med, Div Genet, Dept Pediat, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Childrens Heart Ctr, Indianapolis, IN USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Dept Pediat, Div Cardiol, Gainesville, FL USA. RP Wallace, MR (reprint author), Univ Florida, Coll Med, Div Genet, Dept Pediat, Box 100266, Gainesville, FL 32610 USA. NR 35 TC 29 Z9 32 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2001 VL 59 IS 4 BP 248 EP 256 DI 10.1034/j.1399-0004.2001.590406.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 423KY UT WOS:000168176500008 PM 11298680 ER PT J AU Miller, KD Spooner, K Herpin, BR Rock-Kress, D Metcalf, JA Davey, RT Falloon, J Kovacs, JA Polis, RA Walker, RE Masur, H Lane, HC AF Miller, KD Spooner, K Herpin, BR Rock-Kress, D Metcalf, JA Davey, RT Falloon, J Kovacs, JA Polis, RA Walker, RE Masur, H Lane, HC TI Immunotherapy of HIV-infected patients with intermittent interleukin-2: Effects of cycle frequency and cycle duration on degree of CD4(+) T-lymphocyte expansion SO CLINICAL IMMUNOLOGY LA English DT Article DE HIV infection; interleukin-2; CD4 lymphocyte count; anti-HIV agents ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-DEFICIENCY SYNDROME; BLOOD MONONUCLEAR-CELLS; PHASE-II TRIAL; SUBCUTANEOUS INTERLEUKIN-2; RECOMBINANT INTERLEUKIN-2; INTRAVENOUS INTERLEUKIN-2; NATURAL-KILLER; AIDS AB The ability of IL-2 to induce expansion of the CD4(+) T lymphocyte pool has made it the most studied cytokine in the treatment of HIV infection. The majority of trials have used an empirical regimen of Fi-day IL-2 cycles given every 8 weeks-a regimen based upon early pharmacodynamic studies and patient preference. To better define optimal duration and frequency of cycles, a randomized trial was conducted in which patients who received this "standard" regimen were compared to patients who received cycles of variable duration (based on individual patterns of cell cycle progression) and to patients who received cycles of variable frequency (based on individual CD4(+) T lymphocyte responses to previous cycles). Twenty-two patients with HIV-1 infection and CD4(+) T lymphocyte counts > 280 cells/mm(3) were randomized to one of three treatment groups for 32 weeks of study. Eight participants received four B-day IL-2 cycles (controls) every 8 weeks; 7 participants received four cycles of longer duration (mean 7.7-days); and 7 participants received an increased frequency of B-day cycles (every 4.1 weeks on average). All three groups experienced significant increases in mean CD4(+) T lymphocytes. However, there were no statistically significant differences in CD4(+) T lymphocyte increases between the group that received longer cycles (median increase 239 cells/mm(3), P = 0.78) or between the group that received more frequent cycles (median increase 511 cells/mm(3), P = 0.54) and the control group (median 284 cells/mm(3)). HIV-1 viral loads decreased during the study period in all three groups. Our inability to demonstrate a significant advantage of increased frequency or duration of IL-2 administration provides corroborating experimental evidence for the use of an IL-2 regimen consisting of 5-day cycles administered no more frequently than every 8 weeks in future clinical trials aimed at expanding the CD4(+) T lymphocyte pool, (C) 2001 Academic Press. C1 NIAID, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Miller, KD (reprint author), NIAID, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 44 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC 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 APR PY 2001 VL 99 IS 1 BP 30 EP 42 DI 10.1006/clim.2001.5001 PG 13 WC Immunology SC Immunology GA 424YB UT WOS:000168260600004 PM 11286539 ER PT J AU Stewart, DM Tian, L Nelson, DL AF Stewart, DM Tian, L Nelson, DL TI A case of X-linked agammaglobulinemia diagnosed in adulthood SO CLINICAL IMMUNOLOGY LA English DT Article DE X-linked agammaglobulinemia; Bruton's tyrosine kinase; mRNA splicing; in vitro kinase assay ID COMMON VARIABLE IMMUNODEFICIENCY; BRUTONS TYROSINE KINASE; RNA SPLICE JUNCTIONS; SEQUENCE STATISTICS; BTK GENE; MUTATIONS; PHENOTYPE; HYPOGAMMAGLOBULINEMIA; IDENTIFICATION; DEFICIENCY AB X-linked agammaglobulinemia (XLA), caused by mutations in Bruton's tyrosine kinase (BTK); typically presents in early childhood. We report here the ease of a male diagnosed at age 23 years with hypogammaglobulinemia, originally classified as common variable immunodeficiency (CVID). On further analysis at age 40, flow cytometric analysis of lymphocytes showed only 0.1% B cells and Western blot analysis showed a deficiency of BTK protein in peripheral blood mononuclear cells, indicating the patient has XLA BTK cDNA and genomic DNA analysis revealed a splice site mutation at the 3' end of intron 13. Multiple abnormally spliced mRNA species were identified, one of which was predicted to produce a protein with a 24-amino-acid insert-ion between the SH2 and kinase domains. fn vitro kinase assay of this product showed weak kinase activity, perhaps resulting in milder than usual disease. XLA can present in adult males, and sporadic cases may be misdiagnosed as CVID. (C) 2001 Academic Press. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Stewart, DM (reprint author), 10 Ctr Dr MSC 1374, Bethesda, MD 20892 USA. EM dstew@helix.nih.gov NR 29 TC 23 Z9 23 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 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2001 VL 99 IS 1 BP 94 EP 99 DI 10.1006/clim.2001.5024 PG 6 WC Immunology SC Immunology GA 424YB UT WOS:000168260600010 PM 11286545 ER PT J AU Keel, JC Smith, MJ Wassermann, EM AF Keel, JC Smith, MJ Wassermann, EM TI A safety screening questionnaire for transcranial magnetic stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Letter C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Brain Stimulat Unit, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Keel, JC (reprint author), NIMH, Clin Sci Lab, NIH, Room 3D41,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. NR 2 TC 218 Z9 218 U1 0 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2001 VL 112 IS 4 BP 720 EP 720 DI 10.1016/S1388-2457(00)00518-6 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 422HU UT WOS:000168113100019 PM 11332408 ER PT J AU Kashmiri, SVS Iwahashi, M Tamura, M Padlan, EA Milenic, DE Schlom, J AF Kashmiri, SVS Iwahashi, M Tamura, M Padlan, EA Milenic, DE Schlom, J TI Development of a minimally immunogenic variant of humanized anti-carcinoma monoclonal antibody CC49 SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE antibody; antigen binding; anti-idiotypic antibodies; CDRs; HAMA; humanization; SDRs ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; COMPLEMENTARITY-DETERMINING REGIONS; SPECIFICITY-DETERMINING RESIDUES; METASTATIC COLON-CARCINOMA; PHASE-II; RADIOIMMUNOTHERAPY TRIAL; INTRAPERITONEAL RADIOIMMUNOTHERAPY; ANTIIDIOTYPIC RESPONSE; HYPERVARIABLE REGIONS; CYNOMOLGUS MONKEYS AB Monoclonal antibody (MAb) CC49 reacts with a pancarcinoma antigen, tumor associated glycoprotein (TAG)-72. To circumvent human anti-murine antibody (HAMA) responses in patients, we earlier developed a humanized CC49 (HuCC49 by grafting the complementarity-determining regions (CDRs) of MAb CC49 onto variable light (VL) and variable heavy (VH) frameworks of the human MAbs LEN and 21/28 ' CL, respectively. With the aim of minimizing its immunogenicity further, we have now generated a variant HuCC49 MAb by grafting the specificity-determining residues (SDRs) of MAb CC49 onto the frameworks of the human MAbs. Based on the evaluation of its binding affinity for TAG-72 and its reactivity with anti-idiotypic antibodies present in sera from patients who have been treated with murine CC49, this variant retains its antigen-binding activity and shows minimal reactivity with anti-idiotypic antibodies in patients' sera. Development of this variant, which is a potentially useful clinical reagent for diagnosis and therapy of human carcinomas. demonstrates that for humanization of a xenogeneic antibody grafting of the potential SDRs should be sufficient to retain its antigen-binding properties. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kashmiri, SVS (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B38, Bethesda, MD 20892 USA. NR 90 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD APR PY 2001 VL 38 IS 1 BP 3 EP 16 DI 10.1016/S1040-8428(00)00133-5 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 416EG UT WOS:000167766900002 PM 11255077 ER PT J AU Hurley, JH Meyer, T AF Hurley, JH Meyer, T TI Subcellular targeting by membrane lipids SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID PROTEIN-KINASE-C; CYTOSOLIC PHOSPHOLIPASE A(2); PLECKSTRIN HOMOLOGY DOMAINS; STRUCTURAL BASIS; PLASMA-MEMBRANE; LIVING CELLS; PHOSPHATIDIC-ACID; BINDING DOMAINS; FERM DOMAIN; ENTH DOMAIN AB The reversible localization of signaling proteins to both the plasma and the internal membranes of cells is critical for the selective activation of downstream functions and depends on interactions with both proteins and membrane lipids. New structural and biochemical analyses of C1, C2, PH, FYVE, PERM and other domains have led to an unprecedented amount of information on the molecular interactions of these signaling proteins with regulatory lipids. A wave of studies using GFP-tagged membrane binding domains as reporters has led to new quantitative insights into the kinetics of these signaling mechanisms. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Dept Mol Pharmacol, Stanford, CA 94305 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 47 TC 194 Z9 196 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2001 VL 13 IS 2 BP 146 EP 152 DI 10.1016/S0955-0674(00)00191-5 PG 7 WC Cell Biology SC Cell Biology GA 413NT UT WOS:000167619200005 PM 11248547 ER PT J AU Topalian, SL AF Topalian, SL TI Tumour immunology SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Topalian, SL (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2001 VL 13 IS 2 BP 131 EP 133 DI 10.1016/S0952-7915(00)00194-1 PG 3 WC Immunology SC Immunology GA 409RL UT WOS:000167397800001 ER PT J AU Martin, RG Rosner, JL AF Martin, RG Rosner, JL TI The AraC transcriptional activators SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID MULTIPLE ANTIBIOTIC-RESISTANCE; AMP RECEPTOR PROTEIN; ESCHERICHIA-COLI; DNA-BINDING; INDUCIBLE PROMOTERS; VIRULENCE REGULATOR; RNA-POLYMERASE; FAMILY; SITE; MARA AB The AraC family of bacterial transcriptional activators regulate diverse genetic systems. Recent X-ray diffraction studies show that the monomeric MarA and Rob activators bind to their asymmetric degenerate DNA sites via two different helix-turn-helix elements. Activation by MarA! SoxS or Rob requires a particular orientation of the asymmetric, binding sequence (and hence the activator), depending on its distance from the -10 RNAP signal. Genetic studies are beginning to clarify how the activators interact with RNAP. Growing evidence suggests that for the sugar metabolism activators, multiple binding sites upstream of the promoter anchor the activator in a repressing or nonactivating configuration. By interaction with the sugar and/or CRP, the activator is allosterically altered so it can bind a new set of sites that enable it to activate the promoter. Surprisingly, the virulence activator, Rns, must bind to both upstream and downstream sites in order to activate the ms promoter. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, RG (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 44 TC 144 Z9 147 U1 0 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 2001 VL 4 IS 2 BP 132 EP 137 DI 10.1016/S1369-5274(00)00178-8 PG 6 WC Microbiology SC Microbiology GA 423WQ UT WOS:000168201100005 PM 11282467 ER PT J AU Friedman, DI Court, DL AF Friedman, DI Court, DL TI Bacteriophage lambda: alive and well and still doing its thing SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID SHIGA-LIKE TOXIN; ESCHERICHIA-COLI O157-H7; N-GENE-PRODUCT; TRANSCRIPTION TERMINATION; RNA-POLYMERASE; PHAGE-LAMBDA; TEMPERATE BACTERIOPHAGES; NASCENT RNA; ANTITERMINATION; DNA AB The lambda (h) family of bacteriophages continues to provide significant insights into the understanding of basic biological processes, as well as useful technological innovations. Areas in which recent advances have occurred include transcription elongation, repressor interactions, genomics and posttranscriptional regulation. The homologous lambda recombination functions have been exploited as an efficient in vivo recombinant engineering system for functional genomic studies. The virulence of some pathogenic strains of Escherichia coli is enhanced by the expression of Shiga toxin (stx) genes encoded on a resident lambdoid prophage. Recent work suggests that the phage regulatory network may be a significant contributor to toxin production and release by these pathogenic E. coli. C1 Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. NCI, FCDRC, Frederick, MD 21702 USA. RP Friedman, DI (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RI Friedman, David/G-3198-2015 OI Friedman, David/0000-0002-2741-4671 NR 58 TC 52 Z9 57 U1 4 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 2001 VL 4 IS 2 BP 201 EP 207 DI 10.1016/S1369-5274(00)00189-2 PG 7 WC Microbiology SC Microbiology GA 423WQ UT WOS:000168201100015 PM 11282477 ER PT J AU Murray, EA Richmond, BJ AF Murray, EA Richmond, BJ TI Role of perirhinal cortex in object perception, memory, and associations SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID RHINAL CORTEX; RECOGNITION MEMORY; RHESUS-MONKEYS; TEMPORAL-LOBE; INFEROTEMPORAL CORTEX; STIMULUS ASSOCIATION; REWARD SCHEDULES; TO-SAMPLE; AREA TE; LESIONS AB The perirhinal cortex plays a key role in acquiring knowledge about objects. It contributes to at least four cognitive functions, and recent findings provide new insights into how the perirhinal cortex contributes to each: first, it contributes to recognition memory in an automatic fashion; second, it probably contributes to perception as well as memory; third, it helps identify objects by associating together the different sensory features of an object; and fourth, it associates objects with other objects and with abstractions. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM eam@ln.nimh.nih.gov; bjr@ln.nimh.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 44 TC 150 Z9 150 U1 3 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2001 VL 11 IS 2 BP 188 EP 193 DI 10.1016/S0959-4388(00)00195-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 429FN UT WOS:000168505500007 PM 11301238 ER PT J AU Martin, A Chao, LL AF Martin, A Chao, LL TI Semantic memory and the brain: structure and processes SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID INFERIOR PREFRONTAL CORTEX; FUSIFORM FACE AREA; POSITRON-EMISSION-TOMOGRAPHY; VERB GENERATION; PET ACTIVATION; NEURAL SYSTEMS; TEMPORAL-LOBE; FUNCTIONAL-ANATOMY; BIOLOGICAL MOTION; LEXICAL RETRIEVAL AB Recent functional brain imaging studies suggest that object concepts may be represented, in part, by distributed networks of discrete cortical regions that parallel the organization of sensory and motor systems. In addition, different regions of the left lateral prefrontal cortex, and perhaps anterior temporal cortex, may have distinct roles in retrieving, maintaining and selecting semantic information. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM alex@codon.nih.gov RI martin, alex/B-6176-2009 NR 81 TC 688 Z9 703 U1 7 U2 72 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2001 VL 11 IS 2 BP 194 EP 201 DI 10.1016/S0959-4388(00)00196-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 429FN UT WOS:000168505500008 PM 11301239 ER PT J AU Drevets, WC AF Drevets, WC TI Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID MEDIAL PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; NUCLEUS-ACCUMBENS DOPAMINE; MAJOR DEPRESSION; FACIAL EXPRESSIONS; HUMAN AMYGDALA; POSITRON EMISSION; CONDITIONED FEAR; PARKINSONS-DISEASE; VENTRAL STRIATUM AB Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which primary mood disorders are conceptualized as illnesses that involve abnormalities of brain structure, as well as of brain function. These data suggest specific hypotheses regarding the neural mechanisms underlying pathological emotional processing in mood disorders. They particularly support a role for dysfunction within the prefrontal cortical and striatal systems that normally modulate limbic and brainstem structures involved in mediating emotional behavior in the pathogenesis of depressive symptoms. C1 NIMH, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Drevets, WC (reprint author), NIMH, Mood Anxiety Disorders Program, 1 Ctr Dr,Room B3-07 MSC 0135, Bethesda, MD 20892 USA. EM DrevetsW@intra.nimh.nih.gov NR 106 TC 653 Z9 689 U1 12 U2 84 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2001 VL 11 IS 2 BP 240 EP 249 DI 10.1016/S0959-4388(00)00203-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 429FN UT WOS:000168505500015 PM 11301246 ER PT J AU Balla, T AF Balla, T TI Pharmacology of phosphoinositides, regulators of multiple cellular functions SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID ADRENAL GLOMERULOSA CELLS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; PLECKSTRIN-HOMOLOGY DOMAINS; CAPACITATIVE CALCIUM-ENTRY; PHOSPHOLIPASE C-GAMMA; MYOINOSITOL MONOPHOSPHATASE GENE; MEDIATED SIGNAL-TRANSDUCTION; PTEN TUMOR-SUPPRESSOR; LIGHT CHAIN KINASE; PHOSPHATIDYLINOSITOL 3-KINASE AB Inositol phospholipids represent a small fraction of the phospholipids present in all cellular membranes with remarkable importance in regulating various cell functions. They are synthesized from phosphatidylinositol by sequential phosphorylations on the several hydroxyls of the inositol ring to create polyphosphoinositides that function either as docking sites to promote formation of molecular signaling complexes, or serve as precursors for soluble inositol polyphosphates that act as diffusible intracellular messengers. Phosphoinositides are involved in the control of many processes, including membrane traffic, endo- and exocytosis, mitogenesis and apoptosis. Pharmacological tools have helped to clarify many details of phosphoinositide metabolism and have unveiled the roles of these lipids in the control of specific signaling pathways. However, because of their pleiotropic functions it has been questionable whether pharmacological manipulation of inositide formation and metabolism can be of therapeutic value. This review briefly summarizes the means by which inositide functions have been pharmacologically manipulated, and discusses possibilities for specifically targeting certain aspects of their regulatory functions. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. OI Balla, Tamas/0000-0002-9077-3335 NR 234 TC 44 Z9 44 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD APR PY 2001 VL 7 IS 6 BP 475 EP 507 DI 10.2174/1381612013397906 PG 33 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 421VG UT WOS:000168083800005 PM 11281854 ER PT J AU Plisov, SY Yoshino, K Dove, LF Higinbotham, KG Rubin, JS Perantoni, AO AF Plisov, SY Yoshino, K Dove, LF Higinbotham, KG Rubin, JS Perantoni, AO TI TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis SO DEVELOPMENT LA English DT Article DE induction; kidney; tubulogenesis; Wnt signaling; Stat; TGF beta 2; LIF; FGF2; rat ID LEUKEMIA INHIBITORY FACTOR; CILIARY NEUROTROPHIC FACTOR; COLLECTING DUCT ANLAGEN; GROWTH-FACTOR; TGF-BETA; METANEPHRIC MESENCHYME; KIDNEY DEVELOPMENT; IN-VITRO; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTIONAL ACTIVATION AB The metanephric kidney develops from interactions between the epithelial ureteric bud and adjacent metanephric mesenchyme, which is induced by the bud to form the epithelia of the nephron, We have found that leukemia inhibitory factor (LIF) and transforming growth factor beta2 (TGF beta2) are secreted by inductive rat bud cells and cooperate to enhance and accelerate renal tubule formation in uninduced rat metanephric mesenchymal explants. LIF alone or TGF beta2 with fibroblast growth factor 2 induced numerous tubules in isolated mesenchymes over an 8 day period, while (in combination) all three caused abundant tubule formation in 72 hours. Furthermore, neutralization of Wnt ligands with antagonist-secreted Frizzled-related protein 1 abrogated these responses and combinatorial cytokine/growth factor stimulation of explants augmented nuclear activation of Tcf1/Lef1, suggesting that LIF and TGF beta2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-dependent mechanism. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Perantoni, AO (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NR 66 TC 105 Z9 106 U1 1 U2 3 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 APR PY 2001 VL 128 IS 7 BP 1045 EP 1057 PG 13 WC Developmental Biology SC Developmental Biology GA 426XQ UT WOS:000168374100003 PM 11245570 ER PT J AU Rankin, TL O'Brien, M Lee, E Wigglesworth, K Eppig, J Dean, J AF Rankin, TL O'Brien, M Lee, E Wigglesworth, K Eppig, J Dean, J TI Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development SO DEVELOPMENT LA English DT Article DE zona pellucida; fertilization; embryonic stem cells; sperm-egg interactions; transgenic mice; folliculogenesis; preimplantation development; ZP2; oocyte-granulosa cell interactions ID MOUSE OOCYTES; SPERM-BINDING; MONOCLONAL-ANTIBODIES; PRIMORDIAL FOLLICLES; CELL DIFFERENTIATION; GRANULOSA-CELLS; STEM-CELLS; ZP3; EXPRESSION; PROTEINS AB All vertebrate eggs are surrounded by an extracellular matrix. This matrix is known as the zona pellucida in mammals and is critically important for the survival of growing oocytes, successful fertilization and the passage of early embryos through the oviduct, The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2 and ZP3), each encoded by a single copy gene, Using targeted mutagenesis in embryonic stem cells, Zp2-null mouse lines have been established, ZP1 and ZP3 proteins continue to be synthesized and form a thin zona matrix in early follicles that is not sustained in pre-ovulatory follicles, The abnormal zona matrix does not affect initial folliculogenesis, but there is a significant decrease in the number of antral stage follicles in ovaries isolated from mice lacking a zona pellucida, Few eggs are detected in the oviduct after stimulation with gonadotropins, and no two-cell embryos are recovered after mating Zp2-null females with normal male mice. The structural defect is more severe than that observed in Zp1-null mice, which have decreased fecundity, but not quite as severe as that observed in Zp3-null mice, which never form a visible zona pellucida and are sterile. Although zona-free oocytes matured and fertilized in vitro can progress to the blastocyst stage, the developmental potential of blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and, after transfer to foster mothers, live births have not been observed. Thus, in addition to its role in fertilization and protection of early embryos, these data are consistent with the zona pellucida maintaining interactions between granulosa cells and oocytes during folliculogenesis that are critical to maximize developmental competence of oocytes. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04607 USA. NICHD, Lab Mammalian Genet & Dev, NIH, Bethesda, MD 20892 USA. RP Rankin, TL (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 47 TC 127 Z9 136 U1 0 U2 1 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 APR PY 2001 VL 128 IS 7 BP 1119 EP 1126 PG 8 WC Developmental Biology SC Developmental Biology GA 426XQ UT WOS:000168374100010 PM 11245577 ER PT J AU Demidenko, Z Badenhorst, P Jones, T Bi, XL Mortin, MA AF Demidenko, Z Badenhorst, P Jones, T Bi, XL Mortin, MA TI Regulated nuclear export of the homeodomain transcription factor Prospero SO DEVELOPMENT LA English DT Article DE leptomycin B; neurogenesis; nuclear export; Prospero; subcellular localization; transcription; Drosophila ID HOMEOBOX GENE PROX-1; NERVOUS-SYSTEM; SUBCELLULAR-LOCALIZATION; DROSOPHILA-PROSPERO; PROTEIN; SIGNAL; CELL; EXPRESSION; TRANSPORT; MUTATIONS AB Subcellular distribution of the Prospero protein is dynamically regulated during Drosophila embryonic nervous system development. Prospero is first detected in neuroblasts where it becomes cortically localized and tethered by the adapter protein, Miranda, After division, Prospero enters the nucleus of daughter ganglion mother cells where it functions as a transcription factor. We have isolated a mutation that removes the C-terminal 30 amino acids from the highly conserved 100 amino acid Prospero domain. Molecular dissection of the homeo- and Prospero domains, and expression of chimeric Prospero proteins in mammalian and insect cultured cells indicates that Prospero contains a nuclear export signal that is masked by the Prospero domain. Nuclear export of Prospero, which is sensitive to the drug leptomycin B, is mediated by Exportin. Mutation of the nuclear export signal-mask in Drosophila embryos prevents Prospero nuclear localization in ganglion mother cells. We propose that a combination of cortical tethering and regulated nuclear export controls Prospero subcellular distribution and function in all higher eukaryotes. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mortin, MA (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Bi, Xiaolin/E-7469-2010; Mortin, Mark/B-4251-2008; Bi, Xiaolin/C-7038-2014; OI Bi, Xiaolin/0000-0002-7172-7851; Bi, Xiaolin/0000-0003-2837-9457; Badenhorst, Paul/0000-0002-2542-0250 NR 45 TC 28 Z9 28 U1 0 U2 1 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 APR PY 2001 VL 128 IS 8 BP 1359 EP 1367 PG 9 WC Developmental Biology SC Developmental Biology GA 429CR UT WOS:000168498900013 PM 11262236 ER PT J AU Tschop, M Weyer, C Tataranni, PA Devanarayan, V Ravussin, E Heiman, ML AF Tschop, M Weyer, C Tataranni, PA Devanarayan, V Ravussin, E Heiman, ML TI Circulating Ghrelin levels are decreased in human obesity SO DIABETES LA English DT Article ID PEPTIDE AB Ghrelin is a novel endogenous natural ligand for the growth hormone (GH) secretagogue receptor that has recently been isolated from the rat stomach. Ghrelin administration stimulates GH secretion but also causes weight gain by increasing food intake and reducing fat utilization in rodents. To investigate the possible involvement of ghrelin in the pathogenesis of human obesity, we measured body composition (by dual X-ray absorption) as well as fasting plasma ghrelin concentrations (radioimmunoassay) in 15 Caucasians (8 men and 7 women, 31 +/- 9 years of age, 92 +/- 24 kg body wt, and 29 +/- 10% body fat, mean a SD) and 15 Pima Indians (8 men and 7 women, 33 +/- 5 years of age, 97 +/- 29 kg body wt, and 30 +/- 8% body fat). Pasting plasma ghrelin was negatively correlated with percent body fat (r = -0.45; P = 0,01), fasting insulin (r = - 0.45; P = 0.01) and leptin (r = -0.38; P = 0.03) concentrations. Plasma ghrelin concentration was decreased in obese Cancasians as compared with lean Caucasians (P < 0,01), Also, fasting plasma ghrelin was lower in Pima Indians, a population with a very high prevalence of obesity, compared with Caucasians (87 28 vs. 129 +/- 34 fmol/ml; P < 0,01), This result did not change after adjustment for fasting plasma insulin concentration. There was no correlation between fasting plasma ghrelin and height. Prospective clinical studies are now needed to establish the role of ghrelin in the pathogenesis of human obesity. C1 Eli Lilly & Co, Lilly Res Labs, Corp Ctr, Indianapolis, IN 46285 USA. Eli Lilly & Co, Lilly Res Labs, Dept Stat, Indianapolis, IN 46285 USA. NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Tschop, M (reprint author), Eli Lilly & Co, Lilly Res Labs, Corp Ctr, Drop 0545, Indianapolis, IN 46285 USA. RI Tschoep, Matthias/I-5443-2014; OI Tschoep, Matthias/0000-0002-4744-371X NR 5 TC 1265 Z9 1298 U1 0 U2 35 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2001 VL 50 IS 4 BP 707 EP 709 DI 10.2337/diabetes.50.4.707 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415KB UT WOS:000167719600001 PM 11289032 ER PT J AU Douglas, JA Erdos, MR Watanabe, RM Braun, A Johnston, CL Oeth, P Mohlke, KL Valle, TT Ehnholm, C Buchanan, TA Bergman, RN Collins, FS Boehnke, M Tuomilehto, J AF Douglas, JA Erdos, MR Watanabe, RM Braun, A Johnston, CL Oeth, P Mohlke, KL Valle, TT Ehnholm, C Buchanan, TA Bergman, RN Collins, FS Boehnke, M Tuomilehto, J TI The peroxisome poliferator-activated receptor-gamma 2 Pro12Ala variant - Association with type 2 diabetes and trait differences SO DIABETES LA English DT Article ID BODY-MASS INDEX; PPAR-GAMMA; INSULIN SENSITIVITY; GENE-MUTATIONS; PPAR-GAMMA-2; OBESITY; POLYMORPHISM; MELLITUS; SUBSTITUTION; REGULATOR AB Recent studies have identified a common proline-to-alanine substitution (Pro12Ala) in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), a nuclear receptor that regulates adipocyte differentiation and possibly insulin sensitivity, The Pro12Ala variant has been associated in some studies with diabetes-related traits and/or protection against type 2 diabetes. me examined this variant in 935 Finnish subjects, including 522 subjects with type 2 diabetes, 193 nondiabetic spouses, and 220 elderly nondiabetic control subjects, The frequency of the Pro12Ala variant was significantly lower in diabetic subjects than in nondiabetic subjects (0.15 vs, 0.21; P = 0.001), We also compared diabetes-related traits between subjects with and without the Pro12Ala variant within subgroups. Among diabetic subjects, the variant was associated with greater weight gain after age 20 years (P = 0.023) and lower triglyceride levels (P = 0.033), Diastolic blood pressure was higher in grossly obese (BMI >40 kg/m(2)) diabetic subjects with the variant. In nondiabetic spouses, the variant was associated with higher fasting insulin (P = 0.033), systolic blood pressure (P = 0.021), and diastolic blood pressure (P = 0.045). These findings support a role for the PPAR-gamma2 Pro12Ala variant in the etiology of type 2 diabetes and the insulin resistance syndrome. C1 Univ Michigan, Dept Biostat, Sch Publ Hlth, Ann Arbor, MI 48109 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Natl Publ Hlth Inst, Dept Biochem, Helsinki, Finland. Natl Publ Hlth Inst, Hlth Promot Diabet & Genet Epidemiol Unit, Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol, Helsinki, Finland. Sequenom Inc, San Diego, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA USA. RP Boehnke, M (reprint author), Univ Michigan, Dept Biostat, Sch Publ Hlth, 1420 Washington Hts, Ann Arbor, MI 48109 USA. FU NCRR NIH HHS [M01 RR000043]; NHGRI NIH HHS [HG00040, HG00376]; NHLBI NIH HHS [R01 HL060894, R01 HL060944, R01 HL061019]; NIDA NIH HHS [U54 DA021519]; NIDDK NIH HHS [DK09525, R01 DK061628] NR 19 TC 111 Z9 119 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2001 VL 50 IS 4 BP 886 EP 890 DI 10.2337/diabetes.50.4.886 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415KB UT WOS:000167719600026 PM 11289057 ER PT J AU Tataranni, PA Baier, L Jenkinson, C Harper, I Del Parigi, A Bogardus, C AF Tataranni, PA Baier, L Jenkinson, C Harper, I Del Parigi, A Bogardus, C TI A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure SO DIABETES LA English DT Article ID AUTOSOMAL GENOMIC SCAN; BODY-MASS INDEX; PIMA-INDIANS; DIABETES-MELLITUS; MOLECULAR-BIOLOGY; OBESITY; VARIANTS; DRD2; MICE AB Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Tataranni, PA (reprint author), Obes & Energy Metab Unit, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 26 TC 31 Z9 31 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2001 VL 50 IS 4 BP 901 EP 904 DI 10.2337/diabetes.50.4.901 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415KB UT WOS:000167719600029 PM 11289060 ER PT J AU Clark, CM Fradkin, JE Hiss, RG Lorenz, RA Vinicor, F Warren-Boulton, E AF Clark, CM Fradkin, JE Hiss, RG Lorenz, RA Vinicor, F Warren-Boulton, E TI The National Diabetes Education Program, changing the way diabetes is treated - Comprehensive diabetes care SO DIABETES CARE LA English DT Editorial Material ID MICROVASCULAR COMPLICATIONS; ASSOCIATION; MANAGEMENT; MORTALITY; MELLITUS; GLUCOSE; DISEASE; ADULTS C1 Richard Roudebush VA Med Ctr, Dept Res & Dev, Indianapolis, IN USA. NIH, Bethesda, MD 20892 USA. Univ Michigan, Hlth Syst, Michigan Diabet Res & Training Ctr, Div Demonstrat & Educ, Ann Arbor, MI USA. Univ Illinois, Dept Pediat, Coll Med, Peoria, IL USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. Hagar Sharp, Washington, DC USA. RP Clark, CM (reprint author), Regenstrief Inst Hlth Care, 1001 W 10th St, Indianapolis, IN 46202 USA. NR 20 TC 29 Z9 33 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2001 VL 24 IS 4 BP 617 EP 618 DI 10.2337/diacare.24.4.617 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415BX UT WOS:000167701600003 PM 11315818 ER PT J AU Jensen, RT AF Jensen, RT TI Current diagnosis and management of gastrointestinal neuroendocrine tumours SO DIGESTIVE AND LIVER DISEASE LA English DT Editorial Material ID PANCREATIC ENDOCRINE TUMORS; CHROMOGRANIN-A; OCTREOTIDE ACETATE; LANREOTIDE; SCINTIGRAPHY; SURGERY; ALPHA C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1125-8055 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD APR PY 2001 VL 33 IS 3 BP 212 EP 214 DI 10.1016/S1590-8658(01)80708-8 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 435YR UT WOS:000168910200002 PM 11407663 ER PT J AU Hagenauer, B Salamon, A Thalharmmer, T Kunst, O Haslinger, E Klingler, P Senderoqwicz, AM Sausville, EA Jager, W AF Hagenauer, B Salamon, A Thalharmmer, T Kunst, O Haslinger, E Klingler, P Senderoqwicz, AM Sausville, EA Jager, W TI In vitro glucuronidation of the cyclin-dependent kinase inhibitor flavopiridol by rat and human liver microsomes: Involvement of udpglucuronosyltransferases 1A1 and 1A9 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ACTIVITY IN-VIVO; CARCINOMA-CELLS; UDP-GLUCURONOSYLTRANSFERASES; CANCER-CELLS; APOPTOSIS; METABOLISM; L86-8275; INDUCTION; FLAVONE; GROWTH AB The metabolism of flavopiridol (FLAP), a novel anticancer drug currently undergoing clinical development, was investigated in rat and human liver microsomes. In the presence of uridine 5'-diphosphoglucuronic acid, two biotransformation products (M1 and M2) could be detected. Formation of metabolite M1 and M2 in terms of enzymatic efficacy (V-max/K-M) was about 50- and 5-fold higher in rat (1.58 +/- 2.23 and 7.22 +/- 1.17 mul/min/mg) as compared with human liver microsomes (0.032 +/- 0.016 and 1.52 +/- 0.93 mul/min/mg), indicating species-related differences in FLAP glucuronidation. Incubation in the presence of human recombinant UDP-glucuronosyl-transferases (UGTs) demonstrated that M1 is almost exclusively catalyzed by UGT1A1, whereas M2 is formed by UGT1A9 and only to a minor extent by UGT1A1 and UGT1A10. Chemical inhibition experiments further prove the involvement of UGT1A1 and UGT1A9 in the formation of M1 and M2, as the UGT1A1 substrate bilirubin preferably inhibited M1 over M2 (K-i : 36 and 258 muM, respectively), whereas the UGT1A9 substrate propofol showed a more pronounced decrease in M2 but not in M1 formation (K-i : 47 and 142 mM, respectively). Both conjugates were purified from rat liver microsomes and analyzed by mass spectrometry, NMR, and UV experiments. On the basis of these results, M1 was identified as 5-O-beta -glucopyranuronosyl-flavopiridol and M2 as 7-O-beta -glucopyranuronosyl-flavopiridol. In conclusion, our results elucidate the enzymatic pathways of FLAP in rat and human liver, which must be considered during cancer therapy of patients. C1 Univ Vienna, Inst Pharmaceut Chem, A-1090 Vienna, Austria. Univ Vienna, Dept Pathophysiol, A-1090 Vienna, Austria. Graz Univ, Inst Pharmaceut Chem, Graz, Austria. Univ Innsbruck Hosp, Dept Surg, A-6020 Innsbruck, Austria. NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RP Jager, W (reprint author), Univ Vienna, Inst Pharmaceut Chem, Althanstr 14, A-1090 Vienna, Austria. RI Jager, Walter/I-6242-2013; OI Jager, Walter/0000-0002-4970-8179; Kunert, Olaf/0000-0002-7091-5973 NR 31 TC 46 Z9 48 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2001 VL 29 IS 4 BP 407 EP 414 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 414ML UT WOS:000167670400008 PM 11259324 ER PT J AU Radel, M Goldman, D AF Radel, M Goldman, D TI Pharmacogenetics of alcohol response and alcoholism: The interplay of genes and environmental factors in thresholds for alcoholism SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT Conference on New Directions in Pharmacogenetics and Ecogenetics Genetic Defenses Against Environmental Impacts Responses to Infections, Foods and Environmental Toxicants CY OCT 03-06, 1999 CL UNIV MICHIGAN, ANN ARBOR, MICHIGAN SP Amer Soc Pharmacol & Exptl Therapeut, Amer Assoc Clin Chem, Burroughs Wellcome Fund, Natl Inst Envronm Hlth Sce, Natl Inst Gen Med Sci, Univ Michigan Dept Pathol, Univ Michigan Dept Pharmacol, Univ Mich Med Sch, Univ Michigan Off Vice President Res, Al Rajhi Travel & Tourism, Univ Washington, Ctr Ecogenet & Environm Hlth, ClinTrials Res Inc, Glaxo Wellcome Res & Dev, Int Soc Study Xenobiot, Johnson & Johnson, Karolinska Inst, Parke Davis/Warner Lambert, Pharmacia & Upjohn Co, Phenogenex LLC, Quest Diagnost, SmithKline Beecham, Soc Toxicol, Wayne State Univ, Toxicol Ctr HO UNIV MICHIGAN ID GAMMA-AMINOBUTYRIC-ACID; ACCUMBAL DOPAMINE OVERFLOW; CROSS-FOSTERING ANALYSIS; RECEPTOR GENE; MICE LACKING; PSYCHIATRIC-DISORDERS; METABOLIZING ENZYMES; ETHANOL SENSITIVITY; NUCLEUS-ACCUMBENS; GABA(A) RECEPTOR AB Recent advances in neuroscience and genetics have enabled a better understanding of genetically influenced differences in ethanol ("alcohol")-related responses and differential vulnerability to alcohol dependence at the cellular and molecular levels. Heritability studies reveal that the role of genetic factors in alcoholism is largely substance-specific, with the exception of nicotine. One focus of genetic research in alcoholism is the study of functional polymorphisms influencing alcohol metabolism, such as the aldehyde dehydrogenase type 2 Glu487Lys and alcohol dehydrogenase type 2 His47Arg polymorphisms, which affect vulnerability to alcoholism via pharmacokinetic mechanisms, and cross-population studies have begun to reveal important gene-environment interactions. The other focus is on functional genetic variants of proteins involved in the neuronal response to alcohol, including alcohol sensitivity, reward, tolerance, and withdrawal. Studies on the roles of GABA(A) alpha6-amino acid substitutions in rodents in alcohol and benzodiazepine sensitivity, and potential roles in human alcohol and benzodiazepine sensitivity are reviewed. These studies, together with recently developed knowledge on a GABA(A) receptor gene cluster at a quantitative trait loci for alcohol withdrawal on mouse chromosome 11, indicate that research investigation of variation at GABA(A) neurotransmission is a promising area in the pharmacodynamics of alcohol and in differential susceptibility to alcoholism. Genes for proteins involved in alcohol-mediated reward include genes for transporters and receptors for dopamine, serotonin, opioids, and GABA. These genes and their functional variants also represent important targets for understanding alcohol's effects in humans. Identification of genes for alcoholism vulnerability is important in the near future, not only for prevention, but also for development and targeting treatments. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Radel, M (reprint author), 12420 Parklawn Dr,Pk 5 Bldg,Room MSC-8110, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 85 TC 44 Z9 44 U1 4 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2001 VL 29 IS 4 BP 489 EP 494 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 414ML UT WOS:000167670400022 PM 11259338 ER PT J AU Talbot, LA Fleg, JL Metter, EJ AF Talbot, LA Fleg, JL Metter, EJ TI Absolute versus relative intensity classification of physical activity: Implications for public health policy SO EDUCATIONAL GERONTOLOGY LA English DT Article ID AGE; FITNESS AB A major issue in evaluating the success of educational programs intended to improve public participation in physical activity is how to classify the intensity of activities performed. Currently, there are at least two approaches to estimating intensity of leisure time physical activity (LTPA), based on relative and absolute scales. We examined the impact of using relative versus absolute criteria on reaching physical activity goals set by the American College of Sports Medicine (ACSM; 2000) and the Surgeon General (United States Department of Health and Human Services, USDHHS, 1996). Subjects were healthy men (n = 619) and women (n = 497) aged 18-95 who were participants in the Baltimore Longitudinal Study of Aging. The percentage of subjects meeting the Surgeon General's recommendations for moderate and high intensity LTPA declined with age under the absolute classification system but increased with age when a relative intensity scale was used. Using ACSM recommendations, aging was associated with a decline in high absolute intensity LTPA. However, when a relative classification system was used, high relative intensity LTPA appeared to increase with age, inverting the relationship between high-intensity LTPA and cardiorespiratory fitness. The use of relative intensity LTPA criteria suggests that older subjects are meeting national standards for physical activity, raising questions about the appropriateness of such a scale to motivate older adults to improve their fitness. C1 Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Talbot, LA (reprint author), Johns Hopkins Univ, Sch Nursing, 525 N Wolfe St,Rm 444A, Baltimore, MD 21205 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0360-1277 J9 EDUC GERONTOL JI Educ. Gerontol. PD APR-MAY PY 2001 VL 27 IS 3-4 BP 307 EP 321 DI 10.1080/036012701750195012 PG 15 WC Education & Educational Research; Gerontology SC Education & Educational Research; Geriatrics & Gerontology GA 437TD UT WOS:000169008900008 ER PT J AU Yefimov, S Sjomeling, C Yergey, AL Chrambach, A AF Yefimov, S Sjomeling, C Yergey, AL Chrambach, A TI Stacking of unlabeled sodium dodecyl sulfate-proteins within a fluorimetrically detected moving boundary, electroelution and mass spectrometric identification SO ELECTROPHORESIS LA English DT Article DE sodium dodecyl sulfate-proteins; electroelution; agarose gel electrophoresis ID GEL-ELECTROPHORETIC BANDS; SYSTEMS; STEP AB The previously reported fluorimetric detection of sodium dodecyl sulfate (SDS)-protein in the presence of cascade blue in agarose gel electrophoresis using barbital buffer was found to be equally feasible in the absence of the fluorescent marker and using Tris-Tricinate buffer, provided that SDS was loaded with the sample but not contained in the catholyte. That fluorescent detection is thought to be due to the formation of a moving boundary between leading SDS and trailing barbital, or Tricinate buffer. This hypothesis is supported by the following evidence: Ii) The fluorometrically detected band disappears with addition of SDS to the catholyte; Iii) band area is proportional to protein and/or SDS load; (iii) mobility of SDS-proteins differing in mass is the same at agarose concentrations up to 3%; (iv) lowering of protein mobility by increase in gel concentration and/or increase in the size of the SDS-protein leads to band disappearance. Fluorescent detection of the band is like to be nonspecific and due to the light scattering properties of a stack comprising moving boundaries of any analytes with net mobilities intermediate between SDS (or micellar sos) and the trailing buffer constituent at their regulated very high concentrations. The steady-state stack of SDS-proteins in the size range of 14.4-45.0 kDa, and the transient stack of an SDS-protein of 66.2 kDa have lent themselves to electroelution and characterization by mass of the proteins after removal of SDS and buffer exchange using matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry. The possibility to form a stack of protein between leading SDS and trailing buffer anions under conditions of weak molecular sieving (open-pore gel and small-sized protein) contributes to the understanding of moving boundaries in gel electrophoresis, but in view of the narrowly defined conditions, under which this stack forms, is of limited practical significance for the gel electrophoresis of SDS-proteins. C1 NICHD, Macromol Anal Sect, NIH, Bethesda, MD 20892 USA. NICHD, Sect Mass Spectrometry, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHD, Macromol Anal Sect, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 12 TC 4 Z9 4 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD APR PY 2001 VL 22 IS 6 BP 999 EP 1003 DI 10.1002/1522-2683()22:6<999::AID-ELPS999>3.0.CO;2-Y PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 429HL UT WOS:000168510500004 PM 11358154 ER PT J AU Issaq, HJ Chan, KC Liu, CS Li, QB AF Issaq, HJ Chan, KC Liu, CS Li, QB TI Multidimensional high performance liquid chromatography - capillary electrophoresis separation of a protein digest: An update SO ELECTROPHORESIS LA English DT Article DE protein digest; peptide mapping; multidimensional separations; array capillary electrophoresis; high-performance liquid chromatography AB The trypsin digest of a mixture of two proteins, namely cytochrome c and myoglobin, was first separated in the first dimension by high-performance liquid chromatography (HPLC). Fractions from the HPLC were collected every 30s with the aid of a fraction collector into a 96-well microtiter plate. After concentration, all the collected fractions were analyzed simultaneaosly in the second dimension by a SS-array capillary electrophoresis system. The labeled peptides were detected by laser-induced fluorescence. An internal standard, allura red, was added to all the fractions, prior to capillary electrophoretic analysis. The internal standard serves two functions, migration time correction and signal intensity correction. The data are presented in two different formats, as an electropherogram of all the fractions and in a two-dimensional (2-D) format. The 2-D plot of the data shows the density of each spot, which corresponds to the concentration of the migrating peptides. The total experimental time for the HPLC and capillary electrophoretic analyses ist less than 1 h, which ist much faster than using 2-D slab-gel electrophoresis or single-capillary capillary electrophoresis. C1 NCI, SAIC Frederick, Analyt Chem Lab, Frederick, MD 21702 USA. SpectruMedix Corp, State Coll, PA USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick, Analyt Chem Lab, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 6 TC 37 Z9 42 U1 1 U2 12 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD APR PY 2001 VL 22 IS 6 BP 1133 EP 1135 DI 10.1002/1522-2683()22:6<1133::AID-ELPS1133>3.3.CO;2-J PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 429HL UT WOS:000168510500023 PM 11358138 ER PT J AU Kurebayashi, S Sumitani, S Kasayama, S Jetten, AM Hirose, T AF Kurebayashi, S Sumitani, S Kasayama, S Jetten, AM Hirose, T TI TNF-alpha inhibits 3T3-L1 adipocyte differentiation without downregulating the expression of C/EBP beta and delta SO ENDOCRINE JOURNAL LA English DT Article DE C/EBP alpha,beta,delta; PPAR gamma; TNF-alpha; adipocyte differentiation ID NECROSIS-FACTOR-ALPHA; BINDING-PROTEIN-ALPHA; GENE-EXPRESSION; TRANSCRIPTIONAL REPRESSION; ECTOPIC EXPRESSION; ROR-GAMMA; CELLS; ADIPOGENESIS; PROMOTES; PROGRAM AB Tumor necrosis factor-alpha (TNP-alpha) has been reported to inhibit adipocyte differentiation in which multiple transcription factors including CCAAT enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated receptor (PPAR) gamma play an important role. Induction of C/EBP alpha and PPAR gamma, which regulate the expression of many adipocyte-related genes, is dependent on the expression of C/EBP beta and C/EBP delta at the early phase of adipocyte differentiation. To elucidate the mechanism by which TNF-alpha inhibits adipocyte differentiation, we examined the effect of TNF-alpha on the expression of these transcription factors in mouse 3T3-L1 preadipocytes. TNF-alpha did not abrogate the induction of C/EBP beta and C/EBP delta in response to differentiation stimuli. In fully differentiated adipocytes, TNF-a rapidly induced C/EBP beta and C/EBP delta, whereas it downregulated the expression of C/EBP alpha and PPAR gamma. Our results suggest that TNF-alpha inhibits adipocyte differentiation independently of the downregulation of C/EBP beta and C/EBP delta. C1 Nishinomiya Municipal Cent Hosp, Dept Internal Med, Nishinomiya, Hyogo 6638014, Japan. Osaka Univ, Sch Med, Dept Mol Med, Osaka 5650871, Japan. NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hirose, T (reprint author), Nishinomiya Municipal Cent Hosp, Dept Internal Med, 8-24 Hayashida Cho, Nishinomiya, Hyogo 6638014, Japan. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 20 TC 17 Z9 17 U1 0 U2 2 PU JAPAN ENDOCRINE SOCIETY PI TOKYO PA C/O DEPT VETERINARY PHYSIOL, VET MED SCI, UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 113, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD APR PY 2001 VL 48 IS 2 BP 249 EP 253 DI 10.1507/endocrj.48.249 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428FX UT WOS:000168452000019 PM 11456275 ER PT J AU James, MR Skaar, TC Lee, RY MacPherson, A Zwiebel, JA Ahluwalia, BS Ampy, F Clarke, R AF James, MR Skaar, TC Lee, RY MacPherson, A Zwiebel, JA Ahluwalia, BS Ampy, F Clarke, R TI Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo SO ENDOCRINOLOGY LA English DT Article ID HORMONE-INDEPENDENT GROWTH; ESTRONE SULFATASE; AROMATASE INHIBITORS; 17-BETA-HYDROXYSTEROID DEHYDROGENASE; MESSENGER-RNA; NUDE-MICE; ESTRADIOL; TISSUE; METABOLISM; CARCINOMA AB Many human breast tumors are driven by high intratumor concentrations of 17 beta -estradiol that appear to be locally synthesized. The role of aromatase is well established, but the possible contribution of the steroid sulfatase (STS), which liberates estrogens from their biologically inactive sulfates, has been inadequately assessed and remains unclear. To evaluate the role of STS further, we transduced estrogen-dependent MCF-7 human breast cancer cells with a retroviral vector directing the constitutive expression of the human STS gene. Gene integration was confirmed by Southern hybridization, production of the appropriately sized messenger RNA by Northern hybridization, and expression of functional protein by metabolism of [H-3]estrone sulfate to [H-3]estrone. Maximum velocity estimates of estrone formation are 64.2 pmol estrone/mg protein(.)h in STS-transduced cells (STS Clone 20), levels comparable to those seen in some human breast tumors. Lower levels of endogenous activity are seen in MCF-7 cells (13.0 pmol estrone/mg protein h) and in cells transduced with vector lacking the STS gene (Vector 3 cells; 12.0 pmol estrone/mg protein h). 17 beta -Estradiol sulfate induces expression of the progesterone receptor messenger RNA only in STS Clone 20 cells, whereas estrone sulfate produces the greatest stimulation of anchorage-independent growth in these cells. STS Clone 20 cells retain responsiveness to antiestrogens, which block the ability of estrogen sulfate to increase the proportion of cells in both the S and G(2)/M phases of the cell cycle. Consistent with these in vitro observations, only STS Clone 20 cells exhibit a significant increase in the proportion of proliferating tumors in nude ovariectomized mice supplemented with 17 beta -estradiol sulfate. The primary activity in vivo appears to be from intratumor STS, rather than hepatic STS. Surprisingly, 17 beta -estradiol sulfate appears more effective than 17 beta -estradiol when both are administered at comparable concentrations. This effect, which is seen only in STS Clone 20 cells, may reflect differences in the cellular pharmacology of exogenous estrogens compared with those released by the activity of intracellular STS. These studies directly demonstrate that intratumor STS activity can support estrogen-dependent tumorigenicity in an experimental model and may contribute to the promotion of human breast tumors. C1 Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NCI, NIH, Bethesda, MD 20892 USA. Howard Univ, Dept Genet & Human Genet, Washington, DC 20059 USA. RP Clarke, R (reprint author), Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Room W405A,Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 NR 63 TC 29 Z9 30 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2001 VL 142 IS 4 BP 1497 EP 1505 DI 10.1210/en.142.4.1497 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 417QP UT WOS:000167845900017 PM 11250930 ER PT J AU Ye, F Piver, WT Ando, M Portier, CJ AF Ye, F Piver, WT Ando, M Portier, CJ TI Effects of temperature and air pollutants on cardiovascular and respiratory diseases for males and females older than 65 years of age in Tokyo, July and August 1980-1995 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollutants; cardiovascular disease; elderly; respiratory disease; temperature ID CONGESTIVE-HEART-FAILURE; EMERGENCY ROOM VISITS; HOSPITAL ADMISSIONS; DAILY MORTALITY; LOS-ANGELES; TIME-SERIES; POLLUTION; ASTHMA; OZONE; ASSOCIATION AB We studied exposures to higher daily maximum temperatures and concentrations of air pollutants in Tokyo during the summer months of July and August from 1980 to 1995 and their effects on hospital emergency transports for cardiovascular and respiratory diseases for males and females > 65 years of age. Cardiovascular diseases were angina, cardiac insufficiency, hypertension, and myocardial infarction. Respiratory diseases were asthma, acute and chronic bronchitis, and pneumonia. Except for pneumonia, daily maximum temperatures were not associated with hospital emergency transports. Increasing daily maximum temperatures, however, were associated with decreased hospital emergency transports for hypertension. Concentrations of nitrogen dioxide or particulate matter less than or equal to 10 mum, however, were associated with daily hospital emergency transports for angina, cardiac insufficiency, myocardial infarction, asthma, acute and chronic bronchitis, and pneumonia. For cardiac insufficiency, hypertension, myocardial infarction, asthma, chronic bronchitis, and pneumonia, the expected daily number of emergency transports per million were greater for males than for females. For angina and acute bronchitis, there were no differences for the expected daily numbers of emergency transports per million between males and females. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Studies, Tsukuba, Ibaraki, Japan. RP Piver, WT (reprint author), NIEHS, EC-14,POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 45 TC 45 Z9 46 U1 0 U2 4 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 APR PY 2001 VL 109 IS 4 BP 355 EP 359 DI 10.2307/3454894 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 427NZ UT WOS:000168413600025 PM 11335183 ER PT J AU Avoli, M Rogawski, MA Avanzini, G AF Avoli, M Rogawski, MA Avanzini, G TI Generalized epileptic disorders: An update SO EPILEPSIA LA English DT Review ID PROGRESSIVE MYOCLONUS EPILEPSY; CORTICALLY GENERATED SEIZURES; SPIKE-WAVE COMPLEXES; NEURONAL CEROID-LIPOFUSCINOSES; CAT THALAMOCORTICAL NEURONS; DIEKER LISSENCEPHALY GENE; PETIT-MAL ANTICONVULSANTS; KCNQ2/KCNQ3 K+ CHANNELS; GATED SODIUM CURRENTS; PIG THALAMIC NEURONS C1 McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. McGill Univ, Dept Neurol, Montreal, PQ, Canada. McGill Univ, Dept Neurosurg, Montreal, PQ, Canada. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. Ist Nazl Neurol Carlo Besta, Milan, Italy. RP Avoli, M (reprint author), 3801 Univ St, Montreal, PQ H3A 2B4, Canada. EM navoli@po-box.mcgill.ca RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 118 TC 60 Z9 67 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD APR PY 2001 VL 42 IS 4 BP 445 EP 457 DI 10.1046/j.1528-1157.2001.39800.x PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 423RA UT WOS:000168189500001 PM 11440339 ER PT J AU Nasidze, I Risch, GM Robichaux, M Sherry, ST Batzer, MA Stoneking, M AF Nasidze, I Risch, GM Robichaux, M Sherry, ST Batzer, MA Stoneking, M TI Alu insertion polymorphisms and the genetic structure of human populations from the Caucasus SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE Alu insertion; polymorphisms; Caucasus populations ID ETHNIC-GROUPS; EVOLUTION; MARKERS; DNA AB An analysis of 8 Alu insertion loci (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, B65) has been carried out in six populations from the Caucasus, including Indo-European-speaking Armenians; Altaic-speaking Azerbaijanians; North Caucasian-speaking Cherkessians, Darginians, and Ingushians; and South Caucasian (Kartvelian)-speaking Georgians. The Caucasus populations exhibit low levels of within-population variation and high levels of between-population differentiation, with the average F-st value for the Caucasus of 0.113, which is almost as large as the F-st value of 0.157 for worldwide populations. Maximum likelihood tree and principal coordinate analyses both group the Caucasus populations with European populations. Neither geographic nor linguistic relationships appear to explain the genetic relationships of Caucasus populations. Instead, it appears as if they have been small and relatively isolated, and hence genetic drift has been the dominant influence on the genetic structure of Caucasus populations. C1 Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany. Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, Stanley S Scott Canc Ctr,Dept Biometry & Genet, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, Stanley S Scott Canc Ctr,Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Nasidze, I (reprint author), Max Planck Inst Evolutionary Anthropol, Inselstr 22, D-04103 Leipzig, Germany. NR 24 TC 59 Z9 65 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD APR PY 2001 VL 9 IS 4 BP 267 EP 272 DI 10.1038/sj.ejhg.5200615 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 422HJ UT WOS:000168112200005 PM 11313770 ER PT J AU Wang, ZG Chen, ZJ Wheeler, J Shen, SX Notkins, AL AF Wang, ZG Chen, ZJ Wheeler, J Shen, SX Notkins, AL TI Characterization of murine polyreactive antigen-binding B cells: presentation of antigens to T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE natural antibodies; innate immunity; tolerance; CD5; B-1 cell ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MONOREACTIVE HIGH-AFFINITY; CD5+ LYMPHOCYTE-B; PRESENTING CELLS; IN-VIVO; MONOCLONAL AUTOANTIBODIES; RHEUMATOID-ARTHRITIS; NATURAL ANTIBODIES; PROTEIN ANTIGENS; DENDRITIC CELLS AB Monoclonal polyreactive antibodies (Ab) can bind, at low affinity, a variety of different self and non-self antigens (Ag). Recent studies in humans showed that polyreactive Ab are expressed on the surface of a subset of peripheral B lymphocytes and clonal analysis revealed that a variety of different Ag can bind to single cells expressing these Ab. To see if these polyreactive Ag-binding B (PAB) cells also are present in mice, fluorescein-conjugated Ag and FAGS sorting were used to identify and separate PAB cells from non-polyreactive Ag-binding B cells. Depending on the Ag used for screening, up to one-third of mouse splenic B cells displayed polyreactive Ag-binding properties. Confirmation that the Ag actually bound to surface Ig came from treating PAB cells with anti-Ig which inhibited Ag binding by up to 80 %. Further studies showed that PAB cells could present Ag to Ag-specific T cells, but despite their Ag-presenting ability, PAB cells from normal mice failed to trigger Ag-specific T cells to proliferate. Analysis of the co-stimulatory molecules B7-1 and B7-2 showed that these molecules were not expressed on PAB cells from normal mice. These findings argue that the lack of co-stimulatory molecules on PAB cells is the most likely explanation for their failure to stimulate Ag-specific T cells. The ability of PAB cells from normal mice to bind and present Ag to Ag-specific T cells, without causing them to proliferate, suggests that PAB cells may contribute to the induction and/or maintenance of immunological tolerance. C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 44 TC 19 Z9 20 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2001 VL 31 IS 4 BP 1106 EP 1114 DI 10.1002/1521-4141(200104)31:4<1106::AID-IMMU1106>3.0.CO;2-5 PG 9 WC Immunology SC Immunology GA 421YA UT WOS:000168090100015 PM 11298335 ER PT J AU Collin, C Vicario-Abejon, C Rubio, ME Wenthold, RJ McKay, RDG Segal, M AF Collin, C Vicario-Abejon, C Rubio, ME Wenthold, RJ McKay, RDG Segal, M TI Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; culture; hippocampus; NT-3; rat synapse ID SYNAPTIC PROTEIN DISTRIBUTION; NEUROMUSCULAR-JUNCTION; NERVOUS-SYSTEM; GROWTH CONES; SYNAPTOGENESIS; RECEPTOR; RELEASE; BDNF; TRANSMISSION; LOCALIZATION AB We have recently demonstrated that embryonic E16 hippocampal neurons grown in cultures are unable to form fast synaptic connections unless treated with BDNF or NT-3, This experimental system offers an opportunity to define the roles of neurotrophins in processes leading to formation of functional synaptic connections. We have used ultrastructural and electrophysiological methods to explore the cellular locations underlying neurotrophin action on synaptic maturation. The rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs) evoked by hyperosmotic stimulation was 7-16-fold higher in neurotrophin-treated cells than in controls. In addition, the potent neurotransmitter-releasing drug alpha -latrotoxin was virtually ineffective in the control cells while it stimulated synaptic events in neurotrophin-treated cells. Likewise, the membrane-bound dye FM1-43 was taken up by terminals in neurotrophin-treated cultures five-fold more than in controls. Both the total number and the number of docked synaptic vesicles were increased by neurotrophin treatment. Activation of synaptic responses by neurotrophins occurred even when postsynaptic glutamate receptors and action potential discharges were pharmacologically blocked. These results are consistent with a presynaptic locus of action of neurotrophins to increase synaptic vesicle density which is critical for rapid synaptic transmission. They also suggest that neurotrophins can activate synapses in the absence of pre- and postsynaptic neuronal activity. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Segal, M (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NR 45 TC 63 Z9 63 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2001 VL 13 IS 7 BP 1273 EP 1282 DI 10.1046/j.0953-816x.2001.01500.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 425EH UT WOS:000168275000001 PM 11298787 ER PT J AU Ravary, A Muzerelle, A Darmon, M Murphy, DL Moessner, R Lesch, KP Gaspar, P AF Ravary, A Muzerelle, A Darmon, M Murphy, DL Moessner, R Lesch, KP Gaspar, P TI Abnormal trafficking and subcellular localization of an N-terminally truncated serotonin transporter protein SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE low-affinity uptake; monoamine uptake; mouse; protein trafficking; raphe ID RAT-BRAIN; ENDOPLASMIC-RETICULUM; HIPPOCAMPAL-NEURONS; MESSENGER-RNA; EXPRESSION; DEGRADATION; CLONING; CELLS; NOREPINEPHRINE; TRANSLATION AB We report here that a truncated 5-HTT protein is produced in the neurons of the raphe, in serotonin transporter (5-HTT) knockout (KO) mice. The 5-HTT gene has exon 2 deleted and we found that one main transcript, shortened by 450 bp, is produced in these KO mice. The mutated 5-HTT protein is only recognized by antibodies against the C-terminal portion of 5-HTT. This protein is not functional as there is no high-affinity serotonin uptake in 5-HTT KO mice, in adults or during development. Conversely, low-affinity serotonin uptake was detected in vitro, and in dopaminergic neurons of the substantia nigra in vivo. The truncated 5-HTT, recognized by antibodies to the C-terminus, is present exclusively in the somatodendritic compartment of the raphe neurons instead of being exported to axons. As shown with confocal and electron microscopy, the truncated 5-HTT does not reach the plasma membrane and is essentially retained in the endoplasmic reticulum. However, this does not seem to trigger refolding or degradation responses, as no upregulation of the chaperone BIP or of the degradation signal ubiquitin was detected. Last, as observed in heterozygous mice, the presence of the truncated 5-HTT protein, although produced in large quantities, does not disturb the normal trafficking of the wild-type protein. This study therefore validates the 5-HTT KO model despite the occurrence of an incomplete translation, and brings novel information on the in vivo 5-HT uptake and cellular processing of an abnormal 5-HTT protein. C1 CHU Pitie Salpetriere, INSERM, U106, F-75651 Paris 13, France. CHU Pitie Salpetriere, INSERM, U288, F-75651 Paris, France. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, D-97080 Wurzburg, Germany. RP Gaspar, P (reprint author), CHU Pitie Salpetriere, INSERM, U106, 47 Bd Hop, F-75651 Paris 13, France. RI Gaspar, Patricia/G-8892-2011; Lesch, Klaus-Peter/J-4906-2013; Darmon, Michele/F-8708-2011 OI Gaspar, Patricia/0000-0003-4217-5717; Lesch, Klaus-Peter/0000-0001-8348-153X; Darmon, Michele/0000-0001-9730-6273 NR 48 TC 25 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2001 VL 13 IS 7 BP 1349 EP 1362 DI 10.1046/j.0953-816x.2001.1511.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 425EH UT WOS:000168275000009 PM 11298795 ER PT J AU Hampson, AJ Grimaldi, M AF Hampson, AJ Grimaldi, M TI Cannabinoid receptor activation and elevated cyclic AMP reduce glutamate neurotoxicity SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cannabinoid; cyclic AMP; glutamate; G protein; ischemia; voltage-sensitive calcium channels ID RAT HIPPOCAMPAL-NEURONS; CEREBRAL-ISCHEMIA; CORTICAL-NEURONS; CALCIUM CHANNELS; N-TYPE; ANANDAMIDE; ADENOSINE; BRAIN; NEUROTRANSMISSION; EXCITOTOXICITY AB Cannabinoid receptor activation in vivo reduces ischemic injury, a phenomenon that has not been successfully reproduced in vitro. Because cyclic adenosine monophosphate (cAMP) levels are radically elevated during ischemic reperfusion, but cannabinoid receptor activation reduces cAMP levels, we hypothesized that cannabinoids might prevent in vitro glutamate toxicity if reperfusion was simulated by cAMP supplementation after glutamate removal. Although neuronal cultures were unaffected by the single addition of either cannabinoid or dibutyryl cAMP (dbcAMP), glutamate toxicity was reduced by 20% when cannabinoid was present during glutamate exposure and either dbcAMP or forskolin was added after glutamate removal. Further studies revealed that cannabinoid receptor activation reduces glutamate toxicity by attenuating calcium influx through N- and P/Q-type calcium channels. The effect of glutamate exposure on neuronal cAMP levels was also examined. Glutamate exposure significantly reduced neuronal cAMP levels, although suppression was even greater when cannabinoid was present. Because neurological outcome after ischemia is poor when cAMP levels during reperfusion are low, it is hypothesized that cAMP elevation after glutamate exposure may offset excitotoxic and/or cannabinoid receptor-induced cAMP depletion. Cannabinoids protect against ischemic injury in vivo, but only reduce toxicity in vitro when cAMP levels are elevated, possibly suggesting that cAMP elevation during reperfusion reduces brain injury by off-setting the effect of G(i/o) protein-coupled systems on adenylate cyclase. C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. RP Hampson, AJ (reprint author), Cortex Pharmaceut Inc, 15231 Barranca Pkwy, Irvine, CA 92618 USA. OI Grimaldi, Maurizio/0000-0002-7331-7055 NR 40 TC 40 Z9 41 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2001 VL 13 IS 8 BP 1529 EP 1536 DI 10.1046/j.0953-816x.2001.01536.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 430EG UT WOS:000168560600006 PM 11328347 ER PT J AU Steiner, T Junker, U Henzgen, B Nuske, K Durum, SK Schubert, J AF Steiner, T Junker, U Henzgen, B Nuske, K Durum, SK Schubert, J TI Interferon-alpha suppresses the antiapoptotic effect of NF-kB and sensitizes renal cell carcinoma cells in vitro to chemotherapeutic drugs SO EUROPEAN UROLOGY LA English DT Article DE renal cell carcinoma; interferons; immunochemotherapy ID NITRIC-OXIDE SYNTHASE; KAPPA-B; GENE-EXPRESSION; INHIBITION; IMMUNOTHERAPY; ACTIVATION; THERAPY; BETA AB Background Immunochemotherapy (ICT) with interleukin-2 (IL-2) and interferon-alpha (IFN alpha) with a secondary effector (5-fluorouracil, 5 FU) is the only promising treatment for advanced renal cell carcinoma (RCC). With IFN alpha, besides the activation mechanisms of the immunosystem, a direct antitumor effect on tumor cells is expected. Materials and Methods: NF-kappaB activity in th ree permanent cell lines (Hep2, HepG2, HT29) and in primary RCC cell lines was measured after incubation with tumor necrosis factor-alpha (TNF alpha), IFN alpha, IFN-gamma, TNF alpha +IFN alpha, and IFN gamma +TNF alpha, respectively. NF-kB activity and induction of apoptosis by chemotherapeutic drugs (5FU and doxorubicin) were determined in cells transfected with a constitutively active NF-kB p65 or a dominant negative IkB. Results: NF-kB signaling induced by TNF alpha is suppressed by IFN alpha and IFN gamma in the permanent cell fines and in the primary RCC tumor cell cultures. In an in vitro ICT model we show that pretreatment of RCC with IL-2 and IFN alpha leads to a diminished NF-kB response to TNF alpha. In certain tumors, this correlates with increased susceptibility to investigated chemotherapeutic drugs as shown by annexin stain and cell elimination. Modulation of the cellular NF-kB state by a constitutively active p65 or a dominant negative IkB mimics this effect. The IkB construct leads to the same effects as IL-2/IFN alpha pretreatment as shown by predominant elimination of the transfected cells from the overall population, while introduction of p65 leads to a partial rescue from the effect of IL-2 and IFN alpha. The described effect, however, applies only to a selection of primary cell cultures. Conclusions: Besides the immunomodulation effects, treatment of RCC with IL-2/IFN alpha leads to a proapoptotic state in certain tumors. The relevant mediator seems to be IFN alpha by suppression of the antiapoptotic effect of NF-kB. These data can provide an experimental base for correlation with real patient outcome after ICT. Copyright (C) 2001 S. Karger AG. Basel. C1 Univ Jena, Dept Urol, D-07740 Jena, Germany. Univ Jena, Inst Clin Immunol, D-07740 Jena, Germany. NCI, NIH, Frederick, MD 21701 USA. RP Steiner, T (reprint author), Univ Jena, Dept Urol, D-07740 Jena, Germany. NR 25 TC 25 Z9 28 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD APR PY 2001 VL 39 IS 4 BP 478 EP 483 DI 10.1159/000052489 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 422MF UT WOS:000168121600023 PM 11306890 ER PT J AU Caplan, LJ Schooler, C AF Caplan, LJ Schooler, C TI Age effects on analogy-based memory for text SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID MODELS; COMPLEXITY; DOMAIN AB We examined age influences on analogy-based learning, in particular, analogy-based text memory. Adults (20-72 years) read pairs of passages describing analogous topics. We manipulated encoding complexity for the first passage and superficial topic similarity between passages, and assessed second-passage memory. Across all age groups, memory was better in the superficially similar topic condition only when encoding complexity had been simple. More critically, performance was better for similar topics only for the youngest adults. Younger adults performed worse than older adults in the dissimilar condition. Thus, only older adults identified and used the parallels between passages spontaneously. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. RP Caplan, LJ (reprint author), NIMH, Sect Socioenvironm Studies, 7550 Wisconsin Ave,MSC 9005, Bethesda, MD 20892 USA. NR 15 TC 4 Z9 4 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD APR-JUN PY 2001 VL 27 IS 2 BP 151 EP 165 DI 10.1080/036107301750074015 PG 15 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 412LU UT WOS:000167557200003 PM 11330211 ER PT J AU Lin, L Wang, Y Bergman, G Kelloff, GJ Lubet, RA You, M AF Lin, L Wang, Y Bergman, G Kelloff, GJ Lubet, RA You, M TI Detection of differentially expressed genes in mouse lung adenocarcinomas SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 3rd International Mouse Lung Tumorigenesis Symposium CY JUN 16-17, 2000 CL MED COLL OHIO, TOLEDO, OHIO SP Ohio State Univ, NCI, Natl Inst Environm Hlth Sci, Proctor & Gamble, Novartis HO MED COLL OHIO DE differential expression; gene expression; lung tumors; mouse ID CARBONIC-ANHYDRASE-IV; HUMAN COLORECTAL-CANCER; TUMOR-SUPPRESSOR GENE; NUCLEOTIDE-SEQUENCE; CELLS; PROTEIN; CHROMOSOME; INDUCTION; RAT; INHIBITOR AB Increasing evidence suggests that altered gene expression is associated with the induction and maintenance of malignancy in various organs including mouse lung adenocarcinomas. A competitive cDNA library screening (CCLS) was wed to examine gene expression in 4-(methylnitrosamino)-1 (3-pyridyl)-1-butanone- induced lung adenocarcinomas from (C3H/HeJ x A/J])F-1 mice. Comparisons of RNA expression in lung adenocarcinomas to those of normal surrounding lung tissue revealed altered expression in 220 clones from more than 50,000 clones screened. Fifty clones were selected for quantitative reverse transcriptase-polymerase chain reaction (PCR) analysis to verify altered expression. PCR primers were designed based on partial sequence analysis of the clones. Twenty-two clones were found to be differentially expressed in lung adenocarcinomas compared with normal lungs. GenBank database analysis showed that 14 of the 22 clones were homologous with known genes, whereas 8 clones contained novel sequences. Thirteen clones were down regulated In tumors compared to normal lung tissues, and 9 were overexpressed. The clones underexpressed or absent include adipocyte p27, carbonic anhydrase III, carbonyl reductase, cytochrome CYP2E1, skelemin, myosin, major urinary protein, and contrapsin. Overexpressed clones include Bruton's tyrosin kinase, cyclin D3, poly(A)-binding protein, alpha-fetoprotein, transferrin, and mouse B2 family repetitive sequence. Further examination of biologic implications of the differentially expressed genes in lung adenocarcinomas is necessary to understand their role(s) in mouse lung carcinogenesis. C1 Ohio State Univ, James Canc Ctr, Med Res Facil 514, Columbus, OH 43210 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. RP You, M (reprint author), Ohio State Univ, James Canc Ctr, Med Res Facil 514, 420 W 12th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [CA58554, CN75011, CA78797] NR 43 TC 13 Z9 16 U1 1 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD APR-MAY PY 2001 VL 27 IS 3 BP 217 EP 229 DI 10.1080/019021401300053966 PG 13 WC Respiratory System SC Respiratory System GA 414JV UT WOS:000167664000004 PM 11293325 ER PT J AU McDoniels-Silvers, AL Herzog, CR Tyson, FL Malkinson, AM You, M AF McDoniels-Silvers, AL Herzog, CR Tyson, FL Malkinson, AM You, M TI Inactivation of both Rb and p53 pathways in mouse lung epithelial cell lines SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 3rd International Mouse Lung Tumorigenesis Symposium CY JUN 16-17, 2000 CL MED COLL OHIO, TOLEDO, OHIO SP Ohio State Univ, NCI, Natl Inst Environm Hlth Sci, Proctor & Gamble, Novartis HO MED COLL OHIO DE cell cycle regulation; cell lines; lung tumor; mouse ID TUMOR-SUPPRESSOR GENE; HUMAN BREAST-CARCINOMA; RETINOBLASTOMA PROTEIN; HUMAN CANCER; DNA-DAMAGE; MOLECULAR PATHOGENESIS; SOMATIC MUTATIONS; INDUCED APOPTOSIS; BETA-TRANSCRIPT; MDM-2 ONCOGENE AB Aberrant expression of key cell cycle regulatory genes is essential for the immortalization and transformation of cells in vitro. We examined 20 mouse lung epithelial cell lines (2 nontumorigenic, 5 nonmetastatic, and 13 metastatic)for mutations or alterations in the expression of key components Of the Rb pathway (pRb and p(16INK4a) ) and the p53 Pathway (p53 and p19(ARF) ). Seven cell lines had a mutation in exons 5 to 8 of p53. P19(ARF) was inactivated in the remaining 13 cell lines, primarily by homozygous deletion. Rb expression was present and unaltered in all cell lines, with both phosphorylated and unphosphorylated protein forms detectable. p16(INK4a) transcripts were undetectable in all cell lines tested except LM1. Loss of p16(INK4a) expression was a result of homozygous deletion in II out of 20 lung cell lines and promoter-exon 1 hypermethylation in 6 out of the remaining 8 cell lines. Other related components that were examined in this study Included p21 WAF1 and cyclin D1. Compared to normal lung tissue, P21WAF1 expression levels were reduced or undetectable in all cell lines, which did not correlate with loss of p53 function, but did correlate with inactivation of either p53 or p19(ARF). Although cyclin D1 expression was variable between cell lines, transcript levels were decreased by at least 50% in the nontumorigenic lines C10 and E10 compared to the tumorigenic cell lines. These results demonstrate mutually exclusive 1 relationships between p53 and p19(ARF) and between Rt, and p16(INK4a), but perhaps not between cyclin DI and p16(INK4a), and further describe the nature of involvement of both pathways in mouse lung tumorigenesis. C1 Ohio State Univ, James Canc Ctr, Med Res Facil 646, Columbus, OH 43210 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO USA. NIEHS, Res Triangle Pk, NC 27709 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. RP You, M (reprint author), Ohio State Univ, James Canc Ctr, Med Res Facil 646, 420 W 12th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [CA58554, CA78797] NR 85 TC 17 Z9 17 U1 0 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD APR-MAY PY 2001 VL 27 IS 3 BP 297 EP 318 DI 10.1080/019021401300054064 PG 22 WC Respiratory System SC Respiratory System GA 414JV UT WOS:000167664000009 PM 11293330 ER PT J AU Cheng, CM Cohen, M Wang, J Bondy, CA AF Cheng, CM Cohen, M Wang, J Bondy, CA TI Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex SO FASEB JOURNAL LA English DT Article DE estradiol; menopause; hormone replacement therapy; Alzheimer's disease; neurodegeneration ID GROWTH-FACTOR-I; BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; POSITRON-EMISSION TOMOGRAPHY; GENE-EXPRESSION; ALZHEIMERS-DISEASE; RAT-BRAIN; MESSENGER-RNA; FACTOR RECEPTOR; SPINE DENSITY AB Estrogen has many positive effects on neural tissue in experimental model systems, including stimulation of neurite growth and neurotransmitter synthesis and protection against diverse types of neural injury. In humans, estrogen treatment is reputed to protect against Alzheimer's disease. To investigate potential mediators of estrogen's action and determine whether selective estrogen receptor modulators (SERMs) such as tamoxifen have estrogen-like effects in the primate brain, we evaluated the expression of glucose transporters and insulin-like growth factor 1 (IGF1) and its receptor in the frontal cortex of ovariectomized rhesus monkeys. We treated one group for 3 days with vehicle, another with 17 beta estradiol (E2), and a third with tamoxifen. The expression of facilitative glucose transporters (Gluts) 1, 3, and 4 was investigated using in situ hybridization, immunohistochemistry, and immunoblot analysis. Gluts 3 and 4 were concentrated in cortical neurons and Glut1 in capillaries and glial cells. E2 treatment induced two- to fourfold increases in Glut3 and Glut4 mRNA levels and lesser but significant increases in Glut3 and 4 protein levels. E2 treatment induced an similar to 70% increase in parenchymal Glut1 mRNA levels, but did not appreciably affect vascular Glut1 gene expression. IGF1 and IGF1 receptor mRNAs were concentrated in cortical neurons in a distribution similar to Gluts 3 and 4. IGF1 mRNA levels were significantly increased in E2-treated animals but IGF1 receptor mRNA levels were not altered by hormone treatment. Tamoxifen increased cerebral cortical Glut3 and 4 mRNA levels, but did not affect Glut1, IGF1, or IGF1 receptor expression. This study provides novel data showing that Gluts 3 and 4 and IGF1 are coexpressed by primate cerebral cortical neurons, where their expression is enhanced by estrogen. These findings suggest that up-regulation of glucose transporter and IGF1 expression may contribute to estrogen's salutary effects on neural tissue. Tamoxifen, an antiestrogen at the breast, is shown to have estrogen-like effects on higher brain centers in the monkey, suggesting that some SERMs may share estrogen's neuroprotective potential for menopausal women. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@exchange.nih.gov NR 70 TC 78 Z9 81 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2001 VL 15 IS 6 BP 907 EP 915 DI 10.1096/fj.00-0398com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 419QC UT WOS:000167959300004 PM 11292650 ER PT J AU Abdo, KM Cunningham, ML Snell, ML Herbert, RA Travlos, GS Eldridge, SR Bucher, JR AF Abdo, KM Cunningham, ML Snell, ML Herbert, RA Travlos, GS Eldridge, SR Bucher, JR TI 14-week toxicity and cell proliferation of methyleugenol administered by gavage to F344 rats and B6C3F1 mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE methyleugenol; cell proliferation; p-alkoxyallylbenzenes; essential oils ID ZERO DOSE CONTROL; HEPATOCELLULAR PROLIFERATION; HEPATOCARCINOGENICITY; CARCINOGENICITY; DERIVATIVES; METABOLISM; ALUMINUM; EUGENOL; LIVER AB Methyleugenol, a food flavor and fragrance agent, was rested for toxicity in male and female F344/N rats and B6C3F1 mice. Groups of 10 males and 10 females per sex per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14 weeks. Additional groups of rats and mice of each sex were dosed similarly and used for hematology and clinical chemistry studies. Groups of 10 male and 10 female rats and mice received the vehicle by gavage on the same dosing schedule and served as vehicle controls. For serum gastrin, gastric pH and cell proliferation studies groups of 10 female rats were given 0, 37, 75 or 150 mg/kg, once daily 5 days per week for 30 or 90 days or 300 or 1000 mg,kg for 30 days; male mice were given 0, 9, 18.5, 37, 75, 150 or 300 mg/kg for 30 or 90 days. For the gastrin, pH and cell proliferation studies, groups of 10 female rats and 10 male mice were given the vehicle for 30 or 90 days and served as controls. Methyleugenol administration to rats induced erythrocyte microcytosis and thrombocytosis in male and female rats. It also caused an increase in serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentration, suggesting hepatocellular injury, cholestasis or altered hepatic function. Additionally, methyleugenol induced hypoproteinemia and hypoalbuminemia, evidenced by decreased total protein and albumin concentrations in both male and female rats, suggesting in inefficiency of dietary protein utilization due to methyleugenol-induced toxic effects on the liver and glandular stomach of rats and mice. The increase in gastrin acid gastric pH of rats and mice given methyleugenol suggests that gastrin feedback was impaired and resulted in conditions not conducive to protein digestion, ln rats, methyleugenol caused an increase in the incidences of hepatocyte cytologic alteration, cytomegaly, Kupffer cell pigmentation, mixed foci of cellular alteration and bile duct hyperplasia of the liver and atrophy and chronic inflammation of the mucosa of the glandular stomach. In mice, it caused an increase in the incidence of cytologic alteration, necrosis, bile duct hyperplasia and subacute inflammation of the liver and atrophy, degeneration, necrosis, edema, mitotic alteration, and cystic glands of the fundic region of the glandular stomach. The increased incidences of adrenal gland cortical hypertrophy and/or cytoplasmic alteration in the submandibular salivary glands, adrenal glands, testis and uterus of rats were considered secondary to the chemical-related effects observed in the liver and glandular stomach. Based on mortality, body weight gain, clinical chemistry and gross and microscopic evaluation of tissues of rats and mice, the no-observed-effect level (NOEL) of methyleugenol for both species was estimated at 10 mg/kg. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Pathol Associates Int, Frederick, MD 21701 USA. RP Abdo, KM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 13 Z9 15 U1 1 U2 4 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 APR PY 2001 VL 39 IS 4 BP 303 EP 316 DI 10.1016/S0278-6915(00)00143-5 PG 14 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 426TR UT WOS:000168364900002 PM 11295478 ER PT J AU Wang, CG Fu, MF Mani, S Wadler, S Senderowicz, AM Pestell, RG AF Wang, CG Fu, MF Mani, S Wadler, S Senderowicz, AM Pestell, RG TI Histone acetylation and the cell-cycle in cancer SO FRONTIERS IN BIOSCIENCE LA English DT Review DE histone acetyltransferases; cyclin-pendent kinase (Cdk) inhibitors; flavopiridol; UCN-01; anticancer agents; review ID PROTEIN-KINASE-C; BREAST-CARCINOMA CELLS; MITOTIC CHROMOSOME CONDENSATION; HUMAN EPIDERMOID CARCINOMA; ELEMENT-BINDING PROTEIN; ACUTE MYELOID-LEUKEMIA; DEPENDENT KINASES; ESTROGEN-RECEPTOR; IN-VIVO; TRANSCRIPTIONAL REPRESSION AB A number of distinct surveillance systems are found in mammalian cells that have the capacity to interrupt normal cell-cycle progression. These are referred to as cell cycle check points. Surveillance systems activated by DNA damage act at three stages, one at the G(1)/S phase boundary, one that monitors progression through S phase and one at the G(2)/M boundary. The initiation of DNA synthesis and irrevocable progression through G(1) phase represents an additional checkpoint when the cell commits to DNA synthesis. Transition through the cell cycle is regulated by a family of protein kinase holoenzymes, the cyclin-dependent kinases (Cdks), and their heterodimeric cyclin partner. Orderly progression through the cell-cycle checkpoints involves coordinated activation of the Cdks that, in the presence of an associated Cdk-activating kinase (CAK), phosphorylate target substrates including members of the "pocket protein" family. One of these, the product of the retinoblastoma susceptibility gene (the pRB protein), is phosphorylated sequentially by both cyclin D/Cdk4 complexes and cyclin E/Cdk2 kinases. Recent studies have identified important cross talk between the cell-cycle regulatory apparatus and proteins regulating histone acetylation. pRB binds both E2F proteins and histone deacetylase (HDAC) complexes. HDAC plays an important role in pRB tumor suppression function and transcriptional repression. Histones are required for accurate assembly of chromatin and the induction of histone gene expression is tightly coordinated. Recent studies have identified an important alternate substrate of cyclin E/Cdk2, NPAT (nuclear protein mapped to the ATM locus) which plays a critical role in promoting cell-cycle progression in the absence of pRB, and contributes to cell-cycle regulated histone gene expression. The acetylation of histones by a number of histone acetyl transferases (HATs) also plays an important role in coordinating gene expression and cell-cycle progression. Components of the cell-cycle regulatory apparatus are both regulated by HATs and bind directly to HATs. Finally transcription factors have been identified as substrate for HATs. Mutations of these transcription factors at their sites of acetylation has been associated with constitutive activity and enhanced cellular proliferation, suggesting an important role for acetylation in transcriptional repression as well as activation. Together these studies provide a working model in which the cell-cycle regulatory kinases phosphorylate and inactivate HDACs, coordinate histone gene expression and bind to histone acetylases themselves. The recent evidence for cross-talk between the cyclin-dependent kinases and histone gene expression on the one hand and cyclin-dependent regulation of histone acetylases on the other, suggests chemotherapeutics targeting histone acetylation may have complex and possibly complementary effects with agents targeting Cdks. C1 Albert Einstein Coll Med, Dept Dev & Mol Biol, Albert Einstein Comprehens Canc Ctr, Bronx, NY 10461 USA. Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Pestell, RG (reprint author), Albert Einstein Coll Med, Dept Dev & Mol Biol, Albert Einstein Comprehens Canc Ctr, Chanin 302,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [5-P30-CA13330-26, R01CA75503, R01CA70897] NR 214 TC 50 Z9 54 U1 3 U2 17 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 APR PY 2001 VL 6 BP D610 EP D629 DI 10.2741/1wang1 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 416LG UT WOS:000167781500004 PM 11282573 ER PT J AU Wheeler, MD Kono, H Yin, M Rusyn, I Froh, M Connor, HD Mason, RP Samulski, RJ Thurman, RG AF Wheeler, MD Kono, H Yin, M Rusyn, I Froh, M Connor, HD Mason, RP Samulski, RJ Thurman, RG TI Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats SO GASTROENTEROLOGY LA English DT Article ID NF-KAPPA-B; MITOCHONDRIAL GLUTATHIONE DEPLETION; CHRONIC ETHANOL-CONSUMPTION; FREE-RADICAL METABOLITE; NECROSIS-FACTOR-ALPHA; KUPFFER CELLS; LIPID-PEROXIDATION; DISEASE; INVIVO; MECHANISM AB Bachground & Aims: Alcohol-induced liver injury is associated with an increase in oxidants from a variety of possible sources. Therefore, it was hypothesized that increased and stable expression of the antioxidant enzyme Cu/Zn-superoxide dismutase (SOD1) would diminish oxygen free radicals and reduce alcohol-induced liver injury. Methods: To test this hypothesis, vats were given recombinant adenovirus containing Cu/Zn-superoxide dismutase (Ad,SOD1) or beta -galactosidase (Ad.lacZ) and fed ethanol enterally for 3 weeks. Results: SOD was increased significantly 3-5-fold over endogenous levels in both hepatocytes as well as Kupffer cells 3 weeks after infection. Serum transaminase levels and pathology weve elevated significantly in Ad.lacZ-treated animals by using an intragastric feeding model. This effect was blunted significantly in Ad,SOD1-infected animals. Importantly, electron spin resonance-detectable free-radical adducts caused by ethanol were also decreased by SOD1 overexpression. Moreover, the increase in nuclear factor kappaB (NF kappaB), tumor necrosis factor alpha (TNF-alpha), and interleukin 1 messenger RNA (mRNA) caused by ethanol was blunted in animals treated with Ad,SOD1. Conclusions: These data support the hypothesis that oxidant production is critical in early alcohol-induced liver injury and that gene delivery of antioxidant enzymes may be useful in prevention and treatment. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Wheeler, MD (reprint author), CB 7365 Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. RI Rusyn, Ivan/S-2426-2016 NR 57 TC 88 Z9 92 U1 1 U2 6 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 APR PY 2001 VL 120 IS 5 BP 1241 EP 1250 DI 10.1053/gast.2001.23253 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 415GW UT WOS:000167713700021 PM 11266387 ER PT J AU Abou-Saif, A Lei, JY McDonald, TJ Chakrabarti, S Waxman, IF Shojamanesh, H Schrump, DS Kleiner, DE Gibril, F Jensen, RT AF Abou-Saif, A Lei, JY McDonald, TJ Chakrabarti, S Waxman, IF Shojamanesh, H Schrump, DS Kleiner, DE Gibril, F Jensen, RT TI A new cause of Zollinger-Ellison syndrome: Non-small cell lung cancer SO GASTROENTEROLOGY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ECTOPIC HORMONE PRODUCTION; ULTRASTRUCTURAL ANALYSIS; USEFUL MARKER; LONG-TERM; CARCINOMA; ULCER; DEATH; SURVIVAL AB Numerous epidemiologic studies suggest a relationship between lung cancer and peptic ulcer disease. Furthermore, various lung cancers synthesize and release a number of peptides such as gastrin and gastrin-releasing peptide that could cause acid hypersecretion; however, Zollinger-Ellison syndrome (ZES), because of a lung tumor, has never been described. We report such a patient for the first time. A 60-year-old man with a non-small cell lung carcinoma (large cell type) presented with diarrhea, heartburn, abdominal pain, and duodenal ulcers, Evaluation showed ZES was present (fasting hypergastrinemia, hyperchlorhydria) and control of all symptoms by omeprazole. No abdominal or cardiac tumor, the other known locations of gastrinomas causing ZES, was found on detailed tumor imaging studies. Resection of the lung tumor resulted in a decrease in gastrin levels to normal values, Plasma radioimmunoassays showed elevated gastrin, chromogranin A and normal levels of gastrin-releasing peptide, and 9 other hormones. The tumor showed similar immunocytochemical results. The characteristics of this case are compared with 100 cases of sporadic abdominal gastrinomas, and the evidence reviewed suggests why ZES should be considered in patients with lung cancer with peptic symptoms. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Pathol, London, ON, Canada. Univ Western Ontario, Dept Med, London, ON, Canada. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 74 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 BP 1271 EP 1278 DI 10.1053/gast.2001.23242 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 415GW UT WOS:000167713700024 PM 11266390 ER PT J AU Abou-Saif, A Shojamanesh, H Bashir, S Ojeaburu, J Gibril, F Jensen, RT AF Abou-Saif, A Shojamanesh, H Bashir, S Ojeaburu, J Gibril, F Jensen, RT TI Prospective study of efficacy of interferon-2 alpha (INF-2 alpha) in metastatic gastrinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3111 BP A613 EP A613 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703041 ER PT J AU Ahlquist, DA Thibodeau, SN Levin, B Jen, J Devens, ME Harrington, JJ Cunningham, JM Laken, SJ Shuber, AP AF Ahlquist, DA Thibodeau, SN Levin, B Jen, J Devens, ME Harrington, JJ Cunningham, JM Laken, SJ Shuber, AP TI Stool Bat-26 testing as adjunct to screening sigmoidoscopy: A feasibility analysis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, NIH, Bethesda, MD 20892 USA. EXACT Sci Corp, Maynard, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3041 BP A599 EP A599 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702971 ER PT J AU Anderson, JD Fleming, SD Basta, M Tsokos, G Shea-Donohue, T AF Anderson, JD Fleming, SD Basta, M Tsokos, G Shea-Donohue, T TI Intravenous immunoglobulin attenuates mesenteric ischemia/reperfusion injury in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. WRAIR, Silver Spring, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1024 BP A195 EP A195 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700962 ER PT J AU Araghi-Niknam, M Lee, HC Arthur, DC Krueger, L Ferrin, LJ AF Araghi-Niknam, M Lee, HC Arthur, DC Krueger, L Ferrin, LJ TI Oncogene amplification occurs via a small number of discrete steps in gastric adenocarcinoma cell lines SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1525 BP A295 EP A295 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701461 ER PT J AU Banumathy, C Tang, Y Mishra, B Mishra, L AF Banumathy, C Tang, Y Mishra, B Mishra, L TI Itih-4, a serine protease inhibitor plays a prominent functional role in IL-6 induced hepatocyte formation SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Fels Inst, Philadelphia, PA 19122 USA. NIH, NHGRI, CGTB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 143 BP A27 EP A28 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700134 ER PT J AU Cobb, S Given, R Velasco, M Wood, T Tessarollo, L Varro, A Singh, P AF Cobb, S Given, R Velasco, M Wood, T Tessarollo, L Varro, A Singh, P TI Loss of functional gastrin gene results in significantly increasing the incidence of pre-neoplastic and neoplastic changes in the colonic mucosa of mice in response to azoxymethane (AOM). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Natl Canc Inst, Bethesda, MD USA. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 869 BP A164 EP A164 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700807 ER PT J AU Cochrane, SW Gibson, MS Myers, DA Schulkin, J Rice, KC Gold, PW Greenwood-Van Meerveld, B AF Cochrane, SW Gibson, MS Myers, DA Schulkin, J Rice, KC Gold, PW Greenwood-Van Meerveld, B TI Role of corticotropin-releasing factor-1 (CRF1)-receptor mediated mechanisms in neural pathways modulating colonic hypersensitivity SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Oklahoma Fdn Digest Res, Basic Sci Lab, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA. Georgetown Univ, Washington, DC USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 30 BP A7 EP A7 DI 10.1016/S0016-5085(08)80032-7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700031 ER PT J AU El-Omar, EM Chow, WH Gammon, MD Vaughan, TL Risch, HA Fraumeni, JF AF El-Omar, EM Chow, WH Gammon, MD Vaughan, TL Risch, HA Fraumeni, JF TI Pro-inflammatory genotypes of IL-1 beta, TNF-alpha and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinomas SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Aberdeen, Aberdeen, Scotland. NCI, Bethesda, MD 20892 USA. Columbia Univ, Sch Publ Hlth, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. Yale Univ, New Haven, CT USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 459 BP A86 EP A86 DI 10.1016/S0016-5085(08)80425-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700424 ER PT J AU El-Omar, EM You, WC Chow, WH Fraumeni, JF Rabkin, CS AF El-Omar, EM You, WC Chow, WH Fraumeni, JF Rabkin, CS TI IL-1beta and IL-10 genotypes in a high gastric cancer risk province in China SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Aberdeen, Aberdeen, Scotland. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3994 BP A743 EP A743 DI 10.1016/S0016-5085(08)83701-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703695 ER PT J AU El-Serag, HB Everhart, JE Richardson, PA AF El-Serag, HB Everhart, JE Richardson, PA TI Risk factors for hepatocellular carcinoma: A case control study among US veterans. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1191 BP A227 EP A227 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701127 ER PT J AU Fan, XF Detre, KM Belle, SH Wei, YL Wiesner, RH Charlton, MR Schafer, D Zetterman, RK Lake, JR Hoofnagle, JH Everhart, JE Di Bisceglie, AM AF Fan, XF Detre, KM Belle, SH Wei, YL Wiesner, RH Charlton, MR Schafer, D Zetterman, RK Lake, JR Hoofnagle, JH Everhart, JE Di Bisceglie, AM TI Competition and selection among different HCV strains SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 St Louis Univ, Sch Med, St Louis, MO USA. Univ Pittsburgh, Pittsburgh, PA USA. Mayo Clin, Rochester, MN USA. Univ Nebraska, Omaha, NE 68182 USA. NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2804 BP A551 EP A551 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702736 ER PT J AU Franchimont, D Galon, J Vacchio, M Visconti, R Chrousos, G Ashwell, J O'Shea, J AF Franchimont, D Galon, J Vacchio, M Visconti, R Chrousos, G Ashwell, J O'Shea, J TI Positive effects of glucocorticoids on T cell function and development by upregulation of interleukin-7 receptor alpha. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Erasme Univ Hosp, B-1070 Brussels, Belgium. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1623 BP A314 EP A315 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701559 ER PT J AU Ghany, MG Alter, H Boone, MH Doo, E Khokar, F Heller, T Park, Y Liang, TJ Hoofnagle, JH AF Ghany, MG Alter, H Boone, MH Doo, E Khokar, F Heller, T Park, Y Liang, TJ Hoofnagle, JH TI False positive results using commercial RT-PCR for hepatitis C virus (HCV) RNA: Frequency and impact on clinical management. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1892 BP A368 EP A368 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701827 ER PT J AU Gibril, F Abou-Saif, A Shojamanesh, H Bashir, S Ojeaburu, J Jensen, RT AF Gibril, F Abou-Saif, A Shojamanesh, H Bashir, S Ojeaburu, J Jensen, RT TI Long-term continuous use of omeprazole in patients with sporadic Zollinger-Ellison Syndrome (ZES): A prospective 17-year study of efficacy and safety. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1252 BP A240 EP A240 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701188 ER PT J AU Gonsky, R Deem, RL Young, HA Targan, SR AF Gonsky, R Deem, RL Young, HA Targan, SR TI Dampened SOCS: An altered balance between STAT activating and SOCS inhibitory signals regulate interferon-gamma expression in LPMC SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 192 BP A38 EP A38 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700183 ER PT J AU Igarashi, H Ito, T Hou, W Pradhan, TK Mantey, SA Coy, DH Jensen, RT AF Igarashi, H Ito, T Hou, W Pradhan, TK Mantey, SA Coy, DH Jensen, RT TI Structural determinants of high affinity VIP2-R (VPAC2) interaction and identification of a simplified high affinity agonist. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1738 BP A337 EP A337 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701674 ER PT J AU Igarashi, H Hou, W Ito, T Pradhan, TK Mantey, SA Coy, DH Jensen, RT AF Igarashi, H Hou, W Ito, T Pradhan, TK Mantey, SA Coy, DH Jensen, RT TI Effect of the carboxyl terminus of the human VIP2 receptor (VPAC2) on receptor affinity, adenylate cyclase activation and receptor internalization. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1600 BP A310 EP A310 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701536 ER PT J AU Iwamoto, M Giardiello, FM Boland, R Romans, K Chauhan, DP Ahnen, DJ AF Iwamoto, M Giardiello, FM Boland, R Romans, K Chauhan, DP Ahnen, DJ TI APC and beta-catenin protein expression in adenomas of patients with familial polyposis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1522 BP A294 EP A294 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701458 ER PT J AU Iwamoto, M Peghini, PL Goebel, SU Serrano, J Jensen, RT AF Iwamoto, M Peghini, PL Goebel, SU Serrano, J Jensen, RT TI Epidermal growth factor receptor (EGFR) is overexpressed in a subset of gastrinomas and correlates with advanced disease SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 4090 BP A762 EP A762 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703791 ER PT J AU Jacoby, RF Cole, CE Lubet, RA You, M AF Jacoby, RF Cole, CE Lubet, RA You, M TI Effects of the nonspecific COX1 and COX2 inhibitor piroxicam and the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) on development of intestinal tumors in mice bearing germline alterations in the MSH2 or APC genes. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI USA. NCI, Chemoprevent Branch, DCP, Bethesda, MD 20892 USA. Med Coll Ohio, Toledo, OH 43699 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 649 BP A121 EP A121 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700593 ER PT J AU Karban, AS Panhuysen, CIM Bailey-Wilson, JE Friedman, Y Ravenhill, G Cho, JH Duerr, RH Bayless, TM Epstein, EH Brant, SR AF Karban, AS Panhuysen, CIM Bailey-Wilson, JE Friedman, Y Ravenhill, G Cho, JH Duerr, RH Bayless, TM Epstein, EH Brant, SR TI A genome wide screen in an unusually large inflammatory bowel disease pedigree: Suggestive evidence for linkage on chromosomes 18p, 7p and 15q; No evidence for IBD1 or IBD2 loci SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Boston Univ, Boston, MA 02215 USA. NIH, NHGRI, Baltimore, MD USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 188 BP A37 EP A37 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700179 ER PT J AU Kullberg, MC Jankovic, D Caspar, P Gorelick, PL Cheever, A Sher, A AF Kullberg, MC Jankovic, D Caspar, P Gorelick, PL Cheever, A Sher, A TI Bacteria-specific CD4(+) T-cell clones induce colitis in Helicobacter hepaticus-infected T-cell-deficient RAG-2 KO mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, NIAID, LPD, Immunobiol Sect, Bethesda, MD USA. NCI, SAIC, Anim Hlth Diagnost Lab, Frederick, MD 21701 USA. Biomed Res Inst, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2643 BP A519 EP A520 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702575 ER PT J AU Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL Farrow, D West, AB Rotterdam, H Blot, WJ Fraumeni, JF AF Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL Farrow, D West, AB Rotterdam, H Blot, WJ Fraumeni, JF TI Epidemiological study of risk factors for gastric carcinoids SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Yale Univ, New Haven, CT 06520 USA. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. NYU Med Ctr, New York, NY 10016 USA. Columbia Univ, New York, NY USA. Inst Int Epidemiol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1326 BP A256 EP A256 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701262 ER PT J AU Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL West, AB Rotterdam, H Blot, WJ Blaser, MJ Fraumeni, JF AF Lew, EA Risch, HA Chow, WH Gammon, MD Vaughan, TL Schoenberg, JB Stanford, JL West, AB Rotterdam, H Blot, WJ Blaser, MJ Fraumeni, JF TI Helicobacter pylori, gastroesophageal reflux, their interrelationships, and the risk of esophageal adenocarcinoma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Yale Univ, New Haven, CT 06520 USA. Natl Canc Inst, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. NYU Med Ctr, New York, NY 10016 USA. Columbia Univ, New York, NY USA. Int Epidemiol Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 159 BP A31 EP A31 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700150 ER PT J AU Lichtenberger, LM Darling, R Romero, JJ Langenbach, R AF Lichtenberger, LM Darling, R Romero, JJ Langenbach, R TI Effect of luminal damaging agents on the gastric mucosal barrier and prostaglandin (PG) metabolism in cyclooxygenase (COX) knockout (KO) mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Texas, Sch Med, Houston, TX USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 763 BP A143 EP A143 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700701 ER PT J AU Ojeaburu, J Bashir, S Shojamanesh, H Abou-Saif, A Gibril, F Jensen, R AF Ojeaburu, J Bashir, S Shojamanesh, H Abou-Saif, A Gibril, F Jensen, R TI Occurrence of prolonged extreme acid hypersecretion post-curative gastrinoma resection: Prospective study SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, DDB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 825 BP A155 EP A155 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700763 ER PT J AU Pisegna, JR Kresse, H Cole, M Lyu, RM Germano, PM Tache, Y Wank, SA AF Pisegna, JR Kresse, H Cole, M Lyu, RM Germano, PM Tache, Y Wank, SA TI Cloning and characterization of the rat calcitonin gene related peptide (rCGRP). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA GLAHS, Los Angeles, CA USA. Univ Calif Los Angeles, Digest Dis Res Ctr, CURE, Los Angeles, CA USA. NIDDK, Digest Dis Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2598 BP A511 EP A511 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702530 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Association of leptin concentration and central adiposity with gallbladder disease SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Social & Sci Syst Inc, Bethesda, MD USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 217 BP A43 EP A43 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700208 ER PT J AU Sass, DA Schoen, RE Weissfeld, JL Kuller, LH Thaete, FL McAdams, M Lanza, E Schatzkin, A AF Sass, DA Schoen, RE Weissfeld, JL Kuller, LH Thaete, FL McAdams, M Lanza, E Schatzkin, A TI Lack of association between colorectal adenoma recurrence and visceral adipose tissue SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. IMS, Bethesda, MD USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 1317 BP A254 EP A254 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514701253 ER PT J AU Servoss, JC Sherman, KE Robbins, G Liou, SH Reisler, R Polsky, B Murphy, R Theodore, D Miskovsky, E Peters, MG Chung, RT AF Servoss, JC Sherman, KE Robbins, G Liou, SH Reisler, R Polsky, B Murphy, R Theodore, D Miskovsky, E Peters, MG Chung, RT TI Hepatotoxicity in the US adult AIDS clinical trial group SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. St Lukes Hosp, New York, NY USA. Northwestern Univ, Chicago, IL 60611 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Texas, Galveston, TX 77555 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 283 BP A54 EP A54 DI 10.1016/S0016-5085(08)80265-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700264 ER PT J AU Shanks, RA Stewart, DM Navarre, J Nelson, DL Tian, L Lapierre, LA Goldenring, JR AF Shanks, RA Stewart, DM Navarre, J Nelson, DL Tian, L Lapierre, LA Goldenring, JR TI AKAP350A binds to CIP4 and is localized to the golgi apparatus in colonic epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Med Coll Georgia, Augusta, GA 30912 USA. VAMC, Augusta, GA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3765 BP A698 EP A698 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514703467 ER PT J AU Shibata, M Hiroishi, K Ito, T Wang, RYH Yoshita, M Shih, JWK Alter, HJ Mitamura, K AF Shibata, M Hiroishi, K Ito, T Wang, RYH Yoshita, M Shih, JWK Alter, HJ Mitamura, K TI Presence of a novel SEN-virus in patients with liver diseases and blood donors in Japan. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Showa Univ, Sch Med, Tokyo, Japan. NIH, Bethesda, MD 20892 USA. Showa Univ, Fujigaoka Hosp, Kanagawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2825 BP A556 EP A556 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702757 ER PT J AU Shojamanesh, H Louie, A Ojeaburu, J Bashir, S Abou-Saif, A Gibril, F Jensen, RT AF Shojamanesh, H Louie, A Ojeaburu, J Bashir, S Abou-Saif, A Gibril, F Jensen, RT TI Prospective study of the efficacy of octreotide in patients with metastatic gastrinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 507 BP A95 EP A95 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514700467 ER PT J AU Summers, RM Jerebko, AK Franaszek, M Malley, JD Johnson, CD AF Summers, RM Jerebko, AK Franaszek, M Malley, JD Johnson, CD TI Complementary role of computer-aided diagnosis for detecting colonic polyps with CT colonography SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 3049 BP A600 EP A601 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702979 ER PT J AU Tang, Y Danovitch, S Fleury, T Mishra, B Deng, CX Mishra, L AF Tang, Y Danovitch, S Fleury, T Mishra, B Deng, CX Mishra, L TI Defects in TGF beta signaling by Smad 4 and ELF spectrins are associated with gastric carcinogenesis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Fels Inst, Philadelphia, PA 19122 USA. George Washington Univ, Washington, DC USA. Sibley Hosp, Washington, DC USA. NHGRI, CGTB, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2001 VL 120 IS 5 SU 1 MA 2519 BP A495 EP A495 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 429KA UT WOS:000168514702452 ER EF