FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Melamed, J Datta, MW Becich, MJ Orenstein, JM Dhir, R Silver, S Fidelia-Lambert, M Kadjacsy-Balla, A Macias, V Patel, A Walden, PD Bosland, MC Berman, JJ AF Melamed, J Datta, MW Becich, MJ Orenstein, JM Dhir, R Silver, S Fidelia-Lambert, M Kadjacsy-Balla, A Macias, V Patel, A Walden, PD Bosland, MC Berman, JJ CA Cooperative Prostate Canc Tissue R TI The Cooperative Prostate Cancer Tissue Resource: A specimen and data resource for cancer researchers SO CLINICAL CANCER RESEARCH LA English DT Article ID RADICAL PROSTATECTOMY; CARCINOMA; SURVIVAL; RATES; PSA AB Purpose: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a National Cancer Institute-supported tissue bank that provides large numbers of clinically annotated prostate cancer specimens to investigators. This communication describes the CPCTR to investigators interested in obtaining prostate cancer tissue samples. Experimental Design: The CPCTR, through its four participating institutions, has collected specimens and clinical data for prostate cancer cases diagnosed from 1989 onward. These specimens include paraffin blocks and frozen tissue from radical prostatectomy specimens and paraffin blocks from prostate needle biopsies. Standardized histopathological characterization and clinical data extraction are performed for all cases. Information on histopathology, demography (including ethnicity), laboratory data (prostate-specific antigen values), and clinical outcome related to prostate cancer are entered into the CPCTR database for all cases. Materials in the CPCTR are available in multiple tissue formats, including tissue microarray sections, paraffin-embedded tissue sections, serum, and frozen tissue specimens. These are available for research purposes following an application process that is described on the CPCTR web site (www.prostatetissues.org). Results: The CPCTR currently (as of October 2003) contains 5135 prostate cancer cases including 4723 radical prostatectomy cases. Frozen tissues, in some instances including patient serum samples, are available for 1226 cases. Biochemical recurrence data allow identification of cases with residual disease, cases with recurrence, and recurrence-free cases. Conclusions: The CPCTR offers large numbers of highly characterized prostate cancer tissue specimens, including tissue microarrays, with associated clinical data for biomarker studies. Interested investigators are encouraged to apply for use of this material (www.prostatetissues.org). C1 NYU, Med Ctr, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Dept Biochem, Sch Med, New York, NY 10016 USA. NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. NYU, Dept Urol, Sch Med, New York, NY 10016 USA. Med Coll Wisconsin, Dept Pathol, Coll Med, Milwaukee, WI 53226 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. George Washington Univ, Dept Pathol, Washington, DC USA. Howard Univ, Dept Pathol, Washington, DC 20059 USA. Univ Illinois, Dept Pathol, Chicago, IL USA. Natl Canc Inst, Bethesda, MD USA. RP Melamed, J (reprint author), NYU, Med Ctr, Sch Med, Dept Pathol, TH-461,560 1st Ave, New York, NY 10016 USA. OI Melamed, Jonathan/0000-0003-2844-7990 FU NCI NIH HHS [U01-CA86739, U01 CA086772, U01-CA86735, U01-CA86743, U01-CA86772] NR 21 TC 31 Z9 33 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2004 VL 10 IS 14 BP 4614 EP 4621 DI 10.1158/1078-0432.CCR-04-0240 PG 8 WC Oncology SC Oncology GA 840ET UT WOS:000222840700004 PM 15269132 ER PT J AU Parkhurst, MR Riley, JP Igarashi, T Li, Y Robbins, PF Rosenberg, SA AF Parkhurst, MR Riley, JP Igarashi, T Li, Y Robbins, PF Rosenberg, SA TI Immunization of patients with the hTERT : 540-548 peptide induces peptide-reactive T lymphocytes that do not recognize tumors endogenously expressing telomerase SO CLINICAL CANCER RESEARCH LA English DT Article ID MELANOMA ANTIGEN TYROSINASE; CATALYTIC SUBUNIT; HUMAN-CELLS; CELLULAR-IMMUNITY; HUMAN CANCER; EPITOPE; IDENTIFICATION; INHIBITION; CD8(+); CLONES AB Purpose: Telomerase is an attractive target antigen for cancer immunotherapies because it is expressed in >85% of human tumors but is rarely found in normal tissues. A HLA-A*0201-restricted T-cell epitope was previously identified within telomerase reverse transcriptase hTERT:540-548. This peptide was reported to induce CTL that recognized tumor cells and transfectants that endogenously expressed telomerase. Therefore, we initiated a clinical protocol to evaluate the therapeutic and immunological efficacy of this peptide. Experimental Design: Fourteen patients with metastatic cancers were vaccinated with hTERT:540-548 emulsified in incomplete Freund's adjuvant. Results: In 7 patients, peripheral blood mononuclear cells collected after immunization recognized hTERT:540548, whereas those collected before vaccination did not. However, none of these CTLs recognized tumors that endogenously expressed telomerase, and none of the patients had an objective clinical response. Several highly avid T-cell clones were generated that recognized T2 cells pulsed with less than or equal to1 nm hTERT:540-548, but none of these recognized HLA-A*0201(+) hTERT(+) tumors or cells transduced with the human telomerase reverse transcriptase (hTERT) gene. Also, an antibody specific for hTERT:540-548/HLA-A*0201 complexes stained peptide-pulsed cells but not telomerase(+) tumors. Conclusions: Our results are discordant with previous studies and those of a clinical trial that claimed peripheral blood mononuclear cells from patients vaccinated with peptide-pulsed dendritic cells lysed hTERT(+) tumors. However, our findings are consistent with a previous study that demonstrated that the hTERT:540-548 peptide is cleaved in the proteasome. These results suggest that hTERT:540-548 is not presented on the surfaces of tumor cells in the context of HLA-A*0201 and will not be useful for the immunotherapy of patients with cancer. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Parkhurst, MR (reprint author), NCI, NIH, Surg Branch, Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Maria_Parkhurst@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 29 TC 83 Z9 93 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2004 VL 10 IS 14 BP 4688 EP 4698 DI 10.1158/1078-0432.CCR-04-0325 PG 11 WC Oncology SC Oncology GA 840ET UT WOS:000222840700012 PM 15269141 ER PT J AU Bates, SE Bakke, S Kang, M Robey, RW Zhai, SP Thambi, P Chen, C Patil, S Smith, T Steinberg, SM Merino, M Goldspiel, B Meadows, B Stein, WD Choyke, P Balis, F Figg, WD Fojo, T AF Bates, SE Bakke, S Kang, M Robey, RW Zhai, SP Thambi, P Chen, C Patil, S Smith, T Steinberg, SM Merino, M Goldspiel, B Meadows, B Stein, WD Choyke, P Balis, F Figg, WD Fojo, T TI A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIDRUG-RESISTANCE MODULATOR; HUMAN CYTOCHROME-P450 3A; ACUTE MYELOID-LEUKEMIA; SDZ PSC 833; IN-VIVO; DRUG-INTERACTIONS; TC-99M SESTAMIBI; CANCER PATIENTS; COMBINATION; INHIBITOR AB Purpose: P-glycoprotein (Pgp) inhibitors have been under clinical evaluation for drug resistance reversal for over a decade. Valspodar (PSC 833) inhibits Pgp-mediated efflux but delays drug clearance, requiring reduction of anticancer drug dosage. We designed an infusional schedule for valspodar and vinblastine to mimic infusional vinblastine alone. The study was designed to determine the maximally tolerated dose of vinblastine, while attempting to understand the pharmacokinetic interactions between vinblastine and valspodar and to determine the response rate in patients with metastatic renal cell cancer. Patients and Methods: Thirty-nine patients received continuous infusion valspodar and vinblastine. Vinblastine was administered for 3 days to compensate for the expected delay in clearance and the required dose reduction. Valspodar was administered initially at a dose of 10 mg/kg/d; the dose of vinblastine varied. Results: The maximum-tolerated dose of vinblastine was 1.3 mg/m(2)/d. As suggested previously, serum valspodar concentrations exceeded those needed for Pgp inhibition. Consequently, the dose of valspodar was reduced to 5 mg/kg, allowing a vinblastine dose of 2.1 mg/m(2)/d to be administered. Pharmacodynamic studies demonstrated continued inhibition of Pgp at lower valspodar doses by functional assay in Pgp-expressing CD56+ cells and by Tc-99m-sesta-mibi imaging. A 15-fold range in cytochrome P450 activity was observed, as measured by midazolam clearance. No major responses were observed. Conclusions: These results suggest that the pharmacokinetic impact of cytochrome P450 inhibition by valspodar can be reduced although not eliminated, while preserving Pgp inhibition, thus separating the pharmacokinetic and pharmacodynamic activities of valspodar. C1 Natl Canc Inst, Canc Res Ctr, Canc Therapeut Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Canc Res Ctr, Biostat Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Canc Res Ctr, Pathol Lab, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Clin Ctr Pharm, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Novartis Pharmaceut, E Hanover, NJ USA. Hebrew Univ Jerusalem, Jerusalem, Israel. RP Bates, SE (reprint author), Natl Canc Inst, Canc Res Ctr, Canc Therapeut Branch, Bldg 10,Room 12C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 41 TC 59 Z9 65 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2004 VL 10 IS 14 BP 4724 EP 4733 DI 10.1158/1078-0432.CCR-0829-03 PG 10 WC Oncology SC Oncology GA 840ET UT WOS:000222840700016 PM 15269145 ER PT J AU Kaur, G Belotti, D Burger, AM Fisher-Nielson, K Borsotti, P Riccardi, E Thillainathan, J Hollingshead, M Sausville, EA Giavazzi, R AF Kaur, G Belotti, D Burger, AM Fisher-Nielson, K Borsotti, P Riccardi, E Thillainathan, J Hollingshead, M Sausville, EA Giavazzi, R TI Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: An orally bioavailable heat shock protein 90 modulator SO CLINICAL CANCER RESEARCH LA English DT Article ID TISSUE DISTRIBUTION; ENDOTHELIAL-CELLS; MOLECULAR TARGET; GROWTH-FACTOR; GELDANAMYCIN; PROTEIN; HSP90; ACTIVATION; CANCER; INHIBITION AB Purpose: The purpose of this study was to investigate the antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG; NSC707545), a water-soluble benzoquinone ansamycin. Experimental Design: The activity of 17-DMAG, in vivo, was evaluated for inhibition of fibroblast growth factor (FGF)-2-induced angiogenesis in s.c. implanted Matrigel in mice. In vitro, the activity of 17-DMAG on endothelial cells (human umbilical vein endothelial cells; HUVEC) was tested in FGF-2; and vascular endothelial growth factor (VEGF)induced proliferation and apoptosis, motility, and extracellular matrix invasion; and on the alignment of capillary like structures in Matrigel. The protein level of heat shock protein (Hsp)90 and client proteins was examined by Western blot in FGF-2 and VEGF-stimulated HUVEC. Results: Daily oral administration of 17-DMAG affected the angiogenic response in Matrigel in a dose-dependent manner. The hemoglobin content in the Matrigel implants was significantly inhibited, and the histological analysis confirmed a decrease of CD31(+) endothelial cells and of structures organized in cord and erythrocyte-containing vessels. In vitro, the compound inhibited dose-dependently the migration and the extracellular matrix-invasiveness of HUVEC and their capacity to form capillary like structures in Matrigel. 17-DMAG treatment also inhibited FGF-2 and VEGF-induced HUVEC proliferation and resulted in apoptosis. Accordingly, the expression of Hsp90 direct client proteins (pAkt and c-Raf-1) or their downstream substrates including pERK was also affected. 17-DMAG consistently increased the expression of Hsp70. Throughout the study similar results were obtained with 17-allylamino-17-demethoxygeldanamycin (17-AAG; NSC3-30507), the analog compound currently undergoing clinical trials. Conclusions: We show that the Hsp90 targeting agents 17-DMAG and 17-AAG inhibit angiogenesis. The strong effects on endothelial cell functions, in vitro, indicate that the antiangiogenic activity of 17-DMAG/17-AAG could also be due to a direct effect on endothelial cells. The oral bioavailability of 17-DMAG might be of advantage in investigating the potential of this compound in clinical trials with antiangiogenic as well as antiproliferative endpoints. C1 Mario Negri Inst Pharmacol Res, I-24125 Bergamo, Italy. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. Sci Applicat Int Corp, Frederick, MD USA. RP Giavazzi, R (reprint author), Mario Negri Inst Pharmacol Res, Via Gavazzeni 11, I-24125 Bergamo, Italy. EM Giavazzi@marionegri.it FU PHS HHS [N01-C0-12400] NR 34 TC 103 Z9 109 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2004 VL 10 IS 14 BP 4813 EP 4821 DI 10.1158/1078-0432.CCR-03-0795 PG 9 WC Oncology SC Oncology GA 840ET UT WOS:000222840700028 PM 15269157 ER PT J AU Steinbach, WJ Benjamin, DK Kontoyiannis, DP Perfect, JR Lutsar, I Marr, KA Lionakis, MS Torres, HA Jafri, H Walsh, TJ AF Steinbach, WJ Benjamin, DK Kontoyiannis, DP Perfect, JR Lutsar, I Marr, KA Lionakis, MS Torres, HA Jafri, H Walsh, TJ TI Infections due to Aspergillus terreus: A multicenter retrospective analysis of 83 cases SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 14-17, 2003 CL CHICAGO, IL ID INVASIVE FUNGAL-INFECTIONS; AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; PULMONARY ASPERGILLOSIS; EPIDEMIOLOGY; VORICONAZOLE; THERAPY AB Current in vitro and in vivo data indicate that invasive aspergillosis due to Aspergillus terreus is resistant to treatment with amphotericin B. Because little clinical data are available to guide therapy, we performed a retrospective cohort study of cases of invasive A. terreus infections from 1997-2002 to determine whether the use of voriconazole, compared with use of other antifungal therapies, led to an improved patient outcome. We analyzed a total of 83 cases of proven or probable invasive A. terreus infection (47% and 53%, respectively). A total of 66.3% of patients (55 of 83) died during management of IA, with 55.8% mortality (19 of 34 patients) in the voriconazole group and 73.4% mortality (36 of 49) in the group that received therapy with other antifungals. By use of Cox proportional hazards modeling, decreased mortality at 12 weeks was observed in those patients who received voriconazole (hazard ratio, 0.29; 95% CI, 0.15-0.56). Voriconazole is likely to be a better treatment choice for A. terreus infection than is a polyene. C1 Duke Univ, Med Ctr, Div Pediat Infect Dis, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Clin Res Inst, Durham, NC USA. MD Anderson Canc Res Ctr, Houston, TX USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Pfizer Inc, Sandwich, Kent, England. RP Steinbach, WJ (reprint author), Duke Univ, Med Ctr, Div Pediat Infect Dis, Dept Pediat, Box 3499, Durham, NC 27710 USA. EM stein022@mc.duke.edu RI lutsar, irja/H-3177-2015 FU NIAID NIH HHS [P01-AI-449175]; NICHD NIH HHS [K12-HD00850, 1 R03 HD42940-02] NR 22 TC 175 Z9 185 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2004 VL 39 IS 2 BP 192 EP 198 DI 10.1086/421950 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 835HV UT WOS:000222474300008 PM 15307028 ER PT J AU Moody, SA Moore, KB Mood, K Daar, IO AF Moody, SA Moore, KB Mood, K Daar, IO TI Interactions between the FGF and ephrinB1 signaling pathways regulate the morphogenetic movements underlying eye field formation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 George Washington Univ, Washington, DC USA. NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 57 BP 559 EP 559 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200079 ER PT J AU Yan, J Fukushige, T McGhee, JD AF Yan, J Fukushige, T McGhee, JD TI Timing and Patterning of gene expression in the C-elegans intestine. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada. NIH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 73 BP 563 EP 563 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200095 ER PT J AU Ohsugi, M Dean, J AF Ohsugi, M Dean, J TI MATER, encoded by a maternal effect gene, associates with microtubules in oocytes but not early embryos. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 100 BP 568 EP 569 PG 2 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200121 ER PT J AU Miura, S Davis, S Klingensmith, J Mishina, Y AF Miura, S Davis, S Klingensmith, J Mishina, Y TI BMP signaling is essential for mesoderm induction in the extraembryonic tissue and regulates mesoderm patterning in the epiblast. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 136 BP 576 EP 576 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200155 ER PT J AU Sherman, LS Adams, C Banine, F Xing, RB Liu, Y Metzger, D Chambon, P Matsumoto, S AF Sherman, LS Adams, C Banine, F Xing, RB Liu, Y Metzger, D Chambon, P Matsumoto, S TI Brg1 is required for the differentiation of specific lineages in the CNS. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Univ Strasbourg 1, F-67404 Illkirch Graffenstaden, France. Oregon Hlth & Sci Univ, Portland, OR 97239 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 162 BP 581 EP 581 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200179 ER PT J AU D'Souza, MF Chen, YT Mackem, S AF D'Souza, MF Chen, YT Mackem, S TI Domain requirements for Gli3-Hoxd protein interaction to reverse Gli3-repressor function and promote digit formation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 NCI, HHMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 201 BP 590 EP 590 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200218 ER PT J AU Childs, S Torres-Vasquez, J Lamont, RE Fishman, MC Chen, JN Weinstein, BM Fraser, SD AF Childs, S Torres-Vasquez, J Lamont, RE Fishman, MC Chen, JN Weinstein, BM Fraser, SD TI Loss of plexinDl sends vascular pattern out of bounds. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the Society-for-Developmental-Biology CY JUL 24-28, 2004 CL Univ Calgary, Calgary, CANADA SP Soc Dev Biol HO Univ Calgary C1 Univ Calgary, Calgary, AB T2N 1N4, Canada. NICHD, Mol Genet Lab, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2004 VL 271 IS 2 MA 318 BP 615 EP 615 PG 1 WC Developmental Biology SC Developmental Biology GA 836LC UT WOS:000222556200334 ER PT J AU Savage, SA Chanock, SJ AF Savage, SA Chanock, SJ TI Using germ-line genetic variation to investigate and treat cancer SO DRUG DISCOVERY TODAY LA English DT Review ID SINGLE-NUCLEOTIDE POLYMORPHISMS; THIOPURINE S-METHYLTRANSFERASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENE; LINKAGE-DISEQUILIBRIUM; BLADDER-CANCER; BREAST-CANCER; HUMAN GENOME; LUNG-CANCER; CANDIDATE GENES AB For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic. variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer susceptibility. Population-based studies should be conducted to determine the influence of germline genetic variation on cancer outcomes, including the efficacy of anti-cancer drugs and the risk for life-threatening toxicities. Although we are early in the investigation of the influence of germline genetics on cancer outcomes, it is likely that, in the future, it will be possible to individualize therapeutic interventions. In turn, knowledge of genetic risk factors could afford opportunities for prevention, early intervention and minimization of deleterious toxicities associated with cancer therapy. C1 Natl Canc Inst, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Core Genotyping Facil, NIH, Bethesda, MD USA. RP Savage, SA (reprint author), Natl Canc Inst, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM sc83a@nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 79 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL 15 PY 2004 VL 9 IS 14 BP 610 EP 618 AR PII S1359-6446(04)03179-4 DI 10.1016/S1359-6446(04)03179-4 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 837RA UT WOS:000222651900008 PM 15239980 ER PT J AU Palta, JR Deye, JA Ibbott, GS Purdy, JA Urie, MM AF Palta, JR Deye, JA Ibbott, GS Purdy, JA Urie, MM TI Credentialing of institutions for IMRT in clinical trials SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 Univ Florida, Resource Ctr Emerging Technol, Gainesville, FL 32611 USA. NCI, Radiat Res Program, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Radial Phys Ctr, Houston, TX 77030 USA. Washington Univ, Image Guided Therapy Ctr, St Louis, MO USA. Qual Assurance Review Ctr, Providence, RI USA. RP Palta, JR (reprint author), Univ Florida, Resource Ctr Emerging Technol, Gainesville, FL 32611 USA. NR 7 TC 34 Z9 35 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2004 VL 59 IS 4 BP 1257 EP 1259 DI 10.1016/j.ijrobp.2004.03.007 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 836FO UT WOS:000222541300040 PM 15234063 ER PT J AU Harrer, M Luhrs, H Bustin, M Scheer, U Hock, R AF Harrer, M Luhrs, H Bustin, M Scheer, U Hock, R TI Dynamic interaction of HMGA1a proteins with chromatin SO JOURNAL OF CELL SCIENCE LA English DT Article DE chromatin; HMGA proteins; dynamics; phosphorylation ID DNA-BINDING PROPERTIES; HIGH-MOBILITY; HISTONE H1; CHROMOSOMAL-PROTEINS; HMGI/Y PROTEINS; GENE-EXPRESSION; LIVING CELLS; NUCLEAR; BETA; PHOSPHORYLATION AB High-mobility-group proteins Al (HMGA1; previously named HMGI/Y) function as architectural chromatin-binding proteins and are involved in the transcriptional regulation of several genes. We have used cells expressing proteins fused to green fluorescent protein (GFP) and fluorescence recovery after photobleaching (FRAP) to analyze the distribution and dynamics of HMGA1a in vivo. HMGA1-GFP proteins localize preferentially to heterochromatin and remain bound to chromosomes during mitosis. FRAP experiments showed that they are highly mobile components of euchromatin, heterochromatin and of mitotic chromosomes, although with different resident times. For a more-detailed investigation on the interaction of HMGA1a with chromatin, the contribution of the AT-hook DNA-binding motifs was analyzed using point-mutated HMGA1a-GFP proteins. Furthermore, by inhibiting kinase or histone deacetylase activities, and with the help of fusion proteins lacking specific phosphorylation sites, we analyzed the effect of reversible modifications of HMGAla on chromatin binding. Collectively our data show that the kinetic properties of HMGA1a proteins are governed by the number of functional AT-hooks and are regulated by specific phosphorylation patterns. The higher residence time in heterochromatin and chromosomes, compared with euchromatic regions, correlates with an increased phosphorylation level of HMGA1a. The regulated dynamic properties of HMGA1a fusion proteins indicate that HMGA1 proteins are mechanistically involved in local and global changes in chromatin structure. C1 Univ Wurzburg, Dept Cell & Dev Biol, D-97080 Wurzburg, Germany. Univ Wurzburg, Div Gastroenterol, Dept Med, D-97080 Wurzburg, Germany. NCI, DBS, LMC, Prot Sect,NIH, Bethesda, MD 20892 USA. RP Hock, R (reprint author), Univ Wurzburg, Dept Cell & Dev Biol, D-97080 Wurzburg, Germany. EM rhock@biozentrum.uni-wuerzburg.de RI Bustin, Michael/G-6155-2015 NR 41 TC 66 Z9 67 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL 15 PY 2004 VL 117 IS 16 BP 3459 EP 3471 DI 10.1242/jcs.01160 PG 13 WC Cell Biology SC Cell Biology GA 849FG UT WOS:000223523500006 PM 15213251 ER PT J AU Dudko, OK Berezhkovskii, AM Weiss, GH AF Dudko, OK Berezhkovskii, AM Weiss, GH TI Rate constant for diffusion-influenced ligand binding to receptors of arbitrary shape on a cell surface SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ORIENTATION CONSTRAINTS; BOUND RECEPTORS; CHEMORECEPTION; ASSOCIATION; PHYSICS AB The theory of ligand binding to receptors, on a cell surface suggested by Berg and Purcell and generalized by Zwanzig and Szabo uses the assumption that receptors are circular absorbing disks on an otherwise reflecting sphere. One of the key-ingredients of this theory is a solution for the rate. constant fore ligand binding to, a single circular receptor on a reflecting plane. We give an exact solution for the rate constant for binding to a single elliptic receptor and an approximate solution for binding to a single receptor of more general shape. The latter was tested by Brownian dynamics simulations: We found that the approximate formula predicted the rate constant with better than 10% accuracy for all studied receptor shapes. Using our solutions one can find the rate-constant for ligand binding to a cell covered by N noncircular receptors by means of the Zwanzig-Szabo formula. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Dudko, OK (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM dudko@mail.nih.gov NR 20 TC 23 Z9 24 U1 2 U2 9 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 15 PY 2004 VL 121 IS 3 BP 1562 EP 1565 DI 10.1063/1.1763137 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 837TN UT WOS:000222663300048 PM 15260704 ER PT J AU Low, JA Wedam, SB Brufsky, A Berman, A Croarkin, E Parks, R Steinberg, SM Mannan, N Fojo, T Swain, SM AF Low, JA Wedam, SB Brufsky, A Berman, A Croarkin, E Parks, R Steinberg, SM Mannan, N Fojo, T Swain, SM TI A phase 2 trial of BMS-247550 (ixabepilone), an epothilone B analog, given daily x 5 in breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Canc Therapeut Branch, CCR, Bethesda, MD 20892 USA. NCI, Biostat & Data Mgmt Sect, CCR, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, CCR, Bethesda, MD 20892 USA. Univ Pittsburgh, Magee Womens Hosp, Inst Canc, Pittsburgh, PA 15213 USA. NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 545 BP 13S EP 13S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400051 PM 28016592 ER PT J AU Wedam, SB Low, JA Yang, X Chow, C Berman, A Eulate, R Danforth, D Hewitt, SM Steinberg, SM Swain, SM AF Wedam, SB Low, JA Yang, X Chow, C Berman, A Eulate, R Danforth, D Hewitt, SM Steinberg, SM Swain, SM TI A pilot study to evaluate response and angiogenesis after treatment with bevacizumab in patients with inflammatory breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, CCR, Canc Therapeut Branch, Bethesda, MD USA. NIH, DRD, CC, Bethesda, MD 20892 USA. NCI, CCR, Med Oncol Clin Res Unit, Bethesda, MD USA. NCI, CCR, Surg Branch, Bethesda, MD USA. NCI, CCR, Pathol Lab, Bethesda, MD USA. NCI, CCR, Biostat & Data Mgmt Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 578 BP 21S EP 21S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400083 PM 28016528 ER PT J AU Yang, X Tan, AR Nguyen, D Lipkowitz, S Swain, SM AF Yang, X Tan, AR Nguyen, D Lipkowitz, S Swain, SM TI Gene expression profile changes following erlotinib treatment in patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 577 BP 21S EP 21S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400081 PM 28016529 ER PT J AU Efficace, F Therasse, P Piccart, M Coens, C Van Steen, K Welnicka-Jaskiewicz, M Cufer, T Lichinitser, M Shepherd, L Bottomley, A AF Efficace, F Therasse, P Piccart, M Coens, C Van Steen, K Welnicka-Jaskiewicz, M Cufer, T Lichinitser, M Shepherd, L Bottomley, A TI Predicting survival with health-related quality of life scores in locally advanced breast cancer: Results from an international randomized controlled trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Eortc Data Ctr, Brussels, Belgium. Inst Jules Bordet, B-1000 Brussels, Belgium. Limburgs Univ Ctr, Diepenbeek, Belgium. Med Univ Gdansk, Gdansk, Poland. Inst Oncol, Ljubljana, Slovenia. Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. NCI, C Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 618 BP 31S EP 31S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400123 PM 28016707 ER PT J AU Lebowitz, PF Eng-Wong, J Balis, F Widemann, B Jayaprakash, N Gantz, S Chow, C Merino, M Zujewski, J AF Lebowitz, PF Eng-Wong, J Balis, F Widemann, B Jayaprakash, N Gantz, S Chow, C Merino, M Zujewski, J TI A phase I trial of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in hormone-receptor positive metastatic breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 644 BP 38S EP 38S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400148 PM 28017053 ER PT J AU Overmoyer, B Silverman, P Leeming, R Shenk, R Lyons, J Ziats, N Jesberger, J Dumadag, L Remick, S Chen, H AF Overmoyer, B Silverman, P Leeming, R Shenk, R Lyons, J Ziats, N Jesberger, J Dumadag, L Remick, S Chen, H TI Phase II trial of neoadjuvant docetaxel with or without bevacizumab in patients with locally advanced breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Hosp Cleveland, Case Comprehens Canc Ctr, Cleveland, OH USA. NCI, CTEP, Bethesda, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 727 BP 58S EP 58S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400231 ER PT J AU Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, MM Tu, D Shepherd, LE Pater, JL AF Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, MM Tu, D Shepherd, LE Pater, JL TI Updated analysis of the NCICCTG MA.17 randomized placebo (P) controlled trial of letrozole (L) after five years of tamoxifen in postmenopausal women with early stage breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. Mayo Clin, Rochester, MN USA. John Wayne Canc Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, Brussels, Belgium. Int Breast Canc Study Grp, Bern, Switzerland. NCI, Kingston, ON, Canada. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 847 BP 88S EP 88S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400348 ER PT J AU Decensi, A Bonanni, B Guerrieri-Gonzaga, A Robertson, C Cazzaniga, M Mariette, F Gulisano, M Latronico, A Franchi, D Johnson, K AF Decensi, A Bonanni, B Guerrieri-Gonzaga, A Robertson, C Cazzaniga, M Mariette, F Gulisano, M Latronico, A Franchi, D Johnson, K TI A randomized 2x2 biomarker trial of low-dose tamoxifen and fenretinide in premenopausal women at-high risk for breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 European Inst Oncol, Milan, Italy. Osped Galliera Genoa, Genoa, Italy. Univ Strathclyde, Glasgow G1 1XQ, Lanark, Scotland. Osped S Bortolo, Vicenza, Italy. NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1001 BP 97S EP 97S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400384 PM 28014657 ER PT J AU Raizer, JJ Abrey, LE Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M AF Raizer, JJ Abrey, LE Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M TI A phase II trial of erlotinib (OSI-774) in patients (pts) with recurrent malignant gliomas (MG) not on EIAEDs. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. NCI, Neurooncol Branch, NIH, Bethesda, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1502 BP 107S EP 107S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400422 PM 28015384 ER PT J AU Fine, HA Kim, L Royce, C Mitchell, S Duic, JP Albert, P Musib, L Thornton, D AF Fine, HA Kim, L Royce, C Mitchell, S Duic, JP Albert, P Musib, L Thornton, D TI A phase II trial of LY317615 in patients with recurrent high grade gliomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Neurooncol Branch, Bethesda, MD USA. NINDS, NIH, Bethesda, MD USA. NCI, Biometr Branch, Bethesda, MD USA. Eli Lilly, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1511 BP 109S EP 109S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400432 PM 28015362 ER PT J AU Lieberman, FS Cloughesy, T Fine, H Kuhn, J Lamborn, K Malkin, M Robbins, HI Yung, WA Wen, P Prados, M AF Lieberman, FS Cloughesy, T Fine, H Kuhn, J Lamborn, K Malkin, M Robbins, HI Yung, WA Wen, P Prados, M TI NABTC phase I/II trial of ZD-1839 for recurrent malignant gliomas and unresectable meningiomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Calif Los Angeles, Los Angeles, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Wisconsin, Madison, WI 53706 USA. MD Anderson Canc Ctr, Houston, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 1510 BP 109S EP 109S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400430 PM 28015363 ER PT J AU De Jong, FA Mathijssen, RHJ Lepper, ER Van Schaik, RH Friberg, L De Bruijn, P Graveland, WJ Figg, WD Verweij, J Sparreboom, A AF De Jong, FA Mathijssen, RHJ Lepper, ER Van Schaik, RH Friberg, L De Bruijn, P Graveland, WJ Figg, WD Verweij, J Sparreboom, A TI Role of CYP3A4 phenotyping by midazolam clearance in predicting irinotecan pharmacokinetics. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Erasmus MC Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. NCI, Bethesda, MD 20892 USA. Uppsala Univ, Uppsala, Sweden. RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2007 BP 128S EP 128S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400508 PM 28015788 ER PT J AU Gelderblom, H Loos, WJ Sissung, TM Burger, H Nooter, K Soepenberg, O Nortier, JWR Verweij, J Figg, WD Sparreboom, A AF Gelderblom, H Loos, WJ Sissung, TM Burger, H Nooter, K Soepenberg, O Nortier, JWR Verweij, J Figg, WD Sparreboom, A TI Effect of ABCG2 genotype and mRNA expression on the bioavailability of topotecan. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Leiden Univ, Med Ctr, Leiden, Netherlands. Erasmus MC, Rotterdam, Netherlands. NCI, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2015 BP 130S EP 130S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400516 PM 28015603 ER PT J AU Chatelut, E Loos, WJ Leger, F Canal, P Bugat, R Verweij, J Sparreboom, A AF Chatelut, E Loos, WJ Leger, F Canal, P Bugat, R Verweij, J Sparreboom, A TI Pharmacokinetic-pharmacodynamic models for topotecan-induced neutropenia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Inst Claudius Regard, Toulouse, France. Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. Natl Canc Inst, Bethesda, MD USA. RI Sparreboom, Alex/B-3247-2008; Chatelut, Etienne/I-7916-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2054 BP 140S EP 140S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400554 PM 28015665 ER PT J AU Grem, JL Wright, M Morrison, G Lin, PX Leonard, G Nguyen, D Guo, XD Szabo, E AF Grem, JL Wright, M Morrison, G Lin, PX Leonard, G Nguyen, D Guo, XD Szabo, E TI Phase I pharmacokinetic (PK) & pharmacogenetic study of sequential infusional irinotecan (IR) and fluorouracil (FU). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Navy GI Tumor Clin Grp, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2075 BP 145S EP 145S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400576 PM 28015698 ER PT J AU Singh, A Paoluzzi, L Price, D Danesi, R Mathijssen, RH Verweij, J Figg, WD Sparreboom, A AF Singh, A Paoluzzi, L Price, D Danesi, R Mathijssen, RH Verweij, J Figg, WD Sparreboom, A TI Influence of genetic variants in UGT1A1 and UGT1A9 on the in vivo glucuronidation of SN-38. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Howard Hughes Med Inst, Bethesda, MD 20817 USA. Regina Elena Inst Canc Res, Rome, Italy. Natl Canc Inst, Bethesda, MD USA. Univ Pisa, Pisa, Italy. Erasmus MC, Rotterdam, Netherlands. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2072 BP 145S EP 145S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400573 PM 28015699 ER PT J AU Abrams, PL Egorin, MJ Ramanathan, RK Parise, RA Lagattuta, TF Hayes, M Peng, B Ivy, SP Murgo, A Remick, S AF Abrams, PL Egorin, MJ Ramanathan, RK Parise, RA Lagattuta, TF Hayes, M Peng, B Ivy, SP Murgo, A Remick, S TI Intrapatient consistency of imatinib pharmacokinetics (PK) in patients (pts) with advanced cancers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Nova Pharmaceut Corp, E Hanover, NJ USA. CTEP, Natl Canc Inst, Rockville, MD USA. Case Western Reserve Univ, Comp Canc Ctr, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2081 BP 147S EP 147S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400583 PM 28015688 ER PT J AU Cho, SY Adamson, PC Hagey, AE Widemann, BC Maris, JM Fox, E Medina, D Cui, Y Gordon, GB Balis, FM AF Cho, SY Adamson, PC Hagey, AE Widemann, BC Maris, JM Fox, E Medina, D Cui, Y Gordon, GB Balis, FM TI Phase I trial and pharmacokinetic (PK) study of ABT-751, an orally bioavailable tubulin binding agent, in pediatric patients with refractory solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2080 BP 147S EP 147S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400581 ER PT J AU Krishnamurthi, SS Brell, JM Coviello, KM Dowlati, A Egorin, MJ Hoppel, CL Ingails, ST Ivy, SP Li, X Remick, SC AF Krishnamurthi, SS Brell, JM Coviello, KM Dowlati, A Egorin, MJ Hoppel, CL Ingails, ST Ivy, SP Li, X Remick, SC TI Phase I study of oxaliplatin (Ox), irinotecan (Irino), and capecitabine (Cape) in patients with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Case Comprehens Canc Ctr, Cleveland, OH USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA 15260 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2111 BP 154S EP 154S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400612 PM 28017119 ER PT J AU Chen, T Molina, A Moore, S Goel, S Desai, K Hamilton, A Griffin, T Colevas, AD Mani, S Muggia, F AF Chen, T Molina, A Moore, S Goel, S Desai, K Hamilton, A Griffin, T Colevas, AD Mani, S Muggia, F TI Epothilone B analog (BMS-247550) at the recommended phase II dose (RPTD) in patients (pts) with gynecologic (gyn) and breast cancers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NYU Med Ctr, New York, NY 10016 USA. Albert Einstein Canc Ctr, Bronx, NY USA. Bristol Myers Squibb Co, Princeton, NJ USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2115 BP 155S EP 155S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400616 PM 28017107 ER PT J AU Kaufman, HL Dipaola, R Von Mehren, M Marshall, J Lyerly, HK Streicher, H Schlom, J Panicali, D Schuetz, T AF Kaufman, HL Dipaola, R Von Mehren, M Marshall, J Lyerly, HK Streicher, H Schlom, J Panicali, D Schuetz, T TI Safety profile of therapeutic pox virus-based vaccines for cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Columbia Univ, New York, NY 10027 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Georgetown Univ, Washington, DC 20057 USA. Duke Univ, Durham, NC 27706 USA. NCI, Bethesda, MD 20892 USA. Therion Biol Corp, Cambridge, MA USA. RI Lyerly, Herbert/B-6528-2014 OI Lyerly, Herbert/0000-0002-0063-4770 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2513 BP 166S EP 166S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400657 PM 28015029 ER PT J AU Arlen, PM Gulley, J Dahut, W Skarupa, L Morin, S Pazdur, M Todd, N Panicali, D Tsang, KY Schlom, J AF Arlen, PM Gulley, J Dahut, W Skarupa, L Morin, S Pazdur, M Todd, N Panicali, D Tsang, KY Schlom, J TI A phase I study of sequential vaccinations with recombinant Fowlpox-PSA (L155)-TRICOM (rF)alone, or in combination with recombinant vaccinia-PSA (L155)-TRICOM (rV), and the role of GM-CSF, in patients (Pts) with prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Therion Biol, Cambridge, MA USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2522 BP 168S EP 168S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400664 ER PT J AU Ibrahim, RA Achtar, MS Herrin, VE Gause, B Bernstein, SA Brent-Steel, TB Maruffi, CM Berzofsky, JA Khleif, SN AF Ibrahim, RA Achtar, MS Herrin, VE Gause, B Bernstein, SA Brent-Steel, TB Maruffi, CM Berzofsky, JA Khleif, SN TI Mutant P53 vaccination of patients with advanced cancers generates specific immunological responses. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2521 BP 168S EP 168S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400665 ER PT J AU Scott, AM Tebbutt, N Lee, FT Cavicchiolo, T Liu, Z Poon, A Brechbiel, MW Stockert, E Hoffman, EW Old, LJ AF Scott, AM Tebbutt, N Lee, FT Cavicchiolo, T Liu, Z Poon, A Brechbiel, MW Stockert, E Hoffman, EW Old, LJ TI Phase I trial of hu3S193 in patients with advanced epithelial cancers which express the Lewis-y antigen. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Ludwig Inst Canc Res, Heidelberg, Vic, Australia. NIH, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2567 BP 179S EP 179S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400710 ER PT J AU Achtar, MS Ibrahim, RA Herrin, VE Gause, B Bernstein, SA Brent-Steel, TB Maruffi, CM Berzofsky, JA Khleif, SN AF Achtar, MS Ibrahim, RA Herrin, VE Gause, B Bernstein, SA Brent-Steel, TB Maruffi, CM Berzofsky, JA Khleif, SN TI Vaccine therapy with tumor specific mutated VHL peptides in adult cancer patients with renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2589 BP 185S EP 185S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400733 PM 28015270 ER PT J AU Heeger, SW Moldenhauer, G Flynn, JM Egerer, G Nikula, T Apostolidis, C Brechbiel, M Haberkorn, U Ho, AD Haas, R AF Heeger, SW Moldenhauer, G Flynn, JM Egerer, G Nikula, T Apostolidis, C Brechbiel, M Haberkorn, U Ho, AD Haas, R TI Radioimmunotherapy of B-lineage non-Hodgkin's lymphoma using anti-CD19 and anti-CD20 conjugates. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 German Canc Res Ctr, D-6900 Heidelberg, Germany. Landstuhl Reg Med Ctr, Landstuhl, Germany. Univ Heidelberg Hosp, Heidelberg, Germany. Inst Transuranium Elements, Kalsruhe, Germany. NCI, Bethesda, MD 20892 USA. Univ Hosp, Dusseldorf, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 2625 BP 194S EP 194S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400767 PM 28014730 ER PT J AU Yao, JC Charnsangavej, C Faria, SC Szklaruk, J Chen, H Hoff, P Phan, A Yeung, SCJ Abbruzzese, JL Ajani, JA AF Yao, JC Charnsangavej, C Faria, SC Szklaruk, J Chen, H Hoff, P Phan, A Yeung, SCJ Abbruzzese, JL Ajani, JA TI Rapid decrease in blood flow (BF), blood volume (BV), and vascular permeability (PS) in carcinoid patients treated with bevacizumab. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3013 BP 198S EP 198S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400782 PM 28015169 ER PT J AU Giantonio, BJ Chen, HX Catalano, PJ Meropol, NJ O'Dwyer, PJ Benson, AIB AF Giantonio, BJ Chen, HX Catalano, PJ Meropol, NJ O'Dwyer, PJ Benson, AIB TI Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. NCI, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3017 BP 199S EP 199S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400786 PM 28015163 ER PT J AU Erlichman, C Toft, D Reid, J Goetz, M Ames, M Mandrekar, S Ajei, A McCollum, A Ivy, P AF Erlichman, C Toft, D Reid, J Goetz, M Ames, M Mandrekar, S Ajei, A McCollum, A Ivy, P TI A phase I trial of 17-allylamino-geldanamycin (17AAG) in patients with advanced cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. NCI, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3030 BP 202S EP 202S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400797 PM 28015188 ER PT J AU Piekarz, R Frye, R Turner, M Wright, J Leonard, J Allen, S Bates, S AF Piekarz, R Frye, R Turner, M Wright, J Leonard, J Allen, S Bates, S TI Update on the phase II trial and correlative studies of depsipeptide in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. N Shore Univ Hosp, Manhasset, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3028 BP 202S EP 202S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400796 ER PT J AU Ramanathan, RK Trump, DL Eiseman, JL Belani, CP Agarwala, SS Zuhowski, EG Lan, J Ivy, P Tutchko, S Egorin, ME AF Ramanathan, RK Trump, DL Eiseman, JL Belani, CP Agarwala, SS Zuhowski, EG Lan, J Ivy, P Tutchko, S Egorin, ME TI A phase I pharmacokinetic (PK) and pharmacodynamic (PD) trial of weekly 17-allylamino-17 demethoxygeldanamycin (17AAG, NSC-704057) in patients with advanced tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3031 BP 202S EP 202S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400799 ER PT J AU Hassan, R Bullock, S Kreitman, RJ Kindler, HL Pastan, I AF Hassan, R Bullock, S Kreitman, RJ Kindler, HL Pastan, I TI Targeted therapy of mesothelin expressing mesotheliomas (MM), ovarian cancer (OC) and pancreatic cancer (PC): Results of phase I study of SS1(dsFv)PE38 (SS1P) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3035 BP 203S EP 203S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400803 PM 28015189 ER PT J AU Messersmith, WA Baker, SD Dinh, K Lassiter, LK Akdamar, RA Wright, JJ Donehower, RC Carducci, MA Armstrong, DK AF Messersmith, WA Baker, SD Dinh, K Lassiter, LK Akdamar, RA Wright, JJ Donehower, RC Carducci, MA Armstrong, DK TI Phase I trial of bortezomib (PS-341) in combination with docetaxel in patients with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3052 BP 208S EP 208S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400820 PM 28015209 ER PT J AU Cristofanilli, M Gonzalez-Angulo, AM Nealy, KN Booser, D Pusztai, L Walters, RD Hortobagyi, GN Reuben, J Esseltine, D Wright, J AF Cristofanilli, M Gonzalez-Angulo, AM Nealy, KN Booser, D Pusztai, L Walters, RD Hortobagyi, GN Reuben, J Esseltine, D Wright, J TI A phase II trial of PS-341 in metastatic breast cancer (MBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. MPI, Cambridge, MA USA. NCI, CTEP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3102 BP 220S EP 220S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400870 PM 28014853 ER PT J AU Mackay, H Major, P Townsley, C Mackenzie, M Vincent, M Degendorfer, P Tsao, M Hedley, D Wright, J Oza, A AF Mackay, H Major, P Townsley, C Mackenzie, M Vincent, M Degendorfer, P Tsao, M Hedley, D Wright, J Oza, A TI A phase II trial of the proteosome inhibitor PS-341 in patients with metastatic colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Princess Margaret Phase II Consortium, Toronto, ON, Canada. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3109 BP 222S EP 222S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400876 PM 28014849 ER PT J AU Fracasso, PM Rudek, MA Naughton, MJ Picus, J Rader, JS Chen, RC Fears, CL Goodner, SA Dancey, J McLeod, HL AF Fracasso, PM Rudek, MA Naughton, MJ Picus, J Rader, JS Chen, RC Fears, CL Goodner, SA Dancey, J McLeod, HL TI Phase I study combining UCN-01 with irinotecan in resistant solid tumor malignancies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Washington State Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. Sidney Kimmel Comprehens Canc Ctr, E Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S BP 229S EP 229S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400906 ER PT J AU Basche, M Pierson, AS Holden, S Gore, L O'Bryant, C Raj, S Morrow, M Gustafson, D Dancey, J Eckhardt, SG AF Basche, M Pierson, AS Holden, S Gore, L O'Bryant, C Raj, S Morrow, M Gustafson, D Dancey, J Eckhardt, SG TI A phase I trial of ZD1839 (Z), capecitabine (Cp), and celecoxib (Cel): Preliminary results of an amended schedule. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Colorado, Ctr Canc, Aurora, CO USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3159 BP 234S EP 234S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400924 PM 28014878 ER PT J AU Sargent, DJ Wieand, S Benedetti, J Labianca, R Haller, DG Shepherd, LE Seitz, JF Francini, G De Gramont, A Goldberg, RM AF Sargent, DJ Wieand, S Benedetti, J Labianca, R Haller, DG Shepherd, LE Seitz, JF Francini, G De Gramont, A Goldberg, RM TI Disease-free survival (OFS) vs. overall survival (OS) as a primary endpoint for adjuvant colon cancer studies: Individual patient data from 12,915 patients on 15 randomized trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCCTG, Mayo Clin, Rochester, MN USA. NSABP, Ctr Stat, Pittsburgh, PA USA. SWOG, Ctr Stat, Seattle, WA USA. Osped Riuniti Bergamo, I-24100 Bergamo, Italy. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. NCIC, CTG, Kingston, ON, Canada. Univ Mediterranean, Marseille, France. Univ Siena, I-53100 Siena, Italy. Hosp St Antoine, Paris, France. Univ N Carolina, Chapel Hill, NC USA. RI Goldberg , Richard/M-1311-2013 NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3502 BP 245S EP 245S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400969 ER PT J AU Wolmark, N Wieand, S Lembersky, B Colangelo, L Smith, R Pazdur, R AF Wolmark, N Wieand, S Lembersky, B Colangelo, L Smith, R Pazdur, R TI A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: Results of NSABP Protocol C-06. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NSABP, Pittsburgh, PA USA. FDA, Rockville, MD USA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3508 BP 247S EP 247S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400976 ER PT J AU Chen, HX Mooney, M Boron, M Grochow, L Zwiebel, J Vena, D Mosby, K Grandinetti, C Kaplan, RS AF Chen, HX Mooney, M Boron, M Grochow, L Zwiebel, J Vena, D Mosby, K Grandinetti, C Kaplan, RS TI Bevacizumab (BV) plus 5-FU/leucovorin (FU/LV) for advanced colorectal cancer (CRC) that progressed after standard chemotherapies: An NCI Treatment Referral Center trial (TRC-0301). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 EMMES Corp, Rockville, MD USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 3515 BP 248S EP 248S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400983 PM 28016469 ER PT J AU Shah, MA Kortmansky, J Gonen, M Tse, A Lefkowitz, R Kelsen, D Colevas, D Winkelman, J Yi, S Schwartz, G AF Shah, MA Kortmansky, J Gonen, M Tse, A Lefkowitz, R Kelsen, D Colevas, D Winkelman, J Yi, S Schwartz, G TI A phase I study of weekly irinotecan (CPT), cisplatin (CIS) and flavopiridol (F). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Rockville, MD USA. RI Gonen, Mithat/E-4826-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4027 BP 320S EP 320S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401266 PM 28016402 ER PT J AU Hussain, M Faulkner, J Vaishampayan, U Lara, P Petrylak, D Colevas, D Sakr, W Crawford, ED AF Hussain, M Faulkner, J Vaishampayan, U Lara, P Petrylak, D Colevas, D Sakr, W Crawford, ED TI Epothilone B (Epo-B) analogue BMS-247550 (NSC #710428) administered every 21 days in patients (pts) with hormone refractory prostate cancer (HRPC). A Southwest Oncology Group Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Michigan, Ann Arbor, MI 48109 USA. SW Oncol Grp, Seattle, WA USA. Wayne State Univ, Detroit, MI USA. Calif State Univ Sacramento, Sacramento, CA 95819 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NCI, Rockville, MD USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4510 BP 384S EP 384S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401523 PM 28016038 ER PT J AU Stiff, PJ Lazarus, HM Childs, RW Perez, W Carreras, J Klein, J Rizzo, DJ AF Stiff, PJ Lazarus, HM Childs, RW Perez, W Carreras, J Klein, J Rizzo, DJ TI Utility of single vs tandem autotransplants for advanced testes/germ cell cancer: An Autologous Blood and Marrow Transplant Registry (ABMTR) analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4536 BP 390S EP 390S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401548 PM 28016049 ER PT J AU Zhuang, SH Menefee, M Kotz, H Agrawal, M Poruchynsky, M Hung, E Zhan, Z Linehan, WM Bates, SE Fojo, T AF Zhuang, SH Menefee, M Kotz, H Agrawal, M Poruchynsky, M Hung, E Zhan, Z Linehan, WM Bates, SE Fojo, T TI A phase II clinical trial of BMS-247550 (ixabepilone), a microtubule-stabilizing agent in renal cell cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 4550 BP 394S EP 394S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401562 ER PT J AU Kristensen, GB Vergote, I Eisenhauer, E Baekelandt, M Stuart, G Aavall-Lundquist, E Del Campo, J Lopez, AB Mirza, M Lorenz, E AF Kristensen, GB Vergote, I Eisenhauer, E Baekelandt, M Stuart, G Aavall-Lundquist, E Del Campo, J Lopez, AB Mirza, M Lorenz, E TI First line treatment of ovarian/tubal/peritoneal cancer FIGO stage IIb-IV with paclitaxel/carboplatin with or without epirubicin (TEC vs TC). A Gynecologic Cancer Intergroup study of the NSGO, EORTC GCG, and NCICCTG. Results on progression free survival. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Norwegian Radium Hosp, Oslo, Norway. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. NCI, Canada Clin Trials Grp, Kingston, ON, Canada. Karolinska Univ Hosp, Stockholm, Sweden. Odense Univ Hosp, DK-5000 Odense, Denmark. Univ Trondheim Hosp, Trondheim, Norway. NR 0 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 5003 BP 449S EP 449S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401782 PM 28015497 ER PT J AU Levine, DA Bonome, T Olshen, AB Bogomolniy, F Brady, J Pise-Masison, C Radonovich, M Chi, DS Birrer, MJ Boyd, J AF Levine, DA Bonome, T Olshen, AB Bogomolniy, F Brady, J Pise-Masison, C Radonovich, M Chi, DS Birrer, MJ Boyd, J TI Gene expression profiling of advanced ovarian cancers to predict the outcome of primary surgical cytoreduction. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 5000 BP 449S EP 449S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401779 PM 28015494 ER PT J AU Bonome, T Buckanovich, R Birrer, M Coukos, G AF Bonome, T Buckanovich, R Birrer, M Coukos, G TI Expression profiling of ovarian epithelial cancers with intratumoral T cells identifies genes mediating the host immune response: Implications for survival. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 5011 BP 451S EP 451S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401790 PM 28015483 ER PT J AU Jasas, KV Fyles, A Elit, L Hoskins, PJ Biagi, J Dubuc-Lissoir, J Matthews, S Dancey, J Eisenhauer, E Oza, AM AF Jasas, KV Fyles, A Elit, L Hoskins, PJ Biagi, J Dubuc-Lissoir, J Matthews, S Dancey, J Eisenhauer, E Oza, AM TI Phase II study of erlotinib (OSI 774) in women with recurrent or metastatic endometrial cancer: NCICCTG IND-148. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S BP 453S EP 453S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512401798 ER PT J AU Joffe, S Harrington, DP George, SL Emanuel, EJ Budzinski, L Weeks, JC AF Joffe, S Harrington, DP George, SL Emanuel, EJ Budzinski, L Weeks, JC TI Fulfillment of the uncertainty principle in cancer clinical trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. NIH, Bethesda, MD 20892 USA. Lesley Coll, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6003 BP 519S EP 519S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402058 PM 28015062 ER PT J AU Soares, HP Kumar, A Daniels, S Sargent, DJ Buckner, JC Swann, S Smith, RE Khyatat, A Wells, RJ Djulbegovic, B AF Soares, HP Kumar, A Daniels, S Sargent, DJ Buckner, JC Swann, S Smith, RE Khyatat, A Wells, RJ Djulbegovic, B TI Lack of publication bias in randomized clinical trials (RCTs) sponsored by the National Cancer Institute MCI) and performed by Cooperative Oncology Groups (COGs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Mayo Clin, N Cent Canc Treatment Grp, Rochester, MN USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Childrens Oncol Grp, Arcadia, CA USA. RI Djulbegovic, Benjamin/I-3661-2012; Kumar, Ambuj/I-4940-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6004 BP 520S EP 520S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402059 PM 28015064 ER PT J AU Earle, CC Schrag, D Neville, BA Yabroff, R Topor, M Fahey, A Warren, J AF Earle, CC Schrag, D Neville, BA Yabroff, R Topor, M Fahey, A Warren, J TI Effect of surgeon specialty an outcomes for ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Informat Management Serv Inc, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6027 BP 525S EP 525S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402082 PM 28015097 ER PT J AU Patel, H Egorin, MJ Remick, SC Mulkerin, D Takimoto, CHM Doroshow, JH Potter, D Ivy, SP Murgo, AJ Ramanathan, RK AF Patel, H Egorin, MJ Remick, SC Mulkerin, D Takimoto, CHM Doroshow, JH Potter, D Ivy, SP Murgo, AJ Ramanathan, RK TI Comparison of Child-Pugh (CP) criteria and NCI organ dysfunction working group (NCI-ODWG) criteria for hepatic dysfunction (HD): Implications for chemotherapy dosing. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NCI, CTEP, Rockville, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6051 BP 531S EP 531S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402106 ER PT J AU Horstmann, E Grady, C McCabe, M Emanuel, EJ AF Horstmann, E Grady, C McCabe, M Emanuel, EJ TI Phase I participants as a vulnerable population. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Natl Inst Hlth, Bethesda, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6059 BP 533S EP 533S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402114 PM 28014972 ER PT J AU Colevas, AD Setser, A AF Colevas, AD Setser, A TI The NCI Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 is the new standard for oncology clinical trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, CTEP, Rockville, MD USA. NR 0 TC 13 Z9 17 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6098 BP 543S EP 543S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402152 PM 28015009 ER PT J AU Weiss, EH Golant, M Thornton, A Kennedy, V Stovall, E Michaels, M Taylor, J Brintzenhofeszoc, K AF Weiss, EH Golant, M Thornton, A Kennedy, V Stovall, E Michaels, M Taylor, J Brintzenhofeszoc, K TI Open to options: A cancer clinical trials education pilot study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Wellness Community, Washington, DC USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Coalit Canc Survivorship, Silver Spring, MD USA. Natl Canc Ctr, Bethesda, MD USA. Amer Soc Clin Oncol, Alexandria, VA USA. Catholic Univ Amer, Washington, DC 20064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6116 BP 547S EP 547S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402170 PM 28014803 ER PT J AU Lin, TS Dalton, JT Wu, D Fischer, B Moran, M Lucas, D Cunningham, K Colevas, AD Grever, MR Byrd, JC AF Lin, TS Dalton, JT Wu, D Fischer, B Moran, M Lucas, D Cunningham, K Colevas, AD Grever, MR Byrd, JC TI Flavopiridol given as a 30-min intravenous (IV) bolus followed by 4-hr continuous IV infusion (CIVI) results in clinical activity and tumor lysis in refractory chronic lymphocytic leukemia (CLL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6564 BP 573S EP 573S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402270 ER PT J AU Pro, B Smith, MR Younes, A Fayad, LE Goy, AH Hagemeister, FB McLaughlin, P Rodriguez, MA Frankel, SR Zwiebel, JA Anderson, MD AF Pro, B Smith, MR Younes, A Fayad, LE Goy, AH Hagemeister, FB McLaughlin, P Rodriguez, MA Frankel, SR Zwiebel, JA Anderson, MD TI Oblimersen sodium (Bcl-2 antisense) plus rituximab in patients with recurrent B-cell non-Hodgkin's lymphoma: Preliminary phase II results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Genta Inc, Berkeley Hts, NJ USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6572 BP 575S EP 575S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402278 PM 28016202 ER PT J AU Dunleavy, KM Butrynski, J Steinberg, S Grant, N White, T Jaffe, ES Wilson, WH AF Dunleavy, KM Butrynski, J Steinberg, S Grant, N White, T Jaffe, ES Wilson, WH TI Phase II study of EPOCH infusional chemotherapy in relapsed or refractory Hodgkin's lymphoma (HL). A report on toxicity, efficacy and prognostic indicators of outcome. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6598 BP 582S EP 582S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402305 PM 28016222 ER PT J AU Bleyer, A Montello, M Budd, T AF Bleyer, A Montello, M Budd, T TI Young adults with leukemia in the United States: Lack of clinical trial participation and mortality reduction during the last decade. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6623 BP 588S EP 588S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402331 ER PT J AU Kreitman, RJ Wilson, WH Stetler-Stevenson, M Noel, P Pastan, I AF Kreitman, RJ Wilson, WH Stetler-Stevenson, M Noel, P Pastan, I TI Long term follow-up of BL22 in cladribine-resistant hairy cell leukemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6624 BP 588S EP 588S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402330 PM 28016304 ER PT J AU Boyiadzis, M Carson, JM Memon, SA Dean, R Pavletic, S Kasten-Sportes, C Fowler, D Bishop, MR Gress, RE Hakim, FT AF Boyiadzis, M Carson, JM Memon, SA Dean, R Pavletic, S Kasten-Sportes, C Fowler, D Bishop, MR Gress, RE Hakim, FT TI Natural killer cell receptor repertoire following HLA-matched allogeneic hematopoietic stem cell transplantation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6635 BP 591S EP 591S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402343 PM 28016351 ER PT J AU Villalona-Calero, MA Otterson, GA Wientjes, G Kobayashi, K Jensen, R Young, D Yeh, T Song, S Grever, M Au, J AF Villalona-Calero, MA Otterson, GA Wientjes, G Kobayashi, K Jensen, R Young, D Yeh, T Song, S Grever, M Au, J TI Phase II study of low dose suramin as a sensitizer of paclitaxel/carboplatin (P/C) in non small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 7108 BP 643S EP 643S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402551 PM 28014449 ER PT J AU Schneider, BJ Worden, F Gadgeel, S Hodges, C Parchment, R Zwiebel, J Kraut, M Kalemkerian, G AF Schneider, BJ Worden, F Gadgeel, S Hodges, C Parchment, R Zwiebel, J Kraut, M Kalemkerian, G TI Phase II study of fenretinide in patients with small cell lung cancer (SCLC) with progression after first- or second-line chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Michigan, Ann Arbor, MI 48109 USA. Wayne State Univ, Detroit, MI USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 7299 BP 690S EP 690S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402740 PM 28013636 ER PT J AU Pavlick, AC Millward, M Farrell, K Hamilton, A Broseus, A Haas, N Shore, T Jacquotte, A Colevas, D Muggia, F AF Pavlick, AC Millward, M Farrell, K Hamilton, A Broseus, A Haas, N Shore, T Jacquotte, A Colevas, D Muggia, F TI A phase II study of epothilone B analog (EpoB)-BMS 247550 (NSC#710428) in stage IV malignant melanoma (MM). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NYU, Inst Canc, New York, NY USA. Sydney Canc Ctr, Sydney, NSW, Australia. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Cornell Univ, New York, NY 10021 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 7542 BP 720S EP 720S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402856 ER PT J AU Pappo, A Ries, L Herzog, C Bleyer, A AF Pappo, A Ries, L Herzog, C Bleyer, A TI Malignant melanoma in the first three decades of life: A report from the US Surveillance, Epidemiology and End Results (SEER) Program. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Natl Canc Inst, Bethesda, MD USA. MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 7557 BP 724S EP 724S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402873 ER PT J AU Strouse, JJ Fears, T Tucker, MA Wayne, AS AF Strouse, JJ Fears, T Tucker, MA Wayne, AS TI Pediatric melanoma: Risk factor and survival analysis of the SEER Cancer Registry database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Baltimore, MD USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 7556 BP 724S EP 724S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402871 PM 28015894 ER PT J AU Stanton, AL Ganz, PA Bower, JE Kwan, L Meyerowitz, BE Rowland, JH Krupnick, JL AF Stanton, AL Ganz, PA Bower, JE Kwan, L Meyerowitz, BE Rowland, JH Krupnick, JL TI The Moving Beyond Cancer trial: A psycho educational intervention for women with breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Calif Los Angeles, Los Angeles, CA USA. Univ So Calif, Los Angeles, CA USA. Natl Canc Inst, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8011 BP 731S EP 731S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402901 PM 28015809 ER PT J AU Donaldson, MS AF Donaldson, MS TI Moving quality of life measurement into clinical oncology practice SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8264 BP 794S EP 794S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403151 PM 28016710 ER PT J AU Daw, NC Furman, WL Stewart, CF Iacono, LC Krailo, M Bernstein, M Dancey, JE Blaney, S Adamson, PC AF Daw, NC Furman, WL Stewart, CF Iacono, LC Krailo, M Bernstein, M Dancey, JE Blaney, S Adamson, PC TI A phase I trial and pharmacolkinetic study of gefitinib in pediatric patients with refractory solid tumors: A Children's Oncology Group Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Oncol Grp, Arcadia, CA USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Natl Canc Inst, Bethesda, MD USA. Texas Childrens Canc Ctr, Houston, TX USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8522 BP 804S EP 804S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403190 PM 28013760 ER PT J AU Paz-Priel, I Long, L Bernstein, D Mackall, CL Helman, LJ Wayne, AS AF Paz-Priel, I Long, L Bernstein, D Mackall, CL Helman, LJ Wayne, AS TI Thromboembolic events (TEE) in children and young adults with sarcoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8524 BP 805S EP 805S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403193 PM 28013764 ER PT J AU Mansky, PJ Gerber, L Hoffman, K Augustine, E Chaudhry, U Parks, B Bernad, M Wiener, L Steinberg, SM Mackall, C AF Mansky, PJ Gerber, L Hoffman, K Augustine, E Chaudhry, U Parks, B Bernad, M Wiener, L Steinberg, SM Mackall, C TI Rehabilitation assessments of pediatric sarcoma survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NIH, NCCAM, Bethesda, MD 20892 USA. NIH, RMD, CC, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8528 BP 806S EP 806S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403197 PM 28013756 ER PT J AU Fox, E Widemann, BC Chen, CC Van Tellingen, O Riches, S Boniface, G Norris, D Bates, S Fojo, T Balis, FM AF Fox, E Widemann, BC Chen, CC Van Tellingen, O Riches, S Boniface, G Norris, D Bates, S Fojo, T Balis, FM TI Pediatric phase I trial and pharmacolkinetic study of P-glycoprotein inhibitor, tariquidar, in combination with doxorubicin, vinorelbine or docetaxel. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Antoni Van Leeuwenhoek Hosp, Amsterdam, Netherlands. QLT Inc, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8541 BP 809S EP 809S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403211 PM 28013815 ER PT J AU D'Adamo, DR Anderson, S Albritton, K Yamada, J Riedel, E Scheu, K Schwartz, GK Chen, H Maki, RG AF D'Adamo, DR Anderson, S Albritton, K Yamada, J Riedel, E Scheu, K Schwartz, GK Chen, H Maki, RG TI Cardiac toxicity in a phase III study of doxorubicin (DOX) and bevacizumab (BEV) for patients (pts) with metastatic soft-tissue sarcomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 MSKCC, New York, NY USA. Univ Utah, Salt Lake City, UT USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 9012 BP 821S EP 821S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403256 PM 28013679 ER PT J AU Azorsa, DO Kiefer, JA White, ML Rojanapraparn, P Caplen, NJ Kallioniemi, O Mousses, S AF Azorsa, DO Kiefer, JA White, ML Rojanapraparn, P Caplen, NJ Kallioniemi, O Mousses, S TI High-throughput RNAi screening identifies sensitizing targets to improve doxorubicin chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Translat Genom Res Inst, Gaithersburg, MD USA. NCI, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 9543 BP 845S EP 845S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403352 PM 28016884 ER PT J AU Posadas, EM Hussain, MM Espina, V Kotz, H Minasian, L Shreeve, SM Premkumar, A Liotta, LA Steinberg, SM Kohn, EC AF Posadas, EM Hussain, MM Espina, V Kotz, H Minasian, L Shreeve, SM Premkumar, A Liotta, LA Steinberg, SM Kohn, EC TI A phase II clinical trial with proteomic profiling of imatinib mesylate in patients with refractory or relapsed epithelial ovarian cancer (EOC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Warren G Magnuson Clin Ctr, Bethesda, MD USA. Ctr Canc Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 9649 BP 872S EP 872S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403460 ER PT J AU Mocellin, S Provenzano, M Rossi, CR Pilati, P Nitti, D Lise, M AF Mocellin, S Provenzano, M Rossi, CR Pilati, P Nitti, D Lise, M TI Induction of endothelial nitric oxide synthase expression by melanoma cells sensitizes tumor endothelium to TNF-driven apoptosis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Univ Padua, I-35100 Padua, Italy. NIH, Bethesda, MD 20892 USA. RI Rossi, Carlo Riccardo/A-7685-2010 OI Rossi, Carlo Riccardo/0000-0001-7875-5655 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 9669 BP 877S EP 877S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403479 PM 28016287 ER PT J AU Ocean, AJ Lane, ME Xiang, Z Huang, X Schnoll-Sussman, F Holloway, SB Yu, B Wright, J Wadler, S AF Ocean, AJ Lane, ME Xiang, Z Huang, X Schnoll-Sussman, F Holloway, SB Yu, B Wright, J Wadler, S TI Genetic analysis of proteasome-related pathways in patients with advanced gastric adenocarcinomas (AGA) treated on a phase II study with PS-341 (bortezomib) with or without irinotecan. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Cornell Univ, Weill Med Coll, New York, NY USA. NCI, CTEP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 9717 BP 889S EP 889S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403527 PM 28016406 ER PT J AU Yu, CR Mahdi, RM Ebong, S Vistica, BP Chen, J Guo, YH Gery, I Egwuagu, CE AF Yu, CR Mahdi, RM Ebong, S Vistica, BP Chen, J Guo, YH Gery, I Egwuagu, CE TI Cell proliferation and STAT6 pathways are negatively regulated in T cells by STAT1 and suppressors of cytokine signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; LINEAGE COMMITMENT; GROWTH-FACTOR; IFN-GAMMA; TH2 DIFFERENTIATION; BINDING PROTEIN; IL-4 RECEPTOR; IN-VIVO; ACTIVATION; TRANSCRIPTION AB Suppressor of cytokine signaling (SOCS) proteins have emerged as important regulators of cytokine signals in lymphocytes. In this study, we have investigated regulation of SOCS expression and their role in Th cell growth and differentiation. We, show that SOCS genes are constitutively expressed in naive Th cells, albeit at low levels, and are differentially induced by Ag and Th-polarizing cytokines. Whereas cytokines up-regulate expression of SOCS1, SOCS2, SOCS3, and cytokine-induced Src homology 2 protein, Ags induce down-regulation of SOCS3 within 48 h of Th cell activation and concomitantly up-regulate SOCS1, SOCS2, and cytokine-induced Src homology 2 protein expression. We further show that STAT1 signals play major roles in inducing SOCS expression in Th cells and that induction of SOCS expression by IL-4, IL-12, or IFN-gamma is compromised in STAT1-deficient primary Th cells. Surprisingly, IL-4 is a potent inducer of STAT1 activation in Th2 but not Th1 cells, and SOCS1 or SOCS3 expression is dramatically reduced in STAT1(-/-) Th2 cells. To our knowledge, this is the first report of IL-4-induced STAT1 activation in Th cells, and suggests that its induction of SOCS, may in part, regulate IL-4 functions in Th2 cells. In fact, overexpression of SOCS1 in Th2 cells represses STAT6 activation and profoundly inhibits IL-4-induced proliferation, while depletion of SOCS1 by an anti-sense SOCS1 cDNA construct enhances cell proliferation and induces constitutive activation of STAT6 in Th2 cells. These results are consistent with a model where IL-4 has dual effects on differentiating T cells: it simulates proliferation/differentiation through STAT6 and autoregulates its effects on Th2 growth and effector functions via STAT1-dependent up-regulation of SOCS proteins. C1 NEI, NIH, Mol Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, NIH, Mol Immunol Sect, Immunol Lab, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM emeka@helix.nih.gov NR 51 TC 40 Z9 40 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 JUL 15 PY 2004 VL 173 IS 2 BP 737 EP 746 PG 10 WC Immunology SC Immunology GA 837IA UT WOS:000222621000005 PM 15240659 ER PT J AU Su, SB Silver, PB Wang, P Chan, CC Caspi, RR AF Su, SB Silver, PB Wang, P Chan, CC Caspi, RR TI Cholera toxin prevents Th1-mediated autoimmune disease by inducing immune deviation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; PERTUSSIS TOXIN; B-SUBUNIT; MUCOSAL ADJUVANT; DENDRITIC CELLS; TH2 CELLS; T-CELLS; INDUCTION; MICE; PROTEIN AB Cholera toxin (CT), a major enterotoxin produced by Vibrio cholerae, is known for its properties as a mucosal adjuvant that promotes Th2 or mixed Th1 + Th2 responses. In this study, we explore the ability of CT to act as a systemic adjuvant to counteract the Th1 response leading to experimental autoimmune uveitis. We report that susceptible B10.RIII mice immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein could be protected from disease by a single systemic injection of as little as 2 mug of CT at the time of immunization. The protected mice were not immunosuppressed, but rather displayed evidence of immune deviation. Subsequent adaptive responses to interphotoreceptor retinoid-binding protein showed evidence of Th2 enhancement, as indicated by reduced delayed-type hypersensitivity in the context of enhanced Ag-specific lymphocyte proliferation and IL-4 production. Ag-specific production of several other cytokines, including IFN-gamma, was not appreciably altered. The inhibitory effect of CT was dependent on the enzymatic A subunit of CT, because the cell-binding B subunit alone could not block disease development. Mice given CT displayed detectable IL-4 levels in their serum within hours of CT administration. This innate IL-4 production was critical for protection, as infusion of neutralizing Ab against IL-4 to mice, given a uveitogenic immunization and treated with CT, counteracted immune deviation and abrogated protection. Our data indicate that systemic administration of CT inhibits experimental autoimmune uveitis by skewing the response to the uveitogenic autoantigen to a nonpathogenic phenotype. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 41 TC 15 Z9 16 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 JUL 15 PY 2004 VL 173 IS 2 BP 755 EP 761 PG 7 WC Immunology SC Immunology GA 837IA UT WOS:000222621000007 PM 15240661 ER PT J AU Le, YY Iribarren, P Gong, WH Cui, YH Zhang, X Wang, JM AF Le, YY Iribarren, P Gong, WH Cui, YH Zhang, X Wang, JM TI TGF-beta 1 disrupts endotoxin signaling in microglial cells through Smad3 and MAPK pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TOLL-LIKE RECEPTORS; TGF-BETA; ALZHEIMERS-DISEASE; BACTERIAL LIPOPOLYSACCHARIDE; INFLAMMATORY CYTOKINES; CHEMOTACTIC AGONIST; ENDOTHELIAL-CELLS; GENE-EXPRESSION; CD14 RECEPTOR AB Human formyl peptide receptor-like I and its mouse homologue formyl peptide receptor 2 (FPR2) are G protein-coupled receptors used by a number of exogenous and host-derived chemotactic peptides, including the 42 aa form of beta amyloid peptide, a causative factor of Alzheimer's disease. Functional FPR2 was induced by bacterial LPS in murine microglial cells, the resident phagocytic cells that play a pivotal role in inflammatory and immunological diseases in the CNS. To identify agents that may suppress microglial cell activation under proinflammatory conditions, we investigated the effect of TGF-beta1 on the expression of functional FPR2 by microglial cells activated by LPS. TGF-beta1 dose-dependently inhibited the mRNA expression and function of FPR2 in,LPS-activated microglial cells. The inhibitory effect of TGF-beta1 was mediated by Smad3, a key signaling molecule coupled to the TGF-beta receptor, and the transcription coactivator, p300. Also, TGF-beta1 activates MAPKs in microglial cells that became refractory to further stimulation by LPS. These,effects of TGF-beta1 culminate in the inhibition of LPS-induced activation of NF-kappaB and the up-regulation of FPR2 in microglial cells. Thus, TGF-beta1 may exert a protective role in CNS diseases characterized by microglial cell activation by proinflammatory stimulants. C1 NCI, Immunogenet Mol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Immunogenet Mol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 FU PHS HHS [N01-C0-12400] NR 44 TC 36 Z9 36 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 JUL 15 PY 2004 VL 173 IS 2 BP 962 EP 968 PG 7 WC Immunology SC Immunology GA 837IA UT WOS:000222621000029 PM 15240683 ER PT J AU Tunyaplin, C Shaffer, AL Angelin-Duclos, CD Yu, X Staudt, LM Calame, KL AF Tunyaplin, C Shaffer, AL Angelin-Duclos, CD Yu, X Staudt, LM Calame, KL TI Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GERMINAL-CENTER FORMATION; B-CELL DIFFERENTIATION; LYMPHOCYTE DIFFERENTIATION; TRANSCRIPTIONAL REPRESSOR; TERMINAL DIFFERENTIATION; NEGATIVE AUTOREGULATION; BLIMP-1 EXPRESSION; IN-VIVO; C-MYC; GENE AB We have identified two intronic regions of mouse prdm1, the gene encoding B lymphocyte-induced maturation protein-1 (Blimp-1), which confer transcriptional repression in response to Bcl-6. The Bcl-6 response element in intron 5, which is conserved between mice and humans, was studied in detail. It binds Bcl-6 in vitro and was shown by chromatin immunoprecipitation to be occupied by Bcl-6 in vivo. Neither Bcl-6 response element functions as a STAT3-response element, showing that STAT3 does not compete with Bcl-6 at these sites. Bel-6(-/-) mice confirm the biological importance of Bcl-6-dependent repression of prdm1. These mice have elevated Ab response, increased Ig-secreting cells, and increased Blimp-1(+) cells in spleen following immunization and their splenic B cells show accelerated plasmacytic development in vitro. C1 Columbia Univ Coll Phys & Surg, Dept Microbiol & Biochem, Hammer Hlth Sci Ctr 1202, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Mol Biophys, New York, NY 10032 USA. NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Calame, KL (reprint author), Columbia Univ Coll Phys & Surg, Dept Microbiol & Biochem, Hammer Hlth Sci Ctr 1202, 701 W 168th St, New York, NY 10032 USA. EM klc1@columbia.edu FU NIAID NIH HHS [R01-AI43576]; PHS HHS [R01-50659] NR 37 TC 202 Z9 204 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2004 VL 173 IS 2 BP 1158 EP 1165 PG 8 WC Immunology SC Immunology GA 837IA UT WOS:000222621000051 PM 15240705 ER PT J AU Leifer, CA Kennedy, MN Mazzoni, A Lee, CW Kruhlak, MJ Segal, DA AF Leifer, CA Kennedy, MN Mazzoni, A Lee, CW Kruhlak, MJ Segal, DA TI TLR9 Is localized in the endoplasmic reticulum prior to stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; INTESTINAL EPITHELIAL-CELLS; CPG-DNA; BACTERIAL-DNA; MEDIATED PHAGOCYTOSIS; GOLGI-APPARATUS; B-CELLS; LIPOPOLYSACCHARIDE; ACTIVATION; DISTINCT AB In mammals, 10 TLRs recognize conserved pathogen-associated molecular patterns, resulting in the induction of inflammatory innate immune responses. One of these, TLR9, is activated intracellularly by bacterial DNA and synthetic oligodeoxynucleotides (ODN), containing unmethylated CpG dinucleotides. Following treatment with CpG ODN, TLR9 is found in lysosome-associated membrane protein type 1-positive lysosomes, and we asked which intracellular compartment contains TLR9 before CpG exposure. Surprisingly, we found by microscopy and supporting biochemical evidence that both transfected and endogenously expressed human TLR9 is retained in the endoplasmic reticulum. By contrast, human TLR4 trafficked to the cell surface, indicating that endoplasmic reticulum retention is not a property common to all TLRs. Because TLR9 is observed in endocytic vesicles following exposure to CpG ODN, our data indicate that a special mechanism must exist for translocating TLR9 to the signaling compartments that contain the CpG DNA. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Segal, DA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM Dave_segal@nih.gov FU NCI NIH HHS [K22 CA113705-03, K22 CA113705]; NIAID NIH HHS [R01 AI076588] NR 24 TC 205 Z9 215 U1 5 U2 12 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2004 VL 173 IS 2 BP 1179 EP 1183 PG 5 WC Immunology SC Immunology GA 837IA UT WOS:000222621000054 PM 15240708 ER PT J AU Voyich, JM Braughton, KR Sturdevant, DE Vuong, C Kobayashi, SD Porcella, SF Otto, M Musser, JM DeLeo, FR AF Voyich, JM Braughton, KR Sturdevant, DE Vuong, C Kobayashi, SD Porcella, SF Otto, M Musser, JM DeLeo, FR TI Engagement of the pathogen survival response used by group A streptococcus to avert destruction by innate host defense SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FIBRONECTIN-BINDING PROTEIN; CATIONIC ANTIMICROBIAL PEPTIDES; 2-COMPONENT REGULATORY SYSTEM; PSEUDOMONAS-AERUGINOSA; HUMAN-NEUTROPHILS; GENOME SEQUENCE; STREPTOLYSIN-S; MOLECULAR CHARACTERIZATION; VIRULENCE FACTORS; EPITHELIAL-CELLS AB Neutrophils are a critical component of human innate host defense and efficiently kill the vast majority of invading microorganisms. However, bacterial pathogens such as group A Streptococcus (GAS) successfully avert destruction by neutrophils to cause human infections. Relatively little is known about how pathogens detect components of the innate immune system to respond and survive within the host. In this study, we show that inactivation of a two-component gene regulatory system designated Ihk-Irr significantly attenuates streptococcal virulence in mouse models of soft tissue infection and bacteremia. Microarray analysis of wild-type and irr-negative mutant (irr mutant) GAS strains revealed that Ihk-Irr influenced expression of 20% of all transcripts in the pathogen genome. Notably, at least 11 genes involved in cell wall synthesis, turnover, and/or modification were down-regulated in the irr mutant strain. Compared with the wild-type strain, significantly more of the irr mutant strain was killed by human neutrophil components that destroy bacteria by targeting the cell envelope (cell wall and/or membrane). Unexpectedly, expression of ihk and irr was dramatically increased in the wild-type strain exposed to these same neutrophil products under conditions that favored cell envelope damage. We report a GAS mechanism for detection of innate host defense that initiates the pathogen survival response, in which cell wall synthesis is critical. Importantly, our studies identify specific genes in the pathogen survival response as potential targets to control human infections. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov NR 48 TC 42 Z9 43 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2004 VL 173 IS 2 BP 1194 EP 1201 PG 8 WC Immunology SC Immunology GA 837IA UT WOS:000222621000056 PM 15240710 ER PT J AU Goulet, JL Pace, AJ Key, ML Byrum, RS Nguyen, M Tilley, SL Morham, SG Langenbach, R Stock, JL McNeish, JD Smithies, O Coffman, TM Koller, BH AF Goulet, JL Pace, AJ Key, ML Byrum, RS Nguyen, M Tilley, SL Morham, SG Langenbach, R Stock, JL McNeish, JD Smithies, O Coffman, TM Koller, BH TI E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E-2 in acute cutaneous inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ARACHIDONIC-ACID; PROSTANOID RECEPTORS; GENE DISRUPTION; DEFICIENT MICE; EAR EDEMA; MOUSE; SKIN; LEUKOTRIENES; BIOSYNTHESIS; RESPONSES AB PGs are derived from arachidonic acid by PG-endoperoxide synthase (PTGS)-1 and PTGS2. Although enhanced levels of PGs are present during acute and chronic inflammation, a functional role for prostanoids in inflammation has not been clearly defined. Using a series of genetically engineered mice, we find that PTGS1 has the capacity to induce acute inflammation, but PTGS2 has negligible effects on the initiation of this response. Furthermore, we show that the contribution of PTGS1 is mediated by PGE(2) acting through the E-prostanoid (EP)3 receptor. Moreover, in the absence of EP3 receptors, inflammation is markedly attenuated, and the addition of nonsteroidal anti-inflammatory agents does not further impair the response. These studies demonstrate that PGE(2) promotes acute inflammation by activating EP3 receptors and suggest that EP3 receptors may be useful targets for anti-inflammatory therapy. C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Duke Univ, Dept Med, Div Nephrol, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr, Durham, NC 27705 USA. NIEHS, Lab Expt Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Pfizer Inc, Cent Res, Ctr Expt Therapeut, Groton, CT 06340 USA. RP Koller, BH (reprint author), Univ N Carolina, Dept Med, 4341 Mol Biol Res Bldg, Chapel Hill, NC 27599 USA. EM treawouns@aol.com FU NHLBI NIH HHS [R01-HL68141]; NIDDK NIH HHS [P01-DK38108, 5-T32-DK07731] NR 35 TC 40 Z9 41 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 JUL 15 PY 2004 VL 173 IS 2 BP 1321 EP 1326 PG 6 WC Immunology SC Immunology GA 837IA UT WOS:000222621000072 PM 15240726 ER PT J AU Flynn, PM Rudy, BJ Douglas, SD Lathey, J Spector, SA Martinez, J Silio, M Belzer, M Friedman, L D'Angelo, L McNamara, J Hodge, J Hughes, MD Lindsey, JC AF Flynn, PM Rudy, BJ Douglas, SD Lathey, J Spector, SA Martinez, J Silio, M Belzer, M Friedman, L D'Angelo, L McNamara, J Hodge, J Hughes, MD Lindsey, JC CA Pediatric AIDS Clinical Trial Grp TI Virologic and immunologic outcomes after 24 weeks in HIV type 1-infected adolescents receiving highly active antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, IL ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; T-LYMPHOCYTE SUBSETS; HIV-1-INFECTED INDIVIDUALS; IMMUNE RECONSTITUTION; POSITIVE ADOLESCENTS; INFECTED-ADOLESCENTS; EXCISION CIRCLES; ADULTS; NAIVE AB Background. Adolescents represent the fastest growing demographic group of new human immunodeficiency virus (HIV) infections in the United States. At present, there is little information available about their response to therapy. Methods. We studied 120 adolescents infected via high-risk behaviors who began receiving highly active antiretroviral therapy ( HAART), to determine their virologic and immunologic response to therapy. Results. Subjects were enrolled at 28 sites of the Pediatric Acquired Immunodeficiency Syndrome Clinical Trials Group. After 16 - 24 weeks of HAART, 59% of subjects had reproducible undetectable virus loads, according to repeat measurements ( virologic success). As enumerated by flow-cytometric analysis, increases in levels of CD4 helper cells ( both naive and memory) and decreases in levels of CD8 suppressor cells were observed. Partial restoration of some immunologic parameters for patients who did not achieve virologic success was also observed, but to a more limited extent than for adolescents with virologic success. Adherence to HAART was the only predictor of achieving undetectable virus loads. Conclusions. Adolescents have the capacity to improve their immunologic status with HAART. Lower than expected success in virologic control is related to lack of adherence, and efforts to improve treatment outcome must stress measures to assure adherence to medication. C1 St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Stroger Hosp Cook Cty CORE Ctr, Dept Pediat, Chicago, IL USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Childrens Hosp, Natl Med Ctr, Rockville, MD USA. NIAID, Rockville, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Flynn, PM (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA. EM pat.flynn@stjude.org NR 41 TC 58 Z9 58 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2004 VL 190 IS 2 BP 271 EP 279 DI 10.1086/421521 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 832GH UT WOS:000222254800009 PM 15216461 ER PT J AU Vieira, PP Ferreira, MU Alecrim, MDGA Alecrim, WD da Silva, LHP Sihuincha, MSM Joy, DA Mu, JB Su, XZ Zalis, MG AF Vieira, PP Ferreira, MU Alecrim, MDGA Alecrim, WD da Silva, LHP Sihuincha, MSM Joy, DA Mu, JB Su, XZ Zalis, MG TI pfcrt polymorphism and the spread of chloroquine resistance in Plasmodium falciparum populations across the Amazon Basin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIMALARIAL-DRUGS; SOUTH-AMERICA; MALARIA; BRAZIL; MUTATIONS; REGION; MEFLOQUINE; MECHANISMS; EFFICACY; MARKER AB The widespread occurrence of drug-resistant malaria parasites in South America presents a formidable obstacle to disease control in this region. To characterize parasite populations and the chloroquine-resistance profile of Plasmodium falciparum in the Amazon Basin, we analyzed a DNA segment of the pfcrt gene, spanning codons 72 - 76, and genotyped 15 microsatellite (MS) markers in 98 isolates from 6 areas of Brazil, Peru, and Colombia where malaria is endemic. The K76T mutation, which is critical for chloroquine resistance, was found in all isolates. Five pfcrt haplotypes ( S[tct] MNT, S[agt] MNT, CMNT, CMET, and CIET) were observed, including 1 previously found in Asian/African isolates. MS genotyping showed relatively homogeneous genetic backgrounds among the isolates, with an average of 3.8 alleles per marker. Isolates with identical 15-loci MS haplotypes were found in different locations, suggesting relatively free gene flow across the Amazon Basin. Allopatric isolates carrying SMNT and CMNT haplotypes have similar genetic backgrounds, although parasites carrying the CIET haplotype have some exclusive MS alleles, suggesting that parasites with CIET alleles were likely to have been introduced into Brazil from Asia or Africa. This study provides the first evidence of the Asian pfcrt allele in Brazil and a detailed analysis of P. falciparum populations, with respect to pfcrt haplotypes, in the Amazon Basin. C1 Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Biofis Carlos Chagas Filho, BR-21941590 Rio De Janeiro, Brazil. UFRJ, Hosp Univ Clementino Fraga Filho, Dept Doencas Infectoparasitarias, Rio De Janeiro, Brazil. Fdn Med Trop Amazonas, Manaus, Amazonas, Brazil. Ctr Univ Nilton Lins, Manaus, Amazonas, Brazil. Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, Sao Paulo, Brazil. Ctr Pesquisa Med Trop, Porto Velho Rondonia, Brazil. Lab Referencial Loreto, Iquitos, Peru. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Zalis, MG (reprint author), Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Biofis Carlos Chagas Filho, Ilha Fundao, BR-21941590 Rio De Janeiro, Brazil. EM mgzalis@biof.ufrj.br RI Ferreira, Marcelo/G-8289-2011; OI Ferreira, Marcelo/0000-0002-5293-9090; Su, Xinzhuan/0000-0003-3246-3248 NR 30 TC 56 Z9 58 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2004 VL 190 IS 2 BP 417 EP 424 DI 10.1086/422006 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 832GH UT WOS:000222254800029 PM 15216481 ER PT J AU Nelson, ME Loktionova, NA Pegg, AE Moschel, RC AF Nelson, ME Loktionova, NA Pegg, AE Moschel, RC TI 2-amino-O-4-benzylpteridine derivatives: Potent inactivators of O-6-alkylguanine-DNA alkyltransferase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID O-6-BENZYLGUANINE DERIVATIVES; MALIGNANT GLIOMA; REPAIR; DNA; INHIBITION; DEPLETION; AGENTS; TRIAL AB 2-Amino-O-4-benzylpteridine (1), 2-amino-O-4-benzyl-6,7-dimethylpteridine (2), 2-amino-O-4- benzyl-6-hydroxymethylpteridine (4), 2-amino-O-4-benzylpteridine-6-carboxylic acid (5), 2-amino-O-4-benzyl-6-formylpteridine (6), and O-4-benzylfolic acid (7) are shown to be as potent or more potent inactivators of the human DNA repair protein O-6-alkylguanine-DNA alkyltransferase (alkyltransferase) in vitro than O-6-benzylguanine, the prototype alkyltransferase inactivator currently in clinical trials. Additionally, the negatively charged (at physiological pH) inactivators 2-amino-O-4-benzylpteridine-6-carboxylic acid (5) and O-4-benzylfolate (7) are far more water soluble than O-6-benzylguanine. The activity of O-4-benzylfolic acid (7) is particularly noteworthy because it is roughly 30 times more active than O-6-benzylguanine against the wild-type alkyltransferase and is even capable of inactivating the P140K mutant alkyltransferase that is resistant to inactivation by O-6-benzylguanine. All the pteridine derivatives except 2-amino-O-4-benzylpteridine-6-carboxylic acid are effective in enhancing cell killing by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). However, the effectiveness of O-4-benzylfolate as an adjuvant for cell killing by BCNU appears to be a function of a cell's alpha-folate receptor expression. Thus, O-4-benzylfolate is least effective as an adjuvant in A549 cells (which express little if any receptor), is moderately effective in HT29 cells (which express low levels of the receptor), but is very effective in KB cells (which are known to express high levels of the alpha-folate receptor). Therefore, O-4-benzylfolic acid shows promise as an agent for possible tumor-selective alkyltransferase inactivation, which suggests it may prove to be superior to O-6-benzylguanine as a chemotherapy adjuvant. C1 NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. RP Moschel, RC (reprint author), NCI, Lab Comparat Carcinogenesis, POB B,Bldg 538, Frederick, MD 21702 USA. EM moschel@mail.ncifcrf.gov NR 18 TC 35 Z9 35 U1 2 U2 9 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 JUL 15 PY 2004 VL 47 IS 15 BP 3887 EP 3891 DI 10.1021/jm049758+ PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 836BS UT WOS:000222530700018 PM 15239666 ER PT J AU Liu, X Groschner, K Ambudkar, IS AF Liu, X Groschner, K Ambudkar, IS TI Distinct Ca2+-permeable cation currents are activated by internal Ca2+-store depletion in RBL-2H3 cells and human salivary gland cells, HSG and HSY SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE store-operated channels; calcium; cations; salivary epithelial cells; thapsigargin; IP ID OPERATED CRAC CHANNELS; SMOOTH-MUSCLE-CELLS; CA2+ INFLUX; CALCIUM-ENTRY; FEEDBACK INHIBITION; PLASMA-MEMBRANE; STORE DEPLETION; MAST-CELLS; RELEASE; TRPC1 AB Store-operated Ca2+ influx, suggested to be mediated via store-operated cation channel (SOC), is present in all cells. The molecular basis of SOC, and possible heterogeneity of these channels, are still a matter of controversy. Here we have compared the properties of SOC currents (I-SOC) in human sub-mandibular glands cells (HSG) and human parotid gland cells (HSY) with I-CRAC (Ca2+ release-activated Ca2+ current) in RBL cells. Internal Ca2+ store-depletion with IP3 or thapsigargin activated cation channels in all three cell types. 1 muM Gd3+ blocked channel activity in all cells. Washout of Gd3+ induced partial recovery in HSY and HSG but not RBL cells. 2-APB reversibly inhibited the channels in all cells. in RBL cells displayed strong inward rectification with E-rev(Ca) = > + 90 mV and E-rev (Na) = +60 mV. I-SOC in HSG cells showed weaker rectification with E-rev(Ca) = +25 mV and L-rev (Na) + 10 mV. HSY cells displayed a linear current with E-rev = + 5 mV, which was similar in Ca2+_ or Na+-containing medium. pCa/pNa was > 500, 40, and 4.6 while pCs /pNa was 0. 1, 1, and 1. 3, for RBL, HSG, and HSY cells, respectively. Evidence for anomalous mole fraction behavior of Ca2+ /Na+ permeation was obtained with RBL and HSG cells but not HSY cells. Additionally, channel inactivation with Ca (2+) + Na+ or Na+ in the bath was different in the three cell types. In aggregate, these data demonstrate that distinct store-dependent cation currents are stimulated in RBL, HSG, and HSY cells. Importantly, these data suggest a molecular heterogeneity, and possibly cell-specific differences in the function, of these channels. C1 Natl Inst Dent Craniofacial Res, Secretory Physiol Sect, Gene Therapy Therapeut Branch, NIH,DHHS, Bethesda, MD 20892 USA. Graz Univ, Dept Pharmacol & Toxicol, Graz, Austria. RP Ambudkar, IS (reprint author), Natl Inst Dent Craniofacial Res, Secretory Physiol Sect, Gene Therapy Therapeut Branch, NIH,DHHS, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov RI Groschner, Klaus/A-2550-2010 NR 39 TC 42 Z9 44 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUL 15 PY 2004 VL 200 IS 2 BP 93 EP 104 DI 10.1007/s00232-004-0698-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 857YS UT WOS:000224157500004 PM 15520907 ER PT J AU Cheng, CM Hicks, K Wang, J Eagles, DA Bondy, CA AF Cheng, CM Hicks, K Wang, J Eagles, DA Bondy, CA TI Caloric restriction augments brain glutamic acid decarboxylase-65 and-67 expression SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE GABA; seizures; epilepsy; ketones; ketogenic diet ID KETOGENIC DIET INCREASES; GENE-EXPRESSION; CLEFT-PALATE; MICE LACKING; IN-VIVO; GABA; EPILEPSY; EFFICACY; SEIZURES; RECEPTOR AB The ketogenic diet is a very low-carbohydrate, high-fat diet used to treat refractory epilepsy. We hypothesized that this diet may act by increasing expression of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in gamma-aminobutyric acid (GABA) synthesis. Thus, we evaluated brain GAD levels in a well-established, seizuresuppressing, rodent model of the ketogenic diet. Because the diet is most effective when administered with a modest (similar to10%) calorie restriction, we studied three groups of animals: rats fed ad libitum standard rat chow (Ad lib-Std); calorie-restricted standard chow (CR-Std); and an isocaloric, calorie-restricted ketogenic diet (CR-Ket). We found that GAD67 mRNA was significantly increased in the inferior and superior colliculi and cerebellar cortex in both CR diet groups compared with control (e.g., by 45% in the superior colliculus and by 71% in the cerebellar cortex; P < .001). GAD65 mRNA was selectively increased in the superior colliculus and temporal cortex in both CR-Std and CR-Ket diet groups compared with ad lib controls. The only apparent CR-Ket-specific effect was a 30% increase in GAD67 mRNA in the striatum (P = .03). Enhanced GAD immunoreactivity was detected in parallel with the mRNA changes. These data clearly show that calorie restriction increases brain GAD65 and -67 expression in several brain regions, independent of ketogenic effects. These observations may explain why caloric restriction improves the efficacy of the ketogenic diet in treating epilepsy and suggest that diet modification might be useful in treatment of a number of brain disorders characterized by impaired GAD or GABA activity. (C) 2004 Wiley-Liss, Inc. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov NR 38 TC 38 Z9 42 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 15 PY 2004 VL 77 IS 2 BP 270 EP 276 DI 10.1002/jnr.20144 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 834KZ UT WOS:000222411300011 PM 15211593 ER PT J AU Klauda, JB Jiang, JW Sandler, SI AF Klauda, JB Jiang, JW Sandler, SI TI An ab initio study on the effect of carbon surface curvature and ring structure on N-2(O-2)-carbon intermolecular potentials SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID COUPLED-CLUSTER CALCULATIONS; MONTE-CARLO-SIMULATION; INTERACTION ENERGIES; GRAPHITIC CARBON; N-2 ADSORPTION; BASIS-SET; MOLECULES; MODEL; DEPENDENCE; MEMBRANES AB The effect of carbon surface curvature and ring structure on the gas-carbon interaction potential is not well understood. Potentials derived from gas-graphite adsorption measurements are commonly used in molecular simulations with curved carbon surfaces, e.g., nanotubes, fullerenes, and other nanoporous carbons. Presented here are quantum mechanical (QM) calculations of the interactions of nitrogen and oxygen with three carbon surfaces of different curvatures (graphite, C-60 fullerene, and C-168 schwarzite). Generally, QM calculations at the CCSD(T) level are required to obtain accurate interaction energies for these systems; here a recently developed, computationally efficient Hybrid Method for Interaction Energies (HM-IE) of comparable accuracy was used. Atom-site intermolecular potentials fit to the quantum mechanical results produce accurate predictions of the experimentally measured second virial coefficient of adsorption for nitrogen on graphite. The QM-based gas-carbon potentials for C-60 and C-168 were found to be different than for graphite, and result in increased adsorption energies for nitrogen on these surfaces. We conclude that molecular simulations based on the assumption that the gas-carbon interaction potentials are invariant to carbon surface curvature and ring structure may result in incorrect property predictions. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Delaware, Ctr Mol & Engn Thermodynam, Dept Chem Engn, Newark, DE 19716 USA. RP Klauda, JB (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3308,50 S Dr, Bethesda, MD 20892 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008; Sandler, Stanley/A-8866-2009; JIANG, Jianwen/G-1505-2013 NR 42 TC 30 Z9 31 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 15 PY 2004 VL 108 IS 28 BP 9842 EP 9851 DI 10.1021/jp037897h PG 10 WC Chemistry, Physical SC Chemistry GA 837MP UT WOS:000222639900044 ER PT J AU Sandstrom, DJ AF Sandstrom, DJ TI Isoflurane depresses glutamate release by reducing neuronal excitability at the Drosophila neuromuscular junction SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID VOLATILE GENERAL-ANESTHETICS; TRANSMITTER RELEASE; SYNAPTIC-TRANSMISSION; INHALED ANESTHETICS; K+ CHANNELS; MELANOGASTER; HALOTHANE; MUTANTS; TEMPERATURE; SENSITIVITY AB The mechanisms through which volatile general anaesthetics exert their behavioural effects remain unclear. The accessibility of the Drosophila larval neuromuscular junction to genetic and neurophysiological analysis has made it an attractive model system for identification of anaesthetic targets. This study provides a mechanistic basis for the genetic analysis of anaesthetic action, by analysing the neurophysiological effects of the volatile anaesthetic isoflurane on axonal and synaptic function in the Drosophila larva. The most robust effect of isoflurane was a reversible decrease in the amplitude and area of glutamatergic excitatory junctional currents (EJCs) evoked at the neuromuscular junction. Isoflurane did not affect postsynaptic glutamate receptor function detectably, in that the amplitudes, areas and decay times of spontaneous miniature EJCs were unchanged at any concentration. Therefore, decreased EJC amplitude resulted from reduction of neurotransmitter release. Reduced neurotransmitter release was associated with decreased presynaptic excitability, measured as increased delay to EJC onset and reduced axonal conduction velocity. EJC amplitude was rescued to control levels by direct electrotonic stimulation of the synapse in the presence of tetrodotoxin, indicating that isoflurane inhibits neurotransmitter release by reducing presynaptic excitability. In addition, isoflurane reduced release probability, measured as increased paired-pulse facilitation. The EC50 for suppression of larval locomotion was similar to that for reduction of transmitter release, indicating that the axonal and synaptic effects were occurring in a behaviourally relevant range. These results provide a cellular context for ongoing genetic and neurophysiological analyses of volatile anaesthetic action in Drosophila, and suggest candidate anaesthetic target molecules. C1 NIMH, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. RP Sandstrom, DJ (reprint author), NIMH, Lab Mol Biol, NIH, MSC 4034, Bethesda, MD 20892 USA. EM sandstrd@mail.nih.gov NR 47 TC 32 Z9 32 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 15 PY 2004 VL 558 IS 2 BP 489 EP 502 DI 10.1113/jphysiol.2004.065748 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 841JQ UT WOS:000222926500011 PM 15169847 ER PT J AU Pacher, P Batkai, S Kunos, G AF Pacher, P Batkai, S Kunos, G TI Haemodynamic profile and responsiveness to anandamide of TRPV1 receptor knock-out mice SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CANNABINOID CB1 RECEPTORS; SENSITIVE SENSORY NERVES; MESENTERIC ARTERIAL BED; VANILLOID RECEPTORS; ENDOGENOUS CANNABINOIDS; INDUCED VASORELAXATION; INDUCED HYPOTENSION; HYPERTENSIVE-RATS; HEART-FAILURE; MEDIATE AB The endocannabinoid anandamide and cannabinoid (CB) receptors have been implicated in the hypotension in various forms of shock and in advanced liver cirrhosis. Anandamide also activates vanilloid TRPV1 receptors on sensory nerve terminals, triggering the release of calcitonin gene-related peptide which elicits vasorelaxation in isolated blood vessels in vitro. However, the contribution of TRPV1 receptors to the in vivo hypotensive effect of anandamide is equivocal. We compared the cardiac performance of anaesthetized TRPV1 knockout (TRPV1-/-) mice and their wild-type (TRPV1+/+) littermates and analysed in detail the haemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters and systolic and diastolic function at different preloads were similar in TRPV1-/- and TRPV1+/+ mice. The predominant hypotensive response to bolus intravenous injections of anandamide and the associated decrease in cardiac contractility and total peripheral resistance (TPR) were similar in TRPV1+/+ and TRPV1-/- mice, as was the ability of the CB1 receptor antagonist SR141716 to completely block these effects. In TRPV1+/+ mice, this hypotensive response was preceded by a transient, profound drop in cardiac contractility and heart rate and an increase in TPR, followed by a brief pressor response, effects which were unaffected by SR141716 and were absent in TRPV1-/- mice. These results indicate that mice lacking TRPV1 receptors have a normal cardiovascular profile and their predominant cardiovascular depressor response to anandamide is mediated through CB, receptors. The role of TRPV1 receptors is limited to the transient activation of the Bezold-Jarisch reflex by very high initial plasma concentrations of anandamide. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z99 AA999999] NR 43 TC 79 Z9 80 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 15 PY 2004 VL 558 IS 2 BP 647 EP 657 DI 10.1113/jphysiol.2004.064824 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 841JQ UT WOS:000222926500022 PM 15121805 ER PT J AU Meertens, L Pise-Masison, C Quere, N Brady, J Gessain, A Mahieux, R AF Meertens, L Pise-Masison, C Quere, N Brady, J Gessain, A Mahieux, R TI Utilization of the CBP but not the p300 co-activator by human T-lymphotropic virus type-2 Tax for p53 inhibition SO ONCOGENE LA English DT Article DE HTLV; tax; p53; CBP/p300; NF-kappa B ID CELL LEUKEMIA-VIRUS; NF-KAPPA-B; CREB BINDING-PROTEIN; WILD-TYPE P53; II HTLV-II; TRANSCRIPTIONAL ACTIVATION; TRANSACTIVATION FUNCTION; FUNCTIONAL IMPAIRMENT; ABERRANT EXPRESSION; DOMAIN AB We previously reported, both in transfected cells and in human T-cell leukemia virus type-2 subtype B infected cells, that the viral transactivator Tax-2B protein could inhibit p53 functions. We have now investigated the mechanism through which Tax-2B represses p53 using GFPTax-2B fusion proteins. We present evidence that Tax-2B inhibition of p53 function is not linked to CREB/ ATF activation, but is uniquely correlated with the interaction of CREB binding protein (CBP), but not p300, with the C-terminus of Tax-2B. Wild type, but not a Tax-2B-M47 mutant, inhibits p53 function in adherent cells. We demonstrate that both Tax-2B and Tax-2B-M47 can bind p300, while Tax-2B-M47 is impaired for CBP binding. Importantly, transfection of increasing amounts of CBP but not p300 or p300/CBP-associated factor (P/CAF) could rescue p53 transcriptional activity in the presence of Tax-2B in nonlymphocytic cells. In lymphoid cells, Tax-2B mediated inhibition of p53 is correlated with the NF-kappaB pathway activation and could be prevented by the overexpression of an IkappaBalpha mutant. Given the similarities between the functional domains of CBP and p300, these results are intriguing and suggest that Tax-2B must bind the CR2 domain of CBP, but not that of p300 in order to repress p53. C1 Inst Pasteur, Unite Edpidemiol & Physiopathol Virus Oncogenes, F-75724 Paris 15, France. NCI, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Mahieux, R (reprint author), Inst Pasteur, Unite Edpidemiol & Physiopathol Virus Oncogenes, 28 Rue Dr Roux, F-75724 Paris 15, France. EM rmahieux@pasteur.fr RI Meertens, Laurent/E-8043-2017 NR 57 TC 21 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 15 PY 2004 VL 23 IS 32 BP 5447 EP 5458 DI 10.1038/sj.onc.1207719 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 836XB UT WOS:000222588400004 PM 15156194 ER PT J AU Boukari, H Chernomordik, V Krueger, S Nossal, R Sackett, DL AF Boukari, H. Chernomordik, V. Krueger, S. Nossal, R. Sackett, D. L. TI Small-angle neutron scattering studies of tubulin ring polymers SO PHYSICA B-CONDENSED MATTER LA English DT Article DE Neutron scattering; Tubulin rings AB We applied SANS to study nanoscale structures formed from tubulin and either of two similar peptides, cryptophycin1 and dolastatin10. A simple bead ring model adequately describes the cryptophycin-tubulin data, indicating high monodispersity and non-association of the rings. In contrast, dolastatin-tubulin samples show secondary assembly of larger structures. Analysis indicates that these macrostructures may contain locally stacked rings. (C) 2004 Elsevier B.V. All rights reserved. C1 [Boukari, H.; Chernomordik, V.; Nossal, R.; Sackett, D. L.] NIH, Bethesda, MD 20892 USA. [Krueger, S.] NIST, Gaithersburg, MD 20899 USA. RP Boukari, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM boukarih@mail.nih.gov NR 12 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-4526 J9 PHYSICA B JI Physica B PD JUL 15 PY 2004 VL 350 IS 1-3 SU 1 BP E533 EP E535 DI 10.1016/j.physb.2004.03.145 PG 3 WC Physics, Condensed Matter SC Physics GA V16RY UT WOS:000207887900133 ER PT J AU Taha, TE Kumwenda, NI Hoover, DR Fiscus, SA Kafulafula, G Nkhoma, C Nour, S Chen, S Liomba, G Miotti, PG Broadhead, RL AF Taha, TE Kumwenda, NI Hoover, DR Fiscus, SA Kafulafula, G Nkhoma, C Nour, S Chen, S Liomba, G Miotti, PG Broadhead, RL TI Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MOTHER-TO-CHILD; HUMAN-IMMUNODEFICIENCY-VIRUS; PREGNANT-WOMEN; ANTIRETROVIRAL PROPHYLAXIS; ORAL ZIDOVUDINE; COTE-DIVOIRE; DOUBLE-BLIND; PHARMACOKINETICS; INTRAPARTUM; PREVENTION AB Context Antenatal counseling and human immunodeficiency virus (HIV) testing are not universal in Africa; thus, women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine (NVP) regimen (a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth). Objective To determine risk of mother-to-child transmission of HIV when either standard use of NVP alone or in combination with zidovudine (ZDV) was administered to infants of women tested at delivery. Design, Setting, and Participants A randomized, open-label, phase 3 trial conducted between April 1, 2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial included all infants born to 894 women who were HIV positive, received NVP intrapartum, and were previously antiretroviral treatment-naive. Infants were randomly assigned to NVP (n=448) and NVP plus ZDV (n=446). Infants were enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18 months. The HIV status of 90% of all infants was established at 6 to 8 weeks. intervention Mothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg of ZDV twice per day for a week. Main Outcome Measures HIV infection of infant at birth and 6 to 8 weeks, and adverse events. Results The mother-to-child transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only and 10.1% (45/444) in those administered NVP plus ZDV (P=.30). A life table estimate of transmission at 6 to 8 weeks was 14.1% (95% confidence interval [0], 10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those who received NVP plus ZDV (P=.36). For infants not infected at birth and retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who received NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P=.88). Almost all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks. Grades 3 and 4 adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants receiving NVP only and NVP plus ZDV, respectively (P=.76). Conclusions The frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa. The safety of the regimen containing neonatal ZDV was similar to that of a standard NVP regimen. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Rutgers State Univ, Dept Stat, Piscataway, NJ USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. Univ Malawi, Coll Med, Zomba, Malawi. Johns Hopkins Univ, Coll Med, Minist Hlth Res Project, Blantyre, Malawi. NIH, Off AIDS Res, Bethesda, MD 20892 USA. RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Room E7138,615 N Wolfe St, Baltimore, MD 21205 USA. EM ttaha@jhsph.edu FU FIC NIH HHS [5R03TW01199] NR 31 TC 113 Z9 116 U1 1 U2 2 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 JUL 14 PY 2004 VL 292 IS 2 BP 202 EP 209 DI 10.1001/jama.292.2.202 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 836TS UT WOS:000222579300025 PM 15249569 ER PT J AU Kottilil, S Polis, MA Kovacs, JA AF Kottilil, S Polis, MA Kovacs, JA TI HIV infection, hepatitis C infection, and HAART - Hard clinical choices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; LIVER FIBROSIS; PROTEASE INHIBITORS; RISK-FACTORS; PEGINTERFERON ALPHA-2B; LAMIVUDINE WITHDRAWAL; RANDOMIZED-TRIAL; PLUS RIBAVIRIN AB Abnormalities in hepatic function have become one of the most common complications occurring among human immunodeficiency virus (HIV)infected individuals receiving highly active antiretroviral therapy (HAART), and liver disease has become an increasingly important cause of morbidity and mortality in HIV-infected patients. We present a case of a patient with HIV infection and hepatotoxicity that exemplifies the complications currently observed during the treatment of such patients. Hepatotoxicity can be a result of several factors, including a direct effect of HAART, substance abuse, and coinfection with either hepatitis C virus (HCV) or hepatitis B virus. Imaging studies may be helpful in determining the etiology; however, a liver biopsy is often necessary to be able to more accurately determine the relative contributions of different processes. Although coinfection with HCV and HIV has become a common clinical problem, optimal treatment of such patients remains to be defined and must be individualized to maximize benefit and tolerance. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), Bldg 10,Room 7D43,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov OI Polis, Michael/0000-0002-9151-2268 NR 60 TC 19 Z9 20 U1 0 U2 2 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 JUL 14 PY 2004 VL 292 IS 2 BP 243 EP 250 DI 10.1001/jama.292.2.243 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 836TS UT WOS:000222579300030 PM 15249574 ER PT J AU Temple, JL Laing, E Sunder, A Wray, S AF Temple, JL Laing, E Sunder, A Wray, S TI Direct action of estradiol on gonadotropin-releasing hormone-1 neuronal activity via a transcription-dependent mechanism SO JOURNAL OF NEUROSCIENCE LA English DT Article DE estrogen receptor beta; LHRH; calcium imaging; pulsatility; estradiol; GnRH-1 ID ESTROGEN-RECEPTOR-BETA; EMBRYONIC OLFACTORY PLACODE; LUTEINIZING-HORMONE; LHRH NEURONS; EXPLANT CULTURES; STEROID FEEDBACK; RHESUS-MONKEY; MESSENGER-RNA; GNRH NEURONS; MICE LACKING AB Pulsatile secretion of gonadotropin-releasing hormone-1 (GnRH-1) is essential for reproduction. GnRH-1 induces gonadotropin release and is regulated by 17beta-estradiol (E2). Although a subpopulation ofGnRH-1 neurons expresses estrogen receptor (ER) beta, it is unclear whether E2 acts directly on GnRH-1 neurons or indirectly through interneuronal connections. To test the hypothesis that E2 acts directly on GnRH-1 neurons to regulate neuronal activity, we used calcium imaging to monitor intracellular calcium oscillations in GnRH-1 neurons maintained in nasal explants. TTX was used to minimize synaptic input from other cells. Consistent with previous studies, TTX reduced the activity of individual GnRH-1 neurons to a basal level, while the population of cells maintained synchronized calcium oscillations. Exposure of GnRH-1 cells to TTX plus E2 increased the number of calcium peaks/cell, percentage of cells with greater than or equal to10 peaks, mean peak amplitude, and percentage of cells that contributed to each calcium pulse in explants maintained in vitro for 7 d ( 7 div) compared with TTX alone. These effects were induced within 30 min and were not mimicked by 17alpha-estradiol, E2 conjugated to BSA ( which does not cross the plasma membrane), or seen at 21 div, when the percentage of GnRH-1 cells expressing ERbeta transcripts declines. In addition, these effects were inhibited by the ER antagonist ICI 182,780 and prevented by inhibition of gene transcription. These data suggest that, via ERbeta, E2 can rapidly act as a hormone-activated transcription complex and are the first to show that E2 directly increases GnRH-1 neuronal activity and synchronization. C1 Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), 36 Convent Dr,Bldg 36,Room 5A21, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 NR 49 TC 64 Z9 67 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 14 PY 2004 VL 24 IS 28 BP 6326 EP 6333 DI 10.1523/JNEUROSCI.1006-04.2004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 837QI UT WOS:000222650000011 PM 15254088 ER PT J AU Lavezzari, G McCallum, J Dewey, CM Roche, KW AF Lavezzari, G McCallum, J Dewey, CM Roche, KW TI Subunit-specific regulation of NMDA receptor endocytosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE internalization; clathrin; endocytosis; glutamate receptors; trafficking; endocytic sorting ID ER RETENTION SIGNAL; RAT CORTICAL-NEURONS; SURFACE EXPRESSION; GLUTAMATE RECEPTORS; DEVELOPMENTAL-CHANGES; HIPPOCAMPAL-NEURONS; SORTING SIGNALS; INTERNALIZATION; COMPLEX; BINDING AB At excitatory synapses, both NMDA and AMPA receptors are localized to the postsynaptic density (PSD). However, unlike AMPA receptors, synaptic NMDA receptors are stable components of the PSD. Even so, surface-expressed NMDA receptors undergo endocytosis, which is more robust early in development and declines during synaptic development. We investigated the subunit-specific contributions to NMDA receptor endocytosis, specifically defining the endocytic motifs and endocytic pathways preferred by the NR2A and NR2B subunits. We find that NR2A and NR2B have distinct endocytic motifs encoded in their distal C termini and that these interact with clathrin adaptor complexes with differing affinities. We also find that NR2A and NR2B sort into different intracellular pathways after endocytosis, with NR2B preferentially trafficking through recycling endosomes. In mature cultures, we find that NR2B undergoes more robust endocytosis than NR2A, consistent with previous studies showing that NR2A is more highly expressed at stable synaptic sites. Our findings demonstrate fundamental differences between NR2A and NR2B that help clarify developmental changes in NMDA receptor trafficking and surface expression. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Roche, KW (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bldg 36,Room 5B20, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 NR 38 TC 147 Z9 157 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 14 PY 2004 VL 24 IS 28 BP 6383 EP 6391 DI 10.1523/JNEUROSCI.1890-04.2004 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 837QI UT WOS:000222650000017 PM 15254094 ER PT J AU Yip, VLY Varrot, A Davies, GJ Rajan, SS Yang, XJ Thompson, J Anderson, WF Withers, SG AF Yip, VLY Varrot, A Davies, GJ Rajan, SS Yang, XJ Thompson, J Anderson, WF Withers, SG TI An unusual mechanism of glycoside hydrolysis involving redox and elimination steps by a family 4 beta-glycosidase from Thermotoga maritima SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ALPHA-GLUCOSIDASE AGLA; FUSOBACTERIUM-MORTIFERUM; CRYSTAL-STRUCTURE; ASSIGNMENT; HYDROLASE; GLYCOSYLHYDROLASES; IDENTIFICATION; METABOLISM; SUCROSE; DEFINES C1 Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. Univ York, Dept Chem, Struct Biol Lab, York YO10 5YW, N Yorkshire, England. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIDCR, Microbial Biochem & Genet Unit, NIH, Bethesda, MD 20892 USA. RP Withers, SG (reprint author), Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. EM withers@chem.ubc.ca NR 22 TC 72 Z9 77 U1 2 U2 24 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 JUL 14 PY 2004 VL 126 IS 27 BP 8354 EP 8355 DI 10.1021/ja0147632w PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 837EZ UT WOS:000222612600002 PM 15237973 ER PT J AU Yang, LJ Arora, K Beard, WA Wilson, SH Schlick, T AF Yang, LJ Arora, K Beard, WA Wilson, SH Schlick, T TI Critical role of magnesium ions in DNA polymerase beta's closing and active site assembly SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID STATE KINETIC-ANALYSIS; NUCLEOTIDE INCORPORATION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; KLENOW FRAGMENT; CONFORMATIONAL-CHANGES; REVERSE-TRANSCRIPTASE; BIOMOLECULAR DYNAMICS; COMPUTER-SIMULATION; STRUCTURAL INSIGHTS AB To dissect the effects of the nucleotide-binding and catalytic metal ions on DNA polymerase mechanisms for DNA repair and synthesis, aside from the chemical reaction, we investigate their roles in the conformational transitions between closed and open states and assembly/disassembly of the active site of polymerase beta/DNA complexes before and after the chemical reaction of nucleotide incorporation. Using dynamics simulations, we find that closing before chemical reaction requires both divalent metal ions in the active site while opening after the chemical reaction is triggered by release of the catalytic metal ion. The critical closing is stabilized by the interaction of the incoming nucleotide with conserved catalytic residues (Asp190, Asp192, Asp256) and the two functional magnesium ions; without the catalytic ion, other protein residues (Arg180, Arg183, Gly189) coordinate the incomer's triphosphate group through the nucleotide-binding ion. Because we also note microionic heterogeneity near the active site, Mg2+ and Na+ ions can diffuse into the active site relatively rapidly, we suggest that the binding of the catalytic ion itself is not a rate-limiting conformational or overall step. However, geometric adjustments associated with functional ions and proper positioning in the active site, including subtle but systematic motions of protein side chains (e.g., Arg258), define slow or rate-limiting conformational steps that may guide fidelity mechanisms. These sequential rearrangements are likely sensitively affected when an incorrect nucleotide approaches the active site. Our suggestion that subtle and slow adjustments of the nucleotide-binding and catalytic magnesium ions help guide polymerase selection for the correct nucleotide extends descriptions of polymerase pathways and underscores the importance of the delicate conformational events both before and after the chemical reaction to polymerase efficiency and fidelity mechanisms. C1 NYU, Dept Chem, New York, NY 10012 USA. NYU, Courant Inst Math Sci, New York, NY 10012 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Schlick, T (reprint author), NYU, Dept Chem, 251 Mercer St, New York, NY 10012 USA. EM schlick@nyu.edu OI arora, karunesh/0000-0003-3726-5304 FU NIGMS NIH HHS [R01 GM55164] NR 75 TC 81 Z9 82 U1 1 U2 11 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 JUL 14 PY 2004 VL 126 IS 27 BP 8441 EP 8453 DI 10.1021/ja049412o PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 837EZ UT WOS:000222612600030 PM 15238001 ER PT J AU Kim, S AF Kim, S TI Characterization of the prothrombin gene expression during nerve differentiation SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE prothrombin; cAMP; CRE; CREM; neuroblastoma ID PROTEASE-ACTIVATED RECEPTORS; TISSUE-PLASMINOGEN ACTIVATOR; THROMBIN RECEPTOR; MESSENGER-RNA; SYNAPSE ELIMINATION; CELL-DEATH; NEURITE RETRACTION; NEONATAL-RAT; IN-VITRO; MUSCLE AB The transcriptional regulation of the prothrombin gene expression in neuroblastomas was investigated because of the interest in non-hepatic thrombin expression and function in the nervous system. The data indicated that the murine prothrombin gene was distinctively transcribed in proliferating murine N2a cells and that the transcripts were decreased during the differentiation of N2a cells. The gene transcription in proliferating N2a cells was due to the C-I nuclear complex formation in the promoter region, - 248/ - 140. Mutation analyses indicated that nucleotides from - 237 to - 231 are the core C-I binding site while the longer sequence - 248/ - 140 is needed for the C-I binding. The C-I binding to the promoter - 248/ - 140 could be inhibited by the presence of competitor probe - 187/ - 166, and the mutation in nucleotides from - 186 to - 179 significantly diminished not only the formation of C-I binding in the promoter region but also the promoter activity in proliferating neuroblastoma cells. Cyclic AMP response element (CRE) modulator, CREM, appeared to selectively bind to the sequence encompassing - 186/ - 179. Taken together, the results indicate that the prothrombin gene transcription in proliferating N2a, cells was critically dependent on the cooperative interaction between the factor(s) binding to the C-1 cis-acting element ( - 237/ - 231) and the putative CRE site ( - 186/ - 179) in the prothrombin promoter, and that the lack of prothrombin expression that coincided with nerve differentiation was mainly due to the lack of C-I complex formation in the promoter. (C) 2004 Elsevier B.V. All rights reserved. C1 NICHD, Dev Neurobiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kim, S (reprint author), Univ Alabama, Dept Biol Sci, Box 870334,Room 280 Nott Hall, Tuscaloosa, AL 35487 USA. EM skim@bsc.as.ua.edu NR 41 TC 2 Z9 2 U1 1 U2 1 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 JUL 13 PY 2004 VL 1679 IS 1 BP 1 EP 9 DI 10.1016/j.bbaexp.2004.03.007 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 839XS UT WOS:000222818900001 PM 15245911 ER PT J AU Davis, CD Milner, J AF Davis, CD Milner, J TI Frontiers in nutrigenomics, proteomics, metabolomics and cancer prevention SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Mechanisms of Antimutagenesis and Anticarinogenesus CY OCT 04-08, 2003 CL Pisa, ITALY DE nutrigenetics; nutritional transcriptomics; proteomics; metabolomics; cancer prevention ID D-RECEPTOR GENE; HYPOXIA-INDUCIBLE FACTOR-1; HIGH-RISK DIET; VITAMIN-D; BREAST-CANCER; COLON-CANCER; COLORECTAL-CANCER; CELL-CYCLE; METHYLENETETRAHYDROFOLATE REDUCTASE; INTESTINAL TUMORIGENESIS AB While dietary habits continue to surface as a significant factor that may influence cancer incidence and tumor behavior, there is considerable scientific uncertainty about who will benefit most. Inadequate knowledge about how the responses depend on an individual's genetic background (nutrigenetic effects), the cumulative effects of food components on genetic expression profiles (nutritional transcriptomics and nutritional epigenomics effects), the occurrence and activity of proteins (proteomic effects) and/or the dose and temporal changes in cellular small molecular weight compounds (metabolomics effects) may assist in identifying responders and non-responders. Expanding the information about similarities and differences in the "omic" responses across tissues will not only provide clues about specificity in response to bioactive food components but assist in the identification of surrogate tissues and biomarkers that can be used for predicting a response. Deciphering the importance of each of these potential sites of regulation will be particularly challenging but does hold promise in explaining many of the inconsistencies in the literature. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, NIH, Nutrit Sci Res Grp, Bethesda, MD 20892 USA. RP Davis, CD (reprint author), NCI, NIH, Nutrit Sci Res Grp, 6130 Execut Blvd,MSC 7328, Bethesda, MD 20892 USA. EM davisci@mail.nih.gov NR 104 TC 79 Z9 93 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUL 13 PY 2004 VL 551 IS 1-2 BP 51 EP 64 DI 10.1016/j.mrfmmm.2004.01.012 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 839WH UT WOS:000222815100005 PM 15225581 ER PT J AU Schwid, SR Marler, JR AF Schwid, SR Marler, JR TI Clinical trials recruiting section - A new resource for a daunting problem SO NEUROLOGY LA English DT Editorial Material ID METHODOLOGY C1 Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. NINDS, Clin Trials Grp, NIH, Bethesda, MD 20892 USA. RP Schwid, SR (reprint author), 601 Elmwood Ave,Box 605, Rochester, NY 14642 USA. EM steven_schwid@urmc.rochester.edu NR 9 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 13 PY 2004 VL 63 IS 1 BP 4 EP 5 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 839VJ UT WOS:000222812700001 ER PT J AU Hamatani, T Daikoku, T Wang, HB Matsumoto, H Carter, MG Ko, MSH Dey, SK AF Hamatani, T Daikoku, T Wang, HB Matsumoto, H Carter, MG Ko, MSH Dey, SK TI Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE PREIMPLANTATION DEVELOPMENT; GROWTH-FACTOR; DELAYED-IMPLANTATION; TARGETED DISRUPTION; EMBRYO IMPLANTATION; ADULT-MOUSE; RECEPTOR; BINDING; UTERUS; ESTROGEN AB Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular mechanisms that direct this process remain largely unknown. In mice, ovariectomy before preimplantation ovarian estrogen secretion on day 4 of pregnancy initiates blastocyst dormancy, which normally lasts for 1-2 weeks by continued progesterone treatment, although blastocyst survival decreases with time. An estrogen injection rapidly activates blastocysts and initiates their implantation in the progesterone-primed uterus. Using this model, here we show that among -20,000 genes examined, only 229 are differentially expressed between dormant and activated blastocysts. The major functional categories of altered genes include the cell cycle, cell signaling, and energy metabolic pathways, particularly highlighting the importance of heparin-binding epidermal growth factor-like signaling in blastocyst- uterine crosstalk in implantation. The results provide evidence that the two different physiological states of the blastocyst, dormancy and activation, are molecularly distinguishable in a global perspective and underscore the importance of specific molecular pathways in these processes. This study has identified candidate genes that provide a scope for in-depth analysis of their functions and an opportunity for examining their relevance to blastocyst dormancy and activation in numerous other species for which microarray analysis is not available or possible due to very limited availability of blastocysts. C1 Vanderbilt Univ, Med Ctr, Dept Pediat, Div Reprod & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Div Reprod & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Div Reprod & Dev Biol, Nashville, TN 37232 USA. NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. Tohoku Univ, Grad Sch Agr Sci, Lab Anim Reprod, Sendai, Miyagi 9818555, Japan. RP Dey, SK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pediat, Div Reprod & Dev Biol, Nashville, TN 37232 USA. EM sk.dey@vanderbilt.edu RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU NICHD NIH HHS [HD12304, HD33994, P30 HD033994, R37 HD012304, U54 HD033994]; NIDA NIH HHS [DA 06668, R01 DA006668, R37 DA006668] NR 49 TC 139 Z9 149 U1 1 U2 7 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 JUL 13 PY 2004 VL 101 IS 28 BP 10326 EP 10331 DI 10.1073/pnas.0402597101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 837TR UT WOS:000222664200016 PM 15232000 ER PT J AU Mayo-Smith, MF Beecher, LH Fischer, TL Gorelick, DA Guillaume, JL Hill, A Jara, G Kasser, C Melbourne, J AF Mayo-Smith, MF Beecher, LH Fischer, TL Gorelick, DA Guillaume, JL Hill, A Jara, G Kasser, C Melbourne, J CA Working Grp Management Alcohol Practice Guidelines Comm Amer Soc Addiction Med TI Management of alcohol withdrawal delirium - An evidence-based practice guideline SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HOSPITALIZED-PATIENTS; ORAL LORAZEPAM; TREMENS; DIAZEPAM; BENZODIAZEPINES; DRUGS; CHLORDIAZEPOXIDE; PHARMACOKINETICS; CHLORMETHIAZOLE; REQUIREMENTS AB Background: Alcohol withdrawal delirium is the most serious manifestation of alcohol withdrawal. Evidence suggests that appropriate care improves mortality, but systematic reviews are unavailable. Methods: Articles with original data on management of alcohol withdrawal delirium underwent structured review and meta-analysis. Results: Meta-analysis of 9 prospective controlled trials demonstrated that sedative-hypnotic agents are more effective than neuroleptic agents in reducing duration of delirium and mortality, with a relative risk of death when using neuroleptic agents of 6.6. Statistically significant differences among various benzodiazepines and barbiturates were not found. No deaths were reported in 217 patients from trials using benzodiazepines or barbiturates. Conclusions: Control of agitation should be achieved using parenteral rapid-acting sedative-hypnotic agents that are cross-tolerant with alcohol. Adequate doses should be used to maintain light somnolence for the duration of delirium. Coupled with comprehensive supportive medical care, this approach is highly effective in preventing morbidity and mortality. C1 Vet Adm Med Ctr, Primary Care Serv, Manchester, NH 03104 USA. Tri Cty Commiss Alcohol & Drug Abuse, Orangeburg, SC USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Amer Soc Addict Med, Chevy Chase, MD USA. Marlboro Med Ctr, Marlborough, MA USA. Kasser & Associates, Cordova, TN USA. Conifer Pk Rehabil Ctr, Scotia, NY USA. RP Mayo-Smith, MF (reprint author), Vet Adm Med Ctr, Primary Care Serv, 718 Smyth Rd, Manchester, NH 03104 USA. EM Michael.Mayo-Smith@med.va.gov NR 70 TC 156 Z9 160 U1 2 U2 7 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 JUL 12 PY 2004 VL 164 IS 13 BP 1405 EP 1412 DI 10.1001/archinte.164.13.1405 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 836VM UT WOS:000222583900007 PM 15249349 ER PT J AU Iribarren, JI Casanovas, J Zanuy, D Aleman, C AF Iribarren, JI Casanovas, J Zanuy, D Aleman, C TI Influence of the solvation model and the solvent on the gauche-trans equilibrium of 1,1,2-trichloroethane SO CHEMICAL PHYSICS LA English DT Article ID SIMPLE COMPUTATIONAL MODEL; GAS-PHASE; CONTINUUM APPROXIMATION; MOLECULAR-DYNAMICS; ORGANIC-CHEMISTRY; ENERGY; DENSITY; PARAMETRIZATION; SIMULATIONS; QUANTUM AB Computational methods have been used to investigate the gauche-trans equilibrium of 1,1,2-trichloroethane in the gas-phase, carbon tetrachloride, chloroform, octanol and aqueous solutions. Systematic studies have been performed in solution in order to compare the capabilities of continuum and discrete solvation models. More specifically, the solvent effects were simulated using the polarizable continuum model, the continuum Onsager model and classical molecular dynamics. The results allow us to discuss the performance of the different methods to reproduce the conformational preferences of small molecules in solution. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Lleida, Dept Quim, Escola Politecn Super, E-25001 Lleida, Spain. Univ Politecn Catalunya, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Casanovas, J (reprint author), Univ Lleida, Dept Quim, Escola Politecn Super, Jaume 2 69, E-25001 Lleida, Spain. EM jcasanovas@quimica.udl.es; carlos.aleman@upc.es RI Casanovas, Jordi/B-5435-2013; Zanuy, David/G-3930-2014 OI Casanovas, Jordi/0000-0002-4914-9194; Zanuy, David/0000-0001-7704-2178 NR 42 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD JUL 12 PY 2004 VL 302 IS 1-3 BP 77 EP 83 DI 10.1016/j.chemphys.2004.03.018 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 833WI UT WOS:000222371000009 ER PT J AU Seo, BM Miura, M Gronthos, S Bartold, PM Batouli, S Brahim, J Young, M Robey, PG Wang, CY Shi, ST AF Seo, BM Miura, M Gronthos, S Bartold, PM Batouli, S Brahim, J Young, M Robey, PG Wang, CY Shi, ST TI Investigation of multipotent postnatal stem cells from human periodontal ligament SO LANCET LA English DT Article ID ENAMEL MATRIX PROTEINS; IN-VITRO; DENTAL-PULP; ATTACHMENT PROTEIN; PROGENITOR CELLS; REGENERATION; BONE; CEMENTUM; VIVO; FIBROBLASTS AB Background Periodontal diseases that lead to the destruction of periodontal tissues-including periodontal ligament (PDL), cementum, and bone-are a major cause of tooth loss in adults and are a substantial public-health burden worldwide. PDL is a specialised connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. We investigated the notion that human PDL contains stem cells that could be used to regenerate periodontal tissue. 19 Methods PDL tissue was obtained from 25 surgically extracted human third molars and used to isolate PDL stem cells (PDLSCs) by single-colony selection and magnetic activated cell sorting. Immunohistochemical staining, RT-PCR, and northern and western blot analyses were used to identify putative stem-cell markers. Human PDLSCs were transplanted into immunocompromised mice (n=12) and rats (n=6) to assess capacity for tissue regeneration and periodontal repair. Findings PDLSCs expressed the mesenchymal stem-cell markers STRO-1 and CD146/MUC18. Under defined culture conditions, PDLSCs differentiated into cementoblast-like cells, adipocytes, and collagen-forming cells. When transplanted into immunocompromised rodents, PDLSCs showed the capacity to generate a cementum/PDL-like structure and contribute to periodontal tissue repair. Interpretation Our findings suggest that PDL contains stem cells that have the potential to generate cementum/PDL-like tissue in vivo. Transplantation of these cells, which can be obtained from an easily accessible tissue resource and expanded ex vivo, might hold promise as a therapeutic approach for reconstruction of tissues destroyed by periodontal diseases. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, US Dept HHS, Bethesda, MD 20892 USA. Univ Adelaide, Mesenchymal Stem Cell Grp, Div Haematol, Inst Med & Vet Sci, Adelaide, SA 5005, Australia. Univ Adelaide, Sch Dent, Adelaide, SA 5005, Australia. Univ Michigan, Dept Biol & Mat Sci, Lab Mol Signaling & Apoptosis, Ann Arbor, MI 48109 USA. Univ Michigan, Mol & Cellular Biol Program, Ann Arbor, MI 48109 USA. Seoul Natl Univ, Coll Dent, Dept Oral & Maxillofacial Surg, Seoul, South Korea. RP Shi, ST (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, US Dept HHS, Bldg 30,Room 222,30 Convent Dr MSC-4320, Bethesda, MD 20892 USA. EM sshi@dir.nidcr.nih.gov RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Bartold, Peter/0000-0002-5695-3877 NR 37 TC 1162 Z9 1303 U1 20 U2 135 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 10 PY 2004 VL 364 IS 9429 BP 149 EP 155 DI 10.1016/S0140-6736(04)16627-0 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 837EV UT WOS:000222612200025 PM 15246727 ER PT J AU Huang, YP Wange, RL AF Huang, YP Wange, RL TI T cell receptor signaling: Beyond complex complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NF-KAPPA-B; KINASE-C-THETA; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECEPTOR; TRANSCRIPTIONAL REGULATION; LYMPHOCYTE-ACTIVATION; IMMUNE-RESPONSES; TYROSINE KINASES; ROADS LEAD; PKC-THETA C1 NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Wange, RL (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM wanger@grc.nia.nih.gov NR 59 TC 98 Z9 101 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 28827 EP 28830 DI 10.1074/jbc.R400012200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300001 PM 15084594 ER PT J AU Hawkins, LM Prybylowski, K Chang, K Moussan, C Stephenson, FA Wenthold, RJ AF Hawkins, LM Prybylowski, K Chang, K Moussan, C Stephenson, FA Wenthold, RJ TI Export from the endoplasmic reticulum of assembled N-methyl-D-aspartic acid receptors is controlled by a motif in the C terminus of the NR2 subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ER RETENTION SIGNAL; CELL-SURFACE EXPRESSION; NMDA RECEPTORS; GLUTAMATE RECEPTORS; PHARMACOLOGICAL CHAPERONES; MOLECULAR CHARACTERIZATION; TRAFFICKING; NEURONS; PROTEIN; PHOSPHORYLATION AB Functional N-methyl-D-aspartic acid ( NMDA) receptors are formed from the assembly of NR1 and NR2 subunits. When expressed alone, the major NR1 splice variant and the NR2 subunits are retained in the endoplasmic reticulum ( ER), reflecting a quality control mechanism found in many complex multisubunit proteins to ensure that only fully assembled and properly folded complexes reach the cell surface. Recent studies have identified an RRR motif in the C terminus of the NR1 subunit, which controls the ER retention of the unassembled subunit. Here we investigated the mechanisms controlling the ER retention of the NR2 subunit and the export of the assembled complex from the ER. We found that Tac chimeras of the C terminus of the NR2B subunit show that an ER retention signal is also present in the NR2B subunit. In assembled complexes, ER retention signals on the individual subunits must be overcome to allow the complex to leave the ER. One common mechanism involves mutual masking of the signals on the individual subunits. Our data do not support such a mechanism for regulating the release of assembled NMDA receptors from the ER. We found that the motif, HLFY, immediately following transmembrane domain 4 of the NR2 subunit, is required for the assembled complex to exit from the ER. Mutation of this motif allowed the assembly of NR1 and NR2 subunits into a complex that was functional, based on MK-801 binding, but it is retained in the ER. These results are consistent with HLFY functioning as a signal that is necessary for the release of the assembled functional NMDA receptor complex from the ER. C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ London, Sch Pharm, Dept Pharmaceut & Biol Chem, London WC1N 1AX, England. RP Wenthold, RJ (reprint author), NIDCD, Neurochem Lab, NIH, Bldg 50,Rm 4140,50 South Dr, Bethesda, MD 20892 USA. EM wenthold@nidcd.nih.gov NR 44 TC 53 Z9 57 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 28903 EP 28910 DI 10.1074/jbc.M402599200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300011 PM 15102836 ER PT J AU Li, WQ Jiang, Q Khaled, AR Keller, JR Durum, SK AF Li, WQ Jiang, Q Khaled, AR Keller, JR Durum, SK TI Interleukin-7 inactivates the pro-apoptotic protein bad promoting T cell survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-DEFICIENT MICE; DEFECTIVE LYMPHOID DEVELOPMENT; MITOCHONDRIAL APOPTOSIS; GAMMA-CHAIN; BCL-2; PHOSPHORYLATION; KINASE; DEATH; CYTOKINE; IL-7 AB Interleukin-7 (IL-7) is a cytokine that is required for T cell development and survival. The anti-apoptotic function of IL-7 is partly through induction of Bcl-2 synthesis and cytosolic retention of Bax. Here we show that the Bcl-2 homology 3 domain-only protein, Bad, is involved in cell death following IL-7 withdrawal from D1 cells, an IL-7-dependent murine thymocyte cell line. IL-7 stimulation resulted in the inactivation of Bad by phosphorylation at Ser-112, -136, and -155. The phosphoinositide 3-kinase (PI3K)/Akt pathway has been implicated previously in Bad phosphorylation. In response to IL-7, the PI3K/Akt pathway induced phosphorylation at Ser-136 and -155, but Ser-112 was partly independent of the PI3K/Akt pathway, indicating an as yet unknown pathway in this response. Following IL-7 withdrawal, dephosphorylated Bad translocated from cytosol to mitochondria, bound to Bcl-2, and accelerated cell death. Thus, the inactivation of Bad contributes to the survival function of IL-7. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, NIH, Rm 31-71,Bldg 560, Frederick, MD 21702 USA. EM durums@mail.ncifcrf.gov NR 43 TC 66 Z9 67 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 JUL 9 PY 2004 VL 279 IS 28 BP 29160 EP 29166 DI 10.1074/jbc.M401656200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300042 PM 15123689 ER PT J AU Baxter, TK Gagnon, SJ Davis-Harrison, RL Beck, JC Binz, AK Turner, RV Biddison, WE Baker, BM AF Baxter, TK Gagnon, SJ Davis-Harrison, RL Beck, JC Binz, AK Turner, RV Biddison, WE Baker, BM TI Strategic mutations in the class I major histocompatibility complex HLA-A2 independently affect both peptide binding and T cell receptor recognition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKOCYTE ANTIGEN (HLA)-A2; CRYSTAL-STRUCTURES; STRUCTURAL BASIS; VIRAL PEPTIDES; VIRUS TYPE-1; MHC MOLECULE; TAX PEPTIDE; HTLV-1 TAX; ALPHA-BETA; STABILITY AB Mutational studies of T cell receptor (TCR) contact residues on the surface of the human class I major histocompatibility complex (MHC) molecule HLA-A2 have identified a "functional hot spot" that comprises Arg(65) and Lys(66) and is involved in recognition by most peptide-specific HLA-A2-restricted TCRs. Although there is a significant amount of functional data on the effects of mutations at these positions, there is comparatively little biochemical information that could illuminate their mode of action. Here, we have used a combination of fluorescence anisotropy, functional assays, and Biacore binding experiments to examine the effects of mutations at these positions on the peptide-MHC interaction and TCR recognition. The results indicate that mutations at both position 65 and position 66 influence peptide binding by HLA-A2 to various extents. In particular, mutations at position 66 result in significantly increased peptide dissociation rates. However, these effects are independent of their effects on TCR recognition, and the Arg(65)-Lys(66) region thus represents a true "hot spot" for TCR recognition. We also made the observation that in vitro T cell reactivity does not scale with the half-life of the peptide-MHC complex, as is often assumed. Finally, position 66 is implicated in the "dual recognition" of both peptide and TCR, emphasizing the multiple roles of the class I MHC peptide-binding domain. C1 Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Baker, BM (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. EM bbaker2@nd.edu RI Baker, Brian/B-4584-2009 OI Baker, Brian/0000-0002-0864-0964 FU NIGMS NIH HHS [GM067079] NR 55 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29175 EP 29184 DI 10.1074/jbc.M403372200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300044 PM 15131131 ER PT J AU Vorberg, I Raines, A Priola, SA AF Vorberg, I Raines, A Priola, SA TI Acute formation of protease-resistant prion protein does not always lead to persistent scrapie infection in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CELL-FREE FORMATION; NEUROBLASTOMA-CELLS; STRAIN VARIATION; AGENT PROTEIN; MICE; PRP; PROPAGATION; BSE; CONFORMATIONS AB Transmissible spongiform encephalopathies are accompanied by the accumulation of a pathologic isoform of a host-encoded protein, termed prion protein (PrP). Despite the widespread distribution of the cellular isoform of PrP (protease-sensitive PrP; PrP-sen), the disease-associated isoform (protease-resistant PrP; PrP-res) appears to be primarily restricted to cells of the nervous and lymphoreticular systems. In order to study why scrapie infection appears to be restricted to certain cells, we followed acute and persistent PrP-res formation upon exposure of cells to different scrapie agents. We found that, independent of the cell type and scrapie strain, initial PrP-res formation occurred rapidly in cells. However, sustained generation of PrP-res and persistent infection did not necessarily follow acute PrP-res formation. Persistent PrP-res formation and scrapie infection was restricted to one cell line inoculated with the mouse scrapie strain 22L. In contrast to cells that did not become scrapie-infected, the level of PrP-res in the 22L-infected cells rapidly increased in the absence of a concomitant increase in the number of PrP-resproducing cells. Furthermore, the protein banding pattern of PrP-res in these cells changed over time as the cells became chronically infected. Thus, our results suggest that the events leading to the initial formation of PrP-res may differ from those required for sustained PrP-res formation and infection. This may, at least in part, explain the observation that not all PrP-sen-expressing cells appear to support transmissible spongiform encephalopathy agent replication. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM spriola@niaid.nih.gov NR 44 TC 40 Z9 42 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29218 EP 29225 DI 10.1074/jbc.M402576200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300049 PM 15133048 ER PT J AU Wang, HB Faucette, S Moore, R Sueyoshi, T Negishi, M LeCluyse, E AF Wang, HB Faucette, S Moore, R Sueyoshi, T Negishi, M LeCluyse, E TI Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRIMARY HUMAN HEPATOCYTES; RESPONSIVE ENHANCER MODULE; DRUG-METABOLISM; NUCLEAR TRANSLOCATION; XENOBIOTIC INDUCTION; PRIMARY CULTURE; MOUSE-LIVER; CAR; CYTOCHROME-P450; ACTIVATION AB Compared with its rodent orthologs, little is known about the chemical specificity of human constitutive androstane receptor (hCAR) and its regulation of hepatic enzyme expression. Phenytoin (PHY), a widely used antiepileptic drug, is a potent inducer of CYP2B6 in primary human hepatocytes, but does not activate human pregnane X receptor (PXR) significantly in cell-based transfection assays at the same concentrations associated with potent induction of CYP2B6. Based on this observation, we hypothesized that PHY may be a selective activator of hCAR. In primary human hepatocytes, expression of CYP2B6 reporter genes containing phenobarbital-responsive enhancer module (PBREM) or PBREM/xenobiotic- responsive enhancer module (XREM) response elements were activated up to 14- and 28-fold, respectively, by 50 muM PHY. By contrast, parallel experiments in HepG2 cell lines co-transfected with an hPXR expression vector did not show increased reporter activity. These results indicated that a PXR-independent pathway, which is retained in primary hepatocytes, is responsible for PHY induction of CYP2B6. Further experiments revealed that PHY effectively translocates hCAR from the cytoplasm into the nucleus in both primary human hepatocytes and CAR(-/-) mice. Compared with vehicle controls, PHY administration significantly increased CYP2B6 reporter gene expression, when this reporter construct was delivered together with hCAR expression vector into CAR(-/-) mice. However, PHY did not increase reporter gene expression in CAR(-/-) mice in the absence of hCAR vector, implying that CAR is essential for mediating PHY induction of CYP2B6 gene expression. Taken together, these observations demonstrate that, in contrast to most of the known CYP2B6 inducers, PHY is a selective activator of CAR in humans. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA. RP LeCluyse, E (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM ed_lecluyse@unc.edu OI LeCluyse, Edward/0000-0002-2149-8990 FU NIDDK NIH HHS [DK061652] NR 41 TC 94 Z9 100 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29295 EP 29301 DI 10.1074/jbc.M400580200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300059 PM 15123723 ER PT J AU Yang, YP Zhang, ZJ Mukherjee, AB Linnoila, RI AF Yang, YP Zhang, ZJ Mukherjee, AB Linnoila, RI TI Increased susceptibility of mice lacking Clara cell 10-kDa protein to lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen in cigarette smoke SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANCER-CELLS; BLASTOCYST DEVELOPMENT; TRANSFORMED PHENOTYPE; UTEROGLOBIN GENE; EXPRESSION; TUMORS; CC10; ADENOCARCINOMA; OVEREXPRESSION; POLYMORPHISM AB Ninety percent of all human lung cancers are related to cigarette smoking. Both tobacco smoke and lung tumorigenesis are associated with drastically reduced levels of Clara cell 10-kDa protein (CC10), a multifunctional secreted protein, naturally produced by the airway epithelia of virtually all mammals. We previously reported that the expression of CC10 is markedly reduced in animals exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK, a potent carcinogen in tobacco smoke. Furthermore, it has been reported that CC10 expression, induced in certain tumor cells, reverses the transformed phenotype. We demonstrate here that NNK exposure of CC10-knock-out (CC10-KO) mice causes a significantly higher incidence of airway epithelial hyperplasia and lung adenomas compared with wild type (WT) littermates (30% CC10-KO versus 5% WT, p = 0.041). We also found that compared with NNK-treated WT mice, CC10-KO mice manifest increased frequency of K-ras mutation, elevated level of Fas ligand (FasL) expression, and increased MAPK/Erk phosphorylation, all of which are considered predisposing events in NNK-induced lung tumorigenesis. We propose that CC10 has a protective role against NNK-induced lung tumorigenesis mediated via down-regulation of the above-mentioned predisposing events. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Rockville, MD 20850 USA. NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Yang, YP (reprint author), NCI, MCGP, POB B,Bldg 560,Rm 32-12, Frederick, MD 21702 USA. EM yongpiny@mail.nih.gov NR 36 TC 39 Z9 43 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 JUL 9 PY 2004 VL 279 IS 28 BP 29336 EP 29340 DI 10.1074/jbc.C400162200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300064 PM 15148323 ER PT J AU Kono, M Mi, YD Liu, YJ Sasaki, T Allende, ML Wu, YP Yamashita, T Proia, RL AF Kono, M Mi, YD Liu, YJ Sasaki, T Allende, ML Wu, YP Yamashita, T Proia, RL TI The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; SPHINGOSINE 1-PHOSPHATE RECEPTOR; VASCULAR MATURATION; MOLECULAR-CLONING; MICE LACKING; FAMILY; S1P(1); LYSOPHOSPHOLIPIDS; DIFFERENTIATION; EXPRESSION AB Sphingosine-1-phosphate (S1P) elicits diverse cellular responses through a family of G-protein-coupled receptors. We have shown previously that genetic disruption of the S1P(1) receptor, the most widely expressed of the family, results in embryonic lethality because of its key role within endothelial cells in regulating the coverage of blood vessels by vascular smooth muscle cells. To understand the physiologic functions of the two other widely expressed S1P receptors, we generated S1P(2) and S1P(3) null mice. Neither the S1P(2) null mice nor the S1P3 null mice exhibited significant embryonic lethality or obvious phenotypic abnormalities. To unmask possible overlapping or collaborative functions between the S1P(1), S1P(2), and S1P(3) receptors, we examined embryos with multiple S1P receptor mutations. We found that S1P(1) S1P(2) double null and S1P(1) S1P(2) S1P(3) triple null embryos displayed a substantially more severe vascular phenotype than did embryos with only S1P(1) deleted. We also found partial embryonic lethality and vascular abnormalities in S1P(2) S1P(3) double null embryos. Our results indicate that the S1P(1), S1P(2), and S1P(3) receptors have redundant or cooperative functions for the development of a stable and mature vascular system during embryonic development. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 9N-314,10 Ctr Dr MSC 1821, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 NR 40 TC 205 Z9 215 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29367 EP 29373 DI 10.1074/jbc.M403937200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300068 PM 15138255 ER PT J AU Kim, KY Kim, BC Xu, ZL Kim, SJ AF Kim, KY Kim, BC Xu, ZL Kim, SJ TI Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASE; MOLECULAR-CLONING; BINDING MOTIF; CROSS-TALK; IN-VIVO; IDENTIFICATION; PHOSPHORYLATION; PATHWAYS; FAMILY AB Although transforming growth factor beta1 (TGF-beta1) acts via the Smad signaling pathway to initiate de novo gene transcription, the TGF-beta1-induced MAPK kinase activation that is involved in the regulation of apoptosis is less well understood. Even though the p38 MAP kinase and c-Jun NH2-terminal kinases (JNKs) are involved in TGF-beta1- induced cell death in hepatoma cells, the upstream mediators of these kinases remain to be defined. We show here that the members of the mixed lineage kinase (MLK) family ( including MLK1, MLK2, MLK3, and dual leucine zipper-bearing kinase (DLK)) are expressed in FaO rat hepatoma cells and are likely to act between p38 and TGF-beta receptor kinase in death signaling. TGF-beta1 treatment leads to an increase in MLK3 activity. Overexpression of MLK3 enhances TGF-beta1-induced apoptotic death in FaO cells and Hep3B human hepatoma cells, whereas expression of the dominant-negative forms of MLK3 suppresses cell death induced by TGF-beta1. The dominant-negative forms of MLK1 and -2 also suppress TGF-beta1-induced cell death. In MLK3-overexpressing cells, ERK, JNKs, and p38 MAP kinases were further activated in response to TGF-beta1 compared with the control cells. In contrast, overexpression of the dominant-negative MLK3 resulted in suppression of TGF-beta1-induced MAP kinase activation and TGF-beta1-induced caspase-3 activation. We also show that only the inhibition of the p38 pathway suppressed TGF-beta1-induced apoptosis. These observations support a role for MLKs in the TGF-beta1-induced cell death mechanism. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Kangweon Natl Univ, Coll Nat Sci, Chunchon 200701, South Korea. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. EM kims@mail.nih.gov NR 38 TC 62 Z9 68 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29478 EP 29484 DI 10.1074/jbc.M313947200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300080 PM 15069087 ER PT J AU Peschard, P Ishiyama, N Lin, T Lipkowitz, S Park, M AF Peschard, P Ishiyama, N Lin, T Lipkowitz, S Park, M TI A conserved DpYR motif in the juxtamembrane domain of the Met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CBL; PROTEIN; PHOSPHORYLATION; ZAP-70; REGION; CELLS; AUTOINHIBITION; TRANSMEMBRANE; DEGRADATION; HOMOLOGY AB The activation and phosphorylation of Met, the receptor tyrosine kinase (RTK) for hepatocyte growth factor, initiates the recruitment of multiple signaling proteins, one of which is c-Cbl, a ubiquitin-protein ligase. c-Cbl promotes ubiquitination and enhances the down-modulation of the Met receptor and other RTKs, targeting them for lysosomal sorting and subsequent degradation. The ubiquitination of Met by c-Cbl requires the direct interaction of the c-Cbl tyrosine kinase binding (TKB) domain with tyrosine 1003 in the Met juxtamembrane domain. Although a consensus for c-Cbl TKB domain binding has been established ((D/N)XpYXX(D/E0Phi), this motif is not present in Met, suggesting that other c-Cbl TKB domain binding motifs may exist. By alanine-scanning mutagenesis, we have identified a DpYR motif including Tyr(1003) as being important for the direct recruitment of the c-Cbl TKB domain and for ubiquitination of the Met receptor. The substitution of Tyr(1003) with phenylalanine or substitution of either aspartate or arginine residues with alanine impairs c-Cbl-recruitment and ubiquitination of Met and results in the oncogenic activation of the Met receptor. We demonstrate that the TKB domain of Cbl-b, but not Cbl-3, binds to the Met receptor and requires an intact DpYR motif. Modeling studies suggest the presence of a salt bridge between the aspartate and arginine residues that would position pTyr(1003) for binding to the c-Cbl TKB domain. The DpYR motif is conserved in other members of the Met RTK family but is not present in previously identified c-Cbl-binding proteins, identifying DpYR as a new binding motif for c-Cbl and Cbl-b. C1 McGill Univ, Ctr Hlth, Mol Oncol Grp, Dept Biochem, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Oncol, Montreal, PQ H3A 1A1, Canada. NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Park, M (reprint author), McGill Univ, Ctr Hlth, Mol Oncol Grp, Dept Biochem, Montreal, PQ H3A 1A1, Canada. EM morag.park@mcgill.ca OI Peschard, Pascal/0000-0001-6395-5566 NR 43 TC 68 Z9 70 U1 4 U2 6 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 JUL 9 PY 2004 VL 279 IS 28 BP 29565 EP 29571 DI 10.1074/jbc.M403954200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300091 PM 15123609 ER PT J AU Wang, XY Wang, RH Li, WM Xu, XL Hollander, MC Fornace, AJ Deng, CX AF Wang, XY Wang, RH Li, WM Xu, XL Hollander, MC Fornace, AJ Deng, CX TI Genetic interactions between Brca1 and Gadd45a in centrosome duplication, genetic stability, and neural tube closure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE CHECKPOINT; NEK2 PROTEIN-KINASE; FULL-LENGTH ISOFORM; DNA-DAMAGE REPAIR; CANCER SUSCEPTIBILITY; APOPTOSIS; MOUSE; MICE; INSTABILITY; P53 AB GADD45a is a transcription target of the breast tumor suppressor gene BRCA. It was recently shown that mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of Brca1 (Brca1(Delta11/Delta11)) or a Gadd45A-null mutation (Gadd45a(-/-)) suffer centrosome amplification. To study genetic interactions between these genes during centrosome duplication, we generated Brca1(Delta11/Delta11)Gadd45a(-/-) mice by crossing each mutant. We found that all Brca1(Delta11/Delta11)Gadd45a(-/-) embryos at embryonic days 9.5-10.5 were exencephalic and exhibited a high incidence of apoptosis accompanied by altered levels of BAX, BCL-2, and p53. The trigger for these events is likely the genetic instability arising from centrosome amplification that is associated, at least in part, with decreased expression of the NIMA-related kinase NEK2. We demonstrate that small interfering RNA-mediated suppression of Brca1 decreased Nek2 more dramatically in Gadd45a(-/-) cells than in wild-type cells and, conversely, that overexpression of Brca1 and/or Gadd45a up-regulated transcription of Nek2. Furthermore, we show that overexpression of Nek2 in Brca1-specific small interfering RNA-treated wild-type and Gadd45a(-/-) cells repressed abnormal centrosome amplification. These observations suggest that NEK2 plays a role in mediating the actions of BRCA1 and GADD45a in regulating centrosome duplication and in maintaining genetic stability. C1 NIDDK, GDDB, NIH, Bethesda, MD 20892 USA. NCI, Gene Response Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, GDDB, NIH, Bldg 10,Rm 9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI Fornace, Albert/A-7407-2008; deng, chuxia/N-6713-2016 OI Fornace, Albert/0000-0001-9695-085X; NR 51 TC 24 Z9 26 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 2004 VL 279 IS 28 BP 29606 EP 29614 DI 10.1074/jbc.M312279200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834XX UT WOS:000222445300096 PM 15123655 ER PT J AU Byeon, IJL Louis, JM Gronenborn, AM AF Byeon, IJL Louis, JM Gronenborn, AM TI A captured folding intermediate involved in dimerization and domain-swapping of GB1 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE GB1; core mutants; folding; domain-swapping ID STREPTOCOCCAL PROTEIN-G; AQUEOUS-SOLUTION; UNFOLDED STATE; B1 DOMAIN; BACKBONE DYNAMICS; CORE MUTATIONS; NMR METHODS; SIDE-CHAIN; SH3 DOMAIN; STABILITY AB Immunoglobulin binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single domain protein, is one of the most extensively used model systems in the area of protein folding and design. The recently determined NMR structure of a quadruple mutant (HS#124(F26A), L5V/F30V/Y33F/A34F) revealed a domain-swapped dimer that dissociated into a partially folded, monomeric species at low micromolar protein concentrations. Here, we have characterized this monomeric, partially folded species by NMR and show that extensive conformational heterogeneity for a substantial portion of the polypeptide chain exists. Exchange between the conformers within the monomer ensemble on the microsecond to millisecond timescale renders the majority of backbone amide resonances broadened beyond detection. Despite these extensive temporal and spatial fluctuations, the overall architecture of the monomeric mutant protein resembles that of wild-type GB1 and not the monomer unit of the domain-swapped dimer. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gronenborn@nih.gov OI Gronenborn, Angela M/0000-0001-9072-3525 NR 36 TC 30 Z9 30 U1 0 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 9 PY 2004 VL 340 IS 3 BP 615 EP 625 DI 10.1016/j.jmb.2004.04.069 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836MN UT WOS:000222560000017 PM 15210358 ER PT J AU Belshe, R Franchini, G Girard, MP Gotch, F Kaleebu, P Marthas, ML McChesney, MB McCullough, R Mhalu, F Salmon-Ceron, D Sekaly, RP Van Rompay, K Verrier, B Wahren, B AF Belshe, R Franchini, G Girard, MP Gotch, F Kaleebu, P Marthas, ML McChesney, MB McCullough, R Mhalu, F Salmon-Ceron, D Sekaly, RP Van Rompay, K Verrier, B Wahren, B TI Support for the RV144 HIV vaccine trial SO SCIENCE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. St Louis Univ, Hlth Sci Ctr, Sch Med, St Louis, MO 63110 USA. Fdn Merieux, F-69002 Lyon, France. Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept Immunol, London SW10 9NH, England. Uganda Virus Res Inst, Div Immunol, Entebbe, Uganda. Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Capital Area Vaccine Effort, Washington, DC 20013 USA. Muhimbili Univ, Coll Hlth Sci, Dept Microbiol, Dar Es Salaam, Tanzania. Muhimbili Univ, Coll Hlth Sci, Dept Immunol, Dar Es Salaam, Tanzania. Hop Cochin, F-75013 Paris, France. Ctr Hosp Univ Montreal, Hotel Dieu, Res Ctr, Montreal, PQ H2W 1T8, Canada. Canadian Network Vaccines & Immunotherapeut, Montreal, PQ H3A 3C6, Canada. CRNS Biomerieux, FRE 2736, F-69365 Lyon, France. Karolinska Inst, Swedish Inst Infect Dis Control, Ctr Microbiol & Tumor Biol, S-17182 Stockholm, Sweden. Univ Buenos Aires, Fac Med, Dept Microbiol, Natl Ctr Reference Ctr AIDS, RA-1121 Buenos Aires, DF, Argentina. RP Franchini, G (reprint author), NCI, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 0 TC 14 Z9 15 U1 2 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 JUL 9 PY 2004 VL 305 IS 5681 BP 177 EP 177 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 835QQ UT WOS:000222501000016 PM 15247455 ER PT J AU McNeil, JG Johnston, MI Tramont, EC Birx, DL AF McNeil, JG Johnston, MI Tramont, EC Birx, DL TI Outstanding questions on HIV vaccine trial - Response SO SCIENCE LA English DT Letter C1 NIAID, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. RP McNeil, JG (reprint author), NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 9 PY 2004 VL 305 IS 5681 BP 180 EP 180 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 835QQ UT WOS:000222501000021 ER PT J AU Morens, DM Folkers, GK Fauci, AS AF Morens, DM Folkers, GK Fauci, AS TI The challenge of emerging and re-emerging infectious diseases SO NATURE LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; INFLUENZAE BIOGROUP AEGYPTIUS; BRAZILIAN PURPURIC FEVER; GROUP-A STREPTOCOCCUS; NILE-VIRUS-INFECTION; UNITED-STATES; OUTBREAK; IDENTIFICATION; VACCINES; AGENTS AB Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogenic microorganisms and the dynamic relationships between microorganisms, their hosts and the environment. C1 NIAID, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, US Dept HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 98 TC 615 Z9 661 U1 15 U2 132 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 8 PY 2004 VL 430 IS 6996 BP 242 EP 249 DI 10.1038/nature02759 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 835GL UT WOS:000222470600052 PM 15241422 ER PT J AU Coleman, P Kurlan, R Crook, R Werner, J Hardy, J AF Coleman, P Kurlan, R Crook, R Werner, J Hardy, J TI New presenilin Alzheimer's disease case confirms the helical alignment of pathogenic mutations in transmembrane domain 5 SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; presenilin; genetics ID GENE AB In a case of familial early onset Alzheimer's disease, a mutation was detected in exon 7 of the presenilin 1 gene at codon 226 with a resultant amino acid change from leucine (CTC) to arginine (CGC) (L226R). This is a novel finding, yet is consistent with the previously reported mutations at codons 222, 229, 233 and 237 in transmembrane domain 5 which show a helical alignment of mutations in this domain. We conclude that the cause of Alzheimer's disease in this patient is an authentic PSI gene abnormality responsible for the patient's early onset Alzheimer's disease. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Ctr Aging & Dev Biol, Dept Neurol, Rochester, NY 14642 USA. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10-Room 6C103,MSC1589, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009 FU NIA NIH HHS [P50AGO 8665, R01 AG14441] NR 4 TC 8 Z9 8 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 JUL 8 PY 2004 VL 364 IS 3 BP 139 EP 140 DI 10.1016/j.neulet.2004.04.030 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 832TI UT WOS:000222289700002 PM 15196662 ER PT J AU Erez, A Perelman, M Hewitt, SM Cojacaru, G Goldberg, I Shahar, I Yaron, P Muler, I Campaner, S Amariglio, N Rechavi, G Kirsch, IR Krupsky, M Kaminski, N Izraeli, S AF Erez, A Perelman, M Hewitt, SM Cojacaru, G Goldberg, I Shahar, I Yaron, P Muler, I Campaner, S Amariglio, N Rechavi, G Kirsch, IR Krupsky, M Kaminski, N Izraeli, S TI Sil overexpression in lung cancer characterizes tumors with increased mitotic activity SO ONCOGENE LA English DT Article DE Sil; mitosis; lung cancer; carcinogenesis ID CELL-CYCLE; GENE; CHECKPOINT; EXPRESSION; IDENTIFICATION AB Sil (SCL interrupting locus) was cloned from the most common chromosomal rearrangement in T-cell acute lymphoblastic leukemia. It is an immediate early gene whose expression is associated with cell proliferation. Sil protein levels are tightly regulated during the cell cycle, reaching peak levels in mitosis and disappearing on transition to G1. A recent study found Sil to be one of 17 genes whose overexpression in primary adenocarcinomas predicts metastatic spread. We hypothesized that Sil might have a role in carcinogenesis. To address this question, we utilized several approaches. Using a multi-tumor tissue array, we found that Sil protein expression was increased mostly in lung cancer, but also at lower levels, in a subset of other tumors. Microarray gene expression analysis and immunohistochemistry of lung cancer samples verified these observations. Sil gene expression in lung cancer correlated with the expression of several kinetochore check-point genes and with the histopathologic mitotic index. The se observations suggest that overexpression of the Sil gene characterizes tumors with increased mitotic activity. C1 Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Pediat Hematooncol, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Pathol, IL-52621 Tel Hashomer, Israel. NIH, Ctr Adv Technol, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Funct Gen, IL-52621 Tel Hashomer, Israel. Compugen LTD, Tel Aviv, Israel. Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Pulm Med, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NCI, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dorothy P & Richard P Simmons Ctr, Pittsburgh, PA 15261 USA. RP Kaminski, N (reprint author), Univ Pittsburgh, Med Ctr, Dorothy P & Richard P Simmons Ctr Interstitial Lu, NW 628 MUH,3459 5th Av, Pittsburgh, PA 15261 USA. EM kaminskin@upmc.edu; sizraeli@post.tau.ac.il OI Hewitt, Stephen/0000-0001-8283-1788 NR 22 TC 28 Z9 29 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 8 PY 2004 VL 23 IS 31 BP 5371 EP 5377 DI 10.1038/sj.onc.1207685 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 835NX UT WOS:000222491600012 PM 15107824 ER PT J AU Berthou, S Aebersold, DM Schmidt, LS Stroka, D Heigl, C Streit, B Stalder, D Gruber, G Liang, CX Howlett, AR Candinas, D Greiner, RH Lipson, KE Zimmer, Y AF Berthou, S Aebersold, DM Schmidt, LS Stroka, D Heigl, C Streit, B Stalder, D Gruber, G Liang, CX Howlett, AR Candinas, D Greiner, RH Lipson, KE Zimmer, Y TI The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants SO ONCOGENE LA English DT Article DE Met receptor; activating mutation; receptor tyrosine kinase inhibitor ID GROWTH-FACTOR RECEPTOR; GASTROINTESTINAL STROMAL TUMORS; PAPILLARY RENAL-CARCINOMAS; CHRONIC MYELOID-LEUKEMIA; FACTOR SCATTER FACTOR; TYROSINE KINASE; SOMATIC MUTATIONS; C-MET; CYTOGENETIC RESPONSES; IMATINIB MESYLATE AB Point mutations constitute a major mode of oncogenic activation of the Met receptor tyrosine kinase. Met is aberrantly activated in many types of human malignancies and its deregulated activity is correlated with aggressive tumor traits such as abnormal proliferation and survival, leading to tumor growth, local invasion and metastasis. Here we report that the Met kinase inhibitor SU11274 differentially affects the kinase activity and subsequent signaling of various mutant forms of Met. Two Met variants tested, M1268T and H1112Y, were potently inhibited by 2 muM SU11274, while two other variants, L1213V and Y1248H, remained resistant under similar experimental conditions. Inhibition of the kinase altered cell proliferation, morphology and motility, while cells containing resistant mutants appeared unaffected by the compound. The basis for the sensitivity or resistance to SU11274 is discussed in terms of the position of the mutations predicted from a homology model. C1 Univ Bern, Dept Clin Res, CH-3010 Bern, Switzerland. Univ Bern, Inselspital, Dept Radiat Oncol, CH-3010 Bern, Switzerland. SAIC Frederick Inc, Basic Res Program, NCI Frederick, Ft Detrick, MD 21702 USA. Univ Bern, Inselspital, Dept Visceral Surg, CH-3010 Bern, Switzerland. SUGEN Inc, San Francisco, CA 94080 USA. RP Zimmer, Y (reprint author), Univ Bern, Dept Clin Res, Murtenstr 35-D-809, CH-3010 Bern, Switzerland. EM yitzhak.zimmer@dkf5.unibe.ch RI Stroka, Deborah/F-1806-2013 FU PHS HHS [N01-C0-12400] NR 33 TC 129 Z9 132 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 8 PY 2004 VL 23 IS 31 BP 5387 EP 5393 DI 10.1038/sj.onc.1207691 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 835NX UT WOS:000222491600014 PM 15064724 ER PT J AU Kang, JH Siddiqui, MA Sigano, DM Krajewski, K Lewin, NE Pu, YM Blumberg, PM Lee, J Marquez, VE AF Kang, JH Siddiqui, MA Sigano, DM Krajewski, K Lewin, NE Pu, YM Blumberg, PM Lee, J Marquez, VE TI Conformationally constrained analogues of diacylglycerol. 24. Asymmetric synthesis of a chiral (R)-DAG-Lactone template as a versatile precursor for highly functionalized DAG-lactones SO ORGANIC LETTERS LA English DT Article ID PROTEIN-KINASE-C; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; BINDING-AFFINITY; PK-C; LIGANDS AB Commercially available 2-methylenepropane-1,3-diol was converted to chiral epoxide (R)-2 via Sharpless asymmetric epoxidation in >96% ee. Regiospecific epoxide ring opening and reduction of the intermediate alkyne set the stage for a one-pot lactonization to give (R)-6, a convenient precursor for all functionalized chiral DAG-lactones used as potent PK-C ligands. The synthesis of the most potent DAG-lactones known to date, (Z)-10 and (E)-10, served to confirm PK-C's exclusive preference for the (R)-stereochemistry in this class of compounds. C1 NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea. RP Kang, JH (reprint author), NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. EM jeewoo@snu.ac.kr; marquezv@dc37a.nci.nih.gov RI Sigano, Dina/M-6144-2014 OI Sigano, Dina/0000-0001-7489-9555 NR 11 TC 23 Z9 23 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUL 8 PY 2004 VL 6 IS 14 BP 2413 EP 2416 DI 10.1021/ol0492041 PG 4 WC Chemistry, Organic SC Chemistry GA 834OL UT WOS:000222420300031 PM 15228292 ER PT J AU Truglio, JJ Croteau, DL Skorvaga, M DellaVecchia, MJ Theis, K Mandavilli, BS Van Houten, B Kisker, C AF Truglio, JJ Croteau, DL Skorvaga, M DellaVecchia, MJ Theis, K Mandavilli, BS Van Houten, B Kisker, C TI Interactions between UvrA and UvrB: the role of UvrB's domain 2 in nucleotide excision repair SO EMBO JOURNAL LA English DT Article DE crystallography; DNA damage; DNA repair nucleotide excision repair; UvrB ID ESCHERICHIA-COLI UVRAB; DNA-POLYMERASE-I; CRYSTAL-STRUCTURE; THERMUS-THERMOPHILUS; PROTEIN COMPLEX; (A)BC EXCINUCLEASE; DAMAGE RECOGNITION; THYMINE DIMERS; ACTIVE-SITE; HELICASE-II AB Nucleotide excision repair (NER) is a highly conserved DNA repair mechanism present in all kingdoms of life. UvrB is a central component of the bacterial NER system, participating in damage recognition, strand excision and repair synthesis. None of the three presently available crystal structures of UvrB has defined the structure of domain 2, which is critical for the interaction with UvrA. We have solved the crystal structure of the UvrB Y96A variant, which reveals a new fold for domain 2 and identifies highly conserved residues located on its surface. These residues are restricted to the face of UvrB important for DNA binding and may be critical for the interaction of UvrB with UvrA. We have mutated these residues to study their role in the incision reaction, formation of the pre-incision complex, destabilization of short duplex regions in DNA, binding to UvrA and ATP hydrolysis. Based on the structural and biochemical data, we conclude that domain 2 is required for a productive UvrA-UvrB interaction, which is a pre-requisite for all subsequent steps in nucleotide excision repair. C1 SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Slovak Acad Sci, Canc Res Inst, Dept Mol Genet, Bratislava, Slovakia. Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. RP Van Houten, B (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. EM vanhout1@niehs.nih.gov; kisker@pharm.sunysb.edu NR 34 TC 41 Z9 41 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 7 PY 2004 VL 23 IS 13 BP 2498 EP 2509 DI 10.1038/sj.emboj.7600263 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 845MT UT WOS:000223249300005 PM 15192705 ER PT J AU Lakatta, EG Schulman, S AF Lakatta, EG Schulman, S TI Age-associated cardiovascular changes are the substrate for poor prognosis with myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID PULSE PRESSURE; THROMBOLYTIC THERAPY; ENDOTHELIAL DYSFUNCTION; DISEASE ENTERPRISES; MAJOR SHAREHOLDERS; HEART-DISEASE; AGING HEART; ARTERIAL; ANGIOGENESIS; MECHANISMS C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Inst Med, Div Cardiol, Baltimore, MD USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov NR 31 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 7 PY 2004 VL 44 IS 1 BP 35 EP 37 DI 10.1016/j.jacc.2004.04.011 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834OX UT WOS:000222421500007 PM 15234402 ER PT J AU Keaney, JF Massaro, JM Larson, MG Vasan, RS Wilson, PWF Lipinska, I Corey, D Sutherland, P Vita, JA Benjamin, EJ AF Keaney, JF Massaro, JM Larson, MG Vasan, RS Wilson, PWF Lipinska, I Corey, D Sutherland, P Vita, JA Benjamin, EJ TI Heritability and correlates of intercellular adhesion molecule-1 in the Framingham Offspring Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; HUMAN ENDOTHELIAL-CELLS; APPARENTLY HEALTHY-MEN; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; UNSTABLE ANGINA; ARTERY-DISEASE AB OBJECTIVES We sought to determine the clinical factors and heritability associated with inflammation measured as circulating levels of soluble-intercellular adhesion molecule-1 (sICAM-1) in a community-based cohort. BACKGROUND Several prospective studies indicate that circulating sICAM-1 is predictive of future cardiovascular events. However, in some studies this predictive value is lost after multivariable adjustment for traditional cardiovascular disease (CVD) risk factors. We addressed the heritability of sICAM-1 and its relation to CVD risk factors in a community-based cohort. METHODS We examined 3,295 subjects from the Framingham Heart Study and measured sICAM-1 levels. We then used linear and stepwise multivariable regression to determine predictors or sICAM-1 levels. RESULTS In age- and gender-adjusted regression models, increased sICAM-1 levels were positively associated with age, total/high-density lipoprotein cholesterol, systolic blood pressure, body mass index (BMI), blood glucose, diabetes, smoking, and prevalent CVD. In stepwise multivariable regression models, sICAM-1 levels remained associated with age, female gender, total/high-density lipoprotein cholesterol ratio, BMI, blood glucose, smoking, and prevalent CVD. The residual heritability of sICAM-1 was 24%. CONCLUSIONS In addition to prevalent CVD, established CVD risk factors and non-traditional ones such as BMI were associated with systemic inflammation as determined by sICAM-1 levels. There also is significant heritability of sICAM-1, which suggests a genetic component to systemic inflammation.(C) 2004 by the American College of Cardiology Foundation. C1 Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. NHLBI, Framingham Study, Framingham, MA USA. RP Keaney, JF (reprint author), Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA. EM jkeaney@bu.edu OI Vita, Joseph/0000-0001-5607-1797; Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL04334, HL60886, HL64753, HL70139, N01-HC-25195, N01-HV-28178]; NIDDK NIH HHS [DK55656] NR 44 TC 36 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 7 PY 2004 VL 44 IS 1 BP 168 EP 173 DI 10.1016/j.jacc.2004.03.048 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834OX UT WOS:000222421500033 PM 15234428 ER PT J AU Korn, EL AF Korn, EL TI Nontoxicity endpoints in phase I trial designs for targeted, non-cytotoxic agents SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RECOMBINANT HUMAN ENDOSTATIN; ADVANCED SOLID TUMORS; CLINICAL-TRIAL; CANCER C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, NIH, EPN-8129, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov NR 10 TC 38 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 7 PY 2004 VL 96 IS 13 BP 977 EP 978 DI 10.1093/jnci/djh208 PG 2 WC Oncology SC Oncology GA 835QO UT WOS:000222500800001 PM 15240771 ER PT J AU Cho, E Smith-Warner, SA Spiegelman, D Beeson, WL van den Brandt, PA Colditz, GA Folsom, AR Fraser, GE Freudenheim, JL Giovannucci, E Goldbohm, RA Graham, S Miller, AB Pietinen, P Potter, JD Rohan, TE Terry, P Toniolo, P Virtanen, MJ Willett, WC Wolk, A Wu, K Yaun, SS Zeleniuch-Jacquotte, A Hunter, DJ AF Cho, E Smith-Warner, SA Spiegelman, D Beeson, WL van den Brandt, PA Colditz, GA Folsom, AR Fraser, GE Freudenheim, JL Giovannucci, E Goldbohm, RA Graham, S Miller, AB Pietinen, P Potter, JD Rohan, TE Terry, P Toniolo, P Virtanen, MJ Willett, WC Wolk, A Wu, K Yaun, SS Zeleniuch-Jacquotte, A Hunter, DJ TI Dairy foods, calcium, and colorectal cancer: A pooled analysis of 10 cohort studies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; RANDOMIZED CONTROLLED-TRIAL; COLON-CANCER; VITAMIN-D; DIETARY CALCIUM; BREAST-CANCER; FREQUENCY QUESTIONNAIRE; SPORADIC ADENOMA; WOMENS HEALTH; OLDER WOMEN AB Background. Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. Methods: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. Results: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and greater than or equal to250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (P(trend)<.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; P(trend) = .02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; P(trend)<.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (P(trend)<.001) and rectum (P(trend) = .02). Conclusion: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer. C1 Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Loma Linda Univ, Ctr Hlth Res, Sch Med, Loma Linda, CA USA. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. Harvard Ctr Canc Prevent, Boston, MA USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. TNO, Nutr & Food Res Inst, Dept Epidemiol, Zeist, Netherlands. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. NYU, Dept Obstet Gynecol, Sch Med, New York, NY USA. Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. NYU, Sch Med, Nelson Inst Environm Med & Kaplan Canc Ctr, New York, NY USA. RP Cho, E (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [CA55075, CA78548] NR 60 TC 265 Z9 281 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 7 PY 2004 VL 96 IS 13 BP 1015 EP 1022 DI 10.1093/jnci/djh185 PG 8 WC Oncology SC Oncology GA 835QO UT WOS:000222500800012 PM 15240785 ER PT J AU Nathan, PC Sung, L Crump, M Beyene, J AF Nathan, PC Sung, L Crump, M Beyene, J TI Re: Consolidation therapy with autologous bone marrow transplantation in adults with acute myeloid leukemia: A meta-analysis - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Hosp Sick Children, Div Haematol Oncol, Dept Paediat, Toronto, ON M5G 1X8, Canada. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Toronto, Princess Margaret Hosp, Dept Med, Hlth Network, Toronto, ON, Canada. Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. Hosp Sick Children, Program Populat Hlth Sci, Toronto, ON M5G 1X8, Canada. RP Sung, L (reprint author), Hosp Sick Children, Div Haematol Oncol, Dept Paediat, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM lillian.sung@sickkids.ca NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 7 PY 2004 VL 96 IS 13 BP 1039 EP 1040 DI 10.1093/jnci/djh200 PG 2 WC Oncology SC Oncology GA 835QO UT WOS:000222500800018 ER PT J AU Swain, SM Wilson, JW AF Swain, SM Wilson, JW TI Re: Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Natl Canc Inst, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. Univ Pittsburgh, Pittsburgh, PA USA. Natl Surg & Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. RP Swain, SM (reprint author), Natl Canc Inst, Canc Therapeut Branch, Ctr Canc Res, NIH, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM swains@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 7 PY 2004 VL 96 IS 13 BP 1041 EP 1041 DI 10.1093/jnci/djh203 PG 1 WC Oncology SC Oncology GA 835QO UT WOS:000222500800020 ER PT J AU Saroff, HA AF Saroff, HA TI PH effects on the binding of oxygen to non-vertebrate monomeric hemoglobins. A linked function model. SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE X-ray; models; pH effects; oxygen binding; hydrogen bonds; linked functions; monomeric hemoglobins ID NUCLEAR MAGNETIC-RESONANCE; ASCARIS HEMOGLOBIN; CARBON-MONOXIDE; DISTAL TYROSINE; MYOGLOBINS; RESOLUTION; AFFINITY; RESIDUE; MUTANT AB Monomeric invertabrate hemoglobins with high oxygen affinity usually contain a tyrosine in the distal region of the heme. This feature has stimulated investigations revealing that one of the properties resulting from the presence of the distal tyrosines is a decreased off rate on the binding of oxygen, thus developing the high affinity. Despite that fact that the pK value of the tyrosine group differs significantly from the groups it replaces little attention has been paid to the pH dependence of the binding of oxygen to the high affinity hemoglobins. Such a pH dependence has been reported on two of the monomeric hemoglobins with relatively low oxygen affinity and one monomeric hemoglobin of intermediate affinity. The pH data of these hemoglobins has been analysed with a linked function model involving the hydrogen ion. pK values required for the low-affinity hemoglobins vary from 4.5 to 7.5. When applied to the high-affinity hemoglobins, the linked function model provides reasonable values for the binding parameters. These pK values vary from 3.0 to 9.0. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Saroff, HA (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM saroff@helix.nih.gov NR 24 TC 2 Z9 2 U1 3 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 EI 1095-8541 J9 J THEOR BIOL JI J. Theor. Biol. PD JUL 7 PY 2004 VL 229 IS 1 BP 113 EP 118 DI 10.1016/j.jtbi.2004.03.007 PG 6 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 831JZ UT WOS:000222192000010 PM 15178189 ER PT J AU Davis, BR Furberg, CD Wright, JT Cutler, JA Whelton, P AF Davis, BR Furberg, CD Wright, JT Cutler, JA Whelton, P CA ALLHAT Collaborative Res Grp TI ALLHAT: Setting the record straight SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; ISOLATED SYSTOLIC HYPERTENSION; ANTIHYPERTENSIVE DRUG-TREATMENT; CALCIUM-CHANNEL BLOCKER; BLOOD-PRESSURE; RANDOMIZED-TRIAL; ELDERLY PROGRAM; FAILURE EVENTS; OLDER PERSONS AB The findings of the Anti hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have generated worldwide reaction from clinicians and researchers, including a recent commentary in this journal. Such response was expected for a trial of ALLHAT's size and scope, especially since its results challenged some widely held beliefs. This paper reviews key aspects of the ALLHAT design, analyses, findings, and conclusions to provide a perspective on the commentary about the trial's results and implications for clinical practice. Several of the most frequent comments regarding the study's results are addressed, particularly with respect to heart failure and diabetes outcomes. Responses to these comments reinforce the investigators' original conclusion that thiazide-type diuretics should remain the preferred first-step drug class for treating hypertension and should generally be a part of any multidrug regimen. C1 Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Davis, BR (reprint author), Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, 1200 Herman Pressler St,Suite E801, Houston, TX 77030 USA. EM bdavis@sph.uth.tmc.edu FU NHLBI NIH HHS [N01-HC-35130] NR 46 TC 34 Z9 35 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 6 PY 2004 VL 141 IS 1 BP 39 EP 46 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 834RF UT WOS:000222427600006 PM 15238369 ER PT J AU Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C AF Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C TI Meta-analysis: The effect of steroids on survival and shock during sepsis depends on the dose SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID SEPTIC SHOCK; DOUBLE-BLIND; ANTIINFLAMMATORY AGENTS; HYDROCORTISONE; METHYLPREDNISOLONE; THERAPIES; MORTALITY; EFFICACY; EPIDEMIOLOGY; STRATEGIES AB Background: Previous meta-analyses demonstrated that highdose glucocorticoids were not beneficial in sepsis. Recently, lowerdose glucocorticolds have been studied. Purpose: To compare recent trials of glucocorticoids for sepsis with previous glucocorticoid trials. Data Sources: Systematic MEDLINE search for studies published between 1988 and 2003. Study Selection: Randomized, controlled trials of sepsis that examined the effects of glucocorticoids on survival or vasopressor requirements. Data Extraction: Two investigators independently collected data on patient and study characteristics, treatment interventions, and outcomes. Data Synthesis: The 5 included trials revealed a consistent and beneficial effect of glucocorticoids on survival (l(2) = 0%; relative benefit, 1.23, [95% Cl, 1.01 to 1.50]; P= 0.036) and shock reversal (l(2) = 0%; relative benefit, 1.71 [Cl, 1.29 to 2.26]; P < 0.001). These effects were the same regardless of adrenal function. In contrast, 8 trials published before 1989 demonstrated a survival disadvantage with steroid treatment (l(2) = 14%; relative benefit, 0.89 [Cl, 0.82 to 0.97]; P = 0.008). In comparison with the earlier trials, the more recent trials administered steroids later after patients met enrollment criteria (median, 23 hours vs. <2 hours; P = 0.02), for longer courses (6 days vs. 1 day; P = 0.01), and in lower total dosages (hydrocortisone equivalents, 1209 mg vs. 23 975 mg; P = 0.01) to patients with higher control group mortality rates (mean, 57% vs. 34%; P = 0.06) who were more likely to be vasopressor-dependent (100% vs. 65%; P = 0.03). The relationship between steroid dose and survival was linear, characterized by benefit at low doses and increasing harm at higher doses (P = 0.02). Limitations: We could not analyze time-related improvements in medical care and potential bias secondary to nonreporting of negative study results. Conclusions: Although short courses of high-dose glucocorticolds decreased survival during sepsis, a 5- to 7-day course of physiologic hydrocortisone doses with subsequent tapering increases survival rate and shock reversal in patients with vasopressor-dependent septic shock. C1 NHLBI, Ctr Clin, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr, Bethesda, MD 20892 USA. EM pminneci@mail.cc.nih.gov NR 42 TC 205 Z9 223 U1 2 U2 11 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 6 PY 2004 VL 141 IS 1 BP 47 EP 56 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 834RF UT WOS:000222427600007 PM 15238370 ER PT J AU Zhang, PS Sheng, HT Uehara, R AF Zhang, PS Sheng, HT Uehara, R TI A double classification tree search algorithm for index SNP selection SO BMC BIOINFORMATICS LA English DT Article AB Background: In population-based studies, it is generally recognized that single nucleotide polymorphism ( SNP) markers are not independent. Rather, they are carried by haplotypes, groups of SNPs that tend to be coinherited. It is thus possible to choose a much smaller number of SNPs to use as indices for identifying haplotypes or haplotype blocks in genetic association studies. We refer to these characteristic SNPs as index SNPs. In order to reduce costs and work, a minimum number of index SNPs that can distinguish all SNP and haplotype patterns should be chosen. Unfortunately, this is an NP-complete problem, requiring brute force algorithms that are not feasible for large data sets. Results: We have developed a double classification tree search algorithm to generate index SNPs that can distinguish all SNP and haplotype patterns. This algorithm runs very rapidly and generates very good, though not necessarily minimum, sets of index SNPs, as is to be expected for such NP-complete problems. Conclusions: A new algorithm for index SNP selection has been developed. A webserver for index SNP selection is available at http://cognia.cu-genome.org/cgi-bin/genome/snpIndex.cgi/. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. Komazawa Univ, Fac Nat Sci, Setagaya Ku, Tokyo, Japan. RP Zhang, PS (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. EM zhangpeis@mail.nih.gov; hs734@columbia.edu; uehara@komazawa-u.ac.jp NR 8 TC 16 Z9 16 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 6 PY 2004 VL 5 AR 89 DI 10.1186/1471-2105-5-89 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 839ZR UT WOS:000222827300002 PM 15238162 ER PT J AU Jordan, IK Wolf, YI Koonin, EV AF Jordan, IK Wolf, YI Koonin, EV TI Duplicated genes evolve slower than singletons despite the initial rate increase SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID SEQUENCE DIVERGENCE; SUBFUNCTIONALIZATION; EVOLUTION; SUBSTITUTIONS; DEGENERATION; PRESERVATION; PROBABILITY; EUKARYOTES; ORTHOLOGS; SELECTION AB Background: Gene duplication is an important mechanism that can lead to the emergence of new functions during evolution. The impact of duplication on the mode of gene evolution has been the subject of several theoretical and empirical comparative-genomic studies. It has been shown that, shortly after the duplication, genes seem to experience a considerable relaxation of purifying selection. Results: Here we demonstrate two opposite effects of gene duplication on evolutionary rates. Sequence comparisons between paralogs show that, in accord with previous observations, a substantial acceleration in the evolution of paralogs occurs after duplication, presumably due to relaxation of purifying selection. The effect of gene duplication on evolutionary rate was also assessed by sequence comparison between orthologs that have paralogs ( duplicates) and those that do not ( singletons). It is shown that, in eukaryotes, duplicates, on average, evolve significantly slower than singletons. Eukaryotic ortholog evolutionary rates for duplicates are also negatively correlated with the number of paralogs per gene and the strength of selection between paralogs. A tally of annotated gene functions shows that duplicates tend to be enriched for proteins with known functions, particularly those involved in signaling and related cellular processes; by contrast, singletons include an over-abundance of poorly characterized proteins. Conclusions: These results suggest that whether or not a gene duplicate is retained by selection depends critically on the pre-existing functional utility of the protein encoded by the ancestral singleton. Duplicates of genes of a higher biological import, which are subject to strong functional constraints on the sequence, are retained relatively more often. Thus, the evolutionary trajectory of duplicated genes appears to be determined by two opposing trends, namely, the post-duplication rate acceleration and the generally slow evolutionary rate owing to the high level of functional constraints. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM jordan@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov NR 37 TC 108 Z9 114 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JUL 6 PY 2004 VL 4 AR 22 DI 10.1186/1471-2148-4-22 PG 11 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 840IH UT WOS:000222850800001 PM 15238160 ER PT J AU Ida, H Boylan, SA Weigel, AL Smit-McBride, Z Chao, A Gao, J Buchoff, P Wistow, G Hjelmeland, LM AF Ida, H Boylan, SA Weigel, AL Smit-McBride, Z Chao, A Gao, J Buchoff, P Wistow, G Hjelmeland, LM TI EST analysis of mouse retina and RPE/choroid cDNA libraries SO MOLECULAR VISION LA English DT Article ID GENE-EXPRESSION; SERIAL ANALYSIS; SEQUENCE TAGS; DEGENERATION; IDENTIFICATION; TRANSCRIPTOME; APOPTOSIS; MUTATION; NUMBER; MICE/ AB Purpose: cDNA libraries from the mouse retina have recently been reported, but no well characterized library from the retinal pigment epithelium (RPE) or choroid of the mouse has yet appeared in the literature. To complement these libraries and to provide the first mouse RPE/choroid library, we used freshly dissected tissue from adult C57BL/6J mice to construct new retina and RPE/choroid libraries. Methods: Eyes from 100 six to eight week old C57BL/6J mice were dissected in groups of 10. The whole retina and RPE/choroid were isolated individually and then homogenized before RNA isolation. Over 5000 clones each were sequenced from the unamplified and un-normalized retina and RPE/choroid libraries. All sequences were analyzed using GRIST (GRouping and Identification of Sequence Tags), a bioinformatics program for gene identification and clustering. Results: The RPE/choroid library contained 3145 clusters with 76% of the clusters representing single clones. Nearly 87% of the clusters corresponded to named genes in GenBank, and 8% of the RPE clusters remain unidentified. The retina library contained 3190 clusters of which 78% represented only one clone. Approximately 85% of the clusters matched sequences in GenBank, and 9% of the clusters remain unidentified. The clones most abundant in each library were all well-known sequences and both libraries contained a number of tissue specific or tissue-enhanced genes. Conclusions: These new libraries should provide a valuable resource for gene discovery and cDNAs for expression analysis and functional studies. C1 Univ Calif Davis, Sch Med, Dept Biol Chem, Vitreoretinal Res Lab, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Ophthalmol, Davis, CA 95616 USA. Natl Tsing Hua Univ, Inst Stat, Hsinchu, Taiwan. NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Hjelmeland, LM (reprint author), Univ Calif Davis, Sch Med, Dept Biol Chem, Vitreoretinal Res Lab, 1 Shields Ave, Davis, CA 95616 USA. EM lmhjelmeland@ucdavis.edu RI Smit-McBride, Zeljka/F-5524-2010 FU NEI NIH HHS [P30EY12576, EY06473] NR 26 TC 14 Z9 14 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUL 6 PY 2004 VL 10 IS 55 BP 439 EP 444 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 838DB UT WOS:000222692400001 PM 15257269 ER PT J AU Logvinoff, C Major, ME Oldach, D Heyward, S Talal, A Balfe, P Feinstone, SM Alter, H Rice, CM McKeating, JA AF Logvinoff, C Major, ME Oldach, D Heyward, S Talal, A Balfe, P Feinstone, SM Alter, H Rice, CM McKeating, JA TI Neutralizing antibody response during acute and chronic hepatitis C virus infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYPERVARIABLE REGION 1; FOLLOW-UP; HYPOGAMMAGLOBULINEMIC PATIENTS; VIRAL PERSISTENCE; TYPE-1 INFECTION; IMMUNE-RESPONSE; CHIMPANZEES; PROTEIN; DETERMINANTS; VACCINATION AB Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. in seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximate to50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication. C1 Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 10021 USA. Columbia Univ, Div Infect Dis, New York, NY 10032 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP McKeating, JA (reprint author), Rockefeller Univ, Ctr Study Hepatitis C, 1230 York Ave, New York, NY 10021 USA. EM mckeatj@rockefeller.edu OI Oldach, David/0000-0002-8811-2562; McKeating, Jane/0000-0002-7229-5886 FU NCI NIH HHS [R01 CA057973, CA57973, CA85883, R01 CA085883]; NIAID NIH HHS [AI60561, N01AI40034, R01 AI060561] NR 32 TC 243 Z9 260 U1 0 U2 10 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 JUL 6 PY 2004 VL 101 IS 27 BP 10149 EP 10154 DI 10.1073/pnas.0403519101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 836CZ UT WOS:000222534200038 PM 15220475 ER PT J AU Clifton, DR Fields, KA Grieshaber, SS Dooley, CA Fischer, ER Mead, DJ Carabeo, RA Hackstadt, T AF Clifton, DR Fields, KA Grieshaber, SS Dooley, CA Fischer, ER Mead, DJ Carabeo, RA Hackstadt, T TI A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OUTER-MEMBRANE PROTEIN; COLI TIR BINDS; HOST-CELL; EPITHELIAL-CELLS; HELA-CELLS; SALMONELLA-TYPHIMURIUM; RICKETTSIA-RICKETTSII; GENOME SEQUENCE; SEROVAR L2; TRACHOMATIS AB The obligate intracellular bacterium Chlamydia trachomatis rapidly induces its own entry into host cells. Initial attachment is mediated by electrostatic interactions to heparan sulfate moieties on the host cell, followed by irreversible binding to an unknown secondary receptor. This secondary binding leads to the recruitment of actin to the site of attachment, formation of an actin-rich, pedestal-like structure, and finally internalization of the bacteria. How chlamydiae induce this process is unknown. We have identified a high-molecular-mass tyrosine-phosphorylated protein that is rapidly phosphorylated on attachment to the host cell. Immunoelectron microscopy studies revealed that this tyrosine-phosphorylated protein is localized to the cytoplasmic face of the plasma membrane at the site of attachment of surf ace-associated chlamydiae. The phosphoprotein was isolated by immunoprecipitation with the anti phosphotyrosine antibody 4G10 and identified as the chlamydial protein CT456, a hypothetical protein with unknown function. The chlamydial protein (Tarp) appears to be translocated into the host cell by type III secretion because it is exported in a Yersinia heterologous expression assay. Phosphotyrosine signaling across the plasma membrane preceded the recruitment of actin to the site of chlamydial attachment and may represent the initial signal transduced from pathogen to the host cell. These results suggest that C. trachomatis internalization is mediated by a chlamydial type III-secreted effector protein. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM thackstadt@niaid.nih.gov NR 41 TC 218 Z9 224 U1 1 U2 10 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 JUL 6 PY 2004 VL 101 IS 27 BP 10166 EP 10171 DI 10.1073/pnas.0402829101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 836CZ UT WOS:000222534200041 PM 15199184 ER PT J AU Rossner, M Yamada, KM AF Rossner, M Yamada, KM TI What's in a picture? The temptation of image manipulation SO JOURNAL OF CELL BIOLOGY LA English DT Article C1 NIDCR, NIH, Bethesda, MD USA. RP Rossner, M (reprint author), Rockefeller Univ Press, Journal Cell Biol, 1114 1st Ave,3rd Fl, New York, NY 10021 USA. EM rossner@rockefeller.edu OI Rossner, Mike/0000-0002-8821-1747; Yamada, Kenneth/0000-0003-1512-6805 NR 2 TC 172 Z9 172 U1 1 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 JUL 5 PY 2004 VL 166 IS 1 BP 11 EP 15 DI 10.1083/jcb.200406019 PG 5 WC Cell Biology SC Cell Biology GA 836IZ UT WOS:000222550500001 PM 15240566 ER PT J AU Lakhani, NJ Sparreboom, A Dahut, WL Venitz, J Figg, WD AF Lakhani, NJ Sparreboom, A Dahut, WL Venitz, J Figg, WD TI Determination of the antiangiogenesis agent 2-methoxyestradiol in human plasma by liquid chromatography with ultraviolet detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE 2-methoxyestradiol AB A high-performance liquid chromatography (HPLC) assay was developed for the quantitative determination of 2-methoxyestradiol (2ME2) in human plasma. Sample pretreatment involved a solid-phase extraction of 1 ml aliquots of plasma with C-18 micro-columns. Separation was achieved on a Novapak C-18 column (300 mm x 3.9 mum i.d.; 4 mum PS) at room temperature at an isocratic flow rate of 1 ml/min with 50% acetonitrile in water. Detection was performed at a UV wavelength of 205 nm. Calibration curves were linear in the concentration range of 1-50 ng/ml. The accuracy and precision values obtained from three different sets of quality controls analyzed in replicates of four on four separate occasions ranged from 90.7 to 105.2 and 3.17 to 8.27%, respectively. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 7 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUL 5 PY 2004 VL 806 IS 2 BP 289 EP 293 DI 10.1016/j.jchromb.2004.03.046 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 828AV UT WOS:000221945700027 PM 15171941 ER PT J AU Lepper, ER Hicks, JK Verweij, J Zhai, SP Figg, WD Sparreboom, A AF Lepper, ER Hicks, JK Verweij, J Zhai, SP Figg, WD Sparreboom, A TI Determination of midazolam in human plasma by liquid chromatography with mass-spectrometric detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE midazolam ID CYTOCHROME-P450 3A PROBE; HUMAN-SERUM; INTRAINDIVIDUAL VARIABILITY; GAS-CHROMATOGRAPHY; MAJOR METABOLITE; 1-HYDROXYMIDAZOLAM; PHASE; ASSAY; CYP3A; 1'-HYDROXYMIDAZOLAM AB A liquid chromatographic assay with mass-spectrometric detection was developed for the quantitative determination of the cytochrome P450 3A phenotyping probe midazolam in human plasma. Sample pretreatment involved a one-step extraction of 600 mul aliquots with ethyl acetate. Midazolam and the internal standard, lorazepam, were separated on a column (150 mm x 4.6 mm, i.d.) packed with 5 mum Zorbax Eclipse XDB-C8 material, using a mobile phase composed of methanol and 10 mM aqueous ammonium acetate (60:40, v/v). Column effluents were analyzed using mass-spectrometry with an atmospheric pressure chemical ionization source. Calibration curves were linear in the concentration range of 1.00-200ng/ml. The accuracy and precision ranged from 92.8 to 112% and 0.056 to 13.4%, respectively, for four different concentrations of quality control samples analyzed in triplicate on eight separate occasions. The developed method was subsequently applied to study the pharmacokinetics of midazolam in a group of 35 human subjects at a single dose of 25 mug/kg. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, Canc Res Ctr, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Erasmus Univ, Med Ctr, Dr Daniel Denhoed Canc Ctr, Rotterdam, Netherlands. RP Figg, WD (reprint author), NCI, Canc Res Ctr, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 35 TC 19 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUL 5 PY 2004 VL 806 IS 2 BP 305 EP 310 DI 10.1016/j.jchromb.2004.04.003 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 828AV UT WOS:000221945700030 PM 15171944 ER PT J AU Chiang, YJ Sommers, CL Jordan, MS Gu, H Samelson, LE Koretzky, GA Hodes, RJ AF Chiang, YJ Sommers, CL Jordan, MS Gu, H Samelson, LE Koretzky, GA Hodes, RJ TI Inactivation of c-Cbl reverses neonatal lethality and T cell developmental arrest of SLP-76-deficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE c-Cbl; SLP-76; LAT; T cell development; ERK ID ADAPTER PROTEIN SLP-76; SIGNAL-TRANSDUCTION; POSITIVE SELECTION; LAT; ACTIVATION; ZAP-70; MUTATION; RECEPTOR; PHOSPHORYLATION; DIFFERENTIATION AB c-Cbl is an adaptor protein that negatively regulates signal transduction events involved in thymic-positive selection. To further characterize the function of c-Cbl in T cell development, we analyzed the effect of c-Cbl inactivation in mice deficient in the scaffolding molecule SLP-76. SLP-76-deficient mice show a high frequency of neonatal lethality; and in surviving mice, T cell development is blocked at the DN3 stage. Inactivation of c-cbl completely reversed the neonatal lethality seen in SLP-76-deficient mice and partially reversed the T cell development arrest in these mice. SLP-76(-/-) Cbl(-/-) mice exhibited marked expansion of polarized T helper type (Th)1 and Th2 cell peripheral CD4(+) T cells, lymphoid infiltrates of parenchymal organs, and premature death. This rescue of T cell development is T cell receptor dependent because it does not occur in recombination activating gene 2(-/-) SLP-76(-/-) Cbl(-/-) triple knockout mice. Analysis of the signal transduction properties of SLP-76(-/-) Cbl(-/-) T cells reveals a novel SLP-76- and linker for activation of T cells-independent pathway of extracellular signal-regulated kinase activation, which is normally down-regulated by c-Cbl. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Natl Inst Aging, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol, Abramson Family Canc Res Inst, Signal Transduct Program, Philadelphia, PA 19104 USA. Univ Penn, Lab Med, Philadelphia, PA 19104 USA. Columbia Univ, Dept Microbiol, New York, NY 10032 USA. RP Chiang, YJ (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM chiangj@mail.nih.gov NR 30 TC 22 Z9 22 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 5 PY 2004 VL 200 IS 1 BP 25 EP 34 DI 10.1084/jem.20040262 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 837XK UT WOS:000222674500003 PM 15238603 ER PT J AU Martomo, SA Yang, WW Gearhart, PJ AF Martomo, SA Yang, WW Gearhart, PJ TI A role for Msh6 but not Msh3 in somatic hypermutation and class switch recombination SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE DNA repair enzymes; cytosine deamination; class switching; mutation hotspots; B lymphocytes ID SINGLE-STRANDED-DNA; IMMUNOGLOBULIN VARIABLE GENES; MISMATCH REPAIR PROTEIN; CYTIDINE DEAMINASE AID; S-MU REGION; POLYMERASE-ETA; B-CELLS; ANTIBODY DIVERSIFICATION; MICE DEFICIENT; TRANSCRIPTION AB Somatic hypermutation is initiated by activation-induced cytidine deaminase (AID), and occurs in several kilobases of DNA around rearranged immunoglobulin variable (V) genes and switch (S) sites before constant genes. AID deaminates cytosine to uracil, which can produce mutations of C:G nucleotide pairs, and the mismatch repair protein Msh2 participates in generating substitutions of downstream A:T pairs. Msh2 is always found as a heterodimer with either Msh3 or Msh6, so it is important to know which one is involved. Therefore, we sequenced V and S regions from Msh3- and Msh6-deficient mice and compared mutations to those from wild-type mice. Msh6-deficient mice had fewer substitutions of A and T bases in both regions and reduced heavy chain class switching, whereas Msh3-deficient mice had normal antibody responses. This establishes a role for the Msh2-Msh6 heterodimer in hypermutation and switch recombination. When the positions of mutation were mapped, several focused peaks were found in Msh6(-/-) clones, whereas mutations were dispersed in Msh3(-/-) and wild-type clones. The peaks occurred at either G or C in WGCW motifs (W = A or T), indicating that C was mutated on both DNA strands. This suggests that AID has limited entry points into V and S regions in vivo, and subsequent mutation requires Msh2-Msh6 and DNA polymerase. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov NR 43 TC 91 Z9 91 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 5 PY 2004 VL 200 IS 1 BP 61 EP 68 DI 10.1084/jem.20040691 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 837XK UT WOS:000222674500006 PM 15238605 ER PT J AU Martin, AG Nguyen, J Wells, JA Fearnhead, HO AF Martin, AG Nguyen, J Wells, JA Fearnhead, HO TI Apo cytochrome c inhibits caspases by preventing apoptosome formation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Apaf-1; apoptosis; apoptosome; caspase; apo cytochrome c ID WD-40 REPEAT REGION; PROCASPASE-9 ACTIVATION; APOPTOTIC ACTIVITY; CELL-DEATH; FACTOR-I; APAF-1; RELEASE; BINDING; BCL-2; OLIGOMERIZATION AB Caspases are cysteine proteases and potent inducers of apoptosis. Their activation and activity is therefore tightly regulated. There are several mechanisms by which caspases can be activated but one key pathway involves release of holo cytochrome c from mitochondria into the cytoplasm. Cytoplasmic holo cytochrome c binds to apoptotic protease activating factor-1 (Apaf-1), driving the formation of an Apaf-1 oligomer (the apoptosome) which in turn binds and activates caspase-9. Previously we showed that the apo form of cytochrome c (lacking heme) can bind Apaf-1 and block both holo-dependent caspase activation in cell extracts and Bax-induced apoptosis in cells. Here we tested the ability of apo cytochrome c to inhibit caspase-9 activation induced by recombinant Apaf-1. Furthermore, using purified proteins and size exclusion chromatography we show that apo cytochrome c prevents holo cytochrome c-dependent apoptosome formation. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Apoptosis Sect, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. Sunesis Pharmaceut, San Francisco, CA 94080 USA. RP Fearnhead, HO (reprint author), NCI, Apoptosis Sect, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. EM hfearnhead@ncifcrf.gov RI Fearnhead, Howard/D-4826-2012; Wells, Jim/O-9854-2016; OI Garcia Martin, Angel/0000-0002-3831-2769; Fearnhead, Howard/0000-0002-8054-9794 NR 33 TC 19 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 2 PY 2004 VL 319 IS 3 BP 944 EP 950 DI 10.1016/j.bbrc.2004.05.084 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 831LH UT WOS:000222195400034 PM 15184073 ER PT J AU Brewer, BY Malicka, J Blackshear, PJ Wilson, GM AF Brewer, BY Malicka, J Blackshear, PJ Wilson, GM TI RNA sequence elements required for high affinity binding by the zinc finger domain of tristetraprolin - Conformational changes coupled to the bipartite nature of AU-rich mRNA-destabilizing motifs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-DNA; FLUORESCENCE ANISOTROPY; MAMMALIAN-CELLS; STABILITY; DEGRADATION; TURNOVER; ALPHA; THERMODYNAMICS; ASSOCIATION; RECOGNITION AB Tristetraprolin (TTP) binds AU-rich elements (AREs) encoded within selected labile mRNAs and targets these transcripts for rapid cytoplasmic decay. RNA binding by TTP is mediated by an similar to70-amino acid domain containing two tandemly arrayed CCCH zinc fingers. Here we show that a 73-amino acid peptide spanning the TTP zinc finger domain, denoted TTP73, forms a dynamic, equimolar RNA . peptide complex with a 13-nucleotide fragment of the ARE from tumor necrosis factor alpha mRNA, which includes small but significant contributions from ionic interactions. Association of TTP73 with high affinity RNA substrates is accompanied by a large negative change in heat capacity without substantial modification of RNA structure, consistent with conformational changes in the peptide moiety during RNA binding. Analyses using mutant ARE substrates indicate that two adenylate residues located 3 - 6 bases apart within a uridylate-rich sequence are sufficient for high affinity recognition by TTP73 (K-d < 20 nM), with optimal affinity observed for RNA substrates containing AUUUA or AUUUUA. Linkage of conformational changes and binding affinity to the presence and spacing of these adenylate residues provides a thermodynamic basis for the RNA substrate specificity of TTP. C1 Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Ctr Fluorescence Spect, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Wilson, GM (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Ctr Fluorescence Spect, 108 N Greene St, Baltimore, MD 21201 USA. EM gwils001@umaryland.edu FU NCI NIH HHS [R01 CA 10242 8]; NCRR NIH HHS [P41 RR 08119] NR 43 TC 92 Z9 94 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 2 PY 2004 VL 279 IS 27 BP 27870 EP 27877 DI 10.1074/jbc.M402551200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400008 PM 15117938 ER PT J AU Basu, NK Kubota, S Meselhy, MR Ciotti, M Chowdhury, B Hartori, M Owens, IS AF Basu, NK Kubota, S Meselhy, MR Ciotti, M Chowdhury, B Hartori, M Owens, IS TI Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-COMPLEX LOCUS; COS-1 CELLS; I PATIENT; BILIRUBIN; GLUCURONIDATION; UDPGLUCURONOSYLTRANSFERASE; EXPRESSION; CLONING; CDNAS; ALPHA AB Among gastrointestinal distributed isozymes encoded at the UGT1 locus, UDP-glucuronosyltransferase 1A10 (UGT1A10) metabolizes a number of important chemicals. Similar to broad conversion of phytoestrogens (Basu, N. K., Ciotti, M., Hwang, M. S., Kole, L., Mitra, P. S., Cho, J. W., and Owens, I. S. ( 2004) J. Biol. Chem. 279, 1429-1441), UGT1A10 metabolized estrogens and their derivatives, whereas UGT1A1, -1A3, -1A7, and -1A8 differentially exhibited reduced activity toward the same. UGT1A10 compared with UGT1A7, -1A8, and -1A3 generally exhibited high activity toward acidic nonsteroidal anti-inflammatory drugs and natural benzaldehyde derivatives, while UGT1A3 metabolized most efficiently aromatic transcinnamic acids known to be generated from flavonoid glycosides by microflora in the lower gastrointestinal tract. Finally UGT1A10, -1A7, -1A8, and -1A3 converted plant-based salicylic acids; methylsalicylic acid was transformed at high levels, and acetylsalicylic (aspirin) and salicylic acid were transformed at moderate to low levels. Atypically UGT1A10 transformed estrogens between pH 6 and 8 but acidic structures preferentially at pH 6.4. Furthermore evidence indicates UGT1A10 expressed in COS-1 cells depends upon phosphorylation; UGT1A10 versus its single, double, and triple mutants at three predicted protein kinase C phosphorylation sites incorporated [P-33]-orthophosphate and showed a progressive decrease with no detectable label or activity for the triple T73A/T202A/S432G-1A10 mutant. Single and double mutants revealed either null/full activity or null/additive activity, respectively. Additionally UGT1A10-expressing cultures glucuronidated 17beta-[C-14]estradiol, whereas cultures containing null mutants at protein kinase C sites showed no estrogen conversion. Importantly UGT1A10 in cells supported 10-fold higher glucuronidation of 17beta-estradiol than UGT1A1. In summary, our results suggest gastrointestinally distributed UGT1A10 is important for detoxifying estrogens/phytoestrogens and aromatic acids with complementary activity by UGT1A7, -1A8, -1A3, and/or -1A1 evidently dependent upon phosphorylation. C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Res Inst Wakan Yaku, Toyama 93001, Japan. RP Owens, IS (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S-241, Bethesda, MD 20892 USA. EM owensi@mail.nih.gov NR 30 TC 39 Z9 39 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 2 PY 2004 VL 279 IS 27 BP 28320 EP 28329 DI 10.1074/jbc.M401396200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400064 PM 15117964 ER PT J AU Yasumoto, K Watabe, H Valencia, JC Kushimoto, T Kobayashi, T Appella, E Hearing, VJ AF Yasumoto, K Watabe, H Valencia, JC Kushimoto, T Kobayashi, T Appella, E Hearing, VJ TI Epitope mapping of the melanosomal matrix protein gp100 (PMEL17) - Rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; TUMOR-INFILTRATING LYMPHOCYTES; ANTIBODIES NKI-BETEB; HUMAN MELANOCYTES; VESICLE FORMATION; MELANOMA-CELLS; ANTIGEN GENES; TYROSINASE; TRAFFICKING; BIOGENESIS AB Melanosomes, specific organelles produced only by melanocytes, undergo a unique maturation process that involves their transition form amorphous rounded vesicles to fibrillar ellipsoid organelles, during which they move from the perinuclear to the distal areas of the cells. This depends upon the trafficking and processing of gp100 (also known as Pmel17 and the silver protein), a protein of great interest, because it elicits immune responses in melanoma patients but in which specific function(s) remains elusive. In this study, we have used biochemical and immunochemical approaches to more critically assess the synthesis, processing, glycosylation, and trafficking of gp100. We now report that gp100 is processed and sorted in a manner distinct from other melanosomal proteins (such as tyrosinase, Tyrp1 and Dct) and is predominantly delivered directly to immature melanosomes following its rapid processing in the endoplasmic reticulum and cis-Golgi. Following its arrival, gp100 is cleaved at the amino and at the carboxyl termini in a series of specific steps that result in the reorganization of immature melanosomes to the fibrillar mature melanosomes. Once this structural reorganization occurs, melanogenic enzymes begin to be targeted to the melanosomes, which are then competent to synthesize melanin pigment. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Japan Sci & Technol Corp, Exploratory Res Adv Technol, Nagoya, Aichi 4600012, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 38 TC 47 Z9 51 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 2 PY 2004 VL 279 IS 27 BP 28330 EP 28338 DI 10.1074/jbc.M401269200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400065 PM 15096515 ER PT J AU Kim, BC van Gelder, H Kim, TA Lee, HJ Baik, KG Chun, HH Lee, DA Choi, KS Kim, SJ AF Kim, BC van Gelder, H Kim, TA Lee, HJ Baik, KG Chun, HH Lee, DA Choi, KS Kim, SJ TI Activin receptor-like kinase-7 induces apoptosis through activation of MAPKs in a Smad3-dependent mechanism in hepatoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE/THREONINE KINASE; TRANSFORMING GROWTH-FACTOR-BETA-1; RAT HEPATOCYTES; ALK7 SIGNALS; PROTEIN; LINE; DIFFERENTIATION; PHOSPHORYLATION; PROTEASES; CLEAVAGE AB Activin receptor-like kinase (ALK)7 is a type I serine/threonine kinase receptor of the transforming growth factor (TGF)-beta family of proteins that has similar properties to other type I receptors when activated. To see whether ALK7 can induce apoptosis as can some of the other ALK proteins, we infected the FaO rat hepatoma cell line with adenovirus expressing a constitutively active form of the ALK7. Cells infected with active ALK7 adenovirus showed an apoptotic-positive phenotype, as opposed to those that were infected with a control protein. DNA fragmentation assays and fluorescence-activated cell sorter analysis also indicated that ALK7 infection induced apoptosis in FaO cells. We also confirmed this finding in Hep3B human hepatoma cells by transiently transfecting the constitutively active form of ALK7, ALK7(T194D). Investigation into the downstream targets and mechanisms involved in ALK7-induced apoptosis revealed that the TGF-beta signaling intermediates, Smad2 and -3, were activated, as well as the MAPKs JNK and p38. In addition, caspase-3 and -9 were also activated, and cytochrome c release from the mitochondria was observed. Short interfering RNA-mediated inhibition of Smad3 markedly suppressed ALK7-induced caspase-3 activation. Treatment with protein synthesis inhibitors or the expression of the dominant-negative form of the stress-activated protein/extracellular signal-regulated kinase 1 abolished not only JNK activation but apoptosis as well. Taken together, these results suggest that ALK7 induces apoptosis through activation of the traditional TGF-beta pathway components, thus resulting in new gene transcription and JNK and p38 activation that initiates cross-talk with the cellular stress death pathway and ultimately leads to apoptosis. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Kangweon Natl Univ, Coll Nat Sci, Chunchon 200701, South Korea. Ajou Univ, Sch Med, Inst Med Sci, Lab Endocrinol, Suwon 441749, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. EM kims@mail.nih.gov NR 22 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 2 PY 2004 VL 279 IS 27 BP 28458 EP 28465 DI 10.1074/jbc.M313277200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400080 PM 15107418 ER PT J AU Umland, TC Wolff, EC Park, MH Davies, DR AF Umland, TC Wolff, EC Park, MH Davies, DR TI A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme center dot NAD center dot inhibitor ternary complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INITIATION-FACTOR 5A; HYPUSINE-CONTAINING PROTEIN; SUBSTRATE INTERMEDIATE; ANGSTROM RESOLUTION; CELL-CYCLE; SPERMIDINE; HOMOSPERMIDINE; IDENTIFICATION; FEATURES; BINDING AB Deoxyhypusine synthase catalyzes the first step in the two-step post-translational synthesis of hypusine, which is uniquely present in eukaryotic initiation factor 5A (eIF5A). Deoxyhypusine synthase and eIF5A are conserved throughout the eukaryotic kingdom, and both are essential for cell proliferation and survival. A previous study (Liao, D. I., Wolff, E. C., Park, M. H., and Davies, D. R. ( 1998) Structure 6, 23-32) of human deoxyhypusine synthase revealed four active sites of the homotetrameric enzyme located within deep tunnels. These Form I crystals were obtained under conditions of acidic pH and high ionic strength and likely contain an inactive enzyme. Each active-site entrance is blocked by a ball-and-chain motif composed of a region of extended structure capped by a two-turn alpha-helix. We report here at 2.2 Angstrom a new Form II crystal of the deoxyhypusine synthase: NAD holoenzyme grown at low ionic strength and pH 8.0, near the optimal pH for enzymatic activity. The ball-and-chain motif could not be detected in the electron density, suggesting that it swings freely and thus it no longer obstructs the active-site entrance. The deoxyhypusine synthase competitive inhibitor N-1-guanyl-1,7-diaminoheptane (GC(7)) is observed bound within the putative active site of the enzyme in the new crystal form ( Form II) after exposure to the inhibitor. This first structure of a deoxyhypusine synthase.NAD.inhibitor ternary complex under physiological conditions now provides a structural context to discuss the results of previous biochemical investigations of the deoxyhypusine synthase reaction mechanism. This structure also provides a basis for the development of improved inhibitors and antiproliferative agents. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Davies, DR (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM david.davies@nih.gov OI Umland, Timothy/0000-0002-0772-9510 NR 43 TC 40 Z9 43 U1 1 U2 6 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 JUL 2 PY 2004 VL 279 IS 27 BP 28697 EP 28705 DI 10.1074/jbc.M404095200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400107 PM 15100216 ER PT J AU Chan, SL Fu, WM Zhang, PS Cheng, AW Lee, JW Kokame, K Mattson, MP AF Chan, SL Fu, WM Zhang, PS Cheng, AW Lee, JW Kokame, K Mattson, MP TI Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; UNFOLDED-PROTEIN RESPONSE; AMYLOID PRECURSOR PROTEIN; N-TERMINAL KINASE; CELL-DEATH; INDUCED APOPTOSIS; ACTIVATION; BETA; CASPASE-12; DISEASE AB In response to endoplasmic reticulum ( ER) stress, cells launch homeostatic and protective responses, but can also activate cell death cascades. A 54 kDa integral ER membrane protein called Herp was identified as a stress-responsive protein in non-neuronal cells. We report that Herp is present in neurons in the developing and adult brain, and that it is regulated in neurons by ER stress; sublethal levels of ER stress increase Herp levels, whereas higher doses decrease Herp levels and induce apoptosis. The decrease in Herp protein levels following a lethal ER stress occurs prior to mitochondrial dysfunction and cell death, and is mediated by caspases which generate a 30-kDa proteolytic Herp fragment. Mutagenesis of the caspase cleavage site in Herp enhances its neuroprotective function during ER stress. While suppression of Herp induction by RNA interference sensitizes neural cells to apoptosis induced by ER stress, overexpression of Herp promotes survival by a mechanism involving stabilization of ER Ca2+ levels, preservation of mitochondrial function and suppression of caspase 3 activation. ER stress-induced activation of JNK/c-Jun and caspase 12 are reduced by Herp, whereas induction of major ER chaperones is unaffected. Herp prevents ER Ca2+ overload under conditions of ER stress and agonist-induced ER Ca2+ release is attenuated by Herp suggesting a role for Herp in regulating neuronal Ca2+ signaling. By stabilizing ER Ca2+ homeostasis and mitochondrial functions, Herp serves a neuroprotective function under conditions of ER stress. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Natl Cardiovasc Res Inst, Osaka 5658565, Japan. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Chan, SL (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM chanst@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 59 TC 74 Z9 77 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 2 PY 2004 VL 279 IS 27 BP 28733 EP 28743 DI 10.1074/jbc.M404272200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832KC UT WOS:000222265400111 PM 15102845 ER PT J AU Dent, SR Hager, GL AF Dent, SR Hager, GL TI Robert T. Simpson (1938-2004) SO MOLECULAR CELL LA English DT Biographical-Item C1 Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Dent, SR (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. EM syr@mdacc.tmc.edu; hagerg@exchange.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL 2 PY 2004 VL 15 IS 1 BP 3 EP 4 DI 10.1016/j.molcel.2004.06.027 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 834VN UT WOS:000222439100002 ER PT J AU Vuu, K Pandit, SD Li, KCP AF Vuu, K Pandit, SD Li, KCP TI A primer on molecular biology for imagers: V. Genomics: A global approach to the study of genes SO ACADEMIC RADIOLOGY LA English DT Article ID EXPRESSION C1 NIH, Ctr Clin, Mol Imaging Lab, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Vuu, K (reprint author), NIH, Ctr Clin, Mol Imaging Lab, Dept Diagnost Radiol, 10-1N306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kvuu@cc.nih.gov NR 13 TC 2 Z9 2 U1 1 U2 1 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 JUL PY 2004 VL 11 IS 7 BP 817 EP 828 DI 10.1016/j.acra.2004.05.003 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 833VY UT WOS:000222369800014 PM 15217600 ER PT J AU Sevcik, J Dauter, Z Wilson, KS AF Sevcik, J Dauter, Z Wilson, KS TI Crystal structure reveals two alternative conformations in the active site of ribonuclease Sa2 SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID STREPTOMYCES-AUREOFACIENS; ATOMIC-RESOLUTION; REFINEMENT; COMPLEX; MOLSCRIPT; MODEL AB Three different strains of Streptomyces aureofaciens produce the homologous ribonucleases Sa, Sa2 and Sa3. The crystal structures of ribonuclease Sa ( RNase Sa) and its complexes with mononucleotides have previously been reported at high resolution. Here, the structures of two crystal forms ( I and II) of ribonuclease Sa2 ( RNase Sa2) are presented at 1.8 and 1.5Angstrom resolution. The structures were determined by molecular replacement using the coordinates of RNase Sa as a search model and were refined to R factors of 17.5 and 15.0% and R-free factors of 21.8 and 17.2%, respectively. The asymmetric unit of crystal form I contains three enzyme molecules, two of which have similar structures to those seen for ribonuclease Sa, with Tyr87 at the bottom of their active sites. In the third molecule, Tyr87 has moved substantially: the CA atom moves almost 5 Angstrom and the OH of the side chain moves 10 Angstrom, inserting itself into the active site of a neighbouring molecule at a similar position to that observed for the nucleotide base in RNase Sa complexes. The asymmetric unit of crystal form II contains two Sa2 molecules, both of which are similar to the usual Sa structures. In one molecule, two main-chain conformations were modelled in the alpha-helix. Finally, a brief comparison is made between the conformations of the Sa2 molecules and those of 34 independent molecules taken from 20 structures of ribonuclease Sa and two independent molecules taken from two structures of ribonuclease Sa3 in various crystal forms. C1 Slovak Acad Sci, Inst Mol Biol, Bratislava 84551, Slovakia. Brookhaven Natl Lab, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, NCI, Upton, NY 11973 USA. Univ York, Struct Biol Lab, York YO10 5YW, N Yorkshire, England. RP Sevcik, J (reprint author), Slovak Acad Sci, Inst Mol Biol, Dubravska Cesta 21, Bratislava 84551, Slovakia. EM jozef.sevcik@savba.sk NR 25 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL PY 2004 VL 60 BP 1198 EP 1204 DI 10.1107/S0907444904009035 PN 7 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 831EX UT WOS:000222177600002 PM 15213380 ER PT J AU Haley, WE Gitlin, LN Wisniewski, SR Mahoney, DF Coon, DW Winter, L Corcoran, M Schinfeld, S Ory, M AF Haley, WE Gitlin, LN Wisniewski, SR Mahoney, DF Coon, DW Winter, L Corcoran, M Schinfeld, S Ory, M TI Well-being, appraisal, and coping in African-American and Caucasian dementia caregivers: findings from the REACH study SO AGING & MENTAL HEALTH LA English DT Article ID FAMILY CAREGIVERS; WHITE CAREGIVERS; MENTAL-HEALTH; CULTURAL-DIFFERENCES; ALZHEIMERS-DISEASE; FUTURE-DIRECTIONS; BLACK; OUTCOMES; INTERVENTIONS; EXPERIENCE AB Although there has been considerable interest in racial differences in family caregiving for persons with dementia, most research to date has either ignored racial diversity or based conclusions on small numbers of caregivers drawn primarily from single site studies. The current study utilized participants from four sites of the REACH (Resources for Enhancing Alzheimer's Caregiver Health) multi-site study to compare well-being, appraisal, and religious coping by race. African-American (n=295) and Caucasian (n=425) dementia caregivers from four cities (Birmingham, Memphis, Boston, and Philadelphia) were compared in their demographics, care recipient characteristics, mental and physical health, and psychosocial coping resources including appraisal and religious coping. African-American caregivers reported lower anxiety, better well-being, less use of psychotropic medications, more benign appraisals of stress and perceived benefits of caregiving, and greater religious coping and participation, than Caucasian caregivers. Self-rated health did not differ by race, but African-American caregivers reported more unhealthy behaviors than Caucasian caregivers. Some results were specific to site, possibly due to differences in recruitment strategies, inclusion/exclusion criteria, and regional differences. Adjustment for covariates, including caregiver relationship to the care recipient, gender, age, socioeconomic status, and care recipient behavioral problems, altered few of these differences. Results are discussed in terms of their relevance to psychosocial intervention programs for ethnically diverse caregivers. C1 Univ S Florida, Sch Aging Studies, Tampa, FL 33620 USA. Thomas Jefferson Univ, Ctr Collaborat Res, Philadelphia, PA USA. Univ Pittsburgh, Dept Epidemiol, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA USA. George Washington Univ, Dept Hlth Care Serv, Washington, DC 20052 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Texas A&M Univ, Sch Rural Publ Hlth, College Stn, TX 77843 USA. NIA, Behav & Social Sci Program, Bethesda, MD 20892 USA. RP Haley, WE (reprint author), Univ S Florida, Sch Aging Studies, SOC 107, Tampa, FL 33620 USA. EM whaley@chuma1.cas.usf.edu RI Haley, William/B-6133-2017; OI Haley, William/0000-0003-0780-3482; Wisniewski, Stephen/0000-0002-3877-9860; Mahoney, Diane/0000-0002-6415-475X NR 69 TC 80 Z9 80 U1 2 U2 12 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD JUL PY 2004 VL 8 IS 4 BP 316 EP 329 DI 10.1080/13607860410001728998 PG 14 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 839KO UT WOS:000222784200004 PM 15370048 ER PT J AU Kevrekidis, IG Gear, CW Hummer, G AF Kevrekidis, IG Gear, CW Hummer, G TI Equation-free: The computer-aided analysis of comptex multiscale systems SO AICHE JOURNAL LA English DT Editorial Material ID LATTICE-GAS MODEL; BIFURCATION-ANALYSIS; MOLECULAR-DYNAMICS; MONTE-CARLO; MICROSCOPIC SIMULATORS; DIFFERENTIAL-EQUATIONS; OPTIMAL PREDICTION; COARSE STABILITY; TIME-STEPPERS; FREE-ENERGY C1 Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. Princeton Univ, PACM, Princeton, NJ 08544 USA. NEC Labs Emeritus, Princeton, NJ 08540 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Kevrekidis, IG (reprint author), Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. EM yannis@princeton.EDU; wgear@princeton.edu; gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 81 TC 204 Z9 209 U1 2 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-1541 J9 AICHE J JI AICHE J. PD JUL PY 2004 VL 50 IS 7 BP 1346 EP 1355 DI 10.1002/aic.10106 PG 10 WC Engineering, Chemical SC Engineering GA 833TO UT WOS:000222362500001 ER PT J AU Lifson, JD Rossio, JL Piatak, M Bess, J Chertova, E Schneider, DK Coalter, VJ Poore, B Kiser, RF Imming, RJ Scarzello, AJ Henderson, LE Alvord, WG Hirsch, VM Benveniste, RE Arthur, LO AF Lifson, JD Rossio, JL Piatak, M Bess, J Chertova, E Schneider, DK Coalter, VJ Poore, B Kiser, RF Imming, RJ Scarzello, AJ Henderson, LE Alvord, WG Hirsch, VM Benveniste, RE Arthur, LO TI Evaluation of the safety, immunogenicity, and protective efficacy of whole inactivated simian immunodeficiency virus (SIV) vaccines with conformationally and functionally intact envelope glycoproteins SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TYPE-1 NUCLEOCAPSID PROTEIN; ENV TRANSMEMBRANE PROTEIN; ZINC-FINGER STRUCTURES; MURINE LEUKEMIA-VIRUS; RHESUS MACAQUES; HIV VACCINES; COMBINATION IMMUNIZATION; INTRACYTOPLASMIC DOMAIN; VAGINAL CHALLENGE; MACACA-NEMESTRINA AB A novel, general approach to chemical inactivation of retroviruses was used to produce inactivated simian immunodeficiency virus (SIV) particles with functional envelope glycoproteins. Inactivated virions of three different virus isolates (SIVmne E11S, SIVmac239, and SIVmac239 g4,5), prepared by treatment with 2,2'-dithiodipyridine (aldrithol-2, AT-2), were not detectably infectious, in vitro or in vivo. Immunization of pigtailed macaques with inactivated SIVmne E11S particles, without adjuvant, induced both humoral and cellular immune responses. Four of six animals immunized with the inactivated particles did not show measurable SIV RNA in plasma ( < 100 copy Eq/ml) following intravenous challenge with pathogenic, homologous virus (SIVmne E11S), compared to peak values of &GE; 10(6) copy Eq/ml in challenged SIV-naive control animals (p = 0.0001). Despite the absence of measurable viral RNA in plasma in these animals, culturable virus and viral DNA were initially detectable in blood and lymph node specimens; in contrast to control animals, SIV DNA could no longer be detected in PBMC by 10 weeks postchallenge in five of six SIV-immunized animals ( p = 0.0001). However, vaccines did not resist a sequential rechallenge with the heterologous pathogenic virus SIVsm E660. AT-2-inactivated virus with functional envelope glycoproteins is a novel class of vaccine immunogen and was noninfectious, under conditions of rigorous in vivo challenge, and induced both binding and neutralizing antibody responses, along with cellular immune responses. Results suggest that immunization facilitated effective containment of pathogenic homologous challenge virus. With further optimization, AT-2-inactivated viral particles may be a useful class of immunogen in the development of a vaccine to prevent AIDS. C1 NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Comp & Stat Serv, Frederick, MD 21702 USA. NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. RP Lifson, JD (reprint author), NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick Inc, Bldg 535,5th Floor, Frederick, MD 21702 USA. EM lifson@ncifcrf.gov RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-124000] NR 74 TC 63 Z9 65 U1 0 U2 1 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 JUL PY 2004 VL 20 IS 7 BP 772 EP 787 DI 10.1089/0889222041524661 PG 16 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 845VD UT WOS:000223272500015 PM 15307924 ER PT J AU Littleton, JM De Witte, P Litten, R Gessa, GL Spanagel, R Kranzler, H Lehert, P Johnson, B Saunders, J Berglund, M Harris, A Anton, R Mann, K AF Littleton, JM De Witte, P Litten, R Gessa, GL Spanagel, R Kranzler, H Lehert, P Johnson, B Saunders, J Berglund, M Harris, A Anton, R Mann, K TI Challenges to medications development in treating alcohol dependence: An international perspective - Summary of a symposium held at the ESBRA Congress, Prague, 13 September 2003 SO ALCOHOL AND ALCOHOLISM LA English DT Article AB Few medications for treating alcohol dependence exist. Greater partnership is needed between academia and the pharmaceutical industry to develop, licence and market efficacious medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies need to be developed in order to provide sufficient information on safety, toleration, drug-interaction profile and efficacy, with which to guide development decisions. Due to the heterogeneous nature of alcohol dependence, the effort of developing an efficacious medication is likely to be enhanced by clearer choices about the characteristics of the population. Careful consideration of potential mechanism of action of the putative therapeutic medication should enable the appropriate choice of drinking endpoint. The pharmaceutical industry in collaboration with academia might need to develop new approaches to determining appropriate treatment endpoints with regulatory bodies. The investment risk to industry should be appraised not only in terms of the rather poor results of previous marketing efforts but with a view to the opportunity to penetrate a potentially enormous and largely untapped market. C1 Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY 40546 USA. Royal Brisbane Hosp, Dept Psychiat, Brisbane, Qld 4029, Australia. Univ Louvain, Lab Psychobiol Biol Comportement, Louvain, Belgium. Univ Mons, Fac Econ, Dept Stat, B-7000 Mons, Belgium. Univ Heidelberg, Cent Inst Mental Hlth, Dept Psychopharmacol, D-6800 Mannheim, Germany. Univ Heidelberg, Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, D-6800 Mannheim, Germany. Univ Cagliari, Dept Neurosci, Monserrato, Italy. Lund Univ, Malmo Univ Hosp, Dept Clin Alcohol Res, Malmo, Sweden. NIAAA, Treatment Res Branch, Bethesda, MD USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol & Psychiat, San Antonio, TX USA. Univ Texas, Waggoner Ctr Alcohol & Addict Res, Neurobiol Sect, Austin, TX 78712 USA. RP Littleton, JM (reprint author), Univ Kentucky, Dept Mol & Biomed Pharmacol, Cooper & Univ Dr, Lexington, KY 40546 USA. EM jlittlet@uky.edu NR 6 TC 6 Z9 6 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JUL-AUG PY 2004 VL 39 IS 4 BP 271 EP 275 DI 10.1093/alcalc/agh067 PG 5 WC Substance Abuse SC Substance Abuse GA 832LZ UT WOS:000222270300001 PM 15208155 ER PT J AU Barr, CS Newman, TK Lindell, S Becker, ML Shannon, C Champoux, M Suomi, SJ Higley, JD AF Barr, CS Newman, TK Lindell, S Becker, ML Shannon, C Champoux, M Suomi, SJ Higley, JD TI Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus Macaques (Macaca mulatta) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE stress; ACTH; sexual dimorphism; nonhuman primate; alcohol ID CORTICOTROPIN-RELEASING HORMONE; POSTTRAUMATIC-STRESS-DISORDER; NONHUMAN PRIMATE MODEL; GENDER DIFFERENCES; ALLOSTATIC LOAD; FEMALE RATS; HPA AXIS; VASOPRESSIN; DEPRESSION; RESPONSES AB Background: Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Methods: Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Results: Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. Conclusions: These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders. C1 NIAAA, DICBR, Anim Ctr, NIH, Poolesville, MD 20837 USA. RP Barr, CS (reprint author), NIAAA, DICBR, Anim Ctr, NIH, Bldg 112,POB 529, Poolesville, MD 20837 USA. EM cbarr@mail.nih.gov NR 50 TC 29 Z9 29 U1 1 U2 3 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 JUL PY 2004 VL 28 IS 7 BP 1114 EP 1119 DI 10.1097/01.ALC.0000130973.94350.8C PG 6 WC Substance Abuse SC Substance Abuse GA 840AQ UT WOS:000222829800018 PM 15252299 ER PT J AU Kannel, WB D'Agostino, RB Sullivan, L Wilson, PWF AF Kannel, WB D'Agostino, RB Sullivan, L Wilson, PWF TI Concept and usefulness of cardiovascular risk profiles SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-HEART-DISEASE; PRIMARY PREVENTION; TASK-FORCE; FOLLOW-UP; FRAMINGHAM; PREDICTION; MEN; ATHEROSCLEROSIS; PROFESSIONALS; HYPERTENSION AB Despite major advances in the diagnosis and treatment of atherosclerotic cardiovascular disease (CVD) in the past century, it remains a serious clinical and public health problem. Multivariable risk factor analysis is now commonly performed to identify high-risk candidates for CVD who need preventive measures and to seek out clues to the pathogenesis of the disease. The set of risk factors used for the former is constrained by practical considerations, and the set of risk factors used for the latter is constrained by the hypothesis being tested. This report reviews the evolution and usefulness of multivariable risk functions crafted for estimating risk of clinical manifestations of atherosclerosis and for gaining insights into their pathogenesis. Decades of evaluation of CVD risk factors by the Framingham Study led to the conclusion that CVD risk evaluation is most fruitfully appraised from the multivariable risk posed by a set of established risk factors. Such assessment is essential because risk factors seldom occur in isolation, and the risk associated with each varies widely depending on the burden of associated risk factors. About half the CVD in the general population arises from the segment with multiple marginal risk factor abnormalities. Although disease-specific profiles are available, a multivariable risk formulation for coronary disease comprised of age, sex, the total/high-density lipoprotein cholesterol ratio, systolic blood pressure, glucose intolerance, cigarette smoking, and electrocardiography-left ventricular hypertrophy is also predictive of peripheral artery disease, heart failure, and stroke because of shared risk factors. Correcting risk factors for any particular CVD has the potential to protect against greater than or equal to1 of the others. Multivariable risk stratification is now recognized as essential in efficiently identifying likely candidates for CVD and quantifying the hazard. C1 Boston Univ, Sch Med, Natl Heart Lung & Blood Inst Framingham Study, NIH, Framingham, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Kannel, WB (reprint author), Framingham Heart Dis Epidemiol Study, 5 Thurber St, Framingham, MA 01702 USA. EM billkannel@yahoo.com OI Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-38038] NR 45 TC 83 Z9 92 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 JUL PY 2004 VL 148 IS 1 BP 16 EP 26 DI 10.1016/j.ahj.2003.10.022 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833RX UT WOS:000222357700004 PM 15215787 ER PT J AU Brewer, HB AF Brewer, HB TI Focus on high-density lipoproteins in reducing cardiovascular risk SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Satellite Symposium on a New Dawn in the Treatment of Dyslipidemia CY NOV 08, 2003 CL Orlando, FL ID CHOLESTERYL ESTER TRANSFER; APOLIPOPROTEIN-A-I; TRANSFER PROTEIN; GENE-EXPRESSION; ATHEROSCLEROSIS; CELLS; PARTICLES; PROMOTER; RECEPTOR; EFFLUX AB Low high-density lipoprotein (HDL) cholesterol is associated with increased risk of coronary heart disease (CHID). Ongoing investigation into the mechanisms whereby HDL cholesterol might provide protection from atherosclerosis and clinical disease has resulted in improved understanding of the role of HDL in removal of cholesterol from the arterial wall and has suggested a number of strategies for augmenting the beneficial activities of the lipoprotein. Current drug options for increasing HDL cholesterol levels include the statins, fibrates, and niacin. Strategies in development for increasing the function of HDL or apolipoprotein A-I and thereby reducing atherosclerotic progression include use of agents to upregulate the adenosine triphosphate-binding cassette transporter in vessel wall macrophages to increase cholesterol efflux from these cells; use of agents to stimulate endogenous apoA-I synthesis; administration of apoA-I, apoA-I Milano, apoA-I-mimetic peptides, or delipiclated HDL; and use of cholesteryl ester transfer protein inhibitors. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10 Magnuson CC,Room 7N115,10 Ctr Dr,MSC-1666, Bethesda, MD 20892 USA. EM bryon@mdb.nhlbi.nih.gov NR 21 TC 26 Z9 28 U1 0 U2 1 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 JUL PY 2004 VL 148 IS 1 SU S BP S14 EP S18 DI 10.1016/j.ahj.2004.04.027 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834YB UT WOS:000222445700004 PM 15211328 ER PT J AU Brewer, HB AF Brewer, HB TI A symposium: A new dawn in the treatment of dyslipidemia: Cardiovascular risk reduction through emerging science and proven clinical results - Introduction SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID CORONARY-HEART-DISEASE; CHOLESTEROL LEVELS; PRAVASTATIN; PREVENTION; EVENTS; TRIAL; SIMVASTATIN; MEN C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2004 VL 148 IS 1 SU S BP S1 EP S2 DI 10.1016/j.ahj.2004.04.024 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834YB UT WOS:000222445700001 PM 15211325 ER PT J AU Lloyd-Jones, DM Wilson, PWF Larson, MG Beiser, A Leip, EP D'Agostino, RB Levy, D AF Lloyd-Jones, DM Wilson, PWF Larson, MG Beiser, A Leip, EP D'Agostino, RB Levy, D TI Framingham risk score and prediction of lifetime risk for coronary heart disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CLINICAL-PRACTICE; RECOMMENDATIONS; PREVENTION; WOMEN AB We investigated whether the Framingham risk score, which was designed to estimate the 10-year risk of coronary heart disease (CHD), differentiates lifetime risk for CHD. All subjects in the Framingham Heart Study examined from 1971 to 1996 who were free of CHD were included. Subjects were stratified into age- and gender-specific tertiles of Framingham risk score, and lifetime risk for CHD was estimated. We followed 2,716 men and 3,500 women; 939 developed CHID and 1,363 died free of CHD. At age 40 years, in risk score tertiles 1, 2, and 3, respectively, the lifetime risks for CHD were 38.4%, 41.7%, and 50.7% for men and 12.2%, 25.4%, and 33.2% for women. At age 80 years, risks were 16.4%, 17.4%, and 38.8% for men and 12.8%, 22.4%, and 27.4% for women. The Framingham risk score stratified lifetime risk well for women at all ages. It performed less well in younger men but improved at older ages as remaining life expectancy approached 10 years. Lifetime risks contrasted sharply with shorter term risks: at age 40 years, the 10-year risks of CHD in tertiles 1, 2, and 3, respectively, were 0%, 2.2%, and 11.6% for men and 0%, 0.7%, and 2.3% for women. The Framingham 10-year CHD risk prediction model discriminated short-term risk well for men and women. However, it may not identify subjects with low short-term but high lifetime risk for CHD, likely due to changes in risk factor status over time. Further work is needed to generate multivariate risk models that can reliably predict lifetime risk for CHD. (C) 2004 by Excerpta Medica, Inc. C1 Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Stat & Consulting Unit, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1120, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009; OI Larson, Martin/0000-0002-9631-1254; Beiser, Alexa/0000-0001-8551-7778 FU NHLBI NIH HHS [N01-HC 25195, 1 K23 HL04253] NR 19 TC 162 Z9 166 U1 0 U2 7 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 JUL 1 PY 2004 VL 94 IS 1 BP 20 EP 24 DI 10.1016/j.amjcard.2004.03.023 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832QO UT WOS:000222282200004 PM 15219502 ER PT J AU Moorman, PG Terry, PD AF Moorman, PG Terry, PD TI Consumption of dairy products and the risk of breast cancer: a review of the literature SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE breast neoplasms; diet; dairy products; dietary fats; conjugated linoleic acids; vitamin D; epidemiology ID CONJUGATED LINOLEIC-ACID; CALCIUM MESSENGER SYSTEM; SERUM ESTROGEN-LEVELS; DIETARY-FAT INTAKE; NEW-YORK-STATE; VITAMIN-D; MILK CONSUMPTION; FIBROCYSTIC DISEASE; PROSPECTIVE COHORT; NORWEGIAN WOMEN AB Differences in eating patterns and breast cancer rates across countries suggest that several dietary components, including dairy products, could affect breast cancer risk. However, dairy products are a diverse food group in terms of the factors that could potentially influence risk. Some dairy products, such as whole milk and many types of cheese, have a relatively high saturated fat content, which may increase risk. Moreover, milk products may contain contaminants such as pesticides, which have carcinogenic potential, and growth factors such as insulin-like growth factor 1, which have been shown to promote breast cancer cell growth. In contrast, the calcium and vitamin D contents of dairy products have been hypothesized to reduce breast cancer risk. We reviewed the current epidemiologic literature on the relation between dairy product intakes and breast cancer risk, focusing primarily on the results of cohort and case-control studies. Most of the studies reviewed showed no consistent pattern of increased or decreased breast cancer risk with a high consumption of dairy products as a whole or when broken down into high-fat and low-fat dairy products, milk, cheese, or butter. Measurement error may have attenuated any modest association with dairy products. The available epidemiologic evidence does not support a strong association between the consumption of milk or other dairy products and breast cancer risk. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. RP Terry, PD (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM terry2@niehs.nih.gov NR 104 TC 78 Z9 80 U1 3 U2 20 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2004 VL 80 IS 1 BP 5 EP 14 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 830NB UT WOS:000222128000003 PM 15213021 ER PT J AU Elberg, J McDuffie, JR Sebring, NG Salaita, C Keil, M Robotham, D Reynolds, JC Yanovski, JA AF Elberg, J McDuffie, JR Sebring, NG Salaita, C Keil, M Robotham, D Reynolds, JC Yanovski, JA TI Comparison of methods to assess change in children's body composition SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE air-displacement plethysmography; bioelectrical impedance; skinfold thickness; dual-energy X-ray absorptiometry; DXA; adiposity; body fat mass; change; growth; children ID X-RAY ABSORPTIOMETRY; AIR-DISPLACEMENT PLETHYSMOGRAPHY; BIOELECTRICAL-IMPEDANCE; SKINFOLD-THICKNESS; AFRICAN-AMERICAN; ADOLESCENTS; OVERWEIGHT; VALIDATION AB Background: Little is known about how simpler and more available methods to measure change in body fatness compare with criterion methods such as dual-energy X-ray absorptiometry (DXA) in children. Objective: Our objective was to determine the ability of air-displacement plethysmography (ADP) and formulas based on triceps skinfold thickness (TSF) and bioelectrical impedance analysis (BIA) to estimate changes in body fat over time in children. Design: Eighty-six nonoverweight and overweight boys (n = 34) and girls (n = 52) with an average age of 11.0 +/- 2.4 y underwent ADP, TSF measurement, BIA, and DXA to estimate body fatness at baseline and 1 +/- 0.3 y later. Recent equations were used to estimate percentage body fat by TSF measurement (Dezenberg equation) and by BIA (Suprasongsin and Lewy equations). Percentage body fat estimates by ADP, TSF measurement, and BIA were compared with those by DXA. Results: All methods were highly correlated with DXA (P < 0.001). No mean bias for estimates of percentage body fat change was found for ADP (Siri equation) compared with DXA for all subjects examined together, and agreement between body fat estimation by ADP and DXA did not vary with race or sex. Magnitude bias was present for ADP relative to DXA systematically overestimated by BIA equations (1.37 6.98%; P < 0.001). TSF accounted for only 13% of the variance in percentage body fat change. Conclusion: Compared with DXA, there appears to be no noninvasive and simple method to measure changes in children's percentage body fat accurately and precisely, but ADP performed better than did TSF or BIA. ADP could prove useful for measuring changes in adiposity in children. C1 NICHHD, Unit Growth & Obes, DEB, NIH, Bethesda, MD 20892 USA. NIH, Dept Nutr, Warren G Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, DEB, NIH, 10 Ctr Dr,Bldg 10,Room 10N262MSC 1862, Bethesda, MD 20892 USA. EM yanovskj@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999, Z01 HD000641-12]; NICHD NIH HHS [Z01 HD000641] NR 23 TC 72 Z9 75 U1 3 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2004 VL 80 IS 1 BP 64 EP 69 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 830NB UT WOS:000222128000011 PM 15213029 ER PT J AU Leitzmann, MF Stampfer, MJ Michaud, DS Augustsson, K Colditz, GC Willett, WC Giovannucci, EL AF Leitzmann, MF Stampfer, MJ Michaud, DS Augustsson, K Colditz, GC Willett, WC Giovannucci, EL TI Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; n-3 fatty acids; n-6 fatty acids; prostate cancer; cohort study ID ALPHA-LINOLENIC ACID; FOOD FREQUENCY QUESTIONNAIRE; UNITED-STATES; IN-VITRO; DOCOSAHEXAENOIC ACID; NETHERLANDS-COHORT; FISH CONSUMPTION; MEN; METABOLISM; RAT AB Background: Laboratory studies have shown that n-3 fatty acids inhibit and n-6 fatty acids stimulate prostate tumor growth, but whether the dietary intake of these fatty acids affects prostate cancer risk in humans remains unclear. Objective: We prospectively evaluated the association between intakes of alpha-linolenic (ALA; 18:3n-3), eicosapentaenoic (EPA; 20:5n-3), docosahexaenoic (DHA; 22:6n-3), linoleic (LA; 18: 2n-6), and arachidonic (AA; 20:4n-6) acids and prostate cancer risk. Design: A cohort of 47 866 US men aged 40-75 y with no cancer history in 1986 was followed for 14 y. Results: During follow-up, 2965 new cases of total prostate cancer were ascertained, 448 of which were advanced prostate cancer. ALA intake was unrelated to the risk of total prostate cancer. In contrast, the multivariate relative risks (RRs) of advanced prostate cancer from comparisons of extreme quintiles of ALA from nonanimal sources and ALA from meat and dairy sources were 2.02 (95% CL 1.35, 3.03) and 1.53 (0.88, 2.66), respectively. EPA and DHA intakes were related to lower prostate cancer risk. The multivariate RRs of total and advanced prostate cancer from comparisons of extreme quintiles of the combination of EPA and DHA were 0.89 (0.77, 1.04) and 0.74 (0.49, 1.08), respectively. LA and AA intakes were unrelated to the risk of prostate cancer. The multivariate RR of advanced prostate cancer from a comparison of extreme quintiles of the ratio of LA to ALA was 0.62 (0.45, 0.86). Conclusions: Increased dietary intakes of ALA may increase the risk of advanced prostate cancer. In contrast, EPA and DHA intakes may reduce the risk of total and advanced prostate cancer. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. RP Leitzmann, MF (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS MSC 7232, Bethesda, MD 20892 USA. EM leitzmann@mail.nih.gov RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [5T32 CA09001-26, CA0550075]; NHLBI NIH HHS [HL035464] NR 74 TC 156 Z9 168 U1 3 U2 17 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2004 VL 80 IS 1 BP 204 EP 216 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 830NB UT WOS:000222128000032 PM 15213050 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL TI Dietary protein and the risk of cholecystectomy in a cohort of US women - The nurses' health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cholecystectomy; diet; dietary proteins; gallstones; risk; women ID GALLSTONE FORMATION; VEGETABLE PROTEIN; CHOLESTEROL GALLSTONES; HAMSTERS; DISEASE; LIPIDS; SERUM AB In animals, vegetable protein can inhibit gallstone formation. Epidemiologic studies of dietary protein in relation to gallstone disease are sparse, and the effects of dietary protein of different origins are not clear. The authors aimed to examine the relation between dietary protein intake and risk of cholecystectomy among participants in the Nurses' Health Study, a cohort study of US women in 11 states. During 20 years of follow-up (1980-2000), the authors documented 7,831 cases of cholecystectomy. After adjustment for age, other known or suspected risk factors, and specific fats in a multivariate model, the relative risk of cholecystectomy for women in the highest quintile of dietary total protein intake compared with women in the lowest quintile was 1.00 (95% confidence interval (CI): 0.93, 1.08; p for trend = 0.46). When extreme quintiles were compared, the relative risk for animal protein intake was 1.07 (95% CI: 0.98, 1.15; p for trend = 0.08), whereas the relative risk for vegetable protein intake was 0.79 (95% CI: 0.71, 0.88; p for trend < 0.0001), with a significant dose-response relation. Additional mutual adjustment between animal and vegetable proteins did not materially alter the risks. These results suggest that increased consumption of vegetable protein in the context of an energy-balanced diet can reduce the risk of cholecystectomy in women. C1 Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Tsai, CJ (reprint author), Univ Iowa Hosp & Clin, Ctr Digest Dis, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK46200] NR 28 TC 10 Z9 10 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 JUL 1 PY 2004 VL 160 IS 1 BP 11 EP 18 DI 10.1093/aje/kwh170 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834HV UT WOS:000222403100003 PM 15229112 ER PT J AU Rauscher, GH Shore, D Sandler, DP AF Rauscher, GH Shore, D Sandler, DP TI Hair dye use and risk of adult acute leukemia SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; hair dyes; leukemia; measurement ID MULTIPLE-MYELOMA; BREAST-CANCER; COLORING PRODUCTS; EXPOSURE; LYMPHOMA; SMOKING AB Certain chemicals in hair dyes are known animal carcinogens. Darker, more permanent, and earlier dye formulations may be more carcinogenic than other dye types. For 769 adult acute leukemia cases and 623 population-based controls in a US and Canadian case-control study in 1986-1989, the authors asked separately about use of permanent and nonpermanent (semipermanent and temporary) hair dye use. Use was reported by 45% of women and 6% of men. There was a modest positive association for ever use of permanent dyes (odds ratio = 1.5, 95% confidence interval: 1.0, 2.1), which was stronger for long duration (15 or more years) of use (odds ratio = 1.8, 95% confidence interval: 1.0, 3.1). The greatest odds ratio was for 15 or more years of using hair dyes up to six times per year (odds ratio = 2.4, 95% confidence interval: 1.0, 5.8); the corresponding odds ratio for use six or more times a year was lower, suggesting the possibility of misclassification of dye type among frequent users, since nonpermanent dyes tend to be used more frequently than permanent dyes. Nonpermanent dyes were not associated with risk. Long duration of permanent dye use may have a larger impact on the risk of adult acute leukemia and other hematopoietic cancers than prior epidemiologic data suggest. C1 Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60612 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Rauscher, GH (reprint author), Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, 816 SPHPI,M-C 923,1603 W Taylor St,8th Floor, Chicago, IL 60612 USA. EM garthr@uic.edu OI Rauscher, Garth/0000-0003-0374-944X; Sandler, Dale/0000-0002-6776-0018 NR 17 TC 26 Z9 28 U1 0 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 JUL 1 PY 2004 VL 160 IS 1 BP 19 EP 25 DI 10.1093/aje/kwh166 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834HV UT WOS:000222403100004 PM 15229113 ER PT J AU Wright, ME Mayne, ST Stolzenberg-Solomon, RZ Li, ZH Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Wright, ME Mayne, ST Stolzenberg-Solomon, RZ Li, ZH Pietinen, P Taylor, PR Virtamo, J Albanes, D TI Development of a comprehensive dietary antioxidant index and application to lung cancer risk in a cohort of male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE antioxidants; cohort studies; lung neoplasms; principal component analysis ID POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; BETA-CAROTENE SUPPLEMENTATION; VITAMIN-E; ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; TOBACCO-SMOKE; NONHEME IRON; FRUIT JUICES; FERRETS AB In many observational studies, a higher intake of individual antioxidants is inversely associated with lung cancer risk. Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients; therefore, consideration of multiple antioxidants simultaneously may be important in terms of risk estimation. The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline (1985-1988), 27,111 Finnish male smokers aged 50-69 years completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months. A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years (1985-1999). Principal components analyses were individually applied to the carotenoid, flavonoid, and vitamin E nutrient groups, and summation of retained principal component scores, plus selenium and vitamin C, yielded the composite antioxidant index. In multivariate proportional hazards models, the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 (referent), 1.00 (95% confidence interval (CI): 0.87, 1.14), 0.91 (95% CI: 0.79, 1.05), 0.79 (95% CI: 0.68, 0.92), and 0.84 (95% CI: 0.72, 0.98) (p for trend = 0.002). These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wright, ME (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 3029,6120 Execut Blvd, Bethesda, MD 20892 USA. EM wrighmar@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU NCATS NIH HHS [C3TR010137]; NCI NIH HHS [N01CN45035, N01CN45165] NR 47 TC 52 Z9 54 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 JUL 1 PY 2004 VL 160 IS 1 BP 68 EP 76 DI 10.1093/aje/kwh173 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834HV UT WOS:000222403100010 PM 15229119 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL TI Long-term intake of dietary fiber and decreased risk of cholecystectomy in women SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHOLESTEROL GALLSTONE FORMATION; INTESTINAL TRANSIT; DEOXYCHOLIC-ACID; BILIARY LIPIDS; DISEASE; INSULIN; BILE; HAMSTERS; SATURATION; GLUCOSE AB BACKGROUND: Epidemiologic studies on the relationship between dietary fiber and gallstone disease are inconclusive, and the effects of different types of dietary fiber are not clear. METHODS: We examined the association between long-term intake of dietary fiber as well as fiber from different sources and risk of cholecystectomy in a cohort of 69,778 women who were aged from 35 to 61 years in 1984 and had no history of gallstone disease. As part of the Nurses' Health Study, the women reported on questionnaires mailed to them every two years both their fiber intake and whether they had undergone cholecystectomy. RESULTS: During 16 yr of follow-up, we documented 5,771 cases of cholecystectomy. After adjusting for age and other known or suspected risk factors in a multivariate model, compared with women in the lowest quintile of total dietary fiber intake, the relative risk of choleystectomy for those in the highest quintile was 0.87 (95% CI, 0.78-0.96, p for trend = 0.005). For a 5-g increase in total fiber intake, the multivariate relative risk was 0.94 (95% CI, 0.90-0.98). Insoluble fiber, taking soluble fiber into account in the multivariate model, was significantly associated with a reduced risk. The multivariate relative risk was 0.83 (95% CI, 0.73-0.94, p for trend = 0.009) for insoluble fiber, and was 1.01 (95% CI, 0.89-1.15, p for trend = 0.9) for soluble fiber, when extreme quintiles were compared. For a 5-g increase in intake, the relative risk was 0.90 (95% CI, 0.84-0.97) for insoluble fiber, and was 1.01 (95% CI, 0.83-1.23) for soluble fiber. CONCLUSIONS: Our results suggest that increased long-term consumption of dietary fiber, particularly insoluble fiber, can reduce risk of cholecystectomy in women. C1 Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHSS, Bethesda, MD 20892 USA. RP Tsai, CJ (reprint author), Univ Iowa Hosp & Clin, Ctr Digest Dis, 200 Hawkins Dr, Iowa City, IA 52242 USA. FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK46200] NR 30 TC 14 Z9 14 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2004 VL 99 IS 7 BP 1364 EP 1370 DI 10.1111/j.1572-0241.2004.30153.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 837NI UT WOS:000222641800030 PM 15233680 ER PT J AU Leischow, SJ Ranger-Moore, J Muramoto, ML Matthews, E AF Leischow, SJ Ranger-Moore, J Muramoto, ML Matthews, E TI Effectiveness of the nicotine inhaler for smoking cessation in an OTC setting SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE smoking cessation; OTC; nicotine inhaler; nicotine replacement ID OVER-THE-COUNTER; EFFICACY; PATCH; REPLACEMENT; THERAPY AB Objective: To evaluate the effectiveness of the Nicotrol(R) nicotine inhaler as an aid to smoking cessation in over-the-counter (OTC) versus health-care -provider (HCP) conditions. Methods: Five hundred twenty healthy smokers were randomized to the treatment conditions and followed for a year. Results: At most followup visits, abstinence rates for the HCP group were 2 to 3 times those observed in the OTC group. Abstinence at 1 year was .77% in the OTC condition versus 3.08% in the HCP condition [P<.01]. Inhaler use was low. Conclusions: OTC nicotine inhaler appears to be ineffective, though quit rates are improved with HCP assistance. C1 NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Arizona, Arizona Canc Ctr, Dept Community & Family Med, Tucson, AZ 85721 USA. Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ 85721 USA. RP Leischow, SJ (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Execut Plaza N Room 4060,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM scott.leischow@nih.gov FU NIDA NIH HHS [DA08885] NR 18 TC 16 Z9 16 U1 1 U2 2 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD JUL-AUG PY 2004 VL 28 IS 4 BP 291 EP 301 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 891AW UT WOS:000226554700001 PM 15228966 ER PT J AU Kearns, WG Sutton, JF Maciejewski, JP Young, NS Liu, JM AF Kearns, WG Sutton, JF Maciejewski, JP Young, NS Liu, JM TI Genomic instability in bone marrow failure syndromes SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID SEVERE APLASTIC-ANEMIA; MYELODYSPLASTIC SYNDROMES; CYTOGENETIC ABNORMALITIES; PROGNOSIS; SPERM AB Aneuploidy is frequently seen in leukemia and myelodysplasia (MDS) but was thought to be uncommon in aplastic anemia (AA). We examined marrow cells from 96 unselected patients with bone marrow failure syndromes to assess the frequency of undetected aneuploidy for chromosomes 7 and 8 by fluorescence in situ hybridization (FISH) as compared to routine cytogenetic analysis. Twenty-eight percent (27/96) of patients had an abnormal karyotype. FISH identified an additional 27 patients with undetected monosomy 7 or trisomy 8. Those patients with undetected monosomy 7 generally had a poor clinical outcome, suffering from lack of response to medical therapy or early death. In one AA/MDS patient with normal cytogenetics, FISH identified a large population of monosomy 7 cells, which clearly heralded a clinical relapse. In another patient, FISH studies were used to delineate instability of chromosome 8, with apparent disease progression from AA to MDS. We conclude that undetected aneuploidy exists in marrow cells of a significant percentage of patients with bone marrow failure syndromes. Published 2004 Wiley-Liss, Inc. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), CUNY Mt Sinai Sch Med, Div Hematol Oncol, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. EM Johnson.Liu@mssm.edu NR 16 TC 10 Z9 13 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUL PY 2004 VL 76 IS 3 BP 220 EP 224 DI 10.1002/ajh.20101 PG 5 WC Hematology SC Hematology GA 833HY UT WOS:000222329200005 PM 15224355 ER PT J AU Weitz, CA Garruto, RM AF Weitz, CA Garruto, RM TI Growth of han migrants at high altitude in Central Asia SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Human-Biology-Association CY APR 26, 2003 CL Tempe, AZ SP Human Biol Assoc ID PRIMARY-SCHOOL CHILDREN; LUNG-FUNCTION GROWTH; PULMONARY-FUNCTION; EUROPEAN ANCESTRY; PHYSICAL GROWTH; HEALTH-PROGRAM; AIR-POLLUTION; DEVELOPMENTAL ADAPTATION; HEMOGLOBIN CONCENTRATION; POSTNATAL-DEVELOPMENT AB Han Chinese of low-altitude descent have been living in Qinghai Province of Western China for at least two millennia. For most of this time they have lived at elevations under 2,500 m. However, during the last four decades an increasing number of Han have moved into high-altitude towns at elevations over 3,000 m, and some above 4,000 m. There are now sufficient numbers of Han descendants who have been born and raised at high altitude to allow a comparison of their morphological and physiological growth patterns with low-altitude Han to detect the effect of hypoxia. The field study reported here was conducted by collaborating Chinese and American researchers over a 6-year period, and included 1,227 Han living at high altitude in Qinghai and at low altitude near Beijing. This study demonstrates that Han born and raised at high altitude are smaller and lighter than those at low altitude-particularly as children and adolescents. Slower growth at high altitude may be a consequence of hypoxia, but it also corresponds to poorer economic conditions in rural Qinghai Province, and thus may reflect nutritional inadequacies. Differences in altitude and/or nutrition do not seem to affect thorax dimensions, since, relative to stature, chest dimensions are similar at both high and low altitudes. Nevertheless, lung volumes are higher among Han at high altitude, possibly reflecting the influence of hypoxia on alveolar growth. The hematological values of Han growing up at 3,200 m are not different from those at low altitude-an unusual finding relative to other low-altitude groups that may reflect population differences in response to hypoxia. At 3,800 m and 4,300 m, however, Han show elevated hemoglobin relative to Han at low altitude. Published 2004 Wiley-Liss, Inc.(dagger) C1 Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA. SUNY Binghamton, Binghamton, NY 13902 USA. Natl Inst Hlth, Bethesda, MD 20891 USA. RP Weitz, CA (reprint author), Temple Univ, Dept Anthropol, 214 Gladfelter Hall, Philadelphia, PA 19122 USA. EM WEITZ@TEMPLE.EDU NR 89 TC 14 Z9 15 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD JUL-AUG PY 2004 VL 16 IS 4 BP 405 EP 419 DI 10.1002/ajhb.20042 PG 15 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 834QK UT WOS:000222425400006 PM 15214059 ER PT J AU Schurr, TG Sherry, ST AF Schurr, TG Sherry, ST TI Mitochondrial DNA and Y chromosome diversity and the peopling of the Americas: Evolutionary and demographic evidence SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Human-Biology-Association CY APR 26, 2003 CL Tempe, AZ SP Human Biol Assoc ID NATIVE NORTH AMERICANS; MTDNA HAPLOGROUP-X; DEL-FUEGO PATAGONIA; NEW-WORLD; ABORIGINAL POPULATIONS; FOUNDER HAPLOTYPES; SEQUENCE VARIATION; HUMAN COLONIZATION; MATERNAL LINEAGES; LATE PLEISTOCENE AB A number of important insights into the peopling of the New World have been gained through molecular genetic studies of Siberian and Native American populations. While there is no complete agreement on the interpretation of the mitochondrial DNA (mtDNA) and Y chromosome (NRY) data from these groups, several generalizations can be made. To begin with, the primary migration of ancestral Asians expanded from south-central Siberia into the New World and gave rise to ancestral Amerindians. The initial migration seems to have occurred between 20,000-15,000 calendar years before present (cal BP), i.e., before the emergence of Clovis lithic sites (13,350-12,895 cal BP) in North America. Because an interior route through northern North America was unavailable for human passage until 12,550 cal BP, after the last glacial maximum (LGM), these ancestral groups must have used a coastal route to reach South America by 14,675 cal BP, the date of the Monte Verde site in southern Chile. The initial migration appears to have brought mtDNA haplogroups A-D and NRY haplogroups P-M45a and Q-242/Q-M3 to the New World, with these genetic lineages becoming widespread in the Americas. A second expansion that perhaps coincided with the opening of the ice-free corridor probably brought mtDNA haplogroup X and NRY haplogroups P-M45b, C-M130, and R1a1.-M17 to North and Central America. Finally, populations that formerly inhabited Beringia expanded into northern North America after the LGM, and gave rise to Eskimo-Aleuts and Na-Dene Indians. (C) 2004 Wiley-Liss, Inc. C1 Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Schurr, TG (reprint author), Univ Penn, Dept Anthropol, 325 Univ Museum,3260 S St, Philadelphia, PA 19104 USA. EM tgsehurr@sas.upenn.edu NR 127 TC 82 Z9 86 U1 4 U2 31 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD JUL-AUG PY 2004 VL 16 IS 4 BP 420 EP 439 DI 10.1002/ajhb.20041 PG 20 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 834QK UT WOS:000222425400007 PM 15214060 ER PT J AU Newton-Cheh, C Larson, M Kathiresan, S O'Donnell, C AF Newton-Cheh, C Larson, M Kathiresan, S O'Donnell, C TI On the significance of linkage studies of complex traits SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID GENOME-WIDE LINKAGE; SUSCEPTIBILITY LOCUS; MYOCARDIAL-INFARCTION; CHROMOSOME-2; SUGGESTS; SCANS C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP O'Donnell, C (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM codonnell@nih.gov NR 9 TC 2 Z9 2 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 JUL PY 2004 VL 75 IS 1 BP 151 EP 152 DI 10.1086/422220 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 829FG UT WOS:000222031300019 PM 15164311 ER PT J AU Shibayama, A Cook, EH Feng, JN Glanzmann, C Yan, J Craddock, N Jones, IR Goldman, D Heston, LL Sommer, SS AF Shibayama, A Cook, EH Feng, JN Glanzmann, C Yan, J Craddock, N Jones, IR Goldman, D Heston, LL Sommer, SS TI MECP2 structural and 3 '-UTR variants in schizophrenia, autism and other psychiatric diseases: A possible association with autism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE MECP2; 3 '-UTR; schizophrenia; autism; psychiatric diseases; mutation detection ID CPG-BINDING PROTEIN-2; RETT-SYNDROME; HISTONE DEACETYLASE; GENE MECP2; DOVAM-S; MUTATIONS; SEQUENCE; DISORDER; RECEPTOR; COMPLEX AB Mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT) and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, putative mutations recently have been described in a few autistic patients and a boy with language disorder and schizophrenia. In this study, DNA samples from individuals with schizophrenia and other psychiatric diseases were scanned in order to explore whether the phenotypic spectrum of mutations in the MECP2 gene can extend beyond the traditional diagnoses of RTT in females and severe neonatal encephalopathy in males. The coding regions, adjacent splicing junctions, and highly conserved segments of the T-untranslated region (3'-UTR) were examined in 214 patients, including 106 with schizophrenia, 24 with autism, and 84 patients with other psychiatric diseases by detection of virtually all mutations-single strand conformation polymorphism (SSCP) (DOVAM-S). To our knowledge, this is the first analysis of variants in conserved regions of the 3'-UTR of this gene. A total of 5.2 kb per haploid gene was analyzed (1.5 Mb for 214 patients). A higher frequency of missense and 3'-UTR variants was found in autism. One missense and two 3'-UTR variants were found in 24 patients with autism versus one patient with a missense change in 144 ethnically similar individuals without autism (P = 0.009). These mutations suggest that a possible association between MECP2 mutations and autism may warrant further study. (C) 2004 Wiley-Liss, Inc. C1 City Hope Natl Med Ctr, Dept Mol Genet, Duarte, CA 91010 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Birmingham, Queen Elizabeth Psychiat Hosp, Div Neurosci, Birmingham, W Midlands, England. NIAAA, Dept Psychiat, NIH, Bethesda, MD USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Sommer, SS (reprint author), City Hope Natl Med Ctr, Dept Mol Genet & Mol Diag, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM sommerlab@coh.org RI Jones, Ian/B-4925-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 20 TC 82 Z9 83 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 1 PY 2004 VL 128B IS 1 BP 50 EP 53 DI 10.1002/ajmg.b.30016 PG 4 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 834PT UT WOS:000222423700012 PM 15211631 ER PT J AU Rouse, DJ Landon, M Leveno, KJ Leindecker, S Varner, MW Caritis, SN O'Sullivan, MJ Wapner, RJ Meis, PJ Miodovnik, M Sorokin, Y Moawad, AH Mabie, W Conway, D Gabbe, SG Spong, CY AF Rouse, DJ Landon, M Leveno, KJ Leindecker, S Varner, MW Caritis, SN O'Sullivan, MJ Wapner, RJ Meis, PJ Miodovnik, M Sorokin, Y Moawad, AH Mabie, W Conway, D Gabbe, SG Spong, CY CA Natl Inst Child Hlth & Human Dev TI The Maternal-Fetal Medicine Units cesarean registry: Chorioamnionitis at term and its duration-relationship to outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2003 CL SAN FRANCISCO, CA SP Soc Maternal Fetal Med DE chorioamnionitis; complications; duration ID INFECTION AB Objective: The purpose of this study was to evaluate the relationship between chorioamnionitis and its duration to adverse maternal, fetal, and neonatal outcomes. Study design: This was a 13-university center, prospective observational study. All women at term carrying a singleton gestation who underwent primary cesarean from January 1, 1999 to December 3 1, 2000 were eligible. Data abstraction was systematic and performed by trained research nurses. Selected adverse outcomes were compared between pregnancies with, and without, clinically diagnosed chorioamnionitis using relative risks (RRs) and 95% CIs. The duration of chorioamnionitis was stratified into 5 intervals (less than or equal to3 h, >3-6 h, >6-9 h, >9-12 h, and >12 h), and respective outcomes compared by Mantel-Haenszel test for trend. Additionally, regression analysis was used to compute odds ratios (ORs) and 95% CIs for chorioamnionitis duration length as a continuous explanatory variable. Results: 16,650 pregnancies were analyzed, 1965 (12%) with chorioamnionitis, which was associated with significantly increased risks of maternal blood transfusion, uterine atony, septic pelvic thrombophlebitis, and pelvic abscess (RR 2.3-3.7), as well as 5-minute Apgar less than or equal to3, neonatal sepsis, and seizures (RR 2.1-2.8). By test of trend, only uterine atony (P < .01), maternal blood transfusion (P = .03), maternal admission to intensive care unit (P = .02), and 5-minute Apgar less than or equal to3 (P < .01) were associated with duration of chorioamnionitis. By logistic analysis, only uterine atony (OR for each hour of chorioamnionitis 1.03, 95% Cl 1.00-1.06), 5-minute Apgar : 3 (OR 1.09, 95% Cl 1.00-1.16), and neonatal mechanical ventilation within 24 hours of birth (OR 1.07, 95% CI 1.01-1.12) were significantly associated with chorioamnionitis duration. Conclusion: Chorioamnionitis was associated with increased rates of morbidity after cesarean at term. The duration of chorioamnionitis, however, was not related to most measures of adverse maternal or fetal-neonatal outcome. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Alabama, Dept Obstet & Gynecol, Ctr Res Womens Hlth, Birmingham, AL 35249 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Wake Forest Univ, Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH 45221 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Texas, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. NICHHD, Bethesda, MD 20892 USA. RP Rouse, DJ (reprint author), Univ Alabama, Dept Obstet & Gynecol, Ctr Res Womens Hlth, 619 19th St S,OHB 457, Birmingham, AL 35249 USA. EM drouse@uab.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD34136, HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34208, HD34210, HD36801] NR 8 TC 51 Z9 51 U1 2 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2004 VL 191 IS 1 BP 211 EP 216 DI 10.1016/j.ajog.2004.03.003 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 844EB UT WOS:000223139100034 PM 15295368 ER PT J AU Vahratian, A Zhang, J Hasting, J Troendle, JF Klebanoff, MA Thorp, JM AF Vahratian, A Zhang, J Hasting, J Troendle, JF Klebanoff, MA Thorp, JM TI The effect of early epidural versus early intravenous analgesia use on labor progression: A natural experiment SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LA SP Soc Maternal Fetal Med DE epidural analgesia; labor; nulliparous pregnancy ID NULLIPAROUS WOMEN; CESAREAN DELIVERY; FETAL HEAD; ANESTHESIA; STATION; BLOCK; RISK AB Objective: The purpose of this study was to compare the effect of early epidural with the use of early intravenous analgesia on labor progression. Study design: We systematically selected singleton, nulliparous term pregnancies with a spontaneous labor and analgesia placement less than or equal to 4 cm who were delivered at a hospital where the rate of epidural analgesia in labor increased from 1% (before) to 84% (after) in I year (a natural experiment). In the before period (n = 223 pregnancies), 98% of women used intravenous analgesia, and 2% of women used epidural analgesia. In the after period (n = 278 pregnancies), 92% of women used epidural analgesia, and 8% of women used intravenous analgesia. The median duration of labor by each centimeter of cervical dilation was computed and used as a measurement of labor progression. Results: After adjustment had been made for confounders, women in the after period had a slower labor progression only from 4 to 5 cm, compared with those women in the before period. Interestingly, the process of labor admission and epidural analgesia placement, rather than analgesia use per se, appeared to explain most of the slowdown. No significant difference in the rest of the active phase was observed between the 2 groups. Conclusion: Our data support recent American College of Obstetricians and Gynecologists guidelines that the restraining use of epidural analgesia at <4 cm of cervical dilation is unnecessary. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Tripler Army Med Ctr, Dept Obstet & Gynecol, Oahu, HI USA. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. RP Vahratian, A (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Vahratian, Anjel/A-1182-2011 NR 15 TC 17 Z9 17 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 JUL PY 2004 VL 191 IS 1 BP 259 EP 265 DI 10.1016/j.ajog.2003.11.021 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 844EB UT WOS:000223139100042 PM 15295376 ER PT J AU Iqbal, J Sanger, WG Horsman, DE Rosenwald, A Pickering, DL Dave, B Dave, S Xiao, L Cao, KJ Zhu, QM Sherman, S Hans, CP Weisenburger, DD Greiner, TC Gascoyne, RD Ott, G Muller-Hermelink, HK Delabie, J Braziel, RM Jaffe, ES Campo, E Lynch, JC Connors, JM Vose, JM Armitage, JO Grogan, TM Staudt, LM Chan, WC AF Iqbal, J Sanger, WG Horsman, DE Rosenwald, A Pickering, DL Dave, B Dave, S Xiao, L Cao, KJ Zhu, QM Sherman, S Hans, CP Weisenburger, DD Greiner, TC Gascoyne, RD Ott, G Muller-Hermelink, HK Delabie, J Braziel, RM Jaffe, ES Campo, E Lynch, JC Connors, JM Vose, JM Armitage, JO Grogan, TM Staudt, LM Chan, WC CA Leukemia Lymphoma Molecular Profil TI BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; MITOTIC CHECKPOINT; HODGKIN LYMPHOMA; IN-VIVO; GENE; KINASE; EXPRESSION; FAMILY; APOPTOSIS; RECEPTOR AB Gene expression profiling of diffuse large B-cen lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32; q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14; 18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell. cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Eppley Canc Inst, Omaha, NE 68198 USA. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Comp Sci, Omaha, NE 68182 USA. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Oregon, Hlth Sci Ctr, Dept Pathol, Portland, OR USA. Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain. Univ Arizona, Dept Pathol, Tucson, AZ USA. RP Chan, WC (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 983135, Omaha, NE 68198 USA. EM jchan@unmc.edu OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [CA 36727, CA 84967, P30 CA036727, U01 CA084967] NR 44 TC 156 Z9 169 U1 1 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 JUL PY 2004 VL 165 IS 1 BP 159 EP 166 DI 10.1016/S0002-9440(10)63284-1 PG 8 WC Pathology SC Pathology GA 831SI UT WOS:000222216000015 PM 15215171 ER PT J AU Shan, L Yu, MS Schut, HAJ Snyderwine, EG AF Shan, L Yu, MS Schut, HAJ Snyderwine, EG TI Susceptibility of rats to mammary gland carcinogenesis by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) varies with age and is associated with the induction of differential gene expression SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SPRAGUE-DAWLEY RATS; BREAST-CANCER RISK; 7,12-DIMETHYLBENZANTHRACENE-INDUCED DNA-BINDING; HEAT-SHOCK PROTEINS; LOW-FAT DIETS; EPITHELIAL-CELLS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; HETEROCYCLIC AMINES; REPAIR SYNTHESIS; MEMBRANE AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, induces mammary gland cancer when administered to adolescent female rats (43-day-old). In contrast, mature virgin rats (150-day-old) were resistant to mammary carcinogenesis by PhIP. To explore the possible mechanisms for the age-related differences in susceptibility, PhIP-DNA adduct levels, mutations, and gene expression were examined in glands from 43-day and 150-day-old PhIP-treated rats. In rats of different ages, PhIP-DNA adduct levels detected by the P-32-post-labeling assay and mutant frequency measured in the lacI reporter gene of Big Blue rats were not statistically different. PhIP-DNA adduct levels, adduct removal, and mutation burden did not appear to account for the variation in carcinogen susceptibility with age. However, cDNA microarray analysis indicated that PhIP treatment differentially altered the profile of gene expression in glands from 43-day-old and 150-day-old rats. in 150-day-old rats, PhIP enhanced the expression of genes associated with differentiation (eg, beta-casein, kappa-casein, whey acidic protein) and induced morphological differentiation. In contrast, in 43-day-old rats, PhIP inhibited the expression of differentiation genes and enhanced cellular proliferation. From 3 hours to 6 weeks after PhIP dosing, the number of clones showing altered expression declined more than 50% in 150-day-old rats but increased fourfold in 43-day-old rats (29 clones versus 194, respectively) suggesting that PhIP induced a cascade of gene expression alterations only in susceptible rats. Genes showing altered expression specifically in 43-day-old rats included the Ras superfamily genes and genes associated with protein synthesis/degradation (lysosomal proteins, heat shock proteins, and proteasomes). The microarray data support the notion that the mechanism of age-dependent susceptibility to mammary gland cancer is largely associated with differential responses in expression of genes involved in cellular differentiation, proliferation, and protein homeostasis. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Canc Res Ctr,NIH, Bldg 37,Room 4146, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov NR 67 TC 14 Z9 16 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 JUL PY 2004 VL 165 IS 1 BP 191 EP 202 DI 10.1016/S0002-9440(10)63288-9 PG 12 WC Pathology SC Pathology GA 831SI UT WOS:000222216000019 PM 15215175 ER PT J AU Daniely, Y Liao, G Dixon, D Linnoila, RI Lori, A Randell, SH Oren, M Jetten, AM AF Daniely, Y Liao, G Dixon, D Linnoila, RI Lori, A Randell, SH Oren, M Jetten, AM TI Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE retinoic acid; stem cell; carcinoma; basal cell; differentiation ID SQUAMOUS-CELL CARCINOMAS; P53 HOMOLOG P63; RETINOIC ACID; STEM-CELLS; LUNG-CANCER; DELTA-NP63-ALPHA EXPRESSION; GENE-EXPRESSION; DOWN-REGULATION; BASAL-CELLS; SAM DOMAIN AB The trachea and esophagus originate from the foregut endoderm during early embryonic development. Their epithelia undergo a series of changes involving the differentiation of stem cells into unique cell types and ultimately forming the mature epithelia. In this study, we monitored the expression of p63 in the esophagus and the trachea during development and examined in detail morphogenesis in p63(-/-) mice. At embryonic day 15.5 (E15.5), the esophageal and tracheobronchial epithelia contain two to three layers of cells; however, only the progenitor cells express p63. These progenitor cells differentiate first into ciliated cells (p63(-)/beta-tubulin IV+) and after birth into mature basal cells (p63(+)/K14(+)/K5(+)/BS-I-B4(+)). In the adult pseudostratified, columnar tracheal epithelium, K14(+)/K5(+)/BS-I-B4(+) basal cells stain most intensely for p63, whereas ciliated and mucosecretory cells are negative. In stratified squamous esophageal epithelium and during squamous metaplasia in the trachea, cells in the basal layer stain strongest for p63, whereas p63 staining declines progressively in transient amplifying and squamous differentiated cells. Generally, p63 expression is restricted to human squamous cell carcinomas, and adenocarcinomas and Barrett's metaplasia do not stain for p63. Examination of morphogenesis in newborn p63(-/-) mice showed an abnormal persistence of ciliated cells in the esophagus. Significantly, in both tissues, lack of p63 expression results in the development of a highly ordered, columnar ciliated epithelium deficient in basal cells. These observations indicate that p63 plays a critical role in the development of normal esophageal and tracheobronchial epithelia and appears to control the commitment of early stem cells into basal cell progeny and the maintenance of basal cells. C1 NIEHS, Cell Biol Sect, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NIEHS, Pathol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. NCI, Expt Pathol Sect, Cell & Canc Biol Branch, Rockville, MD 20850 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, MD D2-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU NCI NIH HHS [R01-CA-40099] NR 70 TC 119 Z9 122 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2004 VL 287 IS 1 BP C171 EP C181 DI 10.1152/ajpcell.00226.2003 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 827UG UT WOS:000221926100020 PM 15189821 ER PT J AU Shifflett, DE Bottone, FG Young, KM Moeser, AJ Jones, SL Blikslager, AT AF Shifflett, DE Bottone, FG Young, KM Moeser, AJ Jones, SL Blikslager, AT TI Neutrophils augment recovery of porcine ischemia-injured ileal mucosa by an IL-1 beta- and COX-2-dependent mechanism SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestine; prostaglandin; transepithelial electrical resistance; tight junction ID ACTIVATED PROTEIN-KINASE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; INFLAMMATORY-BOWEL-DISEASE; MESSENGER-RNA STABILITY; NECROSIS-FACTOR-ALPHA; TNF-ALPHA; SIGNALING PATHWAYS; BARRIER FUNCTION; GENE-EXPRESSION; CANCER-CELLS AB Polymorphonuclear neutrophils (PMNs) play a critical role in intestinal mucosal injury and repair. To study effects of PMNs on acutely injured mucosa, we applied PMNs isolated from circulation or peritoneal fluid from animals with chemically induced peritonitis to ischemia-injured porcine ileal mucosa. In preliminary experiments, PMNs enhanced recovery of transepithelial electrical resistance (TER), and this action was inhibited by pretreatment with the nonselective cyclooxygenase ( COX) inhibitor indomethacin. Because COX-2 is upregulated by inflammatory mediators such as IL-1beta, which is released by PMNs, we postulated that PMNs enhance recovery of ischemia-injured mucosa by a pathway involving IL-1beta and COX-2. Application of 5 x 10(6) PMNs to the serosal surface of ischemia-injured mucosa significantly enhanced recovery of TER ( P < 0.05), an effect that was inhibited by the selective COX-2 inhibitor NS-398 ( 5 μM) and by an IL-1β receptor antagonist (0.1 mg/ml). Addition of 10 ng/ml IL-1β to the serosal surface of injured tissues caused a significant increase in TER (P < 0.05) that was inhibited by pretreatment with NS-398. Western blot analysis of mucosal homogenates revealed dramatic upregulation of COX-2 in response to IL-1beta or peritoneal PMNs, and the latter was inhibited by an IL-1beta receptor antagonist. Real-time PCR revealed that increased mRNA COX-2 expression preceded increased COX-2 protein expression in response to IL-1beta. We concluded that PMNs augment recovery of TER in ischemia-injured ileal mucosa via IL-1beta-dependent upregulation of COX-2. C1 N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27606 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Blikslager, AT (reprint author), N Carolina State Univ, Coll Vet Med, Dept Clin Sci, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM Anthony_Blikslager@ncsu.edu FU NIDDK NIH HHS [DK 53284, DK 34987] NR 44 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 2004 VL 287 IS 1 BP G50 EP G57 DI 10.1152/ajpgi.00076.2003 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 828XI UT WOS:000222006600007 PM 15016613 ER PT J AU Lim, SW Li, C Sun, BK Han, KH Kim, WY Oh, YW Lee, JU Kador, PF Knepper, MA Sands, JM Kim, J Yang, CW AF Lim, SW Li, C Sun, BK Han, KH Kim, WY Oh, YW Lee, JU Kador, PF Knepper, MA Sands, JM Kim, J Yang, CW TI Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT 23rd Spring Symposium of the Korean-Society-of-Nephrology CY MAY, 2003 CL Seoul, SOUTH KOREA SP Korean Soc Nephrol DE apoptosis; aldose reductase; urine concentration ID DIABETES-MELLITUS; ADENYLATE-CYCLASE; RENAL AQUAPORINS; EXPRESSION; LOCALIZATION; NEPHROPATHY; NEPHROTOXICITY; FIBROSIS; PROTEIN AB The aim of this study was to evaluate the long-term effects of cyclosporine (CsA) treatment on urinary concentration ability. Rats were treated daily for 4 wk with vehicle (VH; olive oil, 1 ml/kg sc) or CsA (15 mg/kg sc). The influence of CsA on the kidney's ability to concentrate urine was evaluated using functional parameters and expression of aquaporins (AQP1-4) and of urea transporters (UT-A-1-3, and UT-B). Plasma vasopressin levels and the associated signal pathway were evaluated, and the effect of vasopressin infusion on urine concentration was observed in VH- and CsA-treated rats. Toxic effects of CsA on tubular cells in the medulla as well as the cortex were evaluated with aldose reductase (AR), Na-K-ATPase-alpha(1) expression, and by determining the number of terminal transferase-mediated dUTP nick end-labeling ( TUNEL)positive cells. Long-term CsA treatment increased urine volume and fractional excretion of sodium and decreased urine osmolality and free-water reabsorption compared with VH- treated rats. These functional changes were accompanied by decreases in the expression of AQP (1-4) and UT (UT-A2, -A3, and UT-B), although there was no change in AQP2 in the cortex and outer medulla and UT-A1 in the inner medulla (IM). Plasma vasopressin levels were not significantly different between two groups, but infusion of vasopressin restored CsA-induced impairment of urine concentration. cAMP levels and Gsalpha protein expression were significantly reduced in CsA-treated rat kidneys compared with VH- treated rat kidneys. CsA treatment decreased the expression of AR and Na-K-ATPase-alpha(1) and increased the number of TUNEL-positive renal tubular cells in both the cortex and medulla. Moreover, the number of TUNEL-positive cells correlated with AQP2 or UT-A3) expression within the IM. In conclusion, CsA treatment impairs urine-concentrating ability by decreasing AQP and UT expression. Apoptotic cell death within the IM at least partially accounts for the CsA-induced urinary concentration defect. C1 Catholic Univ Korea, Dept Internal Med, Seoul 137701, South Korea. Catholic Univ Korea, Cell Death Dis Res Ctr, Seoul 137701, South Korea. Catholic Univ Korea, Dept Anat, Seoul 137701, South Korea. Chonnam Natl Univ, Res Inst Med Sci, Kwangju 501190, South Korea. YanBian Univ Med Coll, Yanji 133000, Jilin, Peoples R China. NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20814 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20814 USA. Emory Univ, Sch Med, Dept Physiol & Med, Div Renal, Atlanta, GA 30322 USA. RP Yang, CW (reprint author), Catholic Univ Korea, Dept Internal Med, 505 Banpo Dong, Seoul 137701, South Korea. EM yangch@catholic.ac.kr FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [R01 DK041707] NR 32 TC 45 Z9 46 U1 0 U2 0 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 JUL PY 2004 VL 287 IS 1 BP F139 EP F151 DI 10.1152/ajprenal.00240.2003 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 827FB UT WOS:000221883500018 PM 14871880 ER PT J AU Notenboom, S Miller, DS Smits, P Russel, FGM Masereeuw, R AF Notenboom, S Miller, DS Smits, P Russel, FGM Masereeuw, R TI Involvement of guanylyl cyclase and cGMP in the regulation of Mrp2-mediated transport in the proximal tubule SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE endothelin signaling; protein kianse C; xenobiotic transport ID MULTIDRUG-RESISTANCE PROTEIN; BLOOD-BRAIN-BARRIER; ACUTE-RENAL-FAILURE; ORGANIC ANION; NITRIC-OXIDE; DRUG EFFLUX; CYCLIC-GMP; ANGIOTENSIN-II; CYCLOSPORINE-A; K+ CHANNEL AB In killifish renal proximal tubules, endothelin-1 (ET-1), acting through a basolateral ET(B) receptor, nitric oxide synthase (NOS), and PKC, decreases cell-to-lumen organic anion transport mediated by the multidrug resistance protein isoform 2 (Mrp2). In the present study, we examined the roles of guanylyl cyclase and cGMP in ET signaling to Mrp2. Using confocal microscopy and quantitative image analysis to measure Mrp2-mediated transport of the fluorescent drug fluorescein methotrexate (FL-MTX), we found that oxadiazole quinoxalin (ODQ), an inhibitor of NO-sensitive guanylyl cyclase, blocked ET-1 signaling. ODQ was also effective when signaling was initiated by nephrotoxicants (gentamicin, amikacin, diatrizoate, HgCl(2), and CdCl(2)), which appear to stimulate ET release from the tubules themselves. ODQ blocked the effects of the NO donor sodium nitroprusside but not of the phorbol ester that activates PKC. Exposing tubules to 8-bromo-cGMP (8-BrcGMP), a cell-permeable cGMP analog, decreased luminal FL-MTX accumulation. This effect was abolished by bisindoylmaleimide (BIM), a PKC inhibitor, but not by N(G)-methyl-L-arginine, a NOS inhibitor. Together, these data indicate that ET regulation of Mrp2 involves activation of guanylyl cyclase and generation of cGMP. Signaling by cGMP follows NO release and precedes PKC activation. C1 Univ Med Ctr Nijmegen, NCMLS, Dept Pharmacol & Toxicol 233, NL-6500 HB Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Masereeuw, R (reprint author), Univ Med Ctr Nijmegen, NCMLS, Dept Pharmacol & Toxicol 233, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM R.Masereeuw@ncmls.kun.nl RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; FU NIEHS NIH HHS [ES-03828] NR 36 TC 23 Z9 23 U1 0 U2 0 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 JUL PY 2004 VL 287 IS 1 BP F33 EP F38 DI 10.1152/ajprenal.00443.2003 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 827FB UT WOS:000221883500005 PM 14970002 ER PT J AU Paliege, A Mizel, D Medina, C Pasumarthy, A Huang, YG Bachmann, S Briggs, JP Schnermann, JB Yang, TX AF Paliege, A Mizel, D Medina, C Pasumarthy, A Huang, YG Bachmann, S Briggs, JP Schnermann, JB Yang, TX TI Inhibition of nNOS expression in the macula densa by COX-2-derived prostaglandin E(2) SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE juxtaglomerular apparatus; cyclooxygenase-2; neuronal nitric oxide synthase; real-time reverse transcriptase-polymerase chain reaction; plasma renin activity ID NITRIC-OXIDE SYNTHASE; CORTICAL CYCLOOXYGENASE-2 EXPRESSION; GENE-KNOCKOUT MICE; RENIN SECRETION; NEURONAL ISOFORM; BLOOD-PRESSURE; RELEASE; KIDNEY; CELLS; ANGIOTENSIN AB It is well established that cyclooxygenase-2 (COX-2) and the neuronal form of nitric oxide synthase ( nNOS) are coexpressed in macula densa cells and that the expression of both enzymes is stimulated in a number of high-renin states. To further explore the role of nNOS and COX-2 in renin secretion, we determined plasma renin activity in mice deficient in nNOS or COX-2. Plasma renin activity was significantly reduced in nNOS -/- mice on a mixed genetic background and in COX-2 -/- mice on either BALB/c or C57/BL6 congenic backgrounds. In additional studies, we accumulated evidence to show an inhibitory influence of PGE(2) on nNOS expression. In a cultured macula densa cell line, PGE(2) significantly reduced nNOS mRNA expression, as quantified by real-time RT-PCR. In COX-2 -/- mice, nNOS mRNA expression in the kidney, determined by real-time RT-PCR, was upregulated throughout the postnatal periods, ranging from postnatal day (PND) 3 to PND 60. The induction of nNOS protein expression and NOS activity in COX-2 -/- mice was localized to macula densa cells using immunohistochemistry and NADPH-diaphorase staining methods, respectively. Therefore, these findings reveal that the absence of either COX-2 or nNOS is associated with suppressed renin secretion. Furthermore, the inhibitory effect of PGE(2) on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation. C1 Univ Utah, Div Nephrol, Salt Lake City, UT 84148 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Tech Univ Berlin, Dept Anat, D-13353 Berlin, Germany. Vet Affairs Med Ctr, Res Serv 151 E, Salt Lake City, UT 84148 USA. RP Yang, TX (reprint author), Univ Utah, Div Nephrol, Bldg 2,500 Foothill Dr, Salt Lake City, UT 84148 USA. EM tianxin.yang@hsc.utah.edu RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [DK-064981, DK-066592] NR 50 TC 55 Z9 56 U1 0 U2 0 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 JUL PY 2004 VL 287 IS 1 BP F152 EP F159 DI 10.1152/ajprenal.00287.2003 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 827FB UT WOS:000221883500019 PM 15010356 ER PT J AU Volkow, ND Wang, GJ Fowler, JS Telang, F Maynard, L Logan, J Gatley, SJ Pappas, N Wong, C Vaska, P Zhu, W Swanson, JM AF Volkow, ND Wang, GJ Fowler, JS Telang, F Maynard, L Logan, J Gatley, SJ Pappas, N Wong, C Vaska, P Zhu, W Swanson, JM TI Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID C-11 RACLOPRIDE; EXTRACELLULAR DOPAMINE; ORAL METHYLPHENIDATE; NUCLEUS-ACCUMBENS; PET; REWARD; AMPHETAMINE; RELEASE; COCAINE; BINDING AB Objective: Methylphenidate is the most commonly prescribed drug for attention deficit hyperactivity disorder (ADHD), yet its therapeutic mechanisms are poorly understood. The objective of this study was to assess if m ethylphenidate, by increasing dopamine (neurotransmitter involved in motivation) in brain, would enhance the saliency of an academic task, making it more interesting. Method: Healthy subjects (N=16) underwent positron emission tomography with [C-11]raclopride (dopamine D-2 receptor radioligand that competes with endogenous dopamine for binding) to assess the effects of oral methylphenidate (20 mg) on extracellular dopamine in the striatum. The authors compared the effects of methylphenidate during an academic task (solving mathematical problems with monetary reinforcement) and a neutral task (passively viewing cards with no remuneration). in parallel, the effects of methylphenidate on the interest that the academic task elicited were also evaluated. Results: Methylphenidate, when coupled with the mathematical task, significantly increased extracellular dopamine, but this did not occur when coupled with the neutral task. The mathematical task did not increase dopamine when coupled with placebo. Subjective reports about interest and motivation in the mathematical task were greater with methylphenidate than with placebo and were associated with dopamine increases. Conclusions: The significant association between methylphenidate-induced dopamine increases and the interest and motivation for the task confirms the prediction that methylphenidate enhances the saliency of an event by increasing dopamine. The enhanced interest for the task could increase attention and improve performance and could be one of the mechanisms underlying methylphenidate's therapeutic effects. These findings support educational strategies that make schoolwork more interesting as nonpharmacological interventions to treat ADHD. C1 Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11794 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92717 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd, Rockville, MD 20853 USA. EM nvolkow@nida.nih.gov FU NIDA NIH HHS [DA 06278, DA 09490-01] NR 40 TC 145 Z9 152 U1 6 U2 26 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2004 VL 161 IS 7 BP 1173 EP 1180 DI 10.1176/appi.ajp.161.7.1173 PG 8 WC Psychiatry SC Psychiatry GA 835EG UT WOS:000222462700006 PM 15229048 ER PT J AU Mah, L Arnold, MC Grafman, J AF Mah, L Arnold, MC Grafman, J TI Impairment of social perception associated with lesions of the prefrontal cortex SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the American-Neuropsychiatric-Association CY MAR 10-12, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Neuropsychiat Assoc ID FRONTAL-LOBE DAMAGE; DECISION-MAKING; COUNTING STROOP; HEAD-INJURY; MIND; PERFORMANCE; COGNITION; EMOTION; PATIENT; BRAIN AB Objective: Behavioral and social impairments have been frequently reported after damage to the prefrontal cortex in humans. This study evaluated social perception in patients with prefrontal cortex lesions and compared their performance on a social perception task with that of healthy volunteers. Method: Thirty-three patients with prefrontal cortex lesions and 31 healthy volunteers were tested with the Interpersonal Perception Task. In this task, subjects viewed videotaped social interactions and relied primarily on nonverbal cues to make interpersonal judgments, such as determining the degree of intimacy between two persons depicted in the videotaped scene. Patients with prefrontal cortex lesions were classified according to lesion involvement of specific regions, including the orbitotrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. Results: Relative to the comparison subjects, patients whose lesions involved the orbitofrontal cortex demonstrated impaired social perception. Contrary to predictions, patients with lesions in the dorsolateral prefrontal cortex also showed deficits in using social cues to make interpersonal judgments. All patients, particularly those with lesions in the dorsolateral prefrontal cortex, showed poorer insight into their deficits, relative to healthy volunteers. Conclusions: These findings of deficits in social perception after damage to the orbitofrontal cortex extend previous clinical and experimental evidence of damage-related impairment in other aspects of social cognition, such as the ability to accurately evaluate emotional facial expressions. in addition, the results suggest that the dorsolateral prefrontal cortex is recruited when inferences about social interactions are made on the basis of nonverbal information. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 54 TC 90 Z9 92 U1 3 U2 19 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2004 VL 161 IS 7 BP 1247 EP 1255 DI 10.1176/appi.ajp.161.7.1247 PG 9 WC Psychiatry SC Psychiatry GA 835EG UT WOS:000222462700016 PM 15229058 ER PT J AU Neeman, Z AF Neeman, Z TI Percutaneous radiofrequency ablation of chordoma - Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Neeman, Z (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2004 VL 183 IS 1 BP 245 EP 246 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 830ZY UT WOS:000222163900052 ER PT J AU Schooler, C Mulatu, MS Oates, G AF Schooler, C Mulatu, MS Oates, G TI Occupational self-direction, intellectual functioning, and self-directed orientation in older workers: Findings and implications for individuals and societies SO AMERICAN JOURNAL OF SOCIOLOGY LA English DT Article ID AGE-DIFFERENCES; ASSUMPTIONS; COGNITION; CULTURE; MODELS; MEMORY; SKILL AB Using data from 1994-95 third-wave interviews, this study tests whether Kohn and Schooler's findings ( based on 1964 and 1974 interviews) that self-directed occupational conditions increase intellectual functioning and self-directed orientations hold when the respondents are 20 years older. Results confirm that even late in life self-directedness of work continues to affect intellectual functioning and self-directedness of orientation. These psychological characteristics, in turn, affect social-structural position in ways that increase disparities between the advantaged and disadvantaged. From a historical and societal perspective, the findings suggest that the occupational self-directedness of a society's workers may affect its social norms, values, and modes of production. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. Bowling Green State Univ, Bowling Green, OH 43403 USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies, 6006 Execut Blvd,Room 321, Bethesda, MD 20892 USA. EM Carmi.Schooler@nih.gov NR 72 TC 47 Z9 48 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9602 J9 AM J SOCIOL JI Am. J. Sociol. PD JUL PY 2004 VL 110 IS 1 BP 161 EP 197 DI 10.1086/385430 PG 37 WC Sociology SC Sociology GA 845VB UT WOS:000223272300005 ER PT J AU Martinez, A Pittaluga, S Villamor, N Colomer, D Rozman, M Raffeld, M Montserrat, E Campo, E Jaffe, ES AF Martinez, A Pittaluga, S Villamor, N Colomer, D Rozman, M Raffeld, M Montserrat, E Campo, E Jaffe, ES TI Clonal T-cell populations and increased risk for cytotoxic T-cell lymphomas in B-CLL patients - Clinicopathologic observations and molecular analysis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE chronic lymphocytic leukemia; peripheral T-cell lymphoma; large granular lymphocytes; cytotoxic T cells; Richter syndrome ID CHRONIC LYMPHOCYTIC-LEUKEMIA; LARGE GRANULAR LYMPHOCYTES; EPSTEIN-BARR-VIRUS; MYCOSIS-FUNGOIDES; RICHTERS-SYNDROME; LYMPHOPROLIFERATIVE DISORDERS; HODGKINS-DISEASE; IMMUNOGLOBULIN; TRANSFORMATION; NEOPLASMS AB Chronic lymphocytic leukemia (CLL) is associated with increased risk of malignancy, but the occurrence of other lymphomas, in particular T-cell lymphomas, is rare. We identified 7 cases of peripheral T-cell malignancy associated with B-cell-derived CLL from the files of two institutions over a 20-year period. The presence of both B and T lymphoproliferative disorders was confirmed in all cases by immunophenotype and in 6 cases by gene rearrangements. Six patients developed peripheral T-cell lymphoma (PTCL), unspecified, during the course of CLL (10-168 months). In all 5 evaluable cases, the cells had a cytotoxic T-cell phenotype; the sixth case was CD56+, but TIA-1 and Granzyme B could not be studied. A seventh patient with CLL developed mycosis fungoides, and an aggressive NK cell leukemia. To investigate possible risk factors for the development of PTCL, we screened 100 unselected peripheral blood samples from newly diagnosed CLL patients by PCR for the presence of clonal T cell populations. We found evidence of clonal T-cell expansion in 8 patients and increased lymphocytes with large granular lymphocyte morphology in 7 of 8 cases. The immunophenotype was assessed by multicolor flow cytometry and in 4 cases the T-cell expansion was composed of either CD3+/CD8+ or CD3+/CD4-/CD8-cells. The cytotoxic nature of the clonal T-cell expansions in the peripheral blood correlates with the cytotoxic nature of the PTCLs, but their role in the subsequent development of T-cell lymphomas is still unclear. PTCL following CLL should be distinguished from typical Richter syndrome, which it can mimic clinically. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Barcelona, Hematopathol Unit, Pathol Lab, Barcelona, Spain. Univ Barcelona, Dept Hematol, Hosp Clin, IDIBAPS, Barcelona, Spain. RP Jaffe, ES (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N202,MSC-1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov RI Martinez, Antonio/D-8188-2012; OI Martinez, Antonio/0000-0003-0790-9017; COLOMER, DOLORS/0000-0001-7486-8484; Campo, elias/0000-0001-9850-9793 NR 53 TC 33 Z9 33 U1 1 U2 2 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 JUL PY 2004 VL 28 IS 7 BP 849 EP 858 DI 10.1097/00000478-200407000-00002 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 833LS UT WOS:000222339400002 PM 15223953 ER PT J AU McKenzie, FE AF McKenzie, FE TI Untitled SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Letter ID MYCOBACTERIUM-TUBERCULOSIS INFECTION C1 Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. RP McKenzie, FE (reprint author), Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. EM mckenzel@mail.nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 2004 VL 71 IS 1 BP 1 EP 1 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 837HN UT WOS:000222619600001 PM 15238680 ER PT J AU Cannon, MJ Papalia, GA Navratilova, I Fisher, RJ Roberts, LR Worthy, KM Stephen, AG Marchesini, GR Collins, EJ Casper, D Qiu, HW Satpaev, D Liparoto, SF Rice, DA Gorshkova, II Darling, RJ Bennett, DB Sekar, M Hommema, E Liang, AM Day, ES Inman, J Karlicek, SM Ullrich, SJ Hodges, D Chu, T Sullivan, E Simpson, J Rafique, A Luginbuhl, B Westin, SN Bynum, M Cachia, P Li, YJ Kao, D Neurauter, A Wong, M Swanson, M Myszka, DG AF Cannon, MJ Papalia, GA Navratilova, I Fisher, RJ Roberts, LR Worthy, KM Stephen, AG Marchesini, GR Collins, EJ Casper, D Qiu, HW Satpaev, D Liparoto, SF Rice, DA Gorshkova, II Darling, RJ Bennett, DB Sekar, M Hommema, E Liang, AM Day, ES Inman, J Karlicek, SM Ullrich, SJ Hodges, D Chu, T Sullivan, E Simpson, J Rafique, A Luginbuhl, B Westin, SN Bynum, M Cachia, P Li, YJ Kao, D Neurauter, A Wong, M Swanson, M Myszka, DG TI Comparative analyses of a small molecule/enzyme interaction by multiple users of Biacore technology SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PLASMON RESONANCE BIOSENSORS; KINETIC-ANALYSIS; MASS-TRANSPORT; RATE CONSTANTS; CARBONIC-ANHYDRASE; SURFACE; BINDING AB To gauge the experimental variability associated with Biacore analysis, 36 different investigators analyzed a small molecule/ enzyme interaction under similar conditions. Acetazolamide (222 g/mol) binding to carbonic anhydrase II (CAII; 30,000 Da) was chosen as a model system. Both reagents were stable and their interaction posed a challenge to measure because of the low molecular weight of the analyte and the fast association rate constant. Each investigator created three different density surfaces of CAII and analyzed an identical dilution series of acetazolamide (ranging from 4.1 to MOW). The greatest variability in the results was observed during the enzyme immobilization step since each investigator provided their own surface activating reagents. Variability in the quality of the acetazolamide binding responses was likely a product of how well the investigators' instruments had been maintained. To determine the reaction kinetics, the responses from the different density surfaces were fit globally to a 1:1 interaction model that included a term for mass transport. The averaged association and dissociation rate constants were 3.1 +/- 1.6 x 10(6) M-1 s(-1) and 6.7 +/- 2.5 x 10(-2) s(-1). respectively, which corresponded to an average equilibrium dissociation constant (K-D) of 2.6 +/- 1.4 x 10(-8) M. The results provide a benchmark of variability in interpreting binding constants from the biosensor and highlight keys areas that should be considered when analyzing small molecule interactions. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Utah, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. SAIC, Prot Chem Lab, Ft Detrick, MD 21702 USA. Rikilt Inst, Wageningen, Netherlands. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27510 USA. Locus Pharmaceut, St Petersburg 19422, Russia. Genzyme Corp, Framingham, MA 01701 USA. Agensys Inc, Santa Monica, CA 90404 USA. Myriad Pharmaceut, Salt Lake City, UT 84108 USA. NICHD, LMG, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Appl Biosyst Inc, Bedford, MA 01730 USA. Biacore RCS, Durham, NC 27713 USA. Berlex Biosci, Richmond, CA 94804 USA. Biogen Inc, Cambridge, MA 02142 USA. Pfizer, Dept Biochem, San Diego, CA 92121 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. Allergan, Irvine, CA 92612 USA. NCI, Frederick, MD 21702 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Univ Zurich, Dept Biochem, Zurich, Switzerland. Biacore AB, Uppsala, Sweden. Agilent Technol, Palo Alto, CA 94303 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Boulder, CO 80309 USA. Monsanto Co, St Louis, MO 63198 USA. Zyomyx Inc, Hayward, CA USA. EOS Biotechnol, San Francisco, CA USA. Pharmacie, Kalamazoo, MI USA. RP Myszka, DG (reprint author), Univ Utah, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. EM dmyszka@cores.utah.edu RI Fisher, Robert/B-1431-2009; Day, Eric/C-5020-2009 NR 14 TC 57 Z9 58 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 2004 VL 330 IS 1 BP 98 EP 113 DI 10.1016/j.ab.2004.02.027 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 831AG UT WOS:000222164700013 PM 15183767 ER PT J AU Malyarchuk, BA Rogozin, IB AF Malyarchuk, BA Rogozin, IB TI Mutagenesis by transient misalignment in the human mitochondrial DNA control region SO ANNALS OF HUMAN GENETICS LA English DT Article DE mitochondrial DNA; spontaneous substitution; dislocation mutagenesis; context; mutation hotspot ID SUBSTITUTION RATE VARIATION; NUCLEOTIDE SUBSTITUTION; EUROPEAN HAPLOGROUPS; POLYMERASE-GAMMA; MEDIAN NETWORKS; HUMAN MTDNA; MUTATIONS; REPAIR; SITES; SEQUENCES AB To study spontaneous base substitutions in human mitochondrial DNA (mtDNA), we reconstructed the mutation spectra of the hypervariable segments I and II (HVS I and II) using published data on polymorphisms from various human populations. Classification analysis revealed numerous mutation hotspots in HVS I and II mutation spectra. Statistical analysis suggested that strand dislocation mutagenesis, operating in monotonous runs of nucleotides, plays an important role in generating base substitutions in the mtDNA control region. The frequency of mutations compatible with the primer strand dislocation in the HVS I region was almost twice as high as that for template strand dislocation. Frequencies of mutations compatible with the primer and template strand dislocation models are almost equal in the HVS II region. Further analysis of strand dislocation models suggested that an excess of pyrimidine transitions in mutation spectra, reconstructed on the basis of the L-strand sequence, is caused by an excess of both L-strand pyrimidine transitions and H-strand purine transitions. In general, no significant bias toward parent H-strand-specific dislocation mutagenesis was found in the HVS I and II regions. C1 Russian Acad Sci, Inst Biol Problems N, Genet Lab, Far E Branch, Magadan 685000, Russia. Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia. Natl Lib Med, NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Malyarchuk, BA (reprint author), Russian Acad Sci, Inst Biol Problems N, Genet Lab, Far E Branch, Portovaya Str 18, Magadan 685000, Russia. EM malyar@ibpn.kolyma.ru NR 64 TC 27 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JUL PY 2004 VL 68 BP 324 EP 339 DI 10.1046/j.1529-8817.2004.00099.x PN 4 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 838IT UT WOS:000222707600004 PM 15225158 ER PT J AU Singh, JP Larson, MG Levy, D Evans, JC Tsuji, H Benjamin, EJ AF Singh, JP Larson, MG Levy, D Evans, JC Tsuji, H Benjamin, EJ TI Is baseline autonomic tone associated with new onset atrial fibrillation?: Insights from the framingham Heart Study SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE autonomic tone; heart rate variability; atrial fibrillation; cohort study ID RATE-VARIABILITY; INTERVAL DYNAMICS; NERVOUS-SYSTEM; TACHYCARDIA; RISK AB Background: Recent reports have indicated that autonomic tone fluctuations measured by heart rate variability (HRV) precede episodes of paroxysmal atrial fibrillation (AF). Little is known about the impact of baseline autonomic tone and the development of new onset AF in a population-based cohort. The purpose of this study was to assess the role of HRV as a predictor of new onset AF. Method: Ambulatory ECG recordings obtained from the Framingham Heart Study subjects attending a routine examination were processed for HRV. The HRV variables analyzed included standard deviation of normal R-R intervals (SDNN), low frequency power (LF), high frequency power (HF), and LF/HF ratio. There were 1434 women and 1142 men (54 +/- 14.1 years) eligible for the study. Results: In 12 years of follow-up, 65 women and 67 men had new onset AF. The Study had 80% power to detect a hazard ratio (HR) of 1.3 per standard deviation (SD) decrement in HRV. A one SD decrement in log LF/HF was associated with increased risk of developing AF (HR = 1.23; 95% confidence intervals (CI) = 1.06-1.44) in age- and sex-adjusted models; the association was no longer significant (HR = 1.15; 95% CI = 0.98-1.35) after adjusting for potential confounders. Conclusion: Autonomic dysregulation at baseline, as reflected by an altered HRV is associated with risk of AF; however, this association does not persist after adjusting for potential confounders. Much of the apparent association between HRV and AF is mediated by traditional risk factors. C1 Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Cardiol, Beth Israel Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Clin Epidemiol, Beth Israel Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17950] NR 25 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JUL PY 2004 VL 9 IS 3 BP 215 EP 220 DI 10.1111/j.1542-474X.2004.93550.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 836OP UT WOS:000222565600004 PM 15245336 ER PT J AU Dominick, KL Bosworth, HB Jeffreys, AS Grambow, SC Oddone, EZ Horner, RD AF Dominick, KL Bosworth, HB Jeffreys, AS Grambow, SC Oddone, EZ Horner, RD TI Nonsteroidal antiinflammatory drug use among patients with GI bleeding SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE anti-ulcer agents; nonsteroidal antiinflammatory drugs; pharmacoepidemiology ID PEPTIC-ULCER DISEASE; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; OSTEOARTHRITIS; RISK; COMPLICATIONS; POPULATION; NSAIDS; CARE AB BACKGROUND: Previous studies have suggested that recommended gastroprotective strategies such as gastroprotective agents (GPAs) and cyclooxygenase (COX) 2 inhibitors may be underutilized among individuals at risk for nonsteroidal antiinflammatory drug (NSAID)-related gastrointestinal (GI) bleeding. OBJECTIVE: To examine the use of traditional NSAIDs, COX-2 inhibitors, and GPAs among patients recently hospitalized for GI bleeding. METHODS: This was a retrospective cohort study of a national sample of 4338 veterans hospitalized for GI bleeding between January and June 1999. Prescription drug use was examined for 6 months following hospitalization. We examined relationships of subject characteristics (age, race, gender, geographic region, diagnosis of arthritis) to prescription of a high-risk NSAID, defined as a traditional NSAID but no GPA within 60 days before or after the NSAID. RESULTS: Approximately 20% of subjects were prescribed an NSAID or COX-2 inhibitor, but only 5% were prescribed a traditional NSAID with no GPA. In a multivariable analysis, subjects <65 years of age and those with arthritis were more likely to be prescribed a traditional NSAID without a GPA. No other subject characteristics were related to receipt of a high-risk prescription. CONCLUSIONS: In a national sample of veterans with a recent hospitalization for GI bleeding, high-risk NSAID prescriptions were uncommon. Underuse of gastroprotective strategies may be more common in patients with less recent GI bleeding-related hospitalization. Strategies to remind physicians and pharmacists to screen for GI risk factors may help to sustain appropriate prescribing and reduce NSAID-related adverse events. C1 Vet Adm Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Med, Raleigh, NC USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Raleigh, NC USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Raleigh, NC USA. Duke Univ, Med Ctr, Div Gen Internal Med, Raleigh, NC USA. NINDS, Off Minor Hlth & Res, NIH, Bethesda, MD 20892 USA. RP Dominick, KL (reprint author), Vet Adm Med Ctr, Ctr Hlth Serv Res Primary Care, 152,508 Fulton St, Durham, NC 27705 USA. EM domin004@mc.duke.edu RI Grambow, Steven/E-1422-2015 OI Grambow, Steven/0000-0001-6037-3253 NR 26 TC 4 Z9 4 U1 4 U2 4 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 2004 VL 38 IS 7-8 BP 1159 EP 1164 DI 10.1345/aph.1E052 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 831IT UT WOS:000222188800008 PM 15187205 ER PT J AU Lee, J Cho, YJ Chang, JE Lipsky, PE AF Lee, J Cho, YJ Chang, JE Lipsky, PE TI The VLJL repertoire of patients with systemic lupus erythematosus manifests characteristics of natural antibody repertoire SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Ewha Womans Univ, Coll Med, Seoul 120750, South Korea. NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 74 EP 74 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500231 ER PT J AU Van Lent, PLEM Nabbe, KCAM Kolls, JK Holland, SM Van de Loo, FAJ Holthuysen, AEM Van den Berg, WB AF Van Lent, PLEM Nabbe, KCAM Kolls, JK Holland, SM Van de Loo, FAJ Holthuysen, AEM Van den Berg, WB TI Oxygen radical production determines chondrocyte death and regulates MMP-mediated matrix degradation during ifngamma-accelerated immune complex arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY ID FC-GAMMA-RI C1 Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. Univ Pittsburgh, Pittsburgh, PA USA. NIAID, Bethesda, MD 20892 USA. RI van Lent, Peter/A-4269-2014; van de Loo, Fons/A-3425-2014; van Lent, Peter/A-4047-2014; Berg, W.B./H-8010-2014 OI van de Loo, Fons/0000-0002-5851-099X; NR 2 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 79 EP 80 PG 2 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500247 ER PT J AU Girschick, HJ Morbach, H Singh, SK Faber, C Grammer, A Lipsky, R AF Girschick, HJ Morbach, H Singh, SK Faber, C Grammer, A Lipsky, R TI Rag expression by peripheral blood B cells of pediatric patients with systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Univ Wurzburg, Wurzburg, Germany. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 142 EP 142 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500454 ER PT J AU Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM AF Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM TI Increased severity of adjuvant-induced arthitis in congenic rats bearing the Aia5 QTL of DA origin on F344 background SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Univ Utah, Salt Lake City, UT USA. VA Salt Lake City Hlth Care Syst, Div Rheumatol, Salt Lake City, UT USA. NIAMS, NIH, Bethesda, MD USA. Medimmune Inc, NIAMS, NIH, Gaithersburg, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 155 EP 156 PG 2 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500505 ER PT J AU Stork, ACJ Van Laar, JM Krijger, R Longo, N Satorius, C Olson, D Lipsky, PE AF Stork, ACJ Van Laar, JM Krijger, R Longo, N Satorius, C Olson, D Lipsky, PE TI B cell immunoglobulin repertoire abnormalities in severe RA SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 164 EP 164 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500539 ER PT J AU Stummvoll, GH Fritsch, RD Meyer, B Aringer, M Smolen, JS Steiner, G AF Stummvoll, GH Fritsch, RD Meyer, B Aringer, M Smolen, JS Steiner, G TI Characterisation of autoreactive T-cells to histon H1 in SLE patients SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Med Univ Vienna, Vienna, Austria. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 210 EP 210 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500695 ER PT J AU Woodburn, J Nelson, KM Siegel, KL Kepple, TM Gerber, LH AF Woodburn, J Nelson, KM Siegel, KL Kepple, TM Gerber, LH TI Multi-segment foot motion during gait: Proof of concept in rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Univ Leeds, Acad Unit Musculoskeletal Dis, Leeds LS2 9JT, W Yorkshire, England. NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RI Siegel, Karen Lohmann/B-5898-2008 NR 1 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 247 EP 247 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551500829 ER PT J AU Hansen, A Reiter, K Gosemann, M Ziprian, T Lipsky, PE Dorner, T AF Hansen, A Reiter, K Gosemann, M Ziprian, T Lipsky, PE Dorner, T TI Analysis of IGVH-, CXCR4-and CXCR5-specific MRNA transcripts in individual peripheral blood B cells from patients with primary Sjogrens syndrome and normal healthy subjects SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2004) CY JUN 09-12, 2004 CL Berlin, GERMANY C1 Univ Hosp Charite, Outpatients Dept, Berlin, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Rheumatol, D-80539 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 SU 1 BP 355 EP 355 PG 1 WC Rheumatology SC Rheumatology GA 863HH UT WOS:000224551501196 ER PT J AU Singh, JA Arayssi, T Duray, P Schumacher, HR AF Singh, JA Arayssi, T Duray, P Schumacher, HR TI Immunohistochemistry of normal human knee synovium: a quantitative study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID RHEUMATOID-ARTHRITIS; HLA-DR; CELL-POPULATIONS; NEEDLE-BIOPSY; MEMBRANE; TISSUE; JOINTS; FEATURES AB Objective: To describe the immunohistochemical characteristics of knee synovium from normal healthy subjects. Methods: 12 healthy subjects underwent needle biopsy of knee synovium. Using antibodies directed against CD3, CD4, CD8, L26, Kp-1, and HLA-DR, detailed quantitative immunohistochemical analysis of various cell subpopulations was undertaken. Results: The mean (SD) age of the subjects was 37 ( 9) years ( five male, seven female). All had a negative history for arthritis, no knee pain, and a totally normal joint examination except for the presence of retropatellar crepitus in five. For technical reasons staining for all immunohistochemical markers could not be achieved in all subjects. CD3+ T lymphocytes were seen in nine of 10 subjects, either diffusely or, more commonly, in perivascular areas. CD4+ cells were seen in synovium in three of seven subjects and CD8+ cells in six of eight subjects, in almost equal numbers (CD4: CD8, 1.1:1). L26+ B lymphocytes were not seen in any biopsy. Kp1+ macrophages were found in 10 of 10 subjects, predominantly in surface lining cells, and in small numbers in diffuse and perivascular locations. HLA-DR+ cells were seen in 10 of 10 subjects, predominantly in surface lining cells and diffusely, but a few were seen perivascularly. Conclusions: Synovium from apparently normal subjects contained a wide range of different cell subpopulations but no B cells. The significance of these immune cells in normal synovium is unclear. A better understanding of their role in normal synovium may be important in analysing the transition to synovitis. C1 Vet Adm Med Ctr, Minneapolis, MN 55417 USA. Univ Minnesota, Minneapolis, MN USA. Amer Univ Beirut, Beirut, Lebanon. Natl Inst Arthrit & Musculoskeletal Dis, Bethesda, MD USA. Vet Adm Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Singh, JA (reprint author), Vet Adm Med Ctr, 111R,1 Vet Dr, Minneapolis, MN 55417 USA. EM singh046@umn.edu OI singh, jasvinder/0000-0003-3485-0006; Arayssi, Thurayya/0000-0003-2469-0272 NR 28 TC 25 Z9 27 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2004 VL 63 IS 7 BP 785 EP 790 DI 10.1136/ard.2003.013383 PG 6 WC Rheumatology SC Rheumatology GA 829CN UT WOS:000222021200006 PM 15194572 ER PT J AU Mani, S Macapinlac, M Goel, S Verdier-Pinard, D Fojo, T Rothenberg, M Colevas, D AF Mani, S Macapinlac, M Goel, S Verdier-Pinard, D Fojo, T Rothenberg, M Colevas, D TI The clinical development of new mitotic inhibitors that stabilize the microtubule SO ANTI-CANCER DRUGS LA English DT Article DE eluethrobin; epothilones; discodermolide; microtubule binding drugs; taxanes ID EPOTHILONE-B ANALOG; AGENT (+)-DISCODERMOLIDE; BIOLOGICAL EVALUATION; ANTITUMOR EFFICACY; CANCER CELLS; DISCODERMOLIDE; BMS-247550; TAXOL; PACLITAXEL; LINES AB Microtubule-stabilizing agents are increasingly studied for cancer treatment based largely on the prior success of paclitaxel and docetaxel. In this review, we focus on the clinical development of epothilones and discodermolide, and we discuss salient preclinical and clinical highlights of these two novel natural products. These agents are distinguished by their biochemical features making them poor P-glycoprotein substrates and capable of inducing cytotoxicity in cell lines or in vivo tumor models harboring mutations in tubulin. There is now considerable data regarding the efficacy of the epothilones in human beings and discodermolide holds such promise, as well. (C) 2004 Lippincott Williams Wilkins. C1 Albert Einstein Coll Med, Montefiore & Jacobi Med Ctr, Dept Med, Bronx, NY USA. Albert Einstein Coll Med, Montefiore & Jacobi Med Ctr, Dept Oncol, Bronx, NY USA. NCI, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Mani, S (reprint author), Jack D Weiler Hosp, Dept Oncol, 1825 Eastchester Rd,Room 2S-49, Bronx, NY 10461 USA. EM smani64@aol.com NR 41 TC 49 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUL PY 2004 VL 15 IS 6 BP 553 EP 558 DI 10.1097/01.cad.0000131681.21637.b2 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 839NU UT WOS:000222792600002 PM 15205596 ER PT J AU Koshkin, A Zhou, XT Kraus, CN Brenner, JM Bandyopadhyay, P Kuntz, ID Barry, CE de Montellano, PRO AF Koshkin, A Zhou, XT Kraus, CN Brenner, JM Bandyopadhyay, P Kuntz, ID Barry, CE de Montellano, PRO TI Inhibition of Mycobacterium tuberculosis AhpD, an element of the peroxiredoxin defense against oxidative stress SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; ALKYLHYDROPEROXIDASE AHPD; ISONIAZID RESISTANCE; CATALASE PEROXIDASE; ANTIOXIDANT DEFENSE; PEROXYNITRITE; SENSITIVITY; EXPRESSION; ENZYMES; TARGET AB The resistance of Mycobacterium tuberculosis to isoniazid (INH) is largely linked to suppression of a catalase-peroxidase enzyme (KatG) that activates INH. In the absence of KatG, antioxidant protection is provided by enhanced expression of the peroxiredoxin AhpC, which is itself reduced by AhpD, a protein with low alkylhydroperoxidase activity of its own. Inhibition of AhpD might therefore impair the antioxidant protection afforded by AhpC and make KatG-negative strains more sensitive to oxidative stress. We report here that the 3(E),17-dioxime of testosterone is a potent competitive AhpD inhibitor, with a K-i of 50 +/- 2 nM. The inhibitor is stereospecific, in that the 3(E) but not 3(Z) isomer is active. Computational studies provide support for a proposed AhpD substrate binding site. However, the inhibitor does not completely suppress the in vitro activity of AhpC/AhpD, because a low titer of AhpD suffices to maintain AhpC activity. This finding, and the low solubility of the inhibitor, explains its inability to suppress the growth of INH-resistant M. tuberculosis in infected mouse lungs. C1 Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NIAID, TB Res Stn, Rockville, MD 20852 USA. RP de Montellano, PRO (reprint author), Univ Calif San Francisco, Dept Pharmaceut Chem, Genentech Hall N572D,600 16th St, San Francisco, CA 94143 USA. EM ortiz@cgl.ucsf.edu RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11]; NIGMS NIH HHS [GM 56531, P01 GM056531] NR 29 TC 9 Z9 10 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2004 VL 48 IS 7 BP 2424 EP 2430 DI 10.1128/AAC.48.7.2424-2430.2004 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 834RC UT WOS:000222427200012 PM 15215090 ER PT J AU Tsai, HF Bard, M Izumikawa, K Krol, AA Sturm, AM Culbertson, NT Pierson, CA Bennett, JE AF Tsai, HF Bard, M Izumikawa, K Krol, AA Sturm, AM Culbertson, NT Pierson, CA Bennett, JE TI Candida glabrata erg1 mutant with increased sensitivity to azoles and to low oxygen tension SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; FLUCONAZOLE RESISTANCE; TERBINAFINE RESISTANCE; IN-VITRO; GENE; ALBICANS; CONSTRUCTION; MECHANISM; DEPLETION; GROWTH AB A Candida glabrata erg1 (Cgerg1) mutant, CgTn201S, was identified by transposon mutagenesis and by increased fluconazole susceptibility. CgERG1 encodes a 489-amino-acid protein which, on the basis of its homology with Saccharomyces cerevisiae ERG1, is a squalene epoxidase essential for ergosterol synthesis. Interruption following codon 475 of CgErg1p decreased the ergosterol content by 50%; caused accumulation of the squalene precursor; increased the levels of susceptibility to fluconazole, itraconazole, and terbinafine; increased the level of resistance to amphotericin B; increased the levels of rhodamine 6G and [H-3]-fluconazole uptake; reduced the level of growth; and blocked growth under conditions of low oxygen tension. In addition, CgTn201S efficiently took up exogenous cholesterol from cholesterol-containing serum. Cholesterol constituted 34% of the extractable sterols in CgTn201S when it was grown aerobically on serum-containing medium. Under the same conditions, C. albicans contained only 0.1 to 1.2% cholesterol. Exogenous sterols also restored growth under conditions of low oxygen tension. Finally, complementation of the Cgerg1 mutation restored the levels of [H-3]fluconazole uptake and drug susceptibility to wild-type levels. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, Clin Ctr,NIH, Bethesda, MD 20892 USA. Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46202 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, Clin Ctr,NIH, Room 11C304, Bethesda, MD 20892 USA. EM Jbennett@niaid.nih.gov NR 20 TC 37 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2004 VL 48 IS 7 BP 2483 EP 2489 DI 10.1128/AAC.48.7.2483-2489.2004 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 834RC UT WOS:000222427200020 PM 15215098 ER PT J AU Taggart, BR Harrington, P Hollingshead, M AF Taggart, BR Harrington, P Hollingshead, M TI HIV hollow fiber SCID model for antiviral therapy comparison with SCID/hu model SO ANTIVIRAL RESEARCH LA English DT Review DE HIV; SCID model; hollow fiber; antiviral therapy ID IMMUNODEFICIENCY-VIRUS-INFECTION; HU MOUSE; MURINE RETROVIRUSES; CELLS; MICE; GROWTH AB Severe combined inummodeficient (SCID) mice have been evaluated for applicability as hosts for a human immunodeficiency virus (HIV) animal model, compatible with the pathogenesis of HIV disease and/or for testing compounds for antiviral efficacy. McCune et al. [Science 241 (1988) 1632] described the SCID/hu model and Namikawa et al. [J. Exp. Med. 172 (1990) 1055] and Rabin et al. [Antimicrob. Agents Chemother. 40 (1996) 755] described the SCID/hu (Thy/Liv) model which was developed for the evaluation of HIV pathogenic mechanisms and for the prioritization of antiviral compounds that were efficacious in vitro. Hollingshead et al. [Antiviral Res. 28 (1995) 2651 and Xu et al. [Bioorg. Med Chem. Lett. 9 (1999) 133] described the HIV hollow fiber SCID mouse model. This model was developed to be a low cost, high throughput, time efficient, simple in vivo screening system for preliminary anti-HIV efficacy evaluation for the prioritization of antiviral compounds that demonstrated in vitro efficacy. The hollow fiber model is used as a pharmacologic tool to help separate active and inactive agents and direct the best lead compounds into additional animal model testing (e.g. SCID/hu). Compounds that are known to have an antiviral effect in man (e.g. 3'-azo-3'-deoxythymidine (AZT), dideoxyinosine (ddI) and dideoxycytidine (ddC)) were evaluated in both models. The endpoints (e.g. PCR, flow cytometry, MTT, p24, RT) evaluated in both models indicate that HIV-1 virus replicates in both models and infection is suppressed in the SCID/hu and hollow fiber SCID mouse models when treated with approved clinical antiviral agents. While both models are useful for the evaluation of antiviral therapies, there are distinct advantages (e.g. cost, time, material, equipment, expediency) with the hollow fiber assay over the SCID/hu model (Thy/Liv) for antiviral drug evaluations particularly in terms of cost effectiveness. (C) 2004 Elsevier B.V. All rights reserved. C1 So Res Inst, Frederick, MD 21701 USA. NCI, Biol Testing Branch, DTP, DCT, Frederick, MD 21701 USA. RP Taggart, BR (reprint author), So Res Inst, Homeland Secur & Emerging Infect Dis Res Div, 2000 9th Ave S,POB 55305, Birmingham, AL 35255 USA. NR 20 TC 4 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 2004 VL 63 IS 1 BP 1 EP 6 DI 10.1016/j.antiviral.2004.04.001 PG 6 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 834PR UT WOS:000222423500001 PM 15196814 ER PT J AU DeLeo, FR AF DeLeo, FR TI Modulation of phagocyte apoptosis by bacterial pathogens SO APOPTOSIS LA English DT Review DE apoptosis; bacteria; inflammation; macrophage; neutrophil; phagocytosis ID MONOCYTE-DERIVED MACROPHAGES; PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; ADENYLATE CYCLASE-HEMOLYSIN; BACILLUS-CALMETTE-GUERIN; POLYMORPHONUCLEAR LEUKOCYTE APOPTOSIS; MYCOBACTERIUM-TUBERCULOSIS INFECTION; ALVEOLAR EPITHELIAL-CELLS; GROUP-B STREPTOCOCCUS; RECEPTOR-MEDIATED PHAGOCYTOSIS AB Phagocytic leukocytes such as neutrophils and macrophages are essential for the innate immune response against invading bacteria. Binding and ingestion of bacteria by these host cells triggers potent anti-microbial activity, including production of reactive oxygen species. Although phagocytes are highly adept at destroying bacteria, modulation of leukocyte apoptosis or cell death by bacteria has emerged as a mechanism of pathogenesis. Whereas induction of macrophage apoptosis by pathogens may adversely affect the host immune response to infection, acceleration of neutrophil apoptosis following phagocytic interaction with bacteria appears essential for the resolution of infection. This idea is supported by the finding that some bacterial pathogens alter normal phagocytosis-induced neutrophil apoptosis to survive and cause disease. This review summarizes what is currently known about modulation of phagocyte apoptosis by bacteria and describes a paradigm whereby bacteria-induced neutrophil apoptosis plays a role in the resolution of infection. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 NR 269 TC 158 Z9 169 U1 2 U2 21 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JUL PY 2004 VL 9 IS 4 BP 399 EP 413 DI 10.1023/B:APPT.0000031448.64969.fa PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 827ZG UT WOS:000221941600001 PM 15192322 ER PT J AU Foster, JS Kolenbrander, PE AF Foster, JS Kolenbrander, PE TI Development of a multispecies oral bacterial community in a saliva-conditioned flow cell SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-GORDONII; VEILLONELLA-ALCALESCENS; SUBGINGIVAL PLAQUE; BIOFILM FORMATION; ACTIVATED-SLUDGE; DENTAL PLAQUE; CO-ADHESION; COAGGREGATION; MUTANS; ENAMEL AB Microbial communities within the human oral cavity are dynamic associations of more than 500 bacterial species that form biofilms on the soft and hard tissues of the mouth. Understanding the development and spatial organization of oral biofilms has been facilitated by the use of in vitro models. We used a saliva-conditioned flow cell, with saliva as the sole nutritional source, as a model to examine the development of multispecies biofilm communities from an inoculum containing the coaggregation partners Streptococcus gordonii, Actinomyces naeslundii, Veillonella atypica, and Fusobacterium nucleatum. Biofilms inoculated with individual species in a sequential order were compared with biofilms inoculated with coaggregates of the four species. Our results indicated that flow cells inoculated sequentially produced biofilms with larger biovolumes compared to those biofilms inoculated with coaggregates. Individual-species biovolumes within the four-species communities also differed between the two modes of inoculation. Fluorescence in situ hybridization with genus-and species-specific probes revealed that the majority of cells in both sequentially and coaggregate-inoculated biofilms were S. gordonii, regardless of the inoculation order. However, the representation of A. naeslundii and V. atypica was significantly higher in biofilms inoculated with coaggregates compared to sequentially inoculated biofilms. Thus, these results indicate that the development of multispecies biofilm communities is influenced by coaggregations preformed in planktonic phase. Coaggregating bacteria such as certain streptococci are especially adapted to primary colonization of saliva-conditioned surfaces independent of the mode of inoculation and order of addition in the multispecies inoculum. Preformed coaggregations favor other bacterial strains and may facilitate symbiotic relationships. C1 NIDCR, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Oral Infect & Immun Branch, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov NR 35 TC 96 Z9 103 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2004 VL 70 IS 7 BP 4340 EP 4348 DI 10.1128/AEM.70.7.4340-4348.2004 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 839BP UT WOS:000222758600070 PM 15240317 ER PT J AU Kaiser-Kupfer, MI Caruso, RC Valle, D Reed, GF AF Kaiser-Kupfer, MI Caruso, RC Valle, D Reed, GF TI Use of an arginine-restricted diet to slow progression of visual loss in patients with gyrate atrophy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LONG-TERM REDUCTION; RETINAL DEGENERATION AB Objective: To quantify the effect of long-term reduction of plasma ornithine levels through adherence to an arginine-restricted diet on visual function in patients of all ages with gyrate atrophy of the retina and choroid. Methods: A long-term observational study was conducted on 27 patients with gyrate atrophy, 17 of whom elected to comply with the arginine-restricted diet and 10 who were unable to comply. The mean rates of change in the electroretinogram combined response, electroretinogram flicker response, and kinetic and static perimetry were determined. Results: After mean follow-up of 13.9 years for the patients on the diet and 14.1 years for those not on the diet, the mean rates of change for the diet group compared with those of the no-diet group were statistically significantly slower for all outcome measures (age-adjusted P<.05) except for static perimetry (P=.06). Conclusions: Adhering to an arginine-restricted diet so as to lower the plasma ornithine level below an average of 5.29 to 6.61 mg/dL (400-500 mumol/L) will slow the loss of function as measured by sequential electroretinography and visual field examinations. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD USA. NEI, Biometry Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD USA. Johns Hopkins Sch Med, Howard Hughes Med Inst, Baltimore, MD USA. RP Kaiser-Kupfer, MI (reprint author), 6016 Neilwood Dr, Rockville, MD 20852 USA. EM isolde@comcast.net NR 4 TC 16 Z9 18 U1 0 U2 0 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 JUL PY 2004 VL 122 IS 7 BP 982 EP 984 DI 10.1001/archopht.122.7.982 PG 3 WC Ophthalmology SC Ophthalmology GA 838HF UT WOS:000222703400004 PM 15249361 ER PT J AU Cousins, SW Espinosa-Heidmann, DG Csaky, KG AF Cousins, SW Espinosa-Heidmann, DG Csaky, KG TI Monocyte activation in patients with age-related macular degeneration - A biomarker of risk for choroidal neovascularization? SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BRUCHS MEMBRANE; TNF-ALPHA; CELLS; EXPRESSION; DISEASE; MACROPHAGE; ATHEROSCLEROSIS; INFLAMMATION AB Objective: To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of the proinflammatory and angiogenic factor tumor necrosis factor alpha (TNF-alpha) and by correlating its expression with dry and wet AMD. Methods: Circulating monocytes were obtained from the blood of patients with AMD or age-matched control subjects by gradient centrifugation. The monocytes were then analyzed for either TNF-alpha release from cultured macrophages in response to retinal pigment epithelium-derived blebs and cytokines or TNF-alpha. messenger RNA content by reverse transcriptase-polymerase chain reaction. Results: In human monocytes obtained from controls and AMD patients, TNF-alpha was expressed by freshly isolated monocytes and produced by macrophages in culture after stimulation with retinal pigment epithelium-derived blebs. However, wide variability in TNF-alpha expression was observed among different patients. Patients with monocytes that expressed the greatest amount of TNF-alpha demonstrated higher prevalence of choroidal neovascularization. Conclusions: Both controls and AMD patients vary in the activation state (defined as TNF-alpha expression) of circulating monocytes. Partially active monocytes, defined as high TNF-alpha expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization. Clinical Relevance: Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease. C1 Miami Univ, Mcknight Vis Res Ctr, Bascom Palmer Eye Inst, Sch Med,Dept Ophthalmol, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Cousins, SW (reprint author), Miami Univ, Mcknight Vis Res Ctr, Bascom Palmer Eye Inst, Sch Med,Dept Ophthalmol, 1638 NW 10th Ave, Miami, FL 33136 USA. EM scousins@med.miami.edu FU NEI NIH HHS [EY/AI 13318] NR 34 TC 82 Z9 92 U1 0 U2 0 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 JUL PY 2004 VL 122 IS 7 BP 1013 EP 1018 DI 10.1001/archopht.122.7.1013 PG 6 WC Ophthalmology SC Ophthalmology GA 838HF UT WOS:000222703400009 PM 15249366 ER PT J AU Rodriguez-Coleman, H Yuan, P Kim, H Gravlin, L Srivastava, S Csaky, KG Robinson, MR AF Rodriguez-Coleman, H Yuan, P Kim, H Gravlin, L Srivastava, S Csaky, KG Robinson, MR TI Intravitreal injection of triamcinolone for diffuse macular edema SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 NEI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rodriguez-Coleman, H (reprint author), NEI, NIH, Dept Hlth & Human Serv, Bldg 10,Room 218B,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. EM colemanh@nei.nih.gov NR 6 TC 29 Z9 30 U1 0 U2 0 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 JUL PY 2004 VL 122 IS 7 BP 1085 EP 1086 DI 10.1001/archopht.122.7.1085 PG 2 WC Ophthalmology SC Ophthalmology GA 838HF UT WOS:000222703400032 PM 15249388 ER PT J AU Zinn, S Dudley, TK Bosworth, HB Hoenig, HM Duncan, PW Horner, RD AF Zinn, S Dudley, TK Bosworth, HB Hoenig, HM Duncan, PW Horner, RD TI The effect of poststroke cognitive impairment on rehabilitation process and functional outcome SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Academy-of-Physical-Medicine-and Rehabilitation CY NOV 20-24, 2002 CL Orlando, FL SP Amer Acad Phys Med & Rehabilitat DE cognition disorders; quality of health care; rehabilitation; stroke; treatment outcome ID MENTAL-STATE-EXAMINATION; TRAUMATIC BRAIN-INJURY; STROKE PATIENTS; INPATIENT REHABILITATION; INDEPENDENCE MEASURE; FOLLOW-UP; DEPRESSION; DISORDERS; PERFORMANCE; GUIDELINES AB Objectives: To determine whether cognitive impairment affects access to, or quality of, rehabilitation services, and to examine the effects of functional outcomes in stroke patients. Design: Secondary analysis of prospective cohort of stroke patients followed for 6 months after stroke. Settings: Eleven large-volume US Department of Veterans Affairs hospitals nationwide. Participants: Stroke patients (N=272) who were candidates for rehabilitation. Interventions: Not applicable. Main Outcome Measures: Rehabilitation process variables were examined for patients assessed as cognitively impaired or unimpaired according to education-adjusted Mini-Mental State Examination score. Functional outcomes were performance of activities of daily living (ADLs), measured by the FonFIM, and instrumental activities of daily living (IADLs), measured by Lawton, at 6-month follow-up. Results: Compliance with guidelines and receipt of and interval to postacute treatment initiation did not differ between cognitively impaired and unimpaired patients. Although most cognition-related treatment elements were similar for both groups, cognitive goals were more frequently charted in impaired patients. Controlling for baseline function and rehabilitation process, cognitively impaired patients had worse IADL performance at 6 months than did unimpaired patients; cognition did not significantly influence ADL performance. Conclusions: Quality of, and access to, rehabilitative care was equivalent for patients with and without cognitive impairment. Despite a similar rehabilitation process, cognitively impaired stroke patients experienced worse recovery of IADLs. C1 Durham Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Durham, NC 27705 USA. Duke Univ, Ctr Med, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Duke Univ, Ctr Med, Dept Med, Durham, NC 27706 USA. Malcolm Randall Vet Affairs Med Ctr, Rehabil Outcomes Res Ctr, Gainesville, FL USA. NINDS, Bethesda, MD 20892 USA. RP Zinn, S (reprint author), Durham Vet Affairs Med Ctr, Dept Phys Med & Rehabil, 151,508 Fulton St, Durham, NC 27705 USA. EM sandra.zinn@duke.edu NR 52 TC 76 Z9 80 U1 2 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2004 VL 85 IS 7 BP 1084 EP 1090 DI 10.1016/j.apmr.2003.10.022 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 835XU UT WOS:000222519600007 PM 15241754 ER PT J AU Lamping, KG Wess, J Cui, YH Nuno, DW Faraci, FM AF Lamping, KG Wess, J Cui, YH Nuno, DW Faraci, FM TI Muscarinic (M) receptors in coronary circulation - Gene-targeted mice define the role of M2 and M3 receptors in response to acetylcholine SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE acetylcholine; muscarinic receptors; genetically altered mice ID CEREBRAL BLOOD-VESSELS; KNOCKOUT MICE; SMOOTH-MUSCLE; PHARMACOLOGICAL CHARACTERIZATION; MEDIATING RELAXATION; HYPERLIPIDEMIC MICE; ARTERY; ENDOTHELIUM; SUBTYPES; CONTRACTION AB Objective - Determining the role of specific muscarinic (M) receptor subtypes mediating responses to acetylcholine (ACh) has been limited by the specificity of pharmacological agents. Deletion of the gene for M-5 receptors abolished response to ACh in cerebral blood vessels but did not affect dilation of coronary arteries. The goal of this study was to determine the M receptors mediating responses to ACh in coronary circulation using mice deficient in M-2 or M-3 receptors (M-2-/-, M-3-/-, respectively). Methods and Results - Coronary arteries from respective wild-type, M-2-/-, or M-3-/- mice were isolated, cannulated, and pressurized. Diameter was measured with video microscopy. After preconstriction with U46619, ACh produced dose-dependent dilation of coronary arteries that was similar in wild-type and M-2-/- mice. In contrast, dilation of coronary arteries from M-3-/- mice to ACh was reduced by approximate to80% compared with wild type. The residual response to ACh was atropine insensitive. Relaxation of coronary arteries to other stimuli was similar in M-2-/- and M-3-/- mice. Similar results were obtained in aorta rings. Conclusion - These findings provide the first direct evidence that relaxation to ACh in coronary circulation is mediated predominantly by activation of M-3 receptors. C1 Univ Iowa, Roy J & Lucille A Carver Sch Med, Dept Internal Med & Pharmacol, Iowa City, IA USA. Vet Adm Med Ctr, Iowa City, IA USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Lamping, KG (reprint author), Vet Affairs Med Ctr, Med Serv 111, 601 Highway 6 W, Iowa City, IA 52246 USA. EM kathryn-lamping@uiowa.edu FU NHLBI NIH HHS [HL39050, HL62984]; NINDS NIH HHS [NS-24621] NR 39 TC 37 Z9 38 U1 0 U2 5 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 JUL PY 2004 VL 24 IS 7 BP 1253 EP 1258 DI 10.1161/01.ATV.0000130661.82773.ca PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 834WR UT WOS:000222442100020 PM 15130910 ER PT J AU Wassef, M AF Wassef, M TI Gardner Craddock McMillan - In memorium SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Biographical-Item C1 NHLBI, Atherosclerosis Res Grp, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Wassef, M (reprint author), NHLBI, Atherosclerosis Res Grp, Div Heart & Vasc Dis, 2 Rockledge Ctr,6701 Rockledge Dr,Suite 10196, Bethesda, MD 20892 USA. EM WassefM@NHLBI.NIH.GOV NR 1 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 JUL PY 2004 VL 24 IS 7 BP 1326 EP 1327 DI 10.1161/01.ATV.0000134967.87210.a2 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 834WR UT WOS:000222442100032 ER PT J AU Illei, GG Tackey, E Lapteva, L Lipsky, PE AF Illei, GG Tackey, E Lapteva, L Lipsky, PE TI Biomarkers in systemic lupus erythematosus - II. Markers of disease activity SO ARTHRITIS AND RHEUMATISM LA English DT Review ID INTERCELLULAR-ADHESION MOLECULE-1; SOLUBLE INTERLEUKIN-2 RECEPTOR; CIRCULATING IMMUNE-COMPLEXES; PERIPHERAL-BLOOD LYMPHOCYTES; CONNECTIVE-TISSUE DISEASES; COMPLEMENT SPLIT PRODUCTS; CELL ACTIVATION MARKERS; NITRIC-OXIDE PRODUCTION; ANTI-DNA ANTIBODIES; NEGATIVE T-CELLS C1 NIAMSD, NIH, DHHS, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), NIAMSD, NIH, DHHS, 10 Ctr Dr,Room 9S205, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov NR 174 TC 84 Z9 90 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2004 VL 50 IS 7 BP 2048 EP 2065 DI 10.1002/art.20345 PG 18 WC Rheumatology SC Rheumatology GA 839YG UT WOS:000222820300003 PM 15248202 ER PT J AU Takada, K Arefayene, M Desta, Z Yarboro, CH Boumpas, DT Balow, JE Flockhart, DA Illei, GG AF Takada, K Arefayene, M Desta, Z Yarboro, CH Boumpas, DT Balow, JE Flockhart, DA Illei, GG TI Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HUMAN LIVER-MICROSOMES; CONTROLLED TRIAL; MEPHENYTOIN METABOLISM; IFOSFAMIDE ACTIVATION; GENETIC-POLYMORPHISM; OVARIAN FAILURE; THERAPY; ERYTHEMATOSUS; METHYLPREDNISOLONE; CHEMOTHERAPY AB Objective. Pulse cyclophosphamide is the treatment of choice for severe lupus nephritis. However, not all patients respond to this therapy, and gonadal toxicity is of particular concern. Cyclophosphamide is a prodrug that requires activation by cytochrome P450 (CYP) enzymes. We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis. Methods. Sixty-two patients with proliferative lupus nephritis treated with cyclophosphamide were genotyped for common variant alleles of CYP2B6, 2C19, 2C9, and 3A5. We examined the association between these genotypes and the following clinical end points: development of premature ovarian failure, end-stage renal disease (ESRD), doubling of serum creatinine level, and achievement of complete renal response. Results. The observed frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0%, and 75.8%, respectively. Patients who were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing premature ovarian failure (relative risk 0.10; 95% confidence interval 0.02-0.52), after adjustment for age and total number of cyclophosphamide pulses received. In a survival analysis, patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n 4) had a higher probability of reaching ESRD (P = 0.0005) and of doubling the creatinine level (P = 0.0005) as well as a trend toward a lower probability of achieving a complete renal response (P = 0.051). Conclusion. Determination of selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk of premature ovarian failure in lupus nephritis patients treated with cyclophosphamide. The association of these genotypes with renal response needs further validation. C1 NIAMSD, Natl Inst Hlth, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Univ Crete, Iraklion, Greece. RP Illei, GG (reprint author), NIAMSD, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 9S205, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov FU NIGMS NIH HHS [U01-GM-61373, 5T32-GM-08425] NR 39 TC 98 Z9 104 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2004 VL 50 IS 7 BP 2202 EP 2210 DI 10.1002/art.20338 PG 9 WC Rheumatology SC Rheumatology GA 839YG UT WOS:000222820300019 PM 15248218 ER PT J AU Sankar, V Brennan, MT Kok, MR Leakan, RA Smith, JA Manny, J Baum, BJ Pillemer, SR AF Sankar, V Brennan, MT Kok, MR Leakan, RA Smith, JA Manny, J Baum, BJ Pillemer, SR TI Etanercept in Sjogren's syndrome - A twelve-week randomized, double-blind, placebo-controlled pilot clinical trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; INDUCED MATRIX-METALLOPROTEINASE-9 PRODUCTION; GLAND ACINAR-CELLS; FACTOR-KAPPA-B; SALIVARY-GLANDS; INFLIXIMAB; EXPRESSION; CLASSIFICATION; SUPPRESSION; DESTRUCTION AB Objective. To assess the safety and potential efficacy of etanercept in the treatment of Sjogren's syndrome (SS). Methods. This pilot study was a 12-week randomized, double-blind, placebo-controlled trial of etanercept, with 14 subjects in each group. Patients received 25 mg of etanercept or placebo (vehicle) by twice-weekly subcutaneous injection. Patients met the American-European Consensus Group criteria for SS. The primary outcome required at least 20% improvement from baseline values for at least 2 of the following 3 domains: subjective or objective measures of dry mouth, subjective or objective measures of dry eyes, and IgG level or erythrocyte sedimentation rate (ESR). Results. Of the 14 patients taking etanercept, 11 had primary SS and 3 had SS secondary to rheumatoid arthritis. Baseline measures did not differ between the 2 groups. Three etanercept-treated patients and 1 placebo-treated patient did not complete the trial. Five etanercept-treated patients and 3 placebo-treated patients showed improvement from baseline in the primary outcome variable at 12 weeks, but the difference was not statistically significant. There were no significant differences between the groups for changes in subjective measures of oral or ocular symptoms (by visual analog scale), the IgG level, Schirmer I test result, van Bijsterveld score, or salivary flow. At 12 weeks, the ESR had decreased in the etanercept group compared with baseline (P = 0.004); however, the mean reduction was only 18.6%. Conclusion. We found no evidence to suggest that treatment with etanercept at a dosage of 25 mg twice weekly for 12 weeks was clinically efficacious in SS. A larger trial will be necessary to definitively address the efficacy of etanercept in the treatment of SS. C1 Natl Inst Hlth, Bethesda, MD USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. RP Sankar, V (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr,Mail Code 7919, San Antonio, TX 78229 USA. EM sankarv@uthscsa.edu NR 26 TC 134 Z9 138 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2004 VL 50 IS 7 BP 2240 EP 2245 DI 10.1002/art.20299 PG 6 WC Rheumatology SC Rheumatology GA 839YG UT WOS:000222820300024 PM 15248223 ER PT J AU Rider, LG Giannini, EH Brunner, HI Ruperto, N James-Newton, L Reed, AM Lachenbruch, PA Miller, FW AF Rider, LG Giannini, EH Brunner, HI Ruperto, N James-Newton, L Reed, AM Lachenbruch, PA Miller, FW CA Int Myositis Assessment Clinical S TI International consensus on preliminary definitions of improvement in adult and juvenile myositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLEGE-OF-RHEUMATOLOGY; IDIOPATHIC INFLAMMATORY MYOPATHIES; PRELIMINARY CORE SET; DISEASE-ACTIVITY; OUTCOME ASSESSMENT; RESPONSE CRITERIA; ARTHRITIS; DERMATOMYOSITIS; POLYMYOSITIS; THERAPY AB Objective. To use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials. Methods. Twenty-nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty-seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data-mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top-performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were greater than or equal to75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation. Results. The definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by greater than or equal to20%, with no more than 2 worse by greater than or equal to25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials. Conclusion. Consensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials. C1 NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Mayo Clin, Rochester, MN USA. IRCCS, Genoa, Italy. Univ Cincinnati, Cincinnati, OH USA. RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, NIH, 9 Mem Dr,Room 1W107,MSC 0958, Bethesda, MD 20892 USA. EM RIDER@niehs.nih.gov RI Song, Yeong Wook/J-2765-2012; OI Harris-Love, Michael/0000-0002-1842-3269; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIAMS NIH HHS [AR-48349-01, P60-AR-47784] NR 30 TC 100 Z9 101 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2004 VL 50 IS 7 BP 2281 EP 2290 DI 10.1002/art.20349 PG 10 WC Rheumatology SC Rheumatology GA 839YG UT WOS:000222820300029 PM 15248228 ER PT J AU Rustay, NR Crabbe, JC AF Rustay, NR Crabbe, JC TI Genetic analysis of rapid tolerance to ethanol's incoordinating effects in mice: Inbred strains and artificial selection SO BEHAVIOR GENETICS LA English DT Article DE ataxia; ethanol; mice; rotarod; selected lines; tolerance ID NMDA-ANTAGONISTS; SEROTONIN 5-HT; D-CYCLOSERINE; MOUSE LINES; SENSITIVITY; HYPOTHERMIA; KETAMINE AB Ethanol tolerance, a decrease in drug responsiveness with repeated administrations, is an important diagnostic criterion for alcoholism. Rapid tolerance develops within 8 - 24 hours of an initial ethanol exposure and shares many similarities with chronic tolerance. The genetic contribution to rapid tolerance to ethanol-induced ataxia was estimated using a panel of inbred strains of mice. Strains differed significantly in the degree of rapid tolerance development, which had a broad-sense heritability estimate of 0.11. Artificial selection was carried out to develop lines of mice that would show High (HRT) and Low (LRT) levels of Rapid Tolerance. Starting with HS/Npt mice, derived from a systematic cross of eight inbred strains, a significant response to selection was seen in replicate 1 by the third selection generation. No difference was found in replicate 2. Heritability estimates after the fourth generation were 0.25 for HRT-1 mice and 0.06 for LRT-1 mice. HRT-1 and LRT-1 mice also differed significantly in chronic tolerance development to four doses of ethanol. These studies provide evidence for a genetic contribution to rapid tolerance and support a genetic link between rapid and chronic tolerance to ethanol's ataxic effects. C1 Oregon Hlth Sci Univ, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97201 USA. Dept Vet Affairs Med Ctr, Portland, OR USA. RP Rustay, NR (reprint author), NIMH, Lab Behav Neurosci, Bldg 10 Room 4D11, Bethesda, MD 20892 USA. EM rustayn@mail.nih.gov FU NIAAA NIH HHS [AA13463, AA10760, P60 AA010760, AA12714] NR 35 TC 32 Z9 32 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JUL PY 2004 VL 34 IS 4 BP 441 EP 451 DI 10.1023/B:BEGE.0000023649.60539.dd PG 11 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 812CW UT WOS:000220818600008 PM 15082941 ER PT J AU Walrath, CM Bruns, EJ Anderson, KL Glass-Siegal, M Weist, MD AF Walrath, CM Bruns, EJ Anderson, KL Glass-Siegal, M Weist, MD TI Understanding expanded school mental health services in Baltimore City SO BEHAVIOR MODIFICATION LA English DT Article DE school-based; mental health services; children; urban ID STUDENTS EMOTIONAL DISTRESS; BEHAVIORAL-PROBLEMS; EFFECTIVE PROGRAMS; MODELS; SEARCH; YOUTH; CARE; GAP AB This article explores the nature of expanded school mental health (ESMH) services in Baltimore City, which at the time of the study were incorporated into 40% of the city's public schools. A provider survey was distributed to ESMH clinicians to gather information on the characteristics of service providers and recipients, types of services being provided, and their proposed outcomes. Provider reports indicated an impressive service capacity, augmentation of traditional school-based services, and the continual need for increased mental health service hours in their buildings. In addition, the most frequently voiced benefits of the ESMH programs were increased mental health awareness and improved school climate. Implications of the findings for future programming development and research are discussed. C1 ORC Macro, Calverton, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21218 USA. NIAAA, Rockville, MD 20852 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baltimore Mental Hlth Syst Inc, Baltimore, MD USA. RP Walrath, CM (reprint author), ORC Macro, Calverton, MD USA. NR 25 TC 7 Z9 7 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2004 VL 28 IS 4 BP 472 EP 490 DI 10.1177/0145445503259501 PG 19 WC Psychology, Clinical SC Psychology GA 827KX UT WOS:000221899600002 PM 15186511 ER PT J AU Piszczek, G D'Auria, S Staiano, M Rossi, M Ginsburg, A AF Piszczek, G D'Auria, S Staiano, M Rossi, M Ginsburg, A TI Conformational stability and domain coupling in D-glucose/D-galactose binding protein from Escherichia coli SO BIOCHEMICAL JOURNAL LA English DT Article DE circular dichroism (CD); differential scanning calorimetry (DSC); D-glucose/D-galactose-binding protein; intrinsic tryptophanyl residue fluorescence; ligand binding; thermal unfolding ID DIFFERENTIAL SCANNING CALORIMETRY; SALMONELLA-TYPHIMURIUM; L-ARABINOSE; ENERGETICS; RECEPTOR; SENSOR AB The monomeric D-glucose/D-galactose-binding protein (GGBP) from Escherichia coli (M, 33 000) is a periplasmic protein that serves as a high-affinity receptor for the active transport and chemotaxis towards both sugars. The effect of D-glucose binding on the thermal unfolding of the GGBP protein at pH 7.0 has been measured by differential scanning calorimetry (DSC), far-UV CD and intrinsic tryptophanyl residue fluorescence (Trp fluorescence). All three techniques reveal reversible, thermal transitions and a midpoint temperature (T-m) increase from 50 to 63degreesC produced by 10 MM D-glucose. Both in the absence and presence of D-glucose a single asymmetric endotherm for GGBP is observed in DSC, although each endotherm consists of two transitions about 4degreesC apart in T-m values. In the absence of D-glucose, the protein unfolding is best described by two non-ideal transitions, suggesting the presence of unfolding intermediates. In the presence of D-glucose protein, unfolding is more co-operative than in the absence of the ligand, and the experimental data are best fitted to a model that assumes two ideal (two-state) sequential transitions. Thus D-glucose binding changes the character of the GGBP protein folding/unfolding by linking the two domains such that protein unfolding becomes a cooperative, two two-state process. A K-A' value of 5.6 x 10(6) M-1 at 63degreesC for D-glucose binding is estimated from DSC results. The domain with the lower stability in DSC measurements has been identified as the C-terminal domain of GGBP from thermally induced Trp fluorescence changes. C1 NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bethesda, MD 20892 USA. CNR, Inst Prot Biochem, I-80131 Naples, Italy. RP Piszczek, G (reprint author), NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM grzegorz_piszczek@nih.gov RI STAIANO, MARIA/B-9584-2015; d'auria, sabato/C-3565-2015 OI STAIANO, MARIA/0000-0003-0223-1825; d'auria, sabato/0000-0001-9320-494X NR 35 TC 19 Z9 19 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 2004 VL 381 BP 97 EP 103 DI 10.1042/BJ20040232 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 838PB UT WOS:000222724200012 PM 15032747 ER PT J AU Topol, IA Cachau, RE Nemukhin, AV Grigorenko, BL Burt, SK AF Topol, IA Cachau, RE Nemukhin, AV Grigorenko, BL Burt, SK TI Quantum chemical modeling of the GTP hydrolysis by the RAS-GAP protein complex SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE RAS-GAP complex; enzyme mechanism; GTP hydrolysis; active site mutation; hybrid QM/MM method ID MOLECULAR-DYNAMICS SIMULATIONS; PHOSPHATE MONOESTER MONOANIONS; SUBSTRATE-ASSISTED CATALYSIS; FREE-ENERGY RELATIONSHIPS; TIME-RESOLVED FTIR; ACTIVATING PROTEINS; AQUEOUS-SOLUTION; SIGNAL-TRANSDUCTION; HA-RAS; FLUORESCENCE SPECTROSCOPY AB We present results of the modeling for the hydrolysis reaction of guanosine triphosphate (GTP) in the RAS-GAP protein complex using essentially ab initio quantum chemistry methods. One of the approaches considers a supermolecular cluster composed of 150 atoms at a consistent quantum level. Another is a hybrid QM/MM method based on the effective fragment potential technique, which describes interactions between quantum and molecular mechanical subsystems at the ab initio level of the theory. Our results show that the GTP hydrolysis in the RAS-GAP protein complex can be modeled by a substrate-assisted catalytic mechanism. We can locate a configuration on the top of the barrier corresponding to the transition state of the hydrolysis reaction such that the straightforward descents from this point lead either to reactants GTP + H(2)O or to products guanosine diphosphate (GDP) + H(2)PO(4)(-). However, in all calculations such a single-step process is characterized by an activation barrier that is too high. Another possibility is a two-step reaction consistent with formation of an intermediate. Here the Pgamma-O(Pbeta) bond is already broken, but the lytic water molecule is still in the pre-reactive state. We present arguments favoring the assumption that the first step of the GTP hydrolysis reaction in the RAS-GAP protein complex may be assigned to the breaking of the Pgamma-O(Pbeta) bond prior to the creation of the inorganic phosphate. (C) 2004 Elsevier B.V. All rights reserved. C1 Natl Canc Inst, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21702 USA. Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. RP Topol, IA (reprint author), Natl Canc Inst, Adv Biomed Comp Ctr, SAIC, POB B, Frederick, MD 21702 USA. EM topol@ncifcrf.gov RI Nemukhin, Alexander/P-9662-2015 FU NCI NIH HHS [N01-CO-12400] NR 82 TC 38 Z9 40 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD JUL 1 PY 2004 VL 1700 IS 1 BP 125 EP 136 DI 10.1016/j.bbapap.2004.04.007 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 833VC UT WOS:000222367400015 PM 15210132 ER PT J AU Ruggiero, M Bottaro, DP Liguri, G Gulisano, M Peruzzi, B Pacini, S AF Ruggiero, M Bottaro, DP Liguri, G Gulisano, M Peruzzi, B Pacini, S TI 0.2 T magnetic field inhibits angiogenesis in chick embryo chorioallantoic membrane SO BIOELECTROMAGNETICS LA English DT Article DE MRI magnet; organogenesis; neoplasia; static field ID GROWTH-FACTORS; CANCER-CELLS; VASCULOGENESIS; EXPOSURE; MODEL AB Inhibition of angiogenesis is a major target in the fight against cancer and other diseases. Although the effects of static magnetic fields on cancer development and cell growth have been investigated, effects on angiogenesis have received no attention so far. In this study we report the effects on angiogenesis of exposure to 0.2 T static magnetic field. Angiogenesis was analyzed using the chick embryo chorioallantoic membrane assay. Exposure to 0.2 T static magnetic field was achieved by placing the eggs for 3 hr in the isocentre of the magnet of a sectorial magnetic resonance tomograph used in clinical practice. In sham exposed specimens treated with phosphate buffered saline (negative control), no significant vascular reaction was detectable; 3 hr exposure to 0.2 T static magnetic field did not affect the basal pattern of vascularization or chick embryo viability. Prostaglandin El and fetal calf serum elicited a strong angiogenic response in sham exposed eggs. This angiogenic response was significantly inhibited by 3 hr exposure to 0.2 T static magnetic field. These findings point to possible use of static magnetic field in inhibiting angiogenesis; this effect could be exploited for treatment of cancer and other diseases where excessive angiogenesis is involved. (C) 2004 Wiley-Liss, Inc. C1 Univ Florence, Dept Expt Pathol & Oncol, Florence, Italy. Univ Florence, Dept Biochem Sci, Florence, Italy. Univ Florence, Dept Anat Histol & Forens Med, Florence, Italy. NIH, NCI, Bethesda, MD USA. RP Ruggiero, M (reprint author), Dipartimento Patol & Oncol Sperimentali, Viale Morgagni 50, I-50134 Florence, Italy. EM biolmol@yahoo.com RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 26 TC 27 Z9 29 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD JUL PY 2004 VL 25 IS 5 BP 390 EP 396 DI 10.1002/bem.20008 PG 7 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 834NG UT WOS:000222417200014 PM 15197764 ER PT J AU Recillas-Targa, F Valadez-Graham, V Farre, CM AF Recillas-Targa, F Valadez-Graham, V Farre, CM TI Prospects and implications of using chromatin insulators in gene therapy and transgenesis SO BIOESSAYS LA English DT Article ID MATRIX ATTACHMENT REGIONS; HUMAN BETA-GLOBIN; LOCUS-CONTROL REGION; ENHANCER-BLOCKING ACTIVITY; POSITION-INDEPENDENT EXPRESSION; HISTONE LYSINE METHYLATION; RETROVIRUS VECTORS; IN-VIVO; LENTIVIRAL VECTORS; ADENOVIRUS VECTORS AB Gene therapy has emerged from the idea of inserting a wild-type copy of a gene in order to restore the proper expression and function of a damaged gene. Initial efforts have focused on finding the proper vector and delivery method to introduce a corrected gene to the affected tissue or cell type. Even though these first attempts are clearly promising, several problems remain unsolved. A major problem is the influence of chromatin structure on transgene expression. To overcome chromatin-dependent repressive transgenic states, researchers have begun to use chromatin regulatory elements to drive transgene expression. Insulators or chromatin boundaries are able to protect a transgene against chromatin position effects at their genomic integration sites, and they are able to maintain transgene expression for long periods of time. Therefore, these elements may be very useful tools in gene therapy applications for ensuring high-level and stable expression of transgenes. (C) 2004 Wiley Periodicals, Inc. C1 Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Mol Genet, Mexico City 04510, DF, Mexico. NIDDK, NIH, Mol Biol Lab, Bethesda, MD USA. RP Recillas-Targa, F (reprint author), Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Mol Genet, Apartado Postal 70-242, Mexico City 04510, DF, Mexico. EM frecilla@ifc.unam.mx NR 79 TC 60 Z9 63 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUL PY 2004 VL 26 IS 7 BP 796 EP 807 DI 10.1002/bies.20059 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 835OY UT WOS:000222494300013 PM 15221861 ER PT J AU Li, LP Umbach, DM Terry, P Taylor, JA AF Li, LP Umbach, DM Terry, P Taylor, JA TI Application of the GA/KNN method to SELDI proteomics data SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION DATA; SAMPLE CLASSIFICATION; PROSTATE-CANCER; OVARIAN-CANCER; SERUM; PATTERNS AB Proteomics technology has shown promise in identifying biomarkers for disease, toxicant exposure and stress. We show by example that the genetic algorithm/k-nearest neighbors method, developed for mining high-dimensional microarray gene expression data, is also capable of mining surface enhanced laser desorption/ionization-time-of-flight proteomics data. C1 NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Li, LP (reprint author), NIEHS, Biostat Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM li3@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 NR 10 TC 46 Z9 50 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2004 VL 20 IS 10 BP 1638 EP 1640 DI 10.1093/bioinformatics/bth098 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 834HO UT WOS:000222402400024 PM 14962943 ER PT J AU Charney, DS AF Charney, DS TI Update on Biological Psychiatry SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Charney, DS (reprint author), NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2004 VL 56 IS 1 BP 1 EP 2 DI 10.1016/j.biopsych.2004.05.016 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 832HF UT WOS:000222257400001 ER PT J AU Vitiello, B Heiligenstein, JH Riddle, MA Greenhill, LL Fegert, JM AF Vitiello, B Heiligenstein, JH Riddle, MA Greenhill, LL Fegert, JM TI The interface between publicly funded and industry-funded research in pediatric psychopharmacology: Opportunities for integration and collaboration SO BIOLOGICAL PSYCHIATRY LA English DT Review DE children; psychopharmacology; industry; government ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND; PSYCHOTROPIC MEDICATIONS; MAJOR DEPRESSION; CHILDREN; ADOLESCENTS; PLACEBO; ATOMOXETINE AB Pediatric psychopharmacology research is undergoing a major expansion consequent to increasing use of psychotropic medications in children and recent legislative incentives to industry. In this rapidly changing context, the interface between publicly and privately funded research needs to be reconsidered to integrate activities and avoid unnecessary duplication of efforts. Once, by default, the almost exclusive domain of public research, child research is now increasingly funded by industry. There are, however, important issues unlikely to be addressed through private funding for which public support is needed, such as direct comparisons between active medications, between pharmacological and psychosocial interventions, or between combined and single treatment modalities; development of effective treatment strategies for patients unresponsive to first-line treatments; development of better research methods to assess efficacy and safety; identification of moderators and mechanisms of treatment response; and impact of treatment on illness databases, which impedes course and prognosis. Industry-sponsored research is limited by the restricted access to proprietary independent analyses and meta-analyses. Translation of basic neuroscience discoveries into treatment applications for children with mental illness is a critical area of inquiry that can benefit from integration of efforts and collaborations among academia, government, and industry. C1 NIMH, Child & Adolescent Treatment & Prevent Inervent R, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Johns Hopkins Univ, Div Child & Adolescent Psychiat, Baltimore, MD USA. Columbia Univ, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. Univ Ulm, Dept Child & Adolescent Psychiat, Ulm, Germany. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Inervent R, Div Serv & Intervent Res, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. NR 51 TC 22 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2004 VL 56 IS 1 BP 3 EP 9 DI 10.1016/j.biopsych.2004.03.011 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 832HF UT WOS:000222257400002 PM 15219466 ER PT J AU Schulze, TG Buervenich, S Badner, JA Steele, CJM Detera-Wadleigh, SD Dick, D Foroud, T Cox, NJ MacKinnon, DF Potash, JB Berrettini, WH Byerley, W Coryell, W DePaulo, JR Gershon, ES Kelsoe, JR McInnis, MG Murphy, DL Reich, T Scheftner, W Nurnberger, JI McMahon, FJ AF Schulze, TG Buervenich, S Badner, JA Steele, CJM Detera-Wadleigh, SD Dick, D Foroud, T Cox, NJ MacKinnon, DF Potash, JB Berrettini, WH Byerley, W Coryell, W DePaulo, JR Gershon, ES Kelsoe, JR McInnis, MG Murphy, DL Reich, T Scheftner, W Nurnberger, JI McMahon, FJ TI Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the National Institute of Mental Health Genetics Initiative pedigrees SO BIOLOGICAL PSYCHIATRY LA English DT Article DE epistasis; GRIK2; LOD score; manic-depressive illness; nonparametric linkage analysis; prolyl endopeptidase ID GENOME-WIDE SCAN; LINKAGE ANALYSIS; 6P22.3 GENE; SCHIZOPHRENIA; HETEROGENEITY; POLYMORPHISM; ASSOCIATION; DEPRESSION; DYSBINDIN; ILLNESS AB Background: We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods: Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6 Nonparametric linkage analysis was performed. Results. Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6-p22.2 (r = .26; p < .0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p < .0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions. These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia. C1 Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-68159 Mannheim, Germany. NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21218 USA. Rush Univ, Dept Psychiat, Chicago, IL 60612 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA. Univ Calif Irvine, Irvine, CA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Iowa, Iowa City, IA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Washington Univ, Dept Psychiat, St Louis, MO USA. RP Schulze, TG (reprint author), Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, J5, D-68159 Mannheim, Germany. EM schulze@zi-mannheim.de RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; Schulze, Thomas/H-2157-2013; OI McInnis, Melvin/0000-0002-0375-6247; Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X FU NHGRI NIH HHS [N01-HG-65403] NR 52 TC 54 Z9 55 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2004 VL 56 IS 1 BP 18 EP 23 DI 10.1016/j.biopsych.2004.04.004 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 832HF UT WOS:000222257400004 PM 15219468 ER PT J AU Zarate, CA Payne, JL Singh, J Quiroz, JA Luckenbaugh, DA Denicoff, KD Charney, DS Manji, HK AF Zarate, CA Payne, JL Singh, J Quiroz, JA Luckenbaugh, DA Denicoff, KD Charney, DS Manji, HK TI Pramipexole for bipolar II depression: A placebo-controlled proof of concept study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE antidepressant; dopaminergic; bipolar depression; pramipexole ID MONOAMINE METABOLITE CONCENTRATIONS; CEREBROSPINAL-FLUID MONOAMINE; DOPAMINE-RECEPTOR AGONISTS; MAJOR DEPRESSION; PARKINSONS-DISEASE; MOOD-DISORDERS; PROTEIN BCL-2; ANTIDEPRESSANT; FLUOXETINE; ILLNESS AB Background: The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants, Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression. Methods: In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo, (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale. Results: All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response ( > 50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p = .02). One subject on pramipexole and two on placebo developed hypomanic symptoms. Conclusions: The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Dept Human & Hlth Serv,NIH, Bethesda, MD 20892 USA. NIMH, Expt Therapeut & Pathophysiol Branch, Mood & Anxiety Disorders Program, Dept Human & Hlth Serv,NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 9000 Rockville Pike,Bldg 10,Unit 3 W,Room 35230, Bethesda, MD 20892 USA. NR 62 TC 202 Z9 208 U1 5 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2004 VL 56 IS 1 BP 54 EP 60 DI 10.1016/j.biopsych.2004.03.013 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 832HF UT WOS:000222257400009 PM 15219473 ER PT J AU Grummer, R Hewitt, SW Traub, O Korach, KS Winterhager, E AF Grummer, R Hewitt, SW Traub, O Korach, KS Winterhager, E TI Different regulatory pathways of endometrial connexin expression: Preimplantation hormonal-mediated pathway versus embryo implantation-initiated pathway SO BIOLOGY OF REPRODUCTION LA English DT Article DE estradiol receptor; female reproductive tract; gene regulation; implantation; uterus ID ESTROGEN-RECEPTOR-ALPHA; DECIDUAL CELL REACTION; OVARIAN-STEROID HORMONES; RAT ENDOMETRIUM; BLASTOCYST IMPLANTATION; MOUSE UTERUS; IN-VITRO; TROPHOBLAST INVASION; TISSUE DISTRIBUTION; MOLECULAR-BASIS AB Transformation of the endometrium into the receptive phase is under the control of ovarian steroid hormones and is modulated by embryonic signals during implantation. We have previously shown that this differentiation process is accompanied by a suppression of gap junction connexins (Cx) 26 and 43 before implantation followed by a local induction of both connexins in the implantation chamber. In the present study, we demonstrate that connexin gene expression in the rodent endometrium is regulated via two distinct signaling pathways during these different stages of early pregnancy. During preimplantation, transcription of connexins can be induced by estrogen via an estrogen receptor (ER)-dependent pathway. Additionally, Cx26 and Cx43 are induced by embryonic signals during implantation and delayed implantation as well as during artificially induced decidualization. In contrast to the estrogen-induced expression, this embryonic/decidual-associated induction of Cx26 and Cx43 could not be blocked by antiestrogen, thus pointing to another regulatory pathway independent of the ER. Studies in ERalpha and ERbeta knockout mice confirmed these different pathways, demonstrating that in the endometrium, estrogen-mediated Cx26 gene induction, but not induction during decidualization, is dependent on functional ERalpha. To evaluate potential embryonic signals regulating Cx26 expression, uteri of pseudopregnant animals were incubated with different mediators in an organ-culture model, showing that catechol estrogen and mediators of the inflammatory cascade such as prostaglandin F2alpha and interleukin-1beta are able to induce Cx26 expression through the ER-independent pathway. Thus, the present study demonstrates that endometrial expression of Cx26 and Cx43 is induced via estrogen and ERoe during preimplantation but then utilizes an ER-independent signaling pathway during embryo implantation and decidualization. C1 Univ Klinikum Essen, Inst Anat, D-45122 Essen, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Bonn, Inst Genet, D-53117 Bonn, Germany. RP Grummer, R (reprint author), Univ Klinikum Essen, Inst Anat, D-45122 Essen, Germany. EM ruth.gruemmer@uni-essen.de OI Korach, Kenneth/0000-0002-7765-418X NR 62 TC 32 Z9 37 U1 0 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2004 VL 71 IS 1 BP 273 EP 281 DI 10.1095/biolreprod.103.024067 PG 9 WC Reproductive Biology SC Reproductive Biology GA 831UC UT WOS:000222220700035 PM 15028626 ER PT J AU Lin-Gibson, S Bencherif, S Cooper, JA Wetzel, SJ Antonucci, JM Vogel, BM Horkay, F Washburn, NR AF Lin-Gibson, S Bencherif, S Cooper, JA Wetzel, SJ Antonucci, JM Vogel, BM Horkay, F Washburn, NR TI Synthesis and characterization of PEG dimethacrylates and their hydrogels SO BIOMACROMOLECULES LA English DT Article ID MASS-SPECTROMETRY; GLYCOL) HYDROGELS; CHONDROCYTES; CYTOTOXICITY; CHEMISTRY AB Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (IPEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M-n = 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of H-1 NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary theology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks. C1 Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Lin-Gibson, S (reprint author), Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. EM slgibson@nist.gov OI BENCHERIF, SIDI/0000-0002-7704-5608; Vogel, Brandon/0000-0002-7370-9577 NR 14 TC 138 Z9 138 U1 6 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD JUL-AUG PY 2004 VL 5 IS 4 BP 1280 EP 1287 DI 10.1021/bm0498777 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 837VG UT WOS:000222668500018 PM 15244441 ER PT J AU Lee, J Kim, SY Lee, J Kang, M Kil, MJ Cho, HK Jin, MK Wang, Y Toth, A Pearce, LV Lundberg, DJ Tran, R Blumberg, PM AF Lee, J Kim, SY Lee, J Kang, M Kil, MJ Cho, HK Jin, MK Wang, Y Toth, A Pearce, LV Lundberg, DJ Tran, R Blumberg, PM TI Analysis of structure-activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N '-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY ANTAGONISTS; CAPSAICIN RECEPTOR; COMPETITIVE ANTAGONIST; IODO-RESINIFERATOXIN; ANALGESIC PROPERTIES; POTENT; ANALOGS; TRPV1; PAIN; AGONISTS AB In a continuing effort to elucidate the structure-activity relationships of the lead antagonist N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N'-[4-(methylsulfonylamino)benzyl]thiourea (1), the distances between the proposed four pharmacophores in 1 have been varied by insertion or deletion of one carbon to optimize their fit to the receptor. In addition, the acyloxy group of the C region was replaced with amide and N-hydroxy amide to identify the pharmacophoric importance of the ester group in the C2 region. The results indicated that the pharmacophoric arrangement of 1 was optimal for receptor binding affinity and antagonism, and the ester of the C2 region was significant for receptor binding. Among the derivatives, compound 19 showed distinct behavior with a 2-fold improvement in antagonism but a 13-fold reduction in binding affinity compared to 1. The partial separation of pharmacophoric requirements of these two assays has been noted before and compound 19 is thus selective for the calcium entry-linked receptor population. The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand. (C) 2004 Elsevier Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. NCI, Canc Res Ctr, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Toth, Attila/F-4859-2010; Kang, Myungshim /K-5331-2014; OI Toth, Attila/0000-0001-6503-3653; Kang, Myungshim /0000-0002-4778-8240; Lee, Jiyoun/0000-0003-3819-5889 NR 33 TC 14 Z9 14 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUL 1 PY 2004 VL 12 IS 13 BP 3411 EP 3420 DI 10.1016/j.bmc.2004.04.040 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 831LM UT WOS:000222195900001 PM 15186827 ER PT J AU Tsai, HH Zanuy, D Haspel, N Gunasekaran, K Ma, BY Tsai, CJ Nussinov, R AF Tsai, HH Zanuy, D Haspel, N Gunasekaran, K Ma, BY Tsai, CJ Nussinov, R TI The stability and dynamics of the human calcitonin amyloid peptide DFNKF SO BIOPHYSICAL JOURNAL LA English DT Article ID YEAST PRION SUP35; SOLID-STATE NMR; ALZHEIMERS-DISEASE; POLYPEPTIDE IAPP; ENERGY LANDSCAPE; FORMING PEPTIDE; BETA-PROTEIN; PI-STACKING; FIBRILS; PATHOGENESIS AB The stability and dynamics of the human calcitonin-derived peptide DFNKF (hCT(15-19)) are studied using molecular dynamics (MD) simulations. Experimentally, this peptide is highly amyloidogenic and forms fibrils similar to the full length calcitonin. Previous comparative MD studies have found that the parallel beta-stranded sheet is a stable organization of the DFNKF protofibril. Here, we probe the stability and dynamics of the small parallel DFNKF oligomers. The results show that even small DFNKF oligomers, such as trimers and tetramers, are stable for a sufficient time in the MD simulations, indicating that the crucial nucleus seed size for amyloid formation can be quite small. The simulations also show that the stability of DFNKF oligomers increases with their sizes. The small but stable seed may reflect the experimental rapid formation of the DFNKF fibrils. Further, a noncooperative process of parallel beta-sheet formation from the out-of-register trimer is observed in the simulations. In general, the residues of DFNKF peptides near the N-/C-termini are more flexible, whereas the interior residues are more stable. Simulations of mutants and capped peptides show that both interstrand hydrophobic and electrostatic interactions play important roles in stabilizing the DFNKF parallel oligomers. This study provides insights into amyloid formation. C1 NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Lab Expt & Computat Biol, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011; Zanuy, David/G-3930-2014; Haspel, Nurit/D-1961-2017 OI Ma, Buyong/0000-0002-7383-719X; Zanuy, David/0000-0001-7704-2178; FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 43 TC 37 Z9 37 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2004 VL 87 IS 1 BP 146 EP 158 DI 10.1529/biophysj.104.040352 PG 13 WC Biophysics SC Biophysics GA 835OJ UT WOS:000222492800015 PM 15240453 ER PT J AU Zimliki, CL Mears, D Sherman, A AF Zimliki, CL Mears, D Sherman, A TI Three roads to islet bursting: Emergent oscillations in coupled phantom bursters SO BIOPHYSICAL JOURNAL LA English DT Article ID PANCREATIC BETA-CELLS; CA2+ OSCILLATIONS; CYTOPLASMIC CA2+; INSULIN-SECRETION; ELECTRICAL-ACTIVITY; GAP-JUNCTIONS; B-CELLS; K+ CHANNELS; GLUCOSE; CALCIUM AB Glucose-induced membrane potential and Ca2+ oscillations in isolated pancreatic beta-cells occur over a wide range of frequencies, from >6/min (fast) to <1/min (slow). However, cells within intact islets generally oscillate with periods of 10-60 s (medium). The phantom bursting concept addresses how β-cells can generate such a wide range of frequencies. Here, we explore an updated phantom bursting model to determine how heterogeneity in a single parameter can explain both the broad frequency range observed in single cells and the rarity of medium oscillations. We then incorporate the single-cell model into an islet model with parameter heterogeneity. We show that strongly coupled islets must be composed of predominantly medium oscillating single cells or a mixture of fast and slow cells to robustly produce medium oscillations. Surprisingly, we find that this constraint does not hold for moderate coupling, and that robustly medium oscillating islets can arise from populations of single cells that are essentially all slow or all fast. Thus, with coupled phantom bursters, medium oscillating islets can be constructed out of cells that are either all fast, all slow, or a combination of the two. C1 NIDDKD, NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. RP Sherman, A (reprint author), NIDDKD, NIH, Lab Biol Modeling, Bldg 12A,Rm 4007,12 South Dr,MSC 5621, Bethesda, MD 20892 USA. EM asherman@nih.gov NR 52 TC 18 Z9 18 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2004 VL 87 IS 1 BP 193 EP 206 DI 10.1529/biophysj.103.038471 PG 14 WC Biophysics SC Biophysics GA 835OJ UT WOS:000222492800019 PM 15240457 ER PT J AU Donovan, DM Rowley, DL Williams, NG AF Donovan, DM Rowley, DL Williams, NG TI Microsoft (R) Excell (R) spreadsheet-based animal colony management for genetically altered animals SO BIOTECHNIQUES LA English DT Article ID LABORATORY MOUSE POPULATIONS; COMPUTER C1 ARS, Biotechnol & Germplasm Lab, USDA, Beltsville, MD 20705 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Donovan, DM (reprint author), ARS, Biotechnol & Germplasm Lab, USDA, Bldg 200,Powder Mill Rd, Beltsville, MD 20705 USA. EM ddonovan@anri.barc.usda.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 2004 VL 37 IS 1 BP 50 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 837VO UT WOS:000222669300011 PM 15283200 ER PT J AU Igarashi, T Wynberg, J Srinivasan, R Becknel, B McCoy, JP Takahashi, Y Suffredini, DA Linehan, WM Caligiuri, MA Childs, RW AF Igarashi, T Wynberg, J Srinivasan, R Becknel, B McCoy, JP Takahashi, Y Suffredini, DA Linehan, WM Caligiuri, MA Childs, RW TI Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells SO BLOOD LA English DT Article ID BLOOD MONONUCLEAR-CELLS; HLA-C; UL16-BINDING PROTEINS; BREAST-CANCER; TRANSPLANTATION; NKG2D; MHC; EXPRESSION; ACTIVATION; MOLECULES AB Cellular inactivation through killer immunoglobulin-like receptors (KIRs) may allow neoplastic cells to evade host natural killer (NK) cell-mediated immunity. Recently, alloreactive NK cells were shown to mediate antileukemic effects against acute myelogenous leukemia (AML) after mismatched transplantation, when KIR ligand incompatibility existed in the direction of graft-versus-host disease (GVHD). Therefore, we investigated whether solid tumor cells would have similar enhanced susceptibility to allogeneic KIR-incompatible NK cells compared with their KIR-matched autologous or allogeneic counterparts. NK populations enriched and cloned from the blood of cancer patients or healthy donors homozygous for HLA-C alleles in group 1 (C-G1) or group 2 (C-G2) were tested in vitro for cytotoxicity against Epstein-Barr virus-transformed lymphoblastic cell lines (EBV-LCLs), renal cell carcinoma (RCC), and melanoma (MEL) cells with or without a matching KIR-inhibitory HLA-C ligand. Allogeneic NK cells were more cytotoxic to tumor targets mismatched for KIR ligands than their KIR ligand-matched counterparts. Bulk NK populations (CD3(-)/CD2(+)/CD56(+)) expanded 10(4)-fold from patients homozygous for C-G1 or C-G2 had enhanced cytotoxicity against KIR ligand-mismatched tumor cells but only minimal cytotoxicity against KIR ligand-matched targets. Further, NK cell lines from C-G1 or C-G2 homozygous cancer patients or healthy donors expanded but failed to kill autologous or KIR-matched MEL and RCC cells yet had significant cytotoxicity (more than 50% lysis at 20:1 effector-target [E/T] ratio) against allogeneic KIR-mismatched tumor lines. These data suggest immunotherapeutic strategies that use KIR-incompatible allogeneic NK cells might have superior antineoplastic effects against solid tumors compared with approaches using autologous NK cells. C1 Natl Inst Hlth, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Flow Cytometry Core Facil, Bethesda, MD 20892 USA. Natl Canc Inst, Urol Oncol Branch, Bethesda, MD USA. Ohio State Univ, Dept Internal Med, Div Hematol Oncol, Columbus, OH 43210 USA. RP Childs, RW (reprint author), Natl Inst Hlth, Hematol Branch, Bldg 10,Rm 7C103,MSC1652,9000 Rockville Pike, Bethesda, MD 20892 USA. EM childsr@nih.gov RI Takahashi, Yoshiyuki/I-1929-2012 NR 41 TC 106 Z9 117 U1 0 U2 3 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 JUL 1 PY 2004 VL 104 IS 1 BP 170 EP 177 DI 10.1182/blood-2003-12-4438 PG 8 WC Hematology SC Hematology GA 832ZZ UT WOS:000222307500034 PM 15016654 ER PT J AU Palena, C Zhu, MZ Scholm, J Tsang, KY AF Palena, C Zhu, MZ Scholm, J Tsang, KY TI Human B cells that hyperexpress a triad of costimulatory molecules via avipox-vector infection: an alternative source of efficient antigen-presenting cells SO BLOOD LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; BLOOD MONONUCLEAR-CELLS; T-LYMPHOCYTE RESPONSES; HUMAN DENDRITIC CELLS; VACCINIA VIRUS; EXOGENOUS ANTIGENS; MHC MOLECULES; IN-VITRO; GENERATION; IMMUNOTHERAPY AB Dendritic cells (DCs) are the most potent of the antigen-presenting cells (APCs). Preparation of sufficient numbers of mature DCs, however, is both costly and time-consuming. We have examined here the possibility of using an alternative source of APCs that would be easier to obtain, would not require extensive culture, and thus would be more applicable to human immunotherapy protocols. We show here that freshly isolated human B cells can be efficiently infected by a replication-defective fowlpox recombinant vector, designated rF-TRICOM (TRlad of COstimulatory Molecules), to markedly increase surface expression of the human costimulatory molecule B7-1 and moderately increase expression of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-3 (LFA-3). Peptide pulsed rF-TRICOM-infected B cells were highly efficient in activating antigen-specific human T cells and shown to be superior to the use of CD40L in enhancing APC potency. Moreover, when infection of freshly isolated B cells with rF-TRICOM was combined with CD40L, a still further marked enhancement of the antigen-presenting potency was observed. Ex vivo-generated antigen-specific T cells activated in this manner might be applied to experimental protocols or used for adoptive transfer in immunotherapy protocols. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Scholm, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Natl Inst Hlth, 10 Ctr Dr,Rm 8809,MSC 1750, Bethesda, MD 20892 USA. EM jsl4lc@nih.gov NR 37 TC 15 Z9 15 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 JUL 1 PY 2004 VL 104 IS 1 BP 192 EP 199 DI 10.1182/blood-2003-09-3211 PG 8 WC Hematology SC Hematology GA 832ZZ UT WOS:000222307500037 PM 15010371 ER PT J AU Tkaczyk, C Horejsi, V Iwaki, S Draber, P Samelson, LE Satterthwaite, AB Nahm, DH Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Horejsi, V Iwaki, S Draber, P Samelson, LE Satterthwaite, AB Nahm, DH Metcalfe, DD Gilfillan, AM TI NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following kit activation and Fc epsilon RI aggregation SO BLOOD LA English DT Article ID PROTEIN-TYROSINE KINASE; AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; C-KIT; HEMATOPOIETIC-CELLS; CROSS-LINKING; TRANSDUCTION; COMPONENT; INHIBITOR; SYK AB Aggregation of high-affinity receptors for immunoglobulin E (FcepsilonRI) on the surface of mast cells results in degranulation, a response that is potentiated by binding of stem cell factor (SCF) to its receptor Kit. We observed that one of the major initial signaling events associated with FcepsilonRI-mediated activation of human mast cells (HuMCs) is the rapid tyrosine phosphorylation of a protein of 25 to 30 kDa. The phosphorylation of this protein was also observed in response to SCF. This protein was identified as non-T-cell activation linker (NTAL), an adaptor molecule similar to linker for activated T cells (LAT). Unlike the FcepsilonRI response, SCF induced NTAL phosphorylation in the absence of detectable LAT phosphorylation. When SCF and antigen were added concurrently, there was a marked synergistic effect on NTAL phosphorylation, however, SCF did not enhance the phosphorylation of LAT induced by FcepsilonRI aggregation. FcepsilonRI- and SCF-mediated NTAL phosphorylation appear to be differentially regulated by Src kinases and/or Kit kinase, respectively. Diminution of NTAL expression by silencing RNA oligonucleotides in HuMCs resulted in a reduction of both Kit- and FcepsilonRI-mediated degranulation. NTAL, thus, appears to,be an important link between the signaling Pathways that are initiated by these receptors, culminating in mast cell degranulation. C1 NIAID, Lab Allerg Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic. Natl Canc Inst, Cellular & Mol Biol Lab, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, Natl Inst Hlth, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov RI Horejsi, Vaclav/G-3113-2014; Draber, Petr/G-3412-2014 OI Draber, Petr/0000-0002-3986-2025 NR 37 TC 85 Z9 87 U1 0 U2 3 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 JUL 1 PY 2004 VL 104 IS 1 BP 207 EP 214 DI 10.1182/blood-2000-08-2769 PG 8 WC Hematology SC Hematology GA 832ZZ UT WOS:000222307500039 PM 15010370 ER PT J AU Jison, ML Munson, PJ Barb, JJ Suffredini, AF Talwar, S Logun, C Raghavachari, N Beigel, JH Shelhamer, JH Danner, RL Gladwin, MT AF Jison, ML Munson, PJ Barb, JJ Suffredini, AF Talwar, S Logun, C Raghavachari, N Beigel, JH Shelhamer, JH Danner, RL Gladwin, MT TI Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACUTE CHEST SYNDROME; HEME OXYGENASE-1 PROTECTS; ESCAPES X-INACTIVATION; ACUTE LUNG INJURY; MYOCARDIAL-INFARCTION; RISK-FACTORS; ADHESIVE INTERACTIONS; VASCULAR ENDOTHELIUM; ACTIVATED MONOCYTES AB In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury. C1 NIH, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD USA. Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD USA. NIDDKD, Biol Chem Lab, Bethesda, MD 20892 USA. NHLBI, Cardivasc Branch, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Bldg 10,9000 Rockville Pike,Rm7D-43, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 67 TC 124 Z9 127 U1 0 U2 3 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 JUL 1 PY 2004 VL 104 IS 1 BP 270 EP 280 DI 10.1182/blood-2003-08-2760 PG 11 WC Hematology SC Hematology GA 832ZZ UT WOS:000222307500048 PM 15031206 ER PT J AU Abnet, CC Huppi, K Carrera, A Armistead, D McKenney, K Hu, N Tang, ZZ Taylor, PR Dawsey, SM AF Abnet, CC Huppi, K Carrera, A Armistead, D McKenney, K Hu, N Tang, ZZ Taylor, PR Dawsey, SM TI Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma SO BMC CANCER LA English DT Article ID SOMATIC MUTATIONS; INCIDENT ESOPHAGEAL; GASTRIC CANCERS; SHANXI-PROVINCE; BREAST-CANCER; TUMORS; CHINA AB Background: North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA ( mtDNA) accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China. Methods: We used DNA samples isolated from tumors, adjacent normal esophageal tissue, and blood from 21 esophageal squamous cell carcinoma cases and DNA isolated from blood from 23 healthy persons. We completely sequenced the control region (D-Loop) from each of these samples and used a PCR assay to assess the presence of the 4977 bp common deletion. Results: Direct DNA sequencing revealed that 7/21 (33%, 95% CI = 17-55%) tumor samples had mutations in the control region, with clustering evident in the hyper-variable segment 1 (HSV1) and the homopolymeric stretch surrounding position 309. The number of mutations per subject ranged from 1 to 16 and there were a number of instances of heteroplasmy. We detected the 4977 bp 'common deletion' in 92% of the tumor and adjacent normal esophageal tissue samples examined, whereas no evidence of the common deletion was found in corresponding peripheral blood samples. Conclusions: Control region mutations were insufficiently common to warrant attempts to develop mtDNA mutation screening as a clinical test for ESCC. The common deletion was highly prevalent in the esophageal tissue of cancer cases but absent from peripheral blood. The potential utility of the common deletion in an early detection system will be pursued in further studies. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Clerant Inc, Gaithersburg, MD 20897 USA. Shanxi Canc Hosp, Taiyuan, Shanxi Province, Peoples R China. RP Abnet, CC (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov; kh2k@nih.gov; Carreraj@appliedbiosystems.com; darmistead@clearant.com; kmckenney@clearant.com; nhu@mail.nih.gov; nhu@mail.nih.gov; ptaylor@mail.nih.gov; dawseys@mail.nih.gov RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 NR 26 TC 49 Z9 54 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUL 1 PY 2004 VL 4 AR 30 DI 10.1186/1471-2407-4-30 PG 8 WC Oncology SC Oncology GA 837GD UT WOS:000222615800001 PM 15230979 ER PT J AU Bielekova, B Martin, R AF Bielekova, B Martin, R TI Development of biomarkers in multiple sclerosis SO BRAIN LA English DT Review DE multiple sclerosis; surrogate markers; autoimmunity; immunological biomarkers ID SECONDARY PROGRESSIVE MS; SURROGATE END-POINTS; SOLUBLE ADHESION MOLECULES; DISEASE-ACTIVITY; MICROARRAY ANALYSIS; MAGNETIC-RESONANCE; MEDICAL LITERATURE; INTERFERON-BETA; USERS GUIDES; CEREBROSPINAL-FLUID AB Multiple sclerosis is a complex disease, as several pathophysiological processes (including inflammation, demyelination, axonal damage and repair mechanisms) participate in the disease process. Furthermore, as new pathological evidence reveals, these processes are not uniformly represented across patient populations but can selectively predominate in individual patients, thus contributing to the heterogeneity in phenotypic expression of the disease, its prognosis and response to therapies. While the armamentarium of available therapies for multiple sclerosis broadens, little is known about factors that predict treatment response in individual patients to a specific drug. More importantly, we are beginning to understand that, analogous to cancer therapy, the successful therapeutic strategy in multiple sclerosis might ultimately involve the combination of different therapeutics targeting several dominant pathophysiological processes. The development of these process-specific therapies will be impossible without the use of biomarkers that reflect the targeted process, can select patient population in which the targeted process is prevailing and can aid during the more rapid screening of therapeutic agents in the early phase of their development. This review summarizes the general concepts of biomarkers and their potential use as surrogate endpoints and tailors these concepts to specific applications in multiple sclerosis research. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. EM bielekob@ninds.nih.gov NR 50 TC 177 Z9 182 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2004 VL 127 BP 1463 EP 1478 DI 10.1093/brain/awh176 PN 7 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 830LY UT WOS:000222124800002 PM 15180926 ER PT J AU Nakagawa, T Schwartz, JP AF Nakagawa, T Schwartz, JP TI Gene expression profiles of reactive astrocytes in dopamine-depleted striatum SO BRAIN PATHOLOGY LA English DT Article ID PARKINSONS-DISEASE; TROPHIC ACTIVITY; NERVOUS-SYSTEM; NIGRAL GRAFTS; GROWTH-FACTOR; RAT-BRAIN; NEURONS; SURVIVAL; TRANSCRIPTION; INCREASES AB We have used cDNA array analysis to examine the expression of genes in reactive astrocytes of dopamine-depleted striatum of rats in vivo, an animal model for Parkinson disease, compared to those from control striatum. The striatum of both normal adult rats and rats whose substantia nigra had been lesioned with 6-hydroxydopamine was removed one week following lesion. After fixing the tissue in RNAlater, individual astrocytes, isolated directly from dissociated striatum and confirmed to be astocytes by expression of glial fibrillary acidic protein (GFAP) mRNA using single cell RT-PCR, were used as the source of mRNA. Co-localization of GFAP with either of 2 antibodies known to label only reactive astrocytes in vivo confirmed that virtually all astrocytes in the lesioned striatum were reactive. The analysis has identified 29 genes whose expression is turned on or enhanced in dopamine-depleted striatal astrocytes and 2 whose expression is decreased. In situ hybridization was used to confirm the localization of 8 of these genes to astrocytes: these included GDNF, NGF, bFGF, TNF-alpha, MIP-1alpha, c-jun, Fra-1 and Fra-2. Understanding these gene differences that occur in astrocytes in response to dopamine depletion should enhance our ability to promote recovery from the injury. C1 NINDS, Neurotroph Factors Sect, NIH, DHHS, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, Neurotroph Factors Sect, NIH, DHHS, Bldg 1,Room 135, Bethesda, MD 20892 USA. EM jps@helix.nih.gov NR 37 TC 31 Z9 34 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI LOS ANGELES PA UCLA MEDICAL CENTER, SECTION NEUROPATHOLGY, C H S 18-126, LOS ANGELES, CA 90095-1732 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2004 VL 14 IS 3 BP 275 EP 280 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 846ZW UT WOS:000223359400006 PM 15446582 ER PT J AU Land, SR Kopec, JA Yothers, G Anderson, S Day, R Tang, G Ganz, PA Fisher, B Wolmark, N AF Land, SR Kopec, JA Yothers, G Anderson, S Day, R Tang, G Ganz, PA Fisher, B Wolmark, N TI Health-related quality of life in axillary node-negative, estrogen receptor-negative breast cancer patients undergoing AC versus CMF chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel Project B-23 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE adjuvant chemotherapy; breast cancer; quality of life ID FUNCTIONAL ASSESSMENT; TAMOXIFEN; THERAPY; PREVENTION; WOMEN; P-1 AB Purpose. NSABP Protocol B-23 compared two chemotherapy regimens: ( 1) cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); and ( 2) doxorubicin and cyclophosphamide (AC) in terms of relapse-free survival, event-free survival, and overall survival in node-negative and estrogen receptor-negative breast cancer patients. There are no previous data regarding the comparison of quality of life (QOL) between the two regimens in this population of breast cancer patients. QOL information was considered especially relevant given the possibility that the two chemotherapy regimens would prove equivalent in terms of clinical outcome. Patients and methods. One hundred and sixty patients participated in the NSABP B-23 QOL study. Patients in B-23 were randomly assigned to one of four arms: CMF plus 5 years of tamoxifen (TAM), CMF plus placebo, AC plus TAM, or AC plus placebo. The questionnaires included the Functional Assessment of Cancer Therapy (FACT-B); the vitality scale, comparative health item and general health item from the Medical Outcomes Study 36-item Short Form Health Status Survey (MOS SF-36); a symptom checklist; and additional items regarding overall QOL and return to normal activity. Statistical comparisons between treatment arms were performed with area under the curve analyses, repeated measures analyses, and Fisher exact tests. Results. Overall QOL as measured by the FACT-B did not significantly differ between chemotherapy treatment arms. However, the pattern of vitality over time during treatment differed between chemotherapy groups. The AC group vitality scores dropped more sharply during treatment and returned to baseline levels more quickly after treatment. Patients in the CMF arm were bothered by bladder problems and diarrhea significantly more often than were patients in the AC arm. Otherwise, no significant differences were found between AC and CMF for any of the QOL outcomes in terms of ( 1) overall QOL during the first 9 months after randomization, ( 2) the average QOL during treatment, or ( 3) the rate of recovery to baseline levels of QOL 1 year after randomization. Conclusion. Overall QOL is equivalent between the two chemotherapy regimens, with some differences in symptoms and in patterns of vitality over time. C1 NSABP, Ctr Biostat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ British Columbia, Arthritis Res Ctr Canada, Vancouver, BC, Canada. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NSABP Operat Ctr, Pittsburgh, PA USA. RP Land, SR (reprint author), NSABP, Ctr Biostat, 201 N Craig St,Suite 350, Pittsburgh, PA 15213 USA. EM land@nsabp.pitt.edu OI Yothers, Greg/0000-0002-7965-7333; Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10-CA-69651] NR 19 TC 36 Z9 37 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2004 VL 86 IS 2 BP 153 EP 164 DI 10.1023/B:BREA.0000032983.87966.4e PG 12 WC Oncology SC Oncology GA 832BV UT WOS:000222243100006 PM 15319567 ER PT J AU Warburton, HE Parsons, KF Linehan, MW Boyd, MT AF Warburton, HE Parsons, KF Linehan, MW Boyd, MT TI Analysis of the role of the MDM2-P53 pathway in tumour evolution in renal cell carcinoma SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract CT British Cancer Research Meeting 2004 CY JUN 27-30, 2004 CL Manchester, ENGLAND C1 Univ Liverpool, Dept Surg, Liverpool L69 3BX, Merseyside, England. Natl Canc Inst, Urol Oncol Branch, Bethesda, MD USA. RI Boyd, Mark/I-6792-2012 OI Boyd, Mark/0000-0002-2336-2106 NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 2004 VL 91 SU 1 BP S65 EP S65 PG 1 WC Oncology SC Oncology GA 841YN UT WOS:000222968700242 ER PT J AU Jemal, A Clegg, LX Ward, E Ries, LAG Wu, XC Jamison, PM Wingo, PA Howe, HL Anderson, RN Edwards, BK AF Jemal, A Clegg, LX Ward, E Ries, LAG Wu, XC Jamison, PM Wingo, PA Howe, HL Anderson, RN Edwards, BK TI Annual report to the nation on the status of cancer, 1975-2001, with a special feature regarding survival SO CANCER LA English DT Editorial Material DE cancer; incidence; mortality; survival; surveillance; epidemiology; and End Results (SEER); National Program of Cancer Registries (NPCR); North American Association of Central Cancer Registries (NAACCR); vital statistics; U.S ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; LOCALIZED PROSTATE-CANCER; ESTROGEN PLUS PROGESTIN; RENAL-CELL CARCINOMA; BLACK-AND-WHITE; BREAST-CANCER; UNITED-STATES; COLORECTAL-CANCER; LUNG-CANCER AB BACKGROUND. The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the U.S. This year's report features a special section on cancer survival. METHODS. information concerning cancer cases was obtained from the NCI, CDC, and NAACCR and information concerning recorded cancer deaths was obtained from the CDC. The authors evaluated trends in age-adjusted cancer incidence and death rates by regression models and described and compared survival rates over time and across racial/ethnic populations. RESULTS. incidence rates for all cancers combined decreased from 1991 through 2001, but stabilized from 1995 through 2001 when adjusted for delay in reporting. The incidence rates for female lung cancer decreased (although not statistically significant for delay adjusted) and mortality leveled off for the first time after increasing for many decades. Colorectal cancer incidence rates also decreased. Death rates decreased for all cancers combined (1.1% per year since 1993) and for many of the top 15 cancers occurring in men and women. The 5-year relative survival rates improved for all cancers combined and for most, but not all, cancers over 2 diagnostic periods (1975-1979 and 1995-2000). However, cancer-specific survival rates were lower and the risk of dying from cancer, once diagnosed, was higher in most minority populations compared with the white population. The relative risk of death from all cancers combined in each racial and ethnic population compared with non-Hispanic white men and women ranged from 1.16 in Hispanic white men to 1.69 in American Indian/Alaska Native men, with the exception of Asian/Pacific Islander women, whose risk of 1.01 was similar to that of non-Hispanic white women. CONCLUSIONS. The continued measurable declines for overall cancer death rates and for many of the top 15 cancers, along with improved survival rates, reflect progress in the prevention, early detection, and treatment of cancer. However, racial and ethnic disparities in survival and the risk of death from cancer, and geographic variation in stage distributions suggest that not a segments of the U.S. population have benefited equally from such advances. Published 2004 by the American Cancer Society.*. C1 Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA. N Amer Assoc Cent Canc Registries, Springfield, IL USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Vital Stat, Hyattsville, MD 20782 USA. RP Jemal, A (reprint author), Amer Canc Soc, Epidemiol & Surveillance Res Dept, 1599 Clifton Rd, Atlanta, GA 30329 USA. EM ajemal@cancer.org NR 139 TC 730 Z9 756 U1 9 U2 35 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2004 VL 101 IS 1 BP 3 EP 27 DI 10.1002/cncr.20288 PG 25 WC Oncology SC Oncology GA 830PF UT WOS:000222134200002 PM 15221985 ER PT J AU Paoluzzi, L Figg, WD AF Paoluzzi, L Figg, WD TI Histone deacetylase inhibitors are potent radiation protectants SO CANCER BIOLOGY & THERAPY LA English DT Article DE histone deacetylase inhibitors; phenylbutyrate; cutaneous radiation syndrome; radiotherapy ID AGENT SODIUM PHENYLBUTYRATE; ACUTE MYELOID-LEUKEMIA; PROSTATE-CANCER CELLS; MYELODYSPLASTIC SYNDROMES; IN-VITRO; DIFFERENTIATION; PROLIFERATION; RADIOTHERAPY; APOPTOSIS; IMPACT AB Radiation-induced acute and late injuries often represent a limit to the optimal delivery of radiotherapy in cancer patients. Chung et al. reported that histone deaceyase (HDAC) inhibitors, a novel class compound of gene modulators, might have a role in controlling different adverse effects from radiotherapy in preclinical models. They also showed how protection of normal tissues and inhibition of tumor growth might be possible at the same time. C1 NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. Regina Elena Inst Canc Res, Div Med Oncol, Rome, Italy. RP Figg, WD (reprint author), NCI, Ctr Canc Res, Canc Therapeut Branch, Bldg 10 Room 5A01 MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 15 TC 9 Z9 9 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL PY 2004 VL 3 IS 7 BP 612 EP 613 PG 2 WC Oncology SC Oncology GA 898RR UT WOS:000227094400009 PM 15136769 ER PT J AU Chang, S Buist, DSM Reid, M Terry, MB Trentham-Dietz, A AF Chang, S Buist, DSM Reid, M Terry, MB Trentham-Dietz, A TI The characteristics and training of professionals in cancer prevention and control: A survey of the American Society for Preventive Oncology SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB To secure continuous stewardship in the field of cancer prevention requires in part training the next generation of scientists and practitioners effectively. We characterized members and meeting registrants of the American Society for Preventive Oncology and assessed their career needs using an electronic survey. From 380 valid email addresses, 233 respondents (61%) included 143 physicians and 81 respondents with other doctorates. More than one third worked at cancer centers (36%), while others worked at schools of medicine (25%) and public health (17%) and other institutions and businesses (22%). Among all respondents, 52% reported having at least one mentor but time spent advising by mentors was generally low. Many were less than satisfied with the amount of mentoring received (44%) and 52% reported interest in matching with an American Society for Preventive Oncology mentor. All were interested in grantsmanship training but junior and senior respondents differed in their preference for other topics, reflecting needs that change with career advancement. Other analyses focused on aspects of institutional commitment, which did not differ by type of degree, even after age adjustment. However, by gender and degree, men were completely supported by institutional funds more often than women among non-medical doctorates [age-adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI) = 1.1-9.8] but not among physicians (age-adjusted OR = 1.3, 95% CI = 0.5-3.1). Men were also more often in tenure-track positions than women (age-adjusted OR = 1.9, 95% CI = 1.1-3.3). In sum, addressing the career development needs of future leaders in the field by providing career and mentoring sessions at annual meetings may help individuals in the field and enrich the discipline overall. C1 NCI, Off Prevent Oncol, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY 10027 USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. RP Chang, S (reprint author), NCI, Off Prevent Oncol, Div Canc Prevent, NIH, 6120 Execut Blvd,Suite T-41 MSC 7105, Bethesda, MD 20892 USA. EM ChangSh@mail.nih.gov NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2004 VL 13 IS 7 BP 1094 EP + PG 130 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 836EW UT WOS:000222539400002 PM 15247118 ER PT J AU Anderson, WF Chu, KC Chang, S Sherman, ME AF Anderson, WF Chu, KC Chang, S Sherman, ME TI Comparison of age-specific incidence rate patterns for different histopathologic types of breast carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE REPLACEMENT THERAPY; FEMALE BREAST; CANCER INCIDENCE; HISTOLOGIC TYPES; RISK; EPIDEMIOLOGY; DEFINITION; HYPOTHESIS; PHENOTYPES; PATHOLOGY AB Objective: The age-specific incidence rate curve for breast carcinoma overall increases rapidly until age 50 years, and then continues to increase at a slower rate for older women. In this analysis, our objective was to compare age-specific incidence rate patterns for different morphologic types of breast carcinoma. Materials and methods: We analyzed age-specific incidence rate curves by histopathologic subclassification using records from 11 standard National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries, diagnosed during the years 1992 to 1999. Data were examined by age <50 and greater than or equal to50 years to simulate menopause. Results: Age-specific incidence rate curves showed three dominant patterns: (1) Rates for infiltrating duct carcinoma of no special type (duct NST), tubular, and lobular carcinomas increased rapidly until age 50 years then rose more slowly. (2) Rates for medullary and inflammatory breast carcinomas increased rapidly until age 50 years then failed to increase. (3) Rates for papillary and mucinous carcinomas increased steadily at all ages. Rate patterns varied by estrogen receptor expression but were. unaffected by SEER registry, race, nodal status, or grade. Conclusion: Age-specific incidence rates for breast carcinomas differed by histopathologic type. Rates that failed to increase after 50 years suggested that menopause had greater impact on medullary and inflammatory carcinomas than on duct NST, tubular, and lobular carcinomas. Menopause did not seem to have any effect on papillary or mucinous carcinomas as evidenced by steadily rising rates at all ages. Future etiologic and/or prevention studies should consider the impact of age-specific risk factors and/or exposures on different histopathologic types of breast carcinomas. C1 NCI, Div Canc Prevent, Dept Hlth & Human Serv, NIH,EPN, Bethesda, MD 20892 USA. NCI, Ctr Reduce Canc Hlth Dispar, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Div Canc Prevent, Dept Hlth & Human Serv, NIH,EPN, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. EM wanderso@mail.nih.gov NR 41 TC 61 Z9 63 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 JUL PY 2004 VL 13 IS 7 BP 1128 EP 1135 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 836EW UT WOS:000222539400007 PM 15247123 ER PT J AU Hughes, C Peterson, SK Ramirez, A Gallion, KJ McDonald, PG Skinner, CS Bowen, D AF Hughes, C Peterson, SK Ramirez, A Gallion, KJ McDonald, PG Skinner, CS Bowen, D TI Minority recruitment in hereditary breast cancer research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN WOMEN; OVARIAN-CANCER; CLINICAL-TRIALS; BRCA1 MUTATION; PROPHYLACTIC SURGERY; TESTING DECISIONS; FAMILY-HISTORY; CASE SERIES; RISK; SUSCEPTIBILITY AB Although recruitment of ethnic and racial minorities in medical research has been evaluated in several studies, much less is known about the methods used to recruit these populations to participate in cancer genetics research. This report reviews the resources that have been used to identify and recruit ethnic and racial minorities to participate in hereditary breast cancer research. Overall, hospital-based resources were used most often to identify potential subjects, and active recruitment methods were used most frequently to enroll eligible subjects. This review suggests that there appears to be a finite number of resources and strategies to identify and recruit potential subjects to participate in cancer genetics research; however, options for improving awareness about cancer genetics research among ethnic and racial minorities have not been extensively evaluated. To study ethnic and racial minority participation in cancer genetics research, stronger evaluation components will need to be integrated into research methods. Both observational and experimental studies are needed to determine resources that are most effective for identifying potential subjects who are ethnic and racial minorities and to evaluate the effects of different recruitment strategies on enrollment decisions among these populations. C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Chron Dis Prevent & Control Res Ctr, Houston, TX 77030 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Hughes, C (reprint author), Univ Penn, Abramson Canc Ctr, 3535 Market St,Suite 4100, Philadelphia, PA 19104 USA. EM chanita@mail.med.upenn.edu FU NCI NIH HHS [U24CA078156] NR 57 TC 33 Z9 33 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2004 VL 13 IS 7 BP 1146 EP + PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 836EW UT WOS:000222539400009 PM 15247125 ER PT J AU Lao, CD Backoff, P Shotland, LI McCarty, D Eaton, T Ondrey, FG Viner, JL Spechler, SJ Hawk, ET Brenner, DE AF Lao, CD Backoff, P Shotland, LI McCarty, D Eaton, T Ondrey, FG Viner, JL Spechler, SJ Hawk, ET Brenner, DE TI Irreversible ototoxicity associated with difluoromethylornithine SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHASE-I CHEMOPREVENTION; ALPHA-DIFLUOROMETHYLORNITHINE; METASTATIC MELANOMA; CANCER PREVENTION; COLON-CANCER; TRIAL; DFMO; POLYAMINES; INHIBITOR; AGENTS AB Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m(2)/d, and generally when the cumulative dose exceeds 250 g/m(2). In a recently completed Barrett's esophagus chemoprevention trial, a participant developed a 15-dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right ear and greater than or equal to20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear after taking 0.5 g/m(2)/d DFMO for approximately 13 weeks (cumulative dose of 45 g/m(2)). The threshold shifts persisted 7 months after DFMO was discontinued. There was no obvious impact on the participant's clinical hearing, but these findings were consistent with irreversible hearing loss. This is the first case reported of irreversible ototoxicity in a clinical trial participant receiving DFMO and, thus, trial participants should be made aware of this small but important risk. C1 Univ Michigan, Ctr Med, Canc Ctr & Geriat Ctr 2150, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Dallas VA Med Ctr, Dallas, TX USA. Univ Minnesota, Dept Otolaryngol, Minneapolis, MN USA. NCI, Div Canc Prevent, Bethesda, MD USA. RP Brenner, DE (reprint author), Univ Michigan, Ctr Med, Canc Ctr & Geriat Ctr 2150, Ann Arbor, MI 48109 USA. EM dbrenner@umich.edu NR 28 TC 7 Z9 7 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 JUL PY 2004 VL 13 IS 7 BP 1250 EP 1252 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 836EW UT WOS:000222539400022 PM 15247138 ER PT J AU Tonon, G Gehlhaus, KS Yonescu, R Kaye, FJ Kirsch, IR AF Tonon, G Gehlhaus, KS Yonescu, R Kaye, FJ Kirsch, IR TI Multiple reciprocal translocations in salivary gland mucoepidermoid carcinomas SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID ETV6-NTRK3 GENE FUSION; IN-SITU HYBRIDIZATION; CANCER CELL-LINES; CHROMOSOME-ABNORMALITIES; MOUSE SPLENOCYTES; X-IRRADIATION; TUMORS; ABERRATIONS; FISH; RISK AB Mucoepidermoid carcinoma, the most common human malignant salivary gland tumor, can arise from both major and minor salivary glands, including sites within the pulmonary tracheobronchial tree. We performed comparative genomic hybridization (CGH) and spectral karyotyping (SKY) on two tumor cell lines: 113118, derived from tumor originating in the parotid gland, and H292, from tumor in the lung. In both cell lines, CGH showed a partial gain within the short arm of chromosome 7 and SKY revealed the presence of the previously reported reciprocal translocation t(11;19)(q21;p12). Additional chromosomal rearrangements were found in both cell lines, including three more reciprocal translocations in cell line H292 [t(1;16), t(6;8)x2] and three other reciprocal translocations in cell line H3118 [t(1;7), t(3;15), and t(7;f5)]. A review of the literature of other reported cases of mucoepidermoid carcinomas analyzed with standard G-banding techniques, as well as distinct benign salivary gland tumors, such as pleomorphic adenomas and Warthin tumor, confirmed the presence of a karyotype dominated by reciprocal translocations. Four chromosomal bands were involved in chromosomal translocations in both cell lines: 1q32, 5p15, 7q22, and 15q22. Fluorescence in situ hybridization studies showed that the breakpoints in these four bands were often within a few megabases of each other. The involvement of similar chromosomal bands in breakpoints in these two cell lines suggests that these regions may be predisposed or selected for chromosomal rearrangements in this tumor type. The presence of multiple reciprocal translocations in both benign and malignant salivary gland tumors may also suggest a particular mechanism within mucous or serous glands mediating chromosomal rearrangements. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Genet Branch, NNMC, Bethesda, MD 20889 USA. RP Kirsch, IR (reprint author), NCI, Genet Branch, NNMC, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM kirschi@exchange.nih.gov RI kaye, frederic/E-2437-2011 NR 41 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUL 1 PY 2004 VL 152 IS 1 BP 15 EP 22 DI 10.1016/j.cancergencyto.2003.10.007 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 831NC UT WOS:000222200100003 PM 15193437 ER PT J AU So, PL Lee, K Hebert, J Walker, P Lu, Y Hwang, J Kopeovich, L Athar, M Bickers, D Aszterbaum, M Epstein, EH AF So, PL Lee, K Hebert, J Walker, P Lu, Y Hwang, J Kopeovich, L Athar, M Bickers, D Aszterbaum, M Epstein, EH TI Topical tazarotene chemoprevention reduces basal cell carcinoma number and size in Ptch1 +/- mice exposed to ultraviolet or ionizing radiation SO CANCER RESEARCH LA English DT Article ID RECEPTOR-SELECTIVE RETINOIDS; TUMOR-SUPPRESSOR; HUMAN HOMOLOG; EXPERIMENTAL PHOTOCARCINOGENESIS; NEVUS SYNDROME; PATCHED GENE; VITAMIN-A; IN-VIVO; SKIN; CANCER AB Oral retinoids can reduce basal cell carcinoma (BCC) incidence in genetically susceptible patients, and one topical retinoid, tazarotene, has been reported to cure some sporadic BCCs. Therefore, we have tested whether this agent would affect BCCs in Ptch1+/- mice in a controlled chemoprevention trial. We found that topical tazarotene dramatically inhibits the formation of BCCs induced with either UV or ionizing radiation. The ability of tazarotene to inhibit BCC formation in this mouse model provides encouragement for the use of tazarotene in skin cancer chemoprevention trials in humans. C1 Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Columbia Presbyterian Med Ctr, Dept Dermatol, New York, NY 10032 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Epstein, EH (reprint author), San Francisco Gen Hosp, Bldg 100,Room 269,1001 Potrero Ave, San Francisco, CA 94110 USA. EM epsteine@derm.ucsf.edu FU NCI NIH HHS [U19 CA81888] NR 39 TC 32 Z9 33 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4385 EP 4389 DI 10.1158/0008-5472.CAN-03-1927 PG 5 WC Oncology SC Oncology GA 834JL UT WOS:000222407300001 PM 15231643 ER PT J AU Ryan, KM O'Prey, J Vousden, KH AF Ryan, KM O'Prey, J Vousden, KH TI Loss of nuclear factor-KB is tumor promoting but does not substitute for loss of p53 SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; P53-DEPENDENT APOPTOSIS; CELL-DEATH; INHIBITION; CANCER; TUMORIGENESIS; ACTIVATION; THERAPY; GENES AB Inactivation of apoptotic pathways is a common event in cancer. Two transcription factors that regulate apoptosis during tumorigenesis are p53 and nuclear factor (NF)-kappaB. Although NF-kappaB is generally considered a suppressor of cell death, we showed previously that NF-kappaB can contribute to p53-induced death. Here, we show that loss of p65, a critical subunit of NF-kappaB, can cause resistance to different agents that signal death through p53. Loss of p65 also enhances tumorigenesis induced by E1a and Ras. Unlike loss of p53, however, loss of p65 does not cause anchorage-independent growth or enable tumor development following expression of a single oncogene. These findings reaffirm the role of NF-kappaB in p53-induced death but show that its loss does not substitute for loss of p53 in tumor development. Moreover, this indicates that, although perhaps central to p53 function, loss of the ability to induce programmed cell death does not completely inactivate p53's tumor-suppressive effects. C1 Beatson Inst Canc Res, Canc Res UK Beatson Labs, Tumor Cell Death Lab, Glasgow G61 1BD, Lanark, Scotland. Beatson Inst Canc Res, Canc Res UK Beatson Labs, Tumor Suppress Lab, Glasgow G61 1BD, Lanark, Scotland. NCI, Regulat Cell Growth Lab, Frederick, MD 21701 USA. RP Ryan, KM (reprint author), Beatson Inst Canc Res, Canc Res UK Beatson Labs, Tumor Cell Death Lab, Garscube Estate, Glasgow G61 1BD, Lanark, Scotland. EM k.ryan@beatson.gla.ac.uk NR 20 TC 26 Z9 26 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4415 EP 4418 DI 10.1158/0008-5472.CAN-04-1474 PG 4 WC Oncology SC Oncology GA 834JL UT WOS:000222407300007 PM 15231649 ER PT J AU Shin, MS Fredrickson, TN Hartley, JW Suzuki, T Agaki, K Morse, HC AF Shin, MS Fredrickson, TN Hartley, JW Suzuki, T Agaki, K Morse, HC TI High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas SO CANCER RESEARCH LA English DT Article ID ZINC-FINGER PROTEIN; MURINE LEUKEMIA VIRUSES; T-CELL LYMPHOMAGENESIS; TRANSGENIC MICE; B-CELL; INSERTIONAL MUTAGENESIS; MYC; CANCER; GFI-1; TRANSCRIPTION AB Human B-cell lymphomas are frequently associated with specific genetic changes caused by chromosomal translocations that activate protooncogenes. For lymphomas of mice expressing murine leukemia virus, mutagenic proviral insertions are thought to play a similar role. Here we report studies designed to determine whether specific retroviral integration sites might be associated with a specific subset of mouse B-cell lymphomas and if the genes associated with these sites are regularly altered in expression. We studied splenic marginal zone lymphomas (MZL) of NFS.V+ mice that are unusual in exhibiting frequent progression from low to high grade, potentially allowing assignment of cancer genes to processes of initiation and progression. We used inverse PCR to clone and analyze 212 retroviral integration sites from 43 MZL at different stages of progression. Sixty-two marked common integration sites and included 31 that had been marked previously. Among the new common integration sites, seven were unique to MZL. Using microarrays and real-time quantitative PIER analysis, we defined differential patterns of gene expression in association with disease progression for Gfi1, Sox4, Brca2, Snf1lk, Nfkb1, Pou2af1, Prdm1, Stat6, and Blnk. Heightened expression of Gfi1 distinguishes MZL from other lymphoma types. The combined use of proviral tagging and analyses of gene expression thus provides a powerful approach to understanding of genes that collaborate in tumorigenesis. C1 NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Morse, HC (reprint author), NIAID, Immunol Lab, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM hmorse@niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 NR 46 TC 53 Z9 55 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4419 EP 4427 DI 10.1158/0008-5472.CAN-03-3885 PG 9 WC Oncology SC Oncology GA 834JL UT WOS:000222407300008 PM 15231650 ER PT J AU Feldman, AL Stetler-Stevenson, WG Costouros, NG Knezevic, V Baibakov, G Alexander, HR Lorang, D Hewitt, SM Seo, DW Miller, MS O'Connor, S Libutti, SK AF Feldman, AL Stetler-Stevenson, WG Costouros, NG Knezevic, V Baibakov, G Alexander, HR Lorang, D Hewitt, SM Seo, DW Miller, MS O'Connor, S Libutti, SK TI Modulation of tumor-host interactions, angiogenesis, and tumor growth by tissue inhibitor of metalloproteinase 2 via a novel mechanism SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; MICROARRAY ANALYSIS; ENDOTHELIAL-CELLS; DOWN-REGULATION; IN-VITRO; PROLIFERATION; SUPPRESSION; ENDOSTATIN; MODELS; MKP-1 AB Solid tumors depend on angiogenesis for sustained growth. Tissue inhibitor of metalloproteinase 2 (TIMP-2) is an angiogenesis inhibitor initially characterized for its ability to block matrix metalloproteinases; however, recent data suggest that the antiangiogenic action of TIMP-2 may rely on matrix metalloproteinase-independent mechanisms. The aim of this study was to identify molecular pathways involved in the effects of TIMP-2 on processes dependent on tumor-host interactions such as angiogenesis. Using in vitro cell culture and a syngeneic murine tumor model, we compared the effects of TIMP-2 overexpression on gene expression profiles in vitro to those observed in vivo. Validating these findings by real-time quantitative PCR and layered protein scanning, we identified up-regulation of mitogen-activated protein kinase phosphatase I as an effector of the antiangiogenic function of TIMP-2. Up-regulation of mitogen-activated protein kinase phosphatase 1 in tumors overexpressing TIMP-2 leads to dephosphorylation of p38 mitogen-activated protein kinase and inhibition of tumor growth and angiogenesis. Phosphatase activity appears important in regulating tumor angiogenesis, offering a promising direction for the identification of novel molecular targets and antiangiogenic compounds for the treatment of cancer. C1 NCI, Metab Sect, Surg Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Vasc Biol Fac, Ctr Canc Res, Bethesda, MD 20892 USA. 20 20 Gene Syst Inc, Rockville, MD USA. RP Libutti, SK (reprint author), NCI, Metab Sect, Surg Branch, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012; Feldman, Andrew/D-5028-2012 OI Hewitt, Stephen/0000-0001-8283-1788; Stetler-Stevenson, William/0000-0002-5500-5808; Seo, Dong-Wan/0000-0003-4971-834X; NR 24 TC 26 Z9 27 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4481 EP 4486 DI 10.1158/0008-5472.CAN-03-2929 PG 6 WC Oncology SC Oncology GA 834JL UT WOS:000222407300015 PM 15231657 ER PT J AU Tian, F Byfield, SD Parks, WT Stuelten, CH Nemani, D Zhang, YE Roberts, AB AF Tian, F Byfield, SD Parks, WT Stuelten, CH Nemani, D Zhang, YE Roberts, AB TI Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines SO CANCER RESEARCH LA English DT Article ID TGF-BETA; MESENCHYMAL TRANSDIFFERENTIATION; SIGNALING PATHWAYS; TUMOR; KINASE; TGF-BETA-1; RESPONSES; INVASION; RAS; GROWTH-FACTOR-BETA-1 AB The role of transforming growth factor beta (TGF-beta) in carcinogenesis is complex, with tumor suppressor and pro-oncogenic activities depending on the particular tumor cell and its stage in malignant progression. We previously have demonstrated in breast cancer cell lines that Smad2/3 signaling played a dominant role in mediating tumor suppressor effects on well-differentiated breast cancer cell lines grown as xenografts and prometastatic effects on a more invasive, metastatic cell line. Our present data based on selective interference with activation of endogenous Smad2 and Smad3 by stable expression of a mutant form of the TGF-beta type I receptor (RImL45) unable to bind Smad2/3 but with a functional kinase again show that reduction in Smad2/3 signaling by expression of RImL45 enhanced the malignancy of xenografted tumors of the well-differentiated MCF10A-derived tumor cell line MCF10CA1h, resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features. In contrast, expression of RImL45 in the more aggressive MCF10CA1a cell line strongly suppressed formation of lung metastases following tail vein injection. These results suggest a causal, dominant role for the endogenous; Smad2/3 signaling pathway in the tumor suppressor and prometastatic activities of TGF-beta in these cells. Using an in vitro assay, we further show that non-Smad signaling pathways, including p38 and c-Jun NH2-terminal kinase, cooperate with TGF-beta/Smads in enhancing migration of metastatic MCF10CA1a cells, but that, although necessary for migration, these other pathways are not sufficient for metastasis. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM Robertsa@dce41.nci.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 NR 39 TC 62 Z9 67 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4523 EP 4530 DI 10.1158/0008-5472.CAN-04-0030 PG 8 WC Oncology SC Oncology GA 834JL UT WOS:000222407300020 PM 15231662 ER PT J AU de Silanes, IL Olmo, N Turnay, J de Buitrago, GG Perez-Ramos, P Guzman-Aranguez, A Garcia-Diez, M Lecona, E Gorospe, M Lizarbe, MA AF de Silanes, IL Olmo, N Turnay, J de Buitrago, GG Perez-Ramos, P Guzman-Aranguez, A Garcia-Diez, M Lecona, E Gorospe, M Lizarbe, MA TI Acquisition of resistance to butyrate enhances survival after stress and induces malignancy of human colon carcinoma cells SO CANCER RESEARCH LA English DT Article ID CHAIN FATTY-ACIDS; SODIUM-BUTYRATE; MULTIDRUG-RESISTANCE; ADENOCARCINOMA CELLS; HISTONE DEACETYLASE; EPITHELIAL-CELLS; ALPHA-SARCIN; CANCER CELLS; APOPTOSIS; EXPRESSION AB Acquired resistance to apoptosis by tumor cells remains a major obstacle for cancer treatment, and hence the analysis of resistance to apoptosis constitutes a major goal in the development of antitumoral drugs. We have established a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.BR2) from nontumorigenic BCS-TC2 cells to analyze whether the acquisition of such phenotype confers resistance to apoptosis and stress. Although BCS-TC2.BR2 cells exhibited a more differentiated phenotype than the parental BCS-TC2 cells, higher butyrate concentrations remained capable of additionally enhancing their differentiation without inducing apoptosis. Survival rates of BCS-TC2.BR2 cells after glucose deprivation and heat shock were higher than those of parental cells, revealing a stress-resistant phenotype. These findings were accompanied by key differences between parental and butyrate-resistant cells in gene expression profiles and the acquisition of in vivo tumorigenicity. In conclusion, cells gaining resistance to an endogenous physiological modulator of growth, differentiation, and apoptosis concurrently acquired resistance to other agents that influence cell survival. C1 Univ Complutense, Fac Ciencias Quim, Dept Bioquim & Biol Mol, E-28040 Madrid, Spain. CSIC, Ctr Nacl Biotecnol, Dept Inmunol & Oncol, Madrid, Spain. NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lizarbe, MA (reprint author), Univ Complutense, Fac Ciencias Quim, Dept Bioquim & Biol Mol, E-28040 Madrid, Spain. EM lizarbe@bbm1.ucm.es RI Turnay, Javier/K-4551-2014; Lizarbe, M Antonia/K-5219-2014; OLMO LOPEZ, NIEVES/K-5266-2014 OI Turnay, Javier/0000-0002-6135-2179; Lizarbe, M Antonia/0000-0003-1722-1240; OLMO LOPEZ, NIEVES/0000-0002-8013-5313 NR 38 TC 17 Z9 17 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2004 VL 64 IS 13 BP 4593 EP 4600 DI 10.1158/0008-5472.CAN-04-0711 PG 8 WC Oncology SC Oncology GA 834JL UT WOS:000222407300029 ER PT J AU Gyorffy, E Anna, L Gyori, Z Segesdi, J Minarovits, J Soltesz, I Kostic, S Csekeo, A Poirier, MC Schoket, B AF Gyorffy, E Anna, L Gyori, Z Segesdi, J Minarovits, J Soltesz, I Kostic, S Csekeo, A Poirier, MC Schoket, B TI DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by P-32-postlabelling and immunoassay SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; 4-AMINOBIPHENYL-DNA ADDUCTS; ALVEOLAR MACROPHAGES; CIGARETTE-SMOKING; PROTEIN ADDUCTS; COAL-TAR; CELLS; SMOKERS; EXPOSURE; HUMANS AB Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by cigarette smoke in target and surrogate tissues. Samples of tumour and normal peripheral lung tissue, normal bronchial tissue and peripheral blood lymphocytes were obtained from a total of 85 lung cancer patients who underwent lung resection. Bulky DNA adducts were determined by P-32-postlabelling, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were detected by (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA chemiluminescence immunoassay (BPDE-DNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/10(8) nucleotides (nt) with mean adduct levels between 2.8 and 11.5 adducts/10(8) nt. Mean PAH-DNA adduct levels were 2.6-6.2 adducts/10(8) nt. Significantly higher bulky DNA adduct levels were detected in smokers' lungs as compared with non-smokers' (P < 0.02). PAH-DNA adduct levels appeared higher in the lungs of smokers compared with non-smokers but the difference was not significant. Lung tumour contained on average a 50% lower DNA adduct level compared with normal lung tissue. A statistically significant positive correlation was found between the DNA adduct levels of the corresponding tumour and normal lung tissue samples in both smokers and non-smokers using both methodologies. Bulky DNA adduct levels in normal lung and blood lymphocytes correlated significantly in non-smokers only (r = 0.55, P = 0.023). In lung tumour DNA samples there was a weak correlation between values obtained by P-32-postlabelling and by the BPDE-DNA immunoassay (r = 0.27, P = 0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate. C1 Jozsef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, H-1097 Budapest, Hungary. Bela Johan Natl Ctr Epidemiol, H-1529 Budapest, Hungary. Koranyi Natl Inst Pulmonol, H-1529 Budapest, Hungary. NCI, NIH, Bethesda, MD 20892 USA. RP Schoket, B (reprint author), Jozsef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, H-1097 Budapest, Hungary. EM schoketb@okk.antsz.hu FU NCI NIH HHS [N02-CO-91012] NR 42 TC 37 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2004 VL 25 IS 7 BP 1201 EP 1209 DI 10.1093/carcin/bgh131 PG 9 WC Oncology SC Oncology GA 830LV UT WOS:000222124500015 PM 15001535 ER PT J AU Koshiji, M Huang, LE AF Koshiji, M Huang, LE TI Dynamic balancing of the dual nature of HIF-1 alpha for cell survival SO CELL CYCLE LA English DT Article DE cell cycle; drug resistance; HIF-1 alpha; hypoxia; Myc; p21(cip1) ID HYPOXIA-INDUCIBLE FACTOR; UBIQUITIN-PROTEASOME PATHWAY; FACTOR 1-ALPHA; FACTOR-I; ALPHA-SUBUNIT; CYCLE ARREST; MYC; CANCER; ANGIOGENESIS; DEGRADATION AB In hypoxic cells, HIF-1alpha escapes from oxygen-dependent proteolysis and binds to the hypoxia-responsive element (HRE) for transcriptional activation of target genes involved in angiogenesis and glycolysis. We recently demonstrated that the G(1) checkpoint gene p21(cip1) is activated by HIF-1alpha with a novel mechanism that involves the HIF-1alpha PAS domains to displace Myc binding from p21(cip1) promoter. This HIF-1alpha-Myc pathway may account for up- and down-regulation of other hypoxia-responsive genes that lack the HRE. Moreover, the role of HIF-1alpha in cell cycle control indicates a dual, yet seemingly conflicting, nature of HIF-1alpha: promoting cell growth and arrest in concomitance. We speculate that a dynamic balance between the two processes is achieved by a "stop-and-go" strategy to maintain cell growth and survival. Tumor cells may adopt such scheme to evade the killing by chemotherapeutic agents. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Huang, LE (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,MSC 4255,Bldg 37,Room 3044B, Bethesda, MD 20892 USA. EM huange@mail.nih.gov NR 22 TC 38 Z9 40 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL PY 2004 VL 3 IS 7 BP 853 EP 854 PG 2 WC Cell Biology SC Cell Biology GA 857AL UT WOS:000224087500007 PM 15190211 ER PT J AU Wang, BD Yang-Gonzalez, V Strunnikov, AV AF Wang, BD Yang-Gonzalez, V Strunnikov, AV TI Cdc14p/FEAR pathway controls segregation of nucleolus in S-cerevisiae by facilitating condensin targeting to rDNA chromatin in anaphase SO CELL CYCLE LA English DT Article DE condensin; rDNA; nucleolus; chromatin; Cdc14; chromosome segregation; anaphase ID CHROMOSOME CONDENSATION; MITOTIC EXIT; BUDDING-YEAST; CELL-CYCLE; CDC14 PHOSPHATASE; SEPARASE; MITOSIS; LOCALIZATION; NETWORK; COMPLEX AB The condensin complex is the chief molecular machine of mitotic chromosome condensation. Nucleolar concentration of condensin in mitosis was previously shown to correlate with proficiency of rDNA condensation and segregation. To uncover the mechanisms facilitating this targeting we conducted a screen for mutants that impair mitotic condensin congression to the nucleolus. Mutants in the cdc14, esp1 and cdc5 genes, which encode FEAR-network components, showed the most prominent defects in mitotic condensin localization. We established that Cdc14p activity released by the FEAR pathway was required for proper condensin-to-rDNA targeting in anaphase. The MEN pathway was dispensable for condensin-to-rDNA targeting, however MEN-mediated release of Cdc14p later in anaphase allowed for proper, albeit delayed, condensin targeting to rDNA and successful segregation of nucleolus in the slk19 FEAR mutant. Although condensin was physically dislodged from rDNA in the cdc14 mutant, it was properly assembled, phosphorylated and chromatin-bound, suggesting that condensin was mis-targeted but active. This study identifies a novel pathway promoting condensin targeting to a specific chromosomal address, the rDNA locus. C1 NICHD, NIH, LGRD, Bethesda, MD 20892 USA. RP Strunnikov, AV (reprint author), NICHD, NIH, LGRD, 18T Lib Dr,Room 106, Bethesda, MD 20892 USA. EM strunnik@box-s.nih.gov OI Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS [Z01 HD001903-11, Z99 AI999999] NR 35 TC 59 Z9 60 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL PY 2004 VL 3 IS 7 BP 960 EP 967 PG 8 WC Cell Biology SC Cell Biology GA 857AL UT WOS:000224087500029 PM 15190202 ER PT J AU Brzeska, H Szczepanowska, J Matsumura, F Korn, ED AF Brzeska, H Szczepanowska, J Matsumura, F Korn, ED TI Rac-induced increase of phosphorylation of myosin regulatory light chain in HeLa cells SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE blebbistatin; myosin; myosin light chain kinase; MLCK; p21-activated kinase; PAK; rho-kinase; ROCK ID ACTIVATED PROTEIN-KINASE; P21-ACTIVATED KINASE; RHO-KINASE; ACTIN CYTOSKELETON; STRESS FIBERS; SUBSTRATE-SPECIFICITY; FOCAL ADHESIONS; ADAPTER PROTEIN; BINDING SUBUNIT; ALPHA-PAK AB The pathways by which activation of the small GTP-binding protein Rac causes cytoskeletal changes are not fully understood but are likely to involve both assembly of new actin filaments and reorganization of actin filaments driven by the actin-dependent ATPase activity of myosin II. Here we show that expression of active RacQ61 in growing HeLa cells, in addition to inducing ruffling, substantially enhances the level of phosphorylation of serine-19 of the myosin II regulatory light chain (MLC), which would increase actomyosin II ATPase and motor activities. Phosphorylated myosin was localized to RacQ61-induced ruffles and stress fibers. RacQ61-induced phosphorylation of MLC was reduced by a maximum of about 38% by an inhibitor (Tat-PAK) of p21-activated kinase (PAK), about 35% by an inhibitor (Y-27632) of Rho kinase, 51% by Tat-PAK plus Y-27632, and 10% by an inhibitor (ML7) of myosin light chain kinase. Staurosporine, a non-specific inhibitor of serine/ threonine kinases, reduced RacQ61-induced phosphorylation of MLC by about 58%, at the maximum concentration that did not kill cells. Since Rac activates PAK and PAK can phosphorylate MLC, these data strongly Suggest that PAK is responsible for a significant fraction of RacQ61-induced MLC phosphorylation. To our knowledge, this is the first evidence that active Rac causes phosphorylation of MLC in cells, thus implicating activation of the ATPase activity of actomyosin II as one of the ways by which Rac may induce cytoskeletal changes. (dagger)Published 2004 Wiley-Liss. Inc. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2517, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012; OI Matsumura, Fumio/0000-0002-8204-153X NR 58 TC 30 Z9 31 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD JUL PY 2004 VL 58 IS 3 BP 186 EP 199 DI 10.1002/cm.20009 PG 14 WC Cell Biology SC Cell Biology GA 834KA UT WOS:000222408800005 PM 15146537 ER PT J AU Rama, P Poremba, A Sala, JB Yee, L Malloy, M Mishkin, M Courtney, SM AF Rama, P Poremba, A Sala, JB Yee, L Malloy, M Mishkin, M Courtney, SM TI Dissociable functional cortical topographies for working memory maintenance of voice identity and location SO CEREBRAL CORTEX LA English DT Article DE auditory system; functional magnetic resonance imaging; nonspatial memory; prefrontal cortex; spatial memory ID PRIMATE PREFRONTAL CORTEX; HUMAN AUDITORY-CORTEX; FRONTAL-CORTEX; AREA; LOCALIZATION; RESPONSES; STIMULI; MONKEY; MECHANISMS; SYSTEMS AB In order to ascertain whether the neural system for auditory working memory exhibits a functional dissociation for spatial and nonspatial information, we used functional magnetic resonance imaging and a single set of auditory stimuli to study working memory for the location and identity of human voices. The subjects performed a delayed recognition task for human voices and voice locations and an auditory sensorimotor control task. Several temporal, parietal, and frontal areas were activated by both memory tasks in comparison with the control task. However, during the delay periods, activation was greater for the location than for the voice identity task in dorsal prefrontal (SFS/PreCG) and parietal regions and, conversely, greater for voices than locations in ventral prefrontal cortex and the anterior portion of the insula. This preferential response to the voice identity task in ventral prefrontal cortex continued during the recognition test period, but the double dissociation was observed only during maintenance, not during encoding or recognition. Together, the present findings suggest that, during auditory working memory, maintenance of spatial and nonspatial information modulates activity preferentially in a dorsal and a ventral auditory pathway, respectively. Furthermore, the magnitude of this dissociation seems to be dependent on the cognitive operations required at different times during task performance. C1 Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, FIN-00014 Helsinki, Finland. Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. Helsinki Brain Res Ctr, Helsinki, Finland. RP Rama, P (reprint author), Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, POB 9, FIN-00014 Helsinki, Finland. EM prama@cc.helsinki.fi FU NIMH NIH HHS [R01 MH61625] NR 39 TC 68 Z9 69 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 2004 VL 14 IS 7 BP 768 EP 780 DI 10.1093/cercor/bhh037 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 830LQ UT WOS:000222124000008 PM 15084491 ER PT J AU Huffman, SW Schlucker, S Levin, IW AF Huffman, SW Schlucker, S Levin, IW TI Reorganizational dynamics of multilamellar lipid bilayer assemblies using continuously scanning Fourier transform infrared spectroscopic imaging SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article DE infrared spectroscopy; spectroscopic imaging; lipid dynamics ID QUANTITATIVE-DETERMINATION; MICROSPECTROSCOPY; MEMBRANES; SECTIONS; DISORDER; COLLAGEN; DENSITY; ORDER; MODEL AB We employ an implementation of rapid-scan Fourier transform infrared (FT-IR) microspectroscopic imaging to acquire time-resolved images for assessing the non-repetitive reorganizational dynamics of aqueous dispersions of multilamellar lipid vesicles (MLVs) derived from distearoylphosphatidylcholine (DSPC). The spatially and temporally resolved images allow direct and simultaneous determinations of various physical and chemical properties of the MLVs, including the main thermal gel to liquid crystalline phase transition, comparisons of vesicle diffusion rates in both phases and the variation in lipid bilayer packing properties between the inner and outer lamellae defining the vesicle. Specifically, in the lipid liquid crystalline phase, the inner bilayers of the MLVs are more intermolecularly ordered than the outer regions, while the intramolecular acyl chain order/disorder parameters, reflecting the overall characteristics of the fluid phase, remain uniform across the vesicle diameter. In contrast, the lipid vesicle gel phase displays no intermolecular or intramolecular dependence as a function of distance from the MLV center. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM iwl@helix.nih.gov RI Schlucker, Sebastian/D-1031-2010 OI Schlucker, Sebastian/0000-0003-4790-4616 NR 30 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD JUL PY 2004 VL 130 IS 2 BP 167 EP 174 DI 10.1016/j.chemphyslip.2004.03.004 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 830QN UT WOS:000222137800009 PM 15172833 ER PT J AU Lee, YS Marcu, MG Neckers, L AF Lee, YS Marcu, MG Neckers, L TI Quantum chemical calculations and mutational analysis suggest heat shock protein 90 catalyzes trans-cis isomerization of geldanamycin SO CHEMISTRY & BIOLOGY LA English DT Article ID IMPORTANT BIOLOGIC ACTIVITIES; HSP90 MOLECULAR CHAPERONE; CRYSTAL-STRUCTURE; PROTEIN CHAPERONE; TERMINAL DOMAIN; RADICICOL; ANSAMYCIN; COMPLEX; BINDING; TRANSFORMATION AB The affinity of geldanamycin (GA) for binding to heat shock protein 90 (HSP90) is 50- to 100-fold weaker than is the affinity of the structurally distinct natural product radicicol. X-ray crystallography shows that although radicicol maintains its free conformation when bound to HSP90, the conformation of GA is dramatically altered from an extended conformation with a trans amide bond to a kinked shape in which the amide group in the ansa ring has the cis configuration. We have performed ab initio quantum chemical calculations to demonstrate that the trans-cis isomeriztion of GA in solution is both kinetically and thermodynamically unfavorable. Thus, we propose that HSP90 catalyzes the isomerization of GA. We identify Ser113, a conserved residue outside the ATIP binding pocket, as essential for the isomerization of GA. In support of this model, we show that radicicol binds equally well to both wild-type HSP90 and the Ser113 mutant, whereas the binding of GA to the Ser113 mutant is decreased significantly from its binding to wild-type HSP90. Based on this finding, a mechanism of keto-enol tautomerization of GA catalyzed by HSP90 is proposed. The added requirement of isomerization prior to tight binding may explain the enhanced binding affinity of GA for HSP90 in a cell extract versus in a purified form. C1 NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, Rockville, MD 20850 USA. RP Lee, YS (reprint author), NIH, Ctr Mol Modeling, Ctr Informat Technol, Bldg 12A,Room 2049, Bethesda, MD 20892 USA. EM leeys@mail.nih.gov NR 29 TC 33 Z9 33 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JUL PY 2004 VL 11 IS 7 BP 991 EP 998 DI 10.1016/j.chembiol.2004.05.010 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 842EY UT WOS:000222987300016 PM 15271357 ER PT J AU Pratt, MR Hang, HC Ten Hagen, KG Rarick, J Gerken, TA Tabak, LA Bertozzi, CR AF Pratt, MR Hang, HC Ten Hagen, KG Rarick, J Gerken, TA Tabak, LA Bertozzi, CR TI Deconvoluting the functions of polypeptide N-alpha-acetylgalactosaminyltransferase family members by glycopeptide substrate profiling SO CHEMISTRY & BIOLOGY LA English DT Article ID MUCIN TANDEM REPEAT; O-GLYCOSYLATION PATTERN; BOVINE UDP-GALNAC; SUBMAXILLARY MUCIN; CDNA CLONING; CAENORHABDITIS-ELEGANS; SUCRASE-ISOMALTASE; PEPTIDE SEQUENCE; EXPRESSION; SITE AB The polypeptide N-alpha-acetylgalactosaminyltransferases (ppGaINAcTs) play a key role in mucin-type O-linked glycan biosynthesis by installing the intial GaINAc residue on the protein scaffold. The preferred substrates and functions of the >20 isoforms in mammals are not well understood. However, current data suggest that glycosylated mucin domains are created by the successive, often hierarchical, action of several specific ppGaINAcTs. Herein we analyzed the glycopeptide substrate preferences of several ppGaINAcT family members using a library screening approach. A 56-member glycopeptide library designed to reflect a diversity of glycan clustering was assayed for substrate activity with ppGaINAcT isoforms using an azido-ELISA. The data suggest that the ppGaINAcTs can be classified into at least four types, which working together, are able to produce densely glycosylated mucin glycoproteins. C1 Univ Calif Berkeley, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. NIDDK, Sect Biol Chem, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Pediat & Biochem, Cleveland, OH 44016 USA. RP Bertozzi, CR (reprint author), Univ Calif Berkeley, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA. EM crb@berkeley.edu FU NCI NIH HHS [R01 CA078834, CA078834]; NIGMS NIH HHS [GM66047] NR 38 TC 58 Z9 59 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JUL PY 2004 VL 11 IS 7 BP 1009 EP 1016 DI 10.1016/j.chembiol.2004.05.009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 842EY UT WOS:000222987300018 PM 15271359 ER PT J AU Gohagan, J Marcus, P Fagerstrom, R Pinsky, P Kramer, B Prorok, P AF Gohagan, J Marcus, P Fagerstrom, R Pinsky, P Kramer, B Prorok, P CA The Lung Screening Study Research TI Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph - The Lung Screening Study of the National Cancer Institute SO CHEST LA English DT Article DE chest radiograph; lung cancer; randomized trial; screening; spiral CT scan ID COMPUTED-TOMOGRAPHY; TRENDS AB Background: Low-radiation-dose spiral CT (LDCT) scanning is capable of detecting lung neoplasms in asymptomatic individuals. To determine whether such detection can reduce lung cancer mortality, a randomized controlled trial (RCT) of LDCT scanning is necessary. Methods: The feasibility of conducting an RCT in asymptomatic individuals who are at high risk for lung cancer was explored in the Lung Screening Study (LSS), a 12-month special project of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. During the fall of 2000, six PLCO screening centers recruited a total of 3,318 heavy or long-term smokers who were not participants in the PLCO trial and randomized them to receive either a screening LDCT scan (1,660 participants) or screening posteroanterior view chest radiograph (CXR) [1,658 participants]. Results: The screens were completed on 96% of subjects in the LDCT scan arm and 93% of subjects in the CXR arm. A total of 20.5% of screened subjects in the LDCT scan arm and 9.8% of those in the CXR arm had findings that were suspicious for lung cancer. Thirty lung cancers in subjects in the LDCT arm and 7 lung cancers in patients in the CXR arm were diagnosed following a positive screening result. Additional data from the LSS indicated that, among persons who were at elevated risk for lung cancer, CT scan use was not pervasive, interest in participating in an RCT of LDCT scanning was strong, and few subjects randomized to CXR either refused their examination or sought a CT scan after their study CXR. Interpretation: The results of the LSS demonstrated convincingly the feasibility of an RCT of LDCT scanning in the United States. C1 NCI, Div Canc Prevent, Writing Comm, Lung Screening Study Res Grp, Bethesda, MD 20892 USA. RP Pinsky, P (reprint author), NCI, Div Canc Prevent, Writing Comm, Lung Screening Study Res Grp, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 15 TC 166 Z9 175 U1 2 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2004 VL 126 IS 1 BP 114 EP 121 DI 10.1378/chest.126.1.114 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 841XP UT WOS:000222965900021 PM 15249451 ER PT J AU Bornstein, MH Cote, LR Maital, S Painter, K Park, SY Pascual, L Pecheux, MG Ruel, J Venuti, P Vyt, A AF Bornstein, MH Cote, LR Maital, S Painter, K Park, SY Pascual, L Pecheux, MG Ruel, J Venuti, P Vyt, A TI Cross-linguistic analysis of vocabulary in young children: Spanish, Dutch, French, Hebrew, Italian, Korean, and American English SO CHILD DEVELOPMENT LA English DT Review ID EARLY LEXICAL DEVELOPMENT; COMMUNICATIVE DEVELOPMENT INVENTORY; SOCIAL DESIRABILITY; NOUN BIAS; REFERENTIAL STYLE; MATERNAL SPEECH; LANGUAGE; VERBS; INPUT; ACQUISITION AB The composition of young children's vocabularies in 7 contrasting linguistic communities was investigated. Mothers of 269 twenty-month-olds in Argentina, Belgium, France, Israel, Italy, the Republic of Korea, and the United States completed comparable vocabulary checklists for their children. In each language and vocabulary size grouping (except for children just learning to talk), children's vocabularies contained relatively greater proportions of nouns than other word classes. Each word class was consistently positively correlated with every other class in each language and for children with smaller and larger vocabularies. Noun prevalence in the vocabularies of young children and the merits of several theories that may account for this pattern are discussed. C1 NICHHD, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Haifa, Dept Educ, IL-31999 Haifa, Israel. Univ Paris 05, Lab Cognit & Dev, F-75270 Paris 06, France. Corso Iaurea Sci & Tech Psicol Cognit Appl, Trento, Italy. RP Bornstein, MH (reprint author), NICHHD, NIH, US Dept Hlth & Human Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 150 TC 99 Z9 104 U1 5 U2 26 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JUL-AUG PY 2004 VL 75 IS 4 BP 1115 EP 1139 DI 10.1111/j.1467-8624.2004.00729.x PG 25 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 843FQ UT WOS:000223064300010 PM 15260868 ER PT J AU Koranteng, RD Swindle, EJ Davis, BJ Dearman, RJ Kimber, I Flanagan, BF Coleman, JW AF Koranteng, RD Swindle, EJ Davis, BJ Dearman, RJ Kimber, I Flanagan, BF Coleman, JW TI Differential regulation of mast cell cytokines by both dexamethasone and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE mast cell; cytokines; glucocorticoids; dexamethasone; mitogen-activated protein kinase (MAPK) inhibitors ID FC-EPSILON-RI; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; TNF-ALPHA; GLUCOCORTICOIDS INHIBIT; CYCLOSPORINE-A; IGE; EXPRESSION; RELEASE; MOUSE AB Activated mast cells generate multiple cytokines but it is not known if these can be differentially regulated by pharmacological agents. We report here that the glucocorticoid dexamethasone (DEX) preferentially inhibited Ag-induced expression of IL-4 and IL-6 mRNA relative to TNF-alpha mRNA in RBL-2H3 cells. Likewise, the drug more readily inhibited release of IL-4 than TNF-alpha protein. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), enhanced Ag-induced TNF-alpha mRNA expression without affecting IL-4 or IL-6 mRNA. At the protein level, SB203580 exerted little effect on TNF-alpha release but inhibited IL-4 release; notably, the ratio of TNF-alpha : IL-4 increased markedly with the concentration of SB203580, confirming the differential regulation of these cytokines. PD98059, an inhibitor of MAPK kinase (MEK), a component of the p44/42 MAPK pathway, partially inhibited Ag-induced expression of mRNA for all three cytokines while cyclosporin A inhibited Ag-induced IL-4 and IL-6 mRNA more readily than TNF-alpha mRNA. Ag activation of the cells led to phosphorylation of p38 and p44/42 MAPK but this was not influenced by DEX. In conclusion, mast cell cytokines can be differentially regulated pre- and post-translationally by DEX and SB203580 but there does not appear to be a direct mechanistic link between the actions of these two drugs. C1 Univ Liverpool, Dept Pharmacol, Liverpool L69 3BX, Merseyside, England. Univ Liverpool, Dept Immunol, Liverpool L69 3BX, Merseyside, England. Syngenta Cent Toxicol Lab, Macclesfield, Cheshire, England. RP Coleman, JW (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C213, Bethesda, MD 20892 USA. EM jwcoleman@niaid.nih.gov NR 34 TC 27 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2004 VL 137 IS 1 BP 81 EP 87 DI 10.1111/j.1365-2249.2004.02510.x PG 7 WC Immunology SC Immunology GA 829LO UT WOS:000222050100012 PM 15196247 ER PT J AU Zhou, ZH Notkins, AL AF Zhou, ZH Notkins, AL TI Polyreactive antigen-binding B (PAB(+)) cells are widely distributed and the PAB(+) population consists of both B-1(+) and B-1(-) phenotypes SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE B cell receptor; immunological tolerance; innate immunity; natural antibodies; natural immunity ID SPLENIC MARGINAL ZONE; HIV-1 MONOCLONAL-ANTIBODY; NATURAL ANTIBODIES; NEGATIVE SELECTION; ESCHERICHIA-COLI; HIGH-AFFINITY; AUTOANTIBODIES; LYMPHOCYTES; EXPRESSION; REPERTOIRE AB B cells that make polyreactive antibodies (PAB(+) cells) express polyreactive Ig receptors on their surface and can bind a variety of different antigens. The present study shows that PAB(+) cells are widely distributed, are present in varying numbers in different lymphoid organs and that their phenotype varies depending on the organs from which they are isolated. Up to 10 times more cells in PAB(+) enriched populations bind antigens as compared to PAB(-) populations. Comparison of PAB(+) with B-1(+) cells showed that a high percentage of PAB(+) cells are B-1(+), but that many PAB(+) cells do not express B-1 cell surface markers and, in fact, are B-1(-). It is concluded that the B cell population consists of PAB(+)/B-1(+), PAB(+)/B-1(-), PAB(-)/B-1(+), and PAB(-)/B-1(-) cells. The presence of PAB(+) cells in the thymus points to the possibility that PAB(+) cells may carry endogenous host antigens from peripheral tissues to the thymus where they may contribute to 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, Bldg 30,Rm 121,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov NR 57 TC 21 Z9 23 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2004 VL 137 IS 1 BP 88 EP 100 DI 10.1111/j.1365-2249.2004.02511.x PG 13 WC Immunology SC Immunology GA 829LO UT WOS:000222050100013 PM 15196248 ER PT J AU Fukuoka, J Fujii, T Shih, JH Dracheva, T Meerzaman, D Player, A Hong, K Settnek, S Gupta, A Buetow, K Hewitt, S Travis, WD Jen, J AF Fukuoka, J Fujii, T Shih, JH Dracheva, T Meerzaman, D Player, A Hong, K Settnek, S Gupta, A Buetow, K Hewitt, S Travis, WD Jen, J TI Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SWI-SNF COMPLEX; TISSUE MICROARRAYS; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE; YEAST; CYCLE; TRANSCRIPTION; MUTATIONS; PURIFICATION; REGULATORS AB We immunohistochemically examined 12 core proteins involved in the chromatin remodeling machinery using a tissue microarray composed of 150 lung adenocarcinoma (AD) and 150 squamous cell carcinoma (SCC) cases. Most of the proteins showed nuclear staining, whereas some also showed cytoplasmic or membranous staining. When the expression patterns of all tested antigens were considered, proteins with nuclear staining clustered into two major groups. Nuclear signals of BRM, Ini-1, retinoblastoma, mSin3A, HDAC1, and HAT1 clustered together, whereas nuclear signals of BRG1, BAF155, HDAC2, BAF170, and RbAP48 formed a second cluster. Additionally, two thirds of the cases on the lung tissue array had follow-up information, and survival analysis was performed for each of the tested proteins. Positive nuclear BRM (N-BRM) staining correlated with a favorable prognosis in SCC and AD patients with a 5 year-survival of 53.5% compared with 32.3% for those whose tumors were negative for N-BRM (P = 0.015). Furthermore, patients whose tumors stained positive for both N-BRM and nuclear BRG1 had a 5 year-survival of 72% compared with 33.6% (P = 0.013) for those whose tumors were positive for either or negative for both markers. In contrast, membranous BRM (M-BRM) staining correlated with a poorer prognosis in AD patients with a 5 year-survival of 16.7% compared with those without M-BRM staining (38.1%; P = 0.016). These results support the notion that BRM and BRG1 participate in two distinct chromosome remodeling complexes that are functionally complementary and that the nuclear presence of BRM, its coexpression with nuclear BRG1, and the altered cellular localization of BRM (M-BRM) are useful markers for non-small cell lung cancer prognosis. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Shiga Univ Med Sci, Dept Pathol, Shiga, Japan. Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21218 USA. RP Jen, J (reprint author), 41 Lib Dr,Room D702, Bethesda, MD 20892 USA. EM jenj@mail.nih.gov RI Fujii, Takeshi/D-5877-2014; OI Fujii, Takeshi/0000-0001-7237-1183; Hewitt, Stephen/0000-0001-8283-1788 NR 49 TC 126 Z9 132 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2004 VL 10 IS 13 BP 4314 EP 4324 DI 10.1158/1078-0432.CCR-03-0489 PG 11 WC Oncology SC Oncology GA 835CK UT WOS:000222457300005 PM 15240517 ER PT J AU Nesterova, MV Cho-Chung, YS AF Nesterova, MV Cho-Chung, YS TI Antisense protein kinase A RI alpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: Blockade at the initial phase of carcinogenesis SO CLINICAL CANCER RESEARCH LA English DT Article ID EMBRYO CELL-CULTURES; DIETARY ANTIOXIDANTS; GENE-EXPRESSION; TUMOR-GROWTH; CYCLIC-AMP; NAD(P)H-QUINONE REDUCTASE; METABOLIZING ENZYMES; REGULATORY SUBUNIT; BINDING-SITES; DNA AB Purpose: There are two types of cyclic AMP (cAMP)dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIalpha gene expression at the initial phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)induced mammary carcinogenesis. Experimental Design: Antisense RIalpha oligodeoxynucleotide (ODN) targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Results: Antisense RIalpha, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIalpha-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland and liver preceded DMBA-induced tumor production, and antisense down-regulation of RIalpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense RIalpha in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein 1 (API)- and cAMP response element (CRE)-directed transcription. In the mammary glands, antisense RIalpha promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIalpha. Conclusions: The results demonstrate that RIalpha antisense produces dual anticarcinogenic effects: (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in the mammary gland by down-regulating PKA-I. C1 NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,HIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,HIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov NR 52 TC 12 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2004 VL 10 IS 13 BP 4568 EP 4577 DI 10.1158/1078-0432.CCR-03-0436 PG 10 WC Oncology SC Oncology GA 835CK UT WOS:000222457300037 PM 15240549 ER PT J AU Sokoll, LJ Wians, FH Remaley, AT AF Sokoll, LJ Wians, FH Remaley, AT TI Rapid intraoperative immunoassay of parathyroid hormone and other hormones: A new paradigm for point-of-care testing SO CLINICAL CHEMISTRY LA English DT Review ID SURGICAL-MANAGEMENT; PRIMARY HYPERPARATHYROIDISM; PTH ASSAY; SECONDARY HYPERPARATHYROIDISM; GASTRIN MEASUREMENTS; NECK EXPLORATION; CUSHINGS-DISEASE; SURGERY; LOCALIZATION; ACTH AB Background: The first description of the use of a rapid assay for the measurement of intact parathyroid hormone (PTH) in patients undergoing parathyroidectomy for hyperparathyroidism was reported in 1988. Subsequent improvements in the analytical performance of the rapid intraoperative PTH assay allowed the establishment of its clinical utility in the surgical management of hyperparathyroidism. These modifications also allowed the assay to be performed in or near the operating suite. Methods: We searched MEDLINE, using the following key words: intraoperative, rapid, quick, parathyroid hormone, hormone, and immunoassay. Relevant articles that focused on the analytical aspects and clinical utility of rapid intraoperative hormone immunoassays were selected for this review. Content: On the basis of the positive impact that the rapid intraoperative PTH test has had on both patient outcomes and cost savings, other rapid intraoperative hormone immunoassays for the diagnosis and/or treatment of other endocrine-hormone-secreting tumors have been developed. These hormones share certain characteristics that make them suitable for use as rapid intraoperative tests, i.e., short analyte half-life and/or large analyte concentration gradient, rapid analysis time, and positive clinical utility. Initial studies with cortisol, gastrin, insulin, adrenocorticotropic hormone, and testosterone have shown promising results in preoperative localization studies and/or for assessing the effectiveness of tumor resection during surgery. Conclusion: The emergence of these rapid intraoperative immunoassays indicates that this test format is likely to provide future opportunities to improve patient care by advances in clinical laboratory testing. (C) 2004 American Association for Clinical Chemistry. C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. NIH, Dept Lab Med, Bethesda, MD USA. RP Sokoll, LJ (reprint author), Johns Hopkins Med Inst, Dept Pathol, 600 N Wolfe St,Meyer B-125, Baltimore, MD 21287 USA. NR 76 TC 48 Z9 48 U1 3 U2 5 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 JUL PY 2004 VL 50 IS 7 BP 1126 EP 1135 DI 10.1373/clinchem.2003.030817 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 833UM UT WOS:000222365400004 PM 15117855 ER PT J AU Rosenzweig, SD Schaffer, AA Ding, L Sullivan, R Enyedi, B Yim, JJ Cook, JL Musser, JM Holland, SM AF Rosenzweig, SD Schaffer, AA Ding, L Sullivan, R Enyedi, B Yim, JJ Cook, JL Musser, JM Holland, SM TI Interferon-gamma receptor 1 promoter polymorphisms: population distribution and functional implications SO CLINICAL IMMUNOLOGY LA English DT Article DE single nucleotide polymorphisms; mycobacteria; pulmonary; disseminated; haplotype; avium ID SINGLE-NUCLEOTIDE POLYMORPHISMS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN-DISEASE; GENE; SUSCEPTIBILITY; TUBERCULOSIS; DIVERSITY; INFECTION; IMMUNITY; VARIANT AB Different polymorphisms have been described in the minimal promoter region (MPR) of the interferon-gamma receptor 1 (IFNGR1), a molecule that plays a critical role in mycobacterial control. We sequenced the IFNGR1 MPR from African American, Caucasian and Korean controls, and from mycobacteria-infected patients. Six different single nucleotide polymorphisms (SNPs) were detected in the IFNGR1 MPR. The three ethnic groups showed different SNP distribution patterns, but no significant differences were detected between mycobacterial cases and controls. Two polymorphisms were found in all populations (G-611A, T-56C). We cloned the four allelic variants (var) of haplotype G-611A/T-56C into a luciferase reporter vector and determined their promoter activity. Polymorphisms at position -611 had a stronger effect on the promoter activity than those at position -56, and constructs carrying G-611 produced a stronger promoter activity than -611A constructs. The IFNGR1 MPR is a polymorphic region with at least two SNPs influencing its activity, but these are not associated with increased mycobacterial susceptibility. Published by Elsevier Inc. C1 NIAID, Immunopathogenesis Sect, Host Def Lab, NIH,DHHS, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA. Univ Illinois, Infect Dis Sect, Dept Med, Chicago, IL 60607 USA. NIAID, Lab Human Bcterial Pathogenesis, NIH, DHHS, Hamilton, MT 59840 USA. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Host Def Lab, NIH,DHHS, Bldg 10,Room 11N103 10,Ctr Dr MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov RI Schaffer, Alejandro/F-2902-2012 NR 24 TC 26 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2004 VL 112 IS 1 BP 113 EP 119 DI 10.1016/j.clim.2004.03.018 PG 7 WC Immunology SC Immunology GA 834KT UT WOS:000222410700013 PM 15207788 ER PT J AU Weinberg, A Pahwa, S Oyomopito, R Carey, VJ Zimmer, B Mofenson, L Kovacs, A Burchett, SK AF Weinberg, A Pahwa, S Oyomopito, R Carey, VJ Zimmer, B Mofenson, L Kovacs, A Burchett, SK CA Pediat AIDS Clin Trials Grp 366 Team TI Antimicrobial-specific cell-mediated immune reconstitution in children with advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, IL ID HIV-INFECTION; 1-INFECTED CHILDREN; MYCOBACTERIUM-AVIUM; PROTEASE INHIBITOR; MICROBIAL ANTIGENS; T-CELLS; RESPONSES; DISEASE; APOPTOSIS; AIDS AB To identify virological and immunological correlates of microbial-specific immune reconstitution in children with advanced human immunodeficiency virus (HIV) infection, Candida- and tetanus-specific lymphocyte proliferation was measured in 165 children initiating a new highly active antiretroviral therapy ( HAART) regimen. During the study, the proportions of children with immunity to Candida and tetanus increased from 53% to 66% and 19% to 22%, respectively. Tetanus immunity was associated with an HIV load less than or equal to400 RNA copies/mL and with Candida immunity. At the end of the study, 23% of the patients with baseline negative lymphocyte proliferation had tetanus immunity, and 65% had Candida immunity. Reconstitution of tetanus immunity correlated with lower end-of-study HIV loads and activated CD8(+) cell percentages and higher baseline and in-study CD4(+) cell percentages, but not with a gain of CD4(+) cells. Reconstitution of Candida immunity showed similar trends. In conclusion, children with advanced HIV infection receiving HAART reconstituted Candida immunity more readily than they did tetanus immunity, suggesting a role for antigen reexposure. Additional factors for immune reconstitution were low HIV load, high CD4(+) cell percentages, and low levels of activated CD8(+) cells. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. N Shore Univ Hosp, Manhasset, NY USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NICHHD, NIH, Rockville, MD USA. Los Angeles Cty Med Ctr, Los Angeles, CA USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. RP Weinberg, A (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave,Campus Box C227, Denver, CO 80262 USA. EM adriana.weinberg@uchsc.edu OI Mofenson, Lynne/0000-0002-2818-9808 NR 35 TC 18 Z9 18 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2004 VL 39 IS 1 BP 107 EP 114 DI 10.1086/420931 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 829YJ UT WOS:000222087800018 PM 15206061 ER PT J AU Arduino, RC Nannini, EC Rodriguez-Barradas, M Schrader, S Losso, M Ruxrungtham, K Allende, MC Emery, S Fosdick, L Neaton, J Tavel, JA Davey, RT Lane, HC AF Arduino, RC Nannini, EC Rodriguez-Barradas, M Schrader, S Losso, M Ruxrungtham, K Allende, MC Emery, S Fosdick, L Neaton, J Tavel, JA Davey, RT Lane, HC CA ESPRIT Vanguard Gro ESPRIT Executive Comm TI CD4 cell response to 3 doses of subcutaneous interleukin 2: Meta-analysis of 3 Vanguard studies SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HIV-1 INFECTION; THERAPY; IMPACT; COUNTS AB Background. In advance of a large clinical end point trial evaluating the effectiveness of subcutaneous interleukin 2 (scIL-2) for treatment of patients with human immunodeficiency virus (HIV) infection, 3 identically designed Vanguard trials were conducted in Buenos Aires, Argentina; Bangkok, Thailand; and Houston, Texas. To more precisely quantitate the effect on CD4 cell response of 3 different doses of scIL-2 that were administered twice daily for 5 days every 8 weeks, the results of these 3 trials were pooled in a meta-analysis. Methods. Two hundred eighteen HIV-1-infected subjects who were receiving antiretroviral therapy and who had a baseline CD4 cell count of greater than or equal to350 cells/mm(3) were consecutively randomized to receive scIL-2 at a dose of 1.5 mIU (n = 36) or a control regimen (n = 36); or scIL-2 at a dose of 4.5 mIU (n = 36) or a control regimen (n = 36); or scIL- 2 at a dose of 7.5 mIU (n = 37) or a control regimen (n = 36). After completion of 3 cycles of therapy, the subjects were enrolled in an extension phase (months 6-12). Subjects were encouraged to receive additional cycles of scIL-2 to maintain a CD4 cell count of more than twice the baseline count or >1000 cells/mm(3). Results. After completion of 3 cycles of scIL-2, the mean CD4 cell count changes from baseline (calculated as changes from baseline in a scIL-2 group minus changes from baseline in its contemporaneous control group) were 67 (P = .14), 339 (P < .0001), and 605 cells/mm(3) (P < .0001) for the 1.5, 4.5, and 7.5 mIU dose groups, respectively ( for differences among dose groups). Between months 6 and 12, a total of 78%, 39%, and 32% of subjects assigned to the 1.5, 4.5, and 7.5 mIU dose groups, respectively, needed at least 1 additional cycle to achieve the CD4 cell count goal. At 12 months, the differences in the mean change in CD4 cell count from baseline between each scIL-2 dose group and its contemporaneous control group were 184, 369, and 432 cells/mm(3), respectively (for differences among dose groups). Conclusions. Although CD4 cell count increases were seen in all 3 dose groups, higher scIL-2 doses resulted in greater CD4 cell count changes after 6 months, compared with control groups. C1 Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Montrose Clin, Houston, TX USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, Coordinating Ctr Biometr Res, Minneapolis, MN 55455 USA. Hosp JM Ramos Mejia, Buenos Aires, DF, Argentina. Chulalongkorn Univ, Dept Med, Bangkok, Thailand. Thai Red Cross AIDS Res Ctr, HIVNAT, Bangkok, Thailand. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Arduino, RC (reprint author), Univ Texas, Hlth Sci Ctr, 6431 Fannin,Rm 1-728 JFB, Houston, TX 77030 USA. EM Roberto.C.Arduino@uth.tmc.edu FU Medical Research Council [MC_U122886352] NR 11 TC 25 Z9 25 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2004 VL 39 IS 1 BP 115 EP 122 DI 10.1086/421775 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 829YJ UT WOS:000222087800019 PM 15206062 ER PT J AU Kurokawa, K de Almeida, DF Zhang, Y Hebert, CD Page, JG Schweikart, KM Oh, SJ AF Kurokawa, K de Almeida, DF Zhang, Y Hebert, CD Page, JG Schweikart, KM Oh, SJ TI Sensory nerve conduction of the plantar nerve compared with other nerve conduction tests in rats SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE sensory nerve conduction; plantar nerve; rat nerve conduction; experimental neuropathy ID TAIL NERVE; NEUROPATHY; GROWTH AB Objective: In rats the available techniques for evaluation of sensory nerve conduction are limited. We report a new method of sensory nerve conduction of the plantar nerve using needle electrodes as the recording electrodes behind the medial malleolus and ring electrodes as the stimulating electrodes around the three middle toes. Methods: We performed this sensory nerve conduction test in 25 rats during their growth over a 6 weeks' period and compared this method with the motor nerve conduction and H-retlex sensory nerve conduction of the tibial nerve in 10 rats, and with the motor and mixed nerve conductions of the tail nerve in 15 rats. Results: There was a highly or moderately significant correlation between the body weight and sensory nerve conduction velocity (NCV) of the plantar nerve, mixed NCV and motor NCV of the tail nerve, indicating a growth-related increase in the NCV. The growth-related increase in the NCV was not observed in the motor and H-reflex sensory nerve conductions of the tibial nerves. Conclusions: This test is simple and reliable and can be used for the sensory nerve conduction test in rats. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Alabama, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. So Res Inst, Dept Safety Assessment, Birmingham, AL USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD USA. RP Oh, SJ (reprint author), Univ Alabama, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. EM shinjoh@uab.edu NR 16 TC 20 Z9 21 U1 0 U2 2 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 JUL PY 2004 VL 115 IS 7 BP 1677 EP 1682 DI 10.1016/j.clinph.2004.02.007 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839WE UT WOS:000222814800021 PM 15203069 ER PT J AU Post, RM AF Post, RM TI Differing psychotropic profiles of the anticonvulsants in bipolar and other psychiatric disorders SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article; Proceedings Paper CT 83rd Conference on Convulsants and AntiConvulsants in Psychiatry and Neurology CY NOV 14-15, 2003 CL New York, NY SP Assoc Res Nervous & Ment Dis DE bipolar disorder; anticonvulsants; mechanisms; tolerance; carbamazepine; valproate; gabapentin; lamotrigine; topiramate; levetiracetam; psychotropic effects; kindling ID POSTTRAUMATIC-STRESS-DISORDER; AMYGDALA-KINDLED SEIZURES; MANIC-DEPRESSIVE ILLNESS; MESSENGER-RNA EXPRESSION; PLACEBO-CONTROLLED TRIAL; COMPARATIVE PROPHYLACTIC EFFICACY; LITHIUM MAINTENANCE TREATMENT; CONTROLLED 18-MONTH TRIAL; BINGE-EATING DISORDER; LONG-TERM TREATMENT AB Several compounds from the anticonvulsant category have played a major role in therapeutic approaches to bipolar illness, particularly carbamazepine, valproate, and lamotrigine. At the same time there is little evidence that covert seizures underlie the affective disorders, or that all anticonvulsants are effective acute antimanic or mood stabilizing agents. For example, recent FDA-approved anticonvulsants (gabapentin, the gamma-aminobutyric acid (GABA) re-uptake inhibitor tiagabine, and topiramate) that exert major effects on GABAergic systems and increase brain GABA in patients as measured by magnetic resonance spectroscopy, do not appear to be effective acute antimanic agents based on controlled clinical trials or detailed open observations. This raises the question as to what mechanistic properties within the anticonvulsant class are associated with positive effects in bipolar illness; candidates include blockade of sodium channels and decreased release of glutamate, decreased calcium influx through the NMDA receptor, increases in potassium efflux, as well as a variety of aminergic effects and effects on gene expression. With the exception of lamotrigine, mood stabilizers (including lithium, valproate, and carbamazepine) appear to be better acute and prophylactic antimanics than antidepressants, and preliminary data suggest this for zonisamide as well. Some of the anticonvulsants appear useful in targeting a variety of other syndromes and ones that are often comorbid with bipolar illness, including anxiety disorders, substance abuse disorders, migraine, eating disorders, and obesity. Gabapentin is effective in panic anxiety and social phobia as well as chronic pain syndromes, whereas a large range of anticonvulsants may be useful in the treatment of sleep disorders and paroxysmal components of posttraumatic stress disorder. Recent data indicate that topiramate has the ability to reduce alcohol intake and craving in patients with primary alcoholism compared with placebo, and both topiramate and zonisamide share the positive side effect of inducing weight loss of a magnitude similar to that achieved with the FDA-approved weight-loss drug sibutramine. Thus, while there is an apparent absence of seizures in bipolar illness, and anticonvulsant efficacy is not sufficient for classifying the psychotropic properties of these agents, some of the mechanisms that are pertinent to inhibiting paroxysmal discharges in the epilepsies may also be pertinent to the wide range of primary or adjunctive uses of the anticonvulsants in a range of neuropsychiatric disorders. (C) 2004 Elsevier B.V. All rights reserved. C1 NIMH, Biol Psychiat Branch, DHHS, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, DHHS, NIH, Bldg 10,Room 3S239,10 Ctr Dr,MSC-1272, Bethesda, MD 20892 USA. EM robert.post@nih.gov NR 147 TC 8 Z9 8 U1 3 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JUL PY 2004 VL 4 IS 1-2 BP 9 EP 30 DI 10.1016/j.cnr.2004.06.003 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 861EU UT WOS:000224399700003 ER PT J AU Sparreboom, A Gelderblom, H Marsh, S Ahluwalia, R Obach, R Principe, P Twelves, C Verweij, J McLeod, HL AF Sparreboom, A Gelderblom, H Marsh, S Ahluwalia, R Obach, R Principe, P Twelves, C Verweij, J McLeod, HL TI Diflomotecan pharmacokinetics in relation to ABCG2 421C > A genotype SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CANCER RESISTANCE PROTEIN; BINDING CASSETTE TRANSPORTERS; MULTIDRUG-RESISTANCE; ACQUIRED MUTATIONS; CELL-LINES; GENE; EXPRESSION; POLYMORPHISMS; CYP3A5; BIOAVAILABILITY AB Objective: The adenosine triphosphate-binding cassette transporter ABCG2 (breast cancer resistance protein [BCRP]) functions as an efflux transporter for many drugs, including the topoisomerase I inhibitor diflomotecan, and is expressed at high levels in the intestine and liver. We performed an exploratory analysis to evaluate the effects of the natural allelic variant ABCG2 421C>A on the pharmacokinetics of diflomotecan. Methods. The drug was administered to 22 adult white patients with cancer as a 20-minute infusion (dose, 0.10-0.27 mg), followed 2 weeks later by an oral solution (dose, 0.10-0.35 mg). Results. The ABCG2 421C>A genotype significantly affected the pharmacokinetics of diflomotecan; in 5 patients heterozygous for this allele, plasma levels after intravenous drug administration were 299% (P = .015) of those in 15 patients with wild-type alleles, at mean values of 138 ng (.) h/mL (.) mg(-1) (95% confidence interval, 11.3-264 ng (.) h/mL (.) mg(-1)) versus 46.1 ng (.) h/mL (.) mg(-1) (95% confidence interval, 25.6-66.7 ng (.) h/mL (.) mg(-1)), respectively. Diflomotecan levels were not significantly influenced by 11 known variants in the ABCB1, ABCC2, cytochrome P450 (CYP) 3A4, and CYP3A5 genes. Conclusion: These findings provide the first evidence linking variant ABCG2 alleles to altered drug exposure and suggest that interindividual variability in substrate drug effects might be influenced, in part, by ABCG2 genotype. C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Beaufour Ipsen Pharma Int Paris, Paris, France. Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. Tom Connors Canc Res Ctr, Bradford, W Yorkshire, England. Erasmus MC Daniel Dent Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM SparrebA@mail.nih.gov RI Sparreboom, Alex/B-3247-2008 FU NIGMS NIH HHS [U01 GM63340] NR 37 TC 172 Z9 183 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2004 VL 76 IS 1 BP 38 EP 44 DI 10.1016/j.clpt.2004.03.003 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 836WF UT WOS:000222586000004 PM 15229462 ER PT J AU Rogawski, MA AF Rogawski, Michael A. TI What Is the Rationale for New Treatment Strategies in Alzheimer's Disease? SO CNS SPECTRUMS LA English DT Article AB Alzheimer's disease (AD) is characterized by the abnormal extracellular accumulation of amyloid beta-peptide (A beta) into neuritic plaques and the intraneuronal aggregation of the microtubule-associated protein tau to form neurofibrillary tangles. These molecular events are implicated in the selective damage to neural systems critical for the brain functions that are impaired in AD. Impairment of cholinergic neurotransmission may be an important factor underlying the defects in cognition and memory that characterize AD. Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and galantamine, cause symptomatic improvement by inhibiting the breakdown of the neurotransmitter acetylcholine to increase its synaptic availability and, in the case of galantamine, by also allosterically potentiating nicotinic cholinergic receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and statins, have shown some benefit in epidemiological studies and clinical trials although compelling evidence of their efficacy is lacking. Memantine, shown to cause cognitive and functional improvement, is not an ChE inhibitor and does not interact with marketed ChE inhibitors. While the mechanism of action of memantine in AD is not known, the principal pharmacologic actions at therapeutic dose are inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D-aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists, memantine causes behavioral activation associated with enhanced cerebral glucose utilization. Studies have shown that memantine can reverse the decreased metabolic activity associated with AD, possibly accounting for its beneficial effects on cognition and global functioning. Memantine also has neuroprotective properties and can inhibit A beta-induced neurodegeneration. CNS Spectr. 2004;9(Suppl 5):6-12,31 C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, NIH, 49 Convent Dr,Rm 5A-75,MSC 4457, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 72 TC 12 Z9 15 U1 0 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUL PY 2004 VL 9 IS 7 BP 6 EP + PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V04RG UT WOS:000207074900002 PM 15241294 ER PT J AU Zheng, G AF Zheng, G TI Some remarks on the Fisher information in ranked set samples SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE best linear unbiased estimate; efficiency; maximum likelihood estimate; modified ranked set samples; partial ranked set samples; subadditivity of Fisher information ID STATISTICS AB We consider Fisher information contained in a partial ranked set under perfect judgment ranking. Chen [Chen, Z. (2000). The efficiency of ranked-set sampling relative to simple random sampling under multi-parameter families. Statist. Sinica 10:247-263] showed that the Fisher information matrix contained in a ranked set sample is equal to that in a random sample with the same size plus a positive definite matrix. We prove a similar result for a partial ranked set sample, which generalizes the result of Chen and shows the subadditivity property of Fisher information in order statistics. Calculating exact Fisher information has applications to inference based on modified ranked set samples. For some distributions, inference based on partial ranked samples or modified ranked set samples is more efficient than that based on random samples of the same size. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,Rockledge 2,Room 8223, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 16 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PD JUL PY 2004 VL 33 IS 7 BP 1511 EP 1525 DI 10.1081/sta-120037257 PG 15 WC Statistics & Probability SC Mathematics GA 831BB UT WOS:000222166800005 ER PT J AU Samuels, J Bienvenu, OJ Cullen, B Costa, PT Eaton, WW Nestadt, G AF Samuels, J Bienvenu, OJ Cullen, B Costa, PT Eaton, WW Nestadt, G TI Personality dimensions and criminal arrest SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID MENTAL-DISORDERS; BIRTH COHORT; VIOLENCE; BEHAVIOR; POPULATION; OFFENDERS; COMMUNITY; FINLAND; HEALTH; CRIME AB Previous studies have implicated antisocial personality disorder in criminal behavior, but little is known about the association between "normal" personality dimensions and arrest. We investigated the relationships between these personality dimensions and prior arrest in a sample of adults participating in a longitudinal epidemiological study. Between 1993 and 1999, psychiatrists re-examined subjects who were originally interviewed in Baltimore in 1981 as part of the Epidemiologic Catchment Area study; the psychiatrists diagnosed axis I and axis 11 disorders according to DSM-IV criteria. A total of 611 subjects also completed the Revised NEO Personality Inventory (NEO-PI-R), which assesses five broad factors and 30 facets of normal personality. History of criminal arrest in Maryland in the period 1981 to 1993 was determined from the state criminal justice database. Student's t test and logistic regression were used to evaluate relationships between NEO personality scores and prior arrest. Controlling for demographic characteristics, alcohol or drug use disorders, and DSM-IV personality disorder scores, the odds of prior arrest increased with scores on angry hostility, impulsiveness, and excitement-seeking dimensions. Prior arrest was inversely related to scores on trust, straightforwardness, compliance, modesty, dutifulness, and deliberation dimensions. The results suggest that specific dimensions of normal personality are related to criminal arrest in the community. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Bloomberg Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Samuels, J (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Meyer 4-181,600 N Wolfe St, Baltimore, MD 21287 USA. OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712 FU NIMH NIH HHS [MH47447, MH50616] NR 31 TC 28 Z9 28 U1 4 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2004 VL 45 IS 4 BP 275 EP 280 DI 10.1016/j.comppsych.2004.03.013 PG 6 WC Psychiatry SC Psychiatry GA 836HQ UT WOS:000222546900006 PM 15224270 ER PT J AU Solomon, J Warren, K Dombi, E Patronas, N Widemann, B AF Solomon, J Warren, K Dombi, E Patronas, N Widemann, B TI Automated detection and volume measurement of plexiform neurofibromas in neurofibromatosis 1 using magnetic resonance imaging SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE image processing; volumetric analysis; edge detection; histogram; neurofibromatosis 1; plexiform neurofibromas ID MR-IMAGES; SEGMENTATION; TUMORS AB An automated technique for segmentation and volumetric measurement of plexiform neurofibromas (PN) in neurofibromatosis I using short T1-inversion recovery magnetic resonance images is presented. The algorithm described implements heuristics derived from human-based recognition of lesions. This technique combines region-based with boundary-based segmentation. Two observers, who performed semi-automated volume calculations and manual tracings to estimate tumor volume, validated this method on 9 PNs of different size and location. This automated method was reproducible (coefficient of variation 0.6-5.6%), yielded similar results to manual tumor tracings (R = 0.999), and will likely improve the ability to measure PNs in ongoing clinical trials. (C) 2004 Elsevier Ltd. All rights reserved. C1 Sensor Syst Inc, Sterling, VA 20164 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Neuro Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, CC, Bethesda, MD 20892 USA. RP Solomon, J (reprint author), Sensor Syst Inc, 103A Carpenter Dr, Sterling, VA 20164 USA. EM jsolomon@sensor.com NR 16 TC 47 Z9 47 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JUL PY 2004 VL 28 IS 5 BP 257 EP 265 DI 10.1016/j.compmedimag.2004.03.002 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 844MI UT WOS:000223162000004 PM 15249071 ER PT J AU St Claire, MB Kennett, MJ Besch-Williford, CL AF St Claire, MB Kennett, MJ Besch-Williford, CL TI Vitamin A toxicity and vitamin E deficiency in a rabbit colony SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID HYPERVITAMINOSIS-A; RETINOIC ACID; NUTRITION AB Vitamin A toxicosis and vitamin E deficiency was diagnosed in a commercial rabbit-breeding colony and was associated with reproductive abnormalities, abortions, and poor survivability of kits in the breeding colony. Paresis and muscular dystrophy were noted in juvenile rabbits. Another group of New Zealand White rabbits from the same commercial colony was used to assess the effect of vitamin E-based therapy on clinical signs, reproduction, and vitamin A and E serum and liver levels. Blood samples were taken before and after dietary changes and vitamin E therapy. Serum vitamin E remained low after feeding a diet containing the recommended levels of vitamin E. Administration of vitamin E for 2 weeks lowered the serum vitamin A levels and increased the vitamin E serum and liver levels. In conclusion, vitamin E therapy appears to be an effective treatment for hypervitaminosis A. C1 NIH, US Dept HHS, Bethesda, MD 20892 USA. Penn State Univ, Cent Biol Lab 101, University Pk, PA 16802 USA. Univ Missouri, Columbia, MO 65211 USA. RP St Claire, MB (reprint author), NIH, US Dept HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JUL PY 2004 VL 43 IS 4 BP 26 EP 30 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 844LO UT WOS:000223159900007 PM 15264766 ER PT J AU Danis, M AF Danis, M TI How will we respond to chronic critical illness? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE chronically ill; critical illness; health priority; mechanical ventilation; Medicare; patient preference; resource allocation ID POTENTIALLY INEFFECTIVE CARE C1 NIH, Ctr Clin, Clin Bioeth Dept, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Ctr Clin, Clin Bioeth Dept, Bethesda, MD 20892 USA. NR 9 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2004 VL 32 IS 7 BP 1617 EP 1618 DI 10.1097/01.CCM.0000130998.96420.C6 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 837QZ UT WOS:000222651800031 PM 15241118 ER PT J AU Newman, DJ Cragg, GM AF Newman, DJ Cragg, GM TI Advanced preclinical and clinical trials of natural products and related compounds from marine sources SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID WHIP PSEUDOPTEROGORGIA-ELISABETHAE; ANTIPROLIFERATIVE AGENT DIDEMNIN; CANDIDATUS ENDOBUGULA SERTULA; POTENT CYTOTOXIC DEPSIPEPTIDE; BEE VENOM PHOSPHOLIPASE-A2; SPONGE AGELAS-MAURITIANUS; PRACTICAL TOTAL-SYNTHESIS; MOLLUSK ELYSIA-RUFESCENS; SENSITIZED GUINEA-PIGS; SP STRAIN GSV-224 AB The marine environment has proven to be a very rich source of extremely potent compounds that have demonstrated significant activities in anti-tumor, anti-inflammatory, analgesia, immuno-modulation, allergy and anti-viral assays. Although the case can and has been made that the nucleosides such as Ara-A and Ara-C are derived from knowledge gained from investigations of bioactive marine nucleosides, no drug directly from marine sources (whether isolated or by total synthesis) has yet made it to the commercial sector in any human disease. However, as shown in this review, there are now significant numbers of very interesting molecules that have come from marine sources, or have been synthesized as a result of knowledge gained from a prototypical compound, that are either in or approaching Phase III clinical trials in cancer, analgesia and allergy, with a very substantial number of other, quite different potential agents following in their wake, in these and in other diseases. C1 NCI, Nat Prod Branch, Fairview Ctr, Dev Therapeut Program, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Fairview Ctr, Dev Therapeut Program, Suite 206,POB B, Frederick, MD 21702 USA. EM newmand@mail.nih.gov NR 191 TC 100 Z9 105 U1 2 U2 16 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD JUL PY 2004 VL 11 IS 13 BP 1693 EP 1713 PG 21 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 836CJ UT WOS:000222532500003 PM 15279577 ER PT J AU Cases, S Zhou, P Shillingford, JM Wiseman, BS Fish, JD Angle, CS Hennighausen, L Werb, Z Farese, RV AF Cases, S Zhou, P Shillingford, JM Wiseman, BS Fish, JD Angle, CS Hennighausen, L Werb, Z Farese, RV TI Development of the mammary gland requires DGAT1 expression in stromal and epithelial tissues SO DEVELOPMENT LA English DT Article DE mammary gland; acyl CoA : diacylglycerol acyl transferase; lipid; triacylglycerol ID COA-DIACYLGLYCEROL ACYLTRANSFERASE-1; CONJUGATED LINOLEIC-ACID; ADIPOSE-TISSUE; TRIGLYCERIDE SYNTHESIS; CELL DIFFERENTIATION; OBESITY RESISTANCE; GROWTH-HORMONE; DEFICIENT MICE; FAT PAD; GENE AB Mammary gland development is a complex process that is dependent on interactions between the developing mammary epithelium and the surrounding stromal tissues. We show that mice lacking the triglyceride synthesis enzyme acyl CoA:diacylglycerol transferase 1 (DGAT1) have impaired mammary gland development, characterized by decreased epithelial proliferation and alveolar development, and reduced expression of markers of functional differentiation. Transplantation studies demonstrate that the impaired development results from a deficiency of DGAT1. in both the stromal and epithelial tissues. Our findings are the first to link defects in stromal lipid metabolism to impaired mammary gland development. C1 Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIDDK, Lab Genet & Physiol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Cases, S (reprint author), Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. EM scases@gladstone.ucsf.edu FU NCI NIH HHS [R01 CA057621, R01 CA057621-08]; NIDDK NIH HHS [DK56084, R01 DK056084, R56 DK056084]; NIEHS NIH HHS [U01 ES012801, ES012801, U01 ES012801-02] NR 45 TC 30 Z9 34 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 2004 VL 131 IS 13 BP 3047 EP 3055 DI 10.1242/dev.01158 PG 9 WC Developmental Biology SC Developmental Biology GA 840PM UT WOS:000222871400003 PM 15163627 ER PT J AU Hou, L Pavan, WJ Shin, MK Arnheiter, H AF Hou, L Pavan, WJ Shin, MK Arnheiter, H TI Cell-autonomous and cell non-autonomous signaling through endothelin receptor B during melanocyte development SO DEVELOPMENT LA English DT Article DE G-protein-coupled receptor; endothelin; Kit ligand; Mitf; phorbol ester; neurocristopathy; neural crest cell culture; tyrosinase; melanogenesis ID CREST-DERIVED MELANOCYTE; NEURAL CREST; STEEL FACTOR; WAARDENBURG-SYNDROME; COAT COLOR; MITF; TRANSCRIPTION; PRECURSORS; LOCUS; SOX10 AB The endothelin receptor B gene (Ednrb) encodes a G-protein-coupled receptor that is expressed in a variety of cell types and is specifically required for the development of neural crest-derived melanocytes and enteric ganglia. In humans, mutations in this gene are associated with Waardenburg-Shah syndrome, a disorder characterized by pigmentation defects, deafness and megacolon. To address the question of whether melanocyte development depends entirely on a cell-autonomous action of Ednrb, we performed a series of tissue recombination experiments in vitro, using neural crest cell cultures from mouse embryos carrying a novel Ednrb-null allele characterized by the insertion of a lacZ marker gene. The results show that Ednrb is not required for the generation of early neural crest-derived melanoblasts but is required for the expression of the differentiation marker tyrosinase. Tyrosinase expression can be rescued, however, by the addition of Ednrb wild-type neural tubes. These Ednrb wild-type neural tubes need not be capable of generating melanocytes themselves, but must be capable of providing KIT ligand, the cognate ligand for the tyrosine kinase receptor KIT. In fact, soluble KIT ligand is sufficient to induce tyrosinase expression in Ednrb-deficient cultures. Nevertheless, these tyrosinase-expressing, Ednrb-deficient cells do not develop to terminally differentiated, pigmented melanocytes. Pigmentation can be induced, however, by treatment with tetradecanoyl phorbol acetate, which mimics EDNRB signaling, but not by treatment with endothelin 1, which stimulates the paralogous receptor EDNRA. The results suggest that Ednrb plays a significant role during melanocyte differentiation and effects melanocyte development by both cell non-autonomous and cell-autonomous signaling mechanisms. C1 NHGRI, Genet Dis Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Program Cell & Dev Biol, Philadelphia, PA 19111 USA. NINDS, Lab Dev Neurogenet, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hou, L (reprint author), NHGRI, Genet Dis Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM lhou@mail.nih.gov OI Hou, Ling/0000-0003-0705-8099 NR 35 TC 34 Z9 35 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 2004 VL 131 IS 14 BP 3239 EP 3247 DI 10.1242/dev.01193 PG 9 WC Developmental Biology SC Developmental Biology GA 844BR UT WOS:000223132600001 PM 15201217 ER PT J AU Torres-Vazquez, J Gitler, AD Fraser, SD Berk, JD Pham, VN Fishman, MC Childs, S Epstein, JA Weinstein, BM AF Torres-Vazquez, J Gitler, AD Fraser, SD Berk, JD Pham, VN Fishman, MC Childs, S Epstein, JA Weinstein, BM TI Semaphorin-plexin signaling guides patterning of the developing vasculature SO DEVELOPMENTAL CELL LA English DT Article ID ENDOTHELIAL GROWTH FACTOR-165; ZEBRAFISH EMBRYOS; IN-VIVO; MOLECULAR-CLONING; NEUROPILIN-1; EXPRESSION; RECEPTOR; DIFFERENTIATION; VASCULOGENESIS; INHIBITION AB Major vessels of the vertebrate circulatory system display evolutionarily conserved and reproducible anatomy, but the cues guiding this stereotypic patterning remain obscure. In the nervous system, axonal pathways are shaped by repulsive cues provided by ligands of the semaphorin family that are sensed by migrating neuronal growth cones through plexin receptors. We show that proper blood vessel pathfinding requires the endothelial receptor PlexinD1 and semaphorin signals, and we identify mutations in plexinD1 in the zebrafish vascular patterning mutant out of bounds. These results reveal the fundamental conservation of repulsive patterning mechanisms between axonal migration in the central nervous system and vascular endothelium during angiogenesis. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. Univ Calgary, Smooth Muscle Res Grp, Calgary, AB T2N 4N1, Canada. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Weinstein, BM (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM bw96w@nih.gov FU NHLBI NIH HHS [R01 HL092263] NR 31 TC 238 Z9 243 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2004 VL 7 IS 1 BP 117 EP 123 DI 10.1016/j.devcel.2004.06.008 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 838EM UT WOS:000222696300015 PM 15239959 ER PT J AU Kubosaki, A Gross, S Miura, J Saeki, K Zhu, M Nakamura, S Hendriks, W Notkins, AL AF Kubosaki, A Gross, S Miura, J Saeki, K Zhu, M Nakamura, S Hendriks, W Notkins, AL TI Targeted disruption of the IA-2 beta gene causes glucose intolerance and impairs insulin secretion but does not prevent the development of diabetes in NOD mice SO DIABETES LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; RECEPTOR-TYPE; TRANSMEMBRANE PROTEIN; MAJOR AUTOANTIGEN; MEMBRANE-PROTEIN; IA-2; MELLITUS; FAMILY; IDENTIFICATION; ASSIGNMENT AB Insulinoma-associated protein (IA)-2beta, also known as phogrin, is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is located in dense-core secretory vesicles. In patients with type I diabetes, autoantibodies to IA-2beta appear years before the development of clinical disease. The genomic structure and function of IA-2beta, however, is not known. In the present study, we determined the genomic structure of IA-2beta and found that both human and mouse IA-2beta consist of 23 exons and span similar to1,000 and 800 kb, respectively. With this information, we prepared a targeting construct and inactivated the mouse IA-2beta gene as demonstrated by lack of IA-2beta mRNA and protein expression. The IA-2beta(-/-) mice, in contrast to wild-type controls, showed mild glucose intolerance and impaired glucose-stimulated insulin secretion. Knockout of the IA-2beta gene in NOD mice, the most widely studied animal model for human type 1 diabetes, failed to prevent the development of cyclophosphamide-induced diabetes. We conclude that IA-2beta is involved in insulin secretion, but despite its importance as a major autoantigen in human type I diabetes, it is not required for the development of diabetes in NOD mice. C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Nijmegen, Dept Cell Biol, Nijmegen Ctr Mol Life Sci, Nijmegen, Netherlands. NIA, Lab Expt Gerontol, Gerontol Res Ctr, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, Natl Inst Hlth, Bldg 30,Room 121,30 Convent Dr, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov RI Hendriks, Wiljan/A-5214-2013 OI Hendriks, Wiljan/0000-0001-9481-8281 NR 33 TC 64 Z9 67 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2004 VL 53 IS 7 BP 1684 EP 1691 DI 10.2337/diabetes.53.7.1684 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FM UT WOS:000222397000008 PM 15220191 ER PT J AU Duttaroy, A Zimliki, CL Gautam, D Cui, YH Mears, D Wess, J AF Duttaroy, A Zimliki, CL Gautam, D Cui, YH Mears, D Wess, J TI Muscarinic stimulation of pancreatic insulin and glucagon release is abolished in M-3 muscarinic acetylcholine receptor-deficient mice SO DIABETES LA English DT Article ID OBESE HYPERGLYCEMIC MICE; CENTRAL-NERVOUS-SYSTEM; RAT ISLETS; BETA-CELL; ENDOCRINE RESPONSES; CONSCIOUS CALVES; VAGUS NERVES; SECRETION; SUBTYPES; GLUCOSE AB Pancreatic muscarinic acetylcholine receptors play an important role in stimulating insulin and glucagon secretion from islet cells. To study the potential role of the M-3 muscarinic receptor subtype in cholinergic stimulation of insulin release, we initially examined the effect of the muscarinic agonist, oxotremorine-M (Oxo-M), on insulin secretion from isolated pancreatic islets prepared from wild-type (WT) and M-3 receptor-deficient mice (M3(+/-) and M3(-/-) mice). At a stimulatory glucose level (16.7 mmol/l), Oxo-M strongly potentiated insulin output from islets of WT mice. Strikingly, this effect was completely abolished in islets from M3(-/-) mice and significantly reduced in islets from M3(-/-) mice. Additional in vitro studies showed that Oxo-M-mediated glucagon release was also virtually abolished in islets from M3(-/-) mice. Consistent with the in vitro data, in vivo studies showed that M3-/- mice displayed reduced serum insulin and plasma glucagon levels and a significantly blunted increase in serum insulin after an oral glucose load. Despite the observed impairments in insulin release, M3(-/-) mice showed significantly reduced blood glucose levels and even improved glucose tolerance, probably due to the reduction in plasma glucagon levels and the fact that M3(-/-) mice are hypophagic and lean. These findings provide important new insights into the metabolic roles of the M-3 muscarinic receptor subtype. C1 NIDDK, Mol Signalling Sect, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD USA. RP Wess, J (reprint author), NIDDK, Mol Signalling Sect, Bioorgan Chem Lab, Natl Inst Hlth, 8A,Rm B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov NR 36 TC 111 Z9 113 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2004 VL 53 IS 7 BP 1714 EP 1720 DI 10.2337/diabetes.53.7.1714 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FM UT WOS:000222397000012 PM 15220195 ER PT J AU Hanley, AJG Festa, A D'Agostino, RB Wagenknecht, LE Savage, PJ Tracy, RP Saad, MF Haffner, SM AF Hanley, AJG Festa, A D'Agostino, RB Wagenknecht, LE Savage, PJ Tracy, RP Saad, MF Haffner, SM TI Metabolic and inflammation variable clusters and prediction of type 2 diabetes - Factor analysis using directly measured insulin sensitivity SO DIABETES LA English DT Article ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; GLUCOSE-TOLERANCE TEST; CARDIOVASCULAR RISK-FACTORS; RESISTANCE SYNDROME PREDICTS; MIDDLE-AGED MEN; MINIMAL MODEL; ATHEROSCLEROSIS RISK; AFRICAN-AMERICAN AB Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of the metabolic syndrome. The majority of previous factor analyses, however, have used only surrogate measures of insulin sensitivity; very few have included nontraditional cardiovascular disease (CVD) risk factors such as plasminogen activator inhibitor (PAI)-1, fibrinogen, and C-reactive protein (CRP); and only a limited number have assessed the ability of factors to predict type 2 diabetes. The objective of this study was to investigate, using factor analysis, the clustering of metabolic and inflammation variables using data from 1,087 nondiabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS) and to determine the association of these clusters with risk of type 2 diabetes at follow-up. This study includes information on directly measured insulin sensitivity (Si) from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. Principal factor analysis of data from nondiabetic subjects at baseline (1992-1994) identified three factors, which explained 28.4, 7.4, and 6% of the total variance in the dataset, respectively. Based on factor loadings of greater than or equal to 0.40, these factors were interpreted as 1) a "metabolic" factor, with positive loadings of BMI, waist circumference, 2-h glucose, log triglyceride, and log PAI-1 and inverse loadings of log S-i + 1 and HDL; 2) an "inflammation" factor, with positive loadings of BMI, waist circumference, fibrinogen, and log CRP and an inverse loading of log Si + 1; and 3) a "blood pressure" factor, with positive loadings of systolic and diastolic blood pressure. The results were similar within strata of ethnicity, and there were only subtle differences in sex-specific analyses. In a prospective analysis, each of the factors was a significant predictor of diabetes after a median follow-up period of 5.2 years, and each factor remained significant in a multivariate model that included all three factors, although this three-factor model was not significantly more predictive than models using either impaired glucose tolerance or conventional CVD risk factors. Factor analysis identified three underlying factors among a group of inflammation and metabolic syndrome variables, with insulin sensitivity loading on both the metabolic and inflammation variable clusters. Each factor significantly predicted diabetes in multivariate analysis. The findings support the emerging hypothesis that chronic subclinical inflammation is associated with insulin resistance and comprises a component of the metabolic syndrome. C1 Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, San Antonio, TX 78229 USA. Univ Toronto, Toronto, ON, Canada. Mt Sinai Hosp, Sinai Ctr Diabet, Dept Publ Hlth Sci, Toronto, ON M5G 1X5, Canada. Mt Sinai Hosp, Sinai Ctr Diabet, Dept Med, Toronto, ON M5G 1X5, Canada. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Univ Calif Los Angeles, Div Clin Epidemiol & Prevent Med, Los Angeles, CA USA. RP Haffner, SM (reprint author), Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, Mail Code 7873,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM haffner@uthscsa.edu RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NCRR NIH HHS [M01-RR-43]; NHLBI NIH HHS [U01-HL47887, U01-HL47889, U01-HL47892, U01-HL47902]; NIDDK NIH HHS [DK-29867]; PHS HHS [R01 58329] NR 71 TC 115 Z9 122 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2004 VL 53 IS 7 BP 1773 EP 1781 DI 10.2337/diabetes.53.7.1773 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FM UT WOS:000222397000018 PM 15220201 ER PT J AU Kovacs, P Harper, I Hanson, RL Infante, AM Bogardus, C Tataranni, PA Baier, LJ AF Kovacs, P Harper, I Hanson, RL Infante, AM Bogardus, C Tataranni, PA Baier, LJ TI A novel missense substitution (Vall483Ile) in the fatty acid synthase gene (FAS) is associated with percentage of body fat and substrate oxidation rates in nondiabetic pima Indians SO DIABETES LA English DT Article ID AUTOSOMAL GENOMIC SCAN; DIABETES-MELLITUS; INSULIN ACTION; FOOD-INTAKE; OBESITY; EXPRESSION; INHIBITOR; CLONING; MICE AB Inhibition of fatty acid synthase (FAS) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. The human FAS gene (FAS) maps to chromosome 17q25, a region previously shown to have suggestive linkage to adiposity in a genome-wide linkage scan for genetic determinants of obesity in Pima Indians. To investigate the potential role of FAS in the pathophysiology of human obesity, the FAS gene was sequenced and 13 single nucleotide polymorphisms (SNPs) were identified. Five representative SNPs were genotyped in 216 full-blooded, nondiabetic Pima Indians for association analyses. A Val1483Ile polymorphism (GTC to ATC; allele frequency of A = 0.10) was associated with percentage of body fat and 24-h substrate oxidation rates measured in a respiratory chamber. Compared with homozygotes for the Val variant, subjects with Ile/x had a lower mean percentage of body fat (30 +/- 1 vs. 33 +/- 1%, P = 0.002; adjusted for age, sex, and family membership) and a lower mean carbohydrate oxidation rate (983 41 vs. 1,094 +/- 19 kcal/day, P = 0.03), which resulted in a lower mean 24-h respiratory quotient (0.845 +/- 0.01 vs. 0.850 +/- 0.01 kcal/day, P = 0.04; both adjusted for age, sex, family membership, percentage of body fat, and energy balance). Our findings indicate that the Val1483Ile substitution in FAS is protective against obesity in Pima Indians, an effect possibly explained by the role of this gene in the regulation of substrate oxidation. C1 NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Baier, LJ (reprint author), NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 21 TC 36 Z9 38 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2004 VL 53 IS 7 BP 1915 EP 1919 DI 10.2337/diabetes.53.7.1915 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FM UT WOS:000222397000037 PM 15220220 ER PT J AU Gregg, EW Sorlie, P Paulose-Ram, R Gu, QP Eberhardt, MS Wolz, M Burt, V Curtin, L Engelgau, M Geiss, L AF Gregg, EW Sorlie, P Paulose-Ram, R Gu, QP Eberhardt, MS Wolz, M Burt, V Curtin, L Engelgau, M Geiss, L TI Prevalence of lower-extremity disease in the US adult population >= 40 years of age with and without diabetes - 1999-2000 National Health and Nutrition Examination Survey SO DIABETES CARE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; RISK-FACTORS; SENSORY NEUROPATHY; UNITED-STATES; FOOT; COMPLICATIONS; ATHEROSCLEROSIS; COMMUNITY; MORTALITY; SYMPTOMS AB OBJECTIVE - Although lower-extremity disease (LED), which includes lower-extremity peripheral arterial disease (PAD) and peripheral neuropathy (PN), is disabling and costly, no nationally representative estimates of its prevalence exist. The aim of this study was to examine the prevalence of lower-extremity PAD, PN, and overall LED in the overall U.S. population and among those with and without diagnosed diabetes. RESEARCH DESIGN AND METHODS - The analysis consisted of data for 2,873 men and women aged greater than or equal to40 years, including 419 with diagnosed diabetes, from the 1999-2000 National Health and Nutrition Examination Survey. The main Outcome measures consisted of the prevalence of lower-extremity PAD (defined as ankle-brachial index <0.9), PN (defined as greater than or equal to1 insensate area based on monofilament testing), and of any LED (defined as either PAD, PN, or history of foot ulcer or lower-extremity amputations). RESULTS - Of the U.S. population aged greater than or equal to40 years, 4.5% (95% CI 3.4-5.6) have lower-extremity PAD, 14.8% (12.8-1.6.8) have PN, and 18.7% (15.9-21.4) have any LED. Prevalence of PAD, PN, and overall LED increases steeply with age and is higher (P < 0.05) in non-Hispanic blacks and Mexican Americans than non-Hispanic whites. The prevalence of LEDs is approximately twice as high for individuals with diagnosed diabetes (PAD 9.5% [5.5-13.4], PN 28.5% [22.0-35.1]; any LED 30.2% [22.1-38.3]) as the overall population. CONCLUSIONS - LED is common in the U.S. and twice as high among individuals with diagnosed diabetes. These conditions disproportionately affect the elderly, non-Hispanic blacks, and Mexican Americans. C1 CDCP, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. CDCP, Natl Ctr Hlth Stat, Div Epidemiol, Hyattsville, MD 20782 USA. CDCP, Natl Ctr Hlth Stat, Div Hlth Examinat Surveys, Hyattsville, MD 20782 USA. NHLBI, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Gregg, EW (reprint author), CDCP, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy,NE Mailstop K-10, Atlanta, GA 30341 USA. EM edg7@cdc.gov NR 39 TC 260 Z9 267 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2004 VL 27 IS 7 BP 1591 EP 1597 DI 10.2337/diacare.27.7.1591 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FN UT WOS:000222397100011 PM 15220233 ER PT J AU Theodorakis, MJ Carlson, O Muller, DC Egan, JM AF Theodorakis, MJ Carlson, O Muller, DC Egan, JM TI Elevated plasma glucose dependent insulinotropic polypeptide associates with hyperinsulinemia in impaired glucose tolerance SO DIABETES CARE LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; BETA-CELL FUNCTION; DIABETES-MELLITUS; RAT; GIP; SECRETION; RELEASE; BIOLOGY; DEGRADATION AB OBJECTIVE - The role of gut-derived incretin, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory peptide [GIP]), in compensatory beta-cell hypersecretion during insulin-resistant states and in transition to beta-cell failure in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS - We carried out oral glucose tolerance testing followed by blood sampling 10 times for 2 h on 68 age- and BMI-matched participants of the Baltimore Longitudinal Study on Aging (BLSA) with normal glucose tolerance (34 subjects), impaired glucose tolerance (IGT) (18 subjects with both impaired fasting and 2-h plasma glucose levels), and type 2 diabetes (16 subjects With both diabetic fasting and 2-h plasma glucose levels). We assayed plasma glucose, insulin, C-peptide, glucagon, and intact and total GIP levels and quantitated glucose and hormone responses to the oral glucose tolerance test. We also compared GIP and insulin release and sensitivity indexes between groups. RESULTS - After glucose ingestion, subjects with IGT had both hyperinsulinemia and hyperemia, while subjects with type 2 diabetes had both beta- and GIP-cell deficiency. In the former group, there was also a significant positive correlation between the augmented plasma intact and total GIP levels and both fasting and post-oral glucose load plasma insulin levels. CONCLUSIONS- Elevated plasma GIP levels are correlated with hyperinsulinemia in the impaired glucose-tolerant state, whereas type 2 diabetes is associated With a failure to secrete adequate amounts of both GIP and insulin, indicating a common pathway of resistance to and eventually failure of glucose responsiveness in beta- and GIP-cells. C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Diabet Sect, NIH, 5600 Nathan Shock Dr,GRC-2B02, Baltimore, MD 21224 USA. EM eganj@vax.grc.nia.nih.gov NR 36 TC 33 Z9 34 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2004 VL 27 IS 7 BP 1692 EP 1698 DI 10.2337/diacare.27.7.1692 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FN UT WOS:000222397100026 PM 15220248 ER PT J AU Goldstein, DE Little, RR Lorenz, RA Malone, JI Nathan, D Peterson, CM Sacks, DB AF Goldstein, DE Little, RR Lorenz, RA Malone, JI Nathan, D Peterson, CM Sacks, DB TI Tests of glycemia in diabetes SO DIABETES CARE LA English DT Review ID SERUM FRUCTOSAMINE CONCENTRATION; GLYCOSYLATED HEMOGLOBIN LEVELS; LONG-TERM COMPLICATIONS; BLOOD-GLUCOSE MONITORS; GLYCATED HEMOGLOBIN; CLINICAL-USEFULNESS; URINE GLUCOSE; GLYCOHEMOGLOBIN DETERMINATIONS; PROTEIN-CONCENTRATION; BIOLOGICAL VARIATION C1 Univ Missouri, Sch Med, Dept Pathol & Anat Sci, Columbia, MO 65212 USA. Univ Missouri, Sch Med, Dept Child Hlth, Columbia, MO 65212 USA. Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO 65212 USA. Univ Illinois, Coll Med, Dept Pediat, Peoria, IL 61656 USA. Univ S Florida, Coll Med, Tampa, FL USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Little, RR (reprint author), Univ Missouri, Sch Med, Dept Pathol & Anat Sci, M7676,1 Hosp Dr, Columbia, MO 65212 USA. EM littler@health.missouri.edu OI Little, Randie/0000-0001-6450-8012; Sacks, David/0000-0003-3100-0735 NR 183 TC 248 Z9 281 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2004 VL 27 IS 7 BP 1761 EP 1773 DI 10.2337/diacare.27.7.1761 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FN UT WOS:000222397100042 PM 15220264 ER PT J AU Volokhov, D Pomerantsev, A Kivovich, V Rasooly, A Chizhikov, V AF Volokhov, D Pomerantsev, A Kivovich, V Rasooly, A Chizhikov, V TI Identification of Bacillus anthracis by multiprobe microarray hybridization SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE multiplex PCR; pXO1; pXO2; virulence factors; anthrax toxins ID POLYMERASE-CHAIN-REACTION; CLOSELY-RELATED BACTERIA; 16S RIBOSOMAL-RNA; DNA-SEQUENCE; GENETIC-RELATIONSHIPS; INFECTIOUS-DISEASES; CHROMOSOMAL MARKER; VIRULENCE FACTORS; GENOME SEQUENCE; MULTIPLEX PCR AB We have developed a rapid assay based on microarray analysis of amplified genetic markers for reliable identification of Bacillus anthracis and its discrimination from other closely related bacterial species of the Bacillus cereus group. By combining polymerase chain reaction (PCR) amplification of six B. anthracis-specific genes (plasmid-associated genes encoding virulence factors (cyaA, pagA, lef, and capA, capB, capC) and one chromosomal marker BA-5449) with analysis of amplicons by microarray hybridization, we were able to unambiguously identify and discriminate B. anthracis among other closely related species. Bacillus identification relied on hybridization with multiple individual microarray oligonucleotide probes (oligoprobes) specific to each target B. anthracis gene. Evaluation of the assay was conducted using several B. anthracis strains (with or without pXO1 and pXO2 plasmids) as well as over 50 other species phylogenetically related to B. anthracis, including B. cereus, B. thuringiensis, B. mycoides, and B. subtilis. The developed microarray analysis of amplified genetic markers protocol provides an efficient method for (i) unambiguous identification and discrimination of B. anthracis from other Bacillus species and (ii) distinguishing between plasmid-containing and plasmid-free Bacillus anthracis strains. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. NIAID, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chizhikov, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. EM chizhikov@cber.fda.gov NR 55 TC 31 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUL PY 2004 VL 49 IS 3 BP 163 EP 171 DI 10.1016/j.diagmicrobio.2004.03.015 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 842EG UT WOS:000222985400003 PM 15246505 ER PT J AU Smith, NF Figg, WD Sparreboom, A AF Smith, NF Figg, WD Sparreboom, A TI Recent advances in pharmacogenetic approaches to anticancer drug development SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE pharmacogenetics; cancer chemotherapy; drug development ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN-LIVER-MICROSOMES; AZATHIOPRINE-INDUCED MYELOSUPPRESSION; MULTIDRUG-RESISTANCE TRANSPORTER; BINDING CASSETTE TRANSPORTERS; METHYLTRANSFERASE GENE LOCUS; HEART-TRANSPLANT RECIPIENT; PREGNANE-X-RECEPTOR; UDP-GLUCURONOSYLTRANSFERASE AB A great deal of effort has been spent in defining the pharmacokinetics and pharmacodynamics of investigational and registered anticancer agents. There is often a marked variability in drug handling between individual patients, which contributes to variability in the pharmacodynamic effects of a given dose of a drug. A combination of physiological variables, genetic characteristics (pharmacogenetics), and environmental factors are known to alter the relationship between the absolute dose and the concentration-time profile in plasma. A variety of strategies is now being evaluated in patients with cancer to improve the therapeutic index of anticancer drugs, by implementation of pharmacogenetic imprinting through genotyping or phenotyping individual patients. The efforts have mainly focused on variants in genes encoding the drug-metabolizing enzymes thiopurine S-methyltransferase, dihydropyrimidine dehydrogenase, members of the cytochrome P450 family, including the CYP2B, 2C, 2D, and 3A subfamilies, members of the UGT family, as well as the ATP-binding cassette transporters ABCB1 (P-glycoprotein) and ABCG2 (breast-cancer resistance protein). Several of these genotyping strategies have been shown to have substantial impact on therapeutic outcome and should eventually lead to improved anticancer chemotherapy. (C) 2004 Wiley-Liss, Inc. C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Natl Canc Inst, Canc Res Ctr, Canc Therapeut Branch, Mol Pharmacol Sect, Bethesda, MD USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 160 TC 23 Z9 29 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUL PY 2004 VL 62 IS 3 BP 233 EP 253 DI 10.1002/ddr.10361 PG 21 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 877DD UT WOS:000225547100009 ER PT J AU Wolf, KK Wood, SG Bement, JL Sinclair, PR Wrighton, SA Jeffery, E Gonzalez, FJ Sinclair, JF AF Wolf, KK Wood, SG Bement, JL Sinclair, PR Wrighton, SA Jeffery, E Gonzalez, FJ Sinclair, JF TI Role of mouse CYP2E1 in the O-hydroxylation of P-nitrophenol: Comparison of activities in hepatic microsomes from CYP2E1(-/-) and wild-type mice SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ACETAMINOPHEN HEPATOTOXICITY; CYTOCHROME-P450 2E1; LIVER; RAT; SUBSTRATE; ETHANOL; SPECIFICITY; HEPATOCYTES; ISOPENTANOL; ISOENZYMES AB Enzymatic activities are routinely used to identify the contribution of individual forms of cytochrome P450 in a particular biotransformation. p-Nitrophenol O-hydroxylation (PNPH) has been widely used as a measure of CYP2E1 catalytic activity. However, rat and human forms of CYP3A have also been shown to catalyze this activity. In mice, the contributions of CYP3A and CYP2E1 to PNPH activity are not known. Here we used hepatic microsomes from Cyp2e1(-/-) and wild-type mice to investigate the contributions of constitutively expressed and alcohol-induced murine CYP2E1 and CYP3A to PNPH activity. In liver microsomes from untreated mice, PNPH activity was much greater in wild-type mice compared with Cyp2e1(-/-) mice, suggesting a major role for CYP2E1 in catalyzing PNPH activity. Hepatic PNPH activities were not significantly different in microsomes from male and female mice, although the microsomes from females have dramatically higher levels of CYP3A. Treatment with a combination of ethanol and isopentanol resulted in induction of CYP3A proteins in wild-type and Cyp2e1(-/-) mice, as well as CYP2E1 protein in wild-type mice. The alcohol treatment increased PNPH activities in hepatic microsomes from wild-type mice but not from Cyp2e1(-/-) mice. Our findings suggest that in untreated and alcohol-treated mice, PNPH activity may be used as a specific probe for CYP2E1 and that constitutively expressed and alcohol-induced forms of mouse CYP3A have little to no role in catalyzing PNPH activity. C1 Vet Adm Med Ctr, White River Jct, VT 05009 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol Toxicol, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Biochem, Hanover, NH 03756 USA. Lilly Res Labs, Dept Drug Disposit, Indianapolis, IN USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Sinclair, JF (reprint author), Vet Adm Med Ctr, White River Jct, VT 05009 USA. EM JSINC@dartmouth.edu FU NIAAA NIH HHS [AA12898] NR 20 TC 9 Z9 11 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL 1 PY 2004 VL 32 IS 7 BP 681 EP 684 DI 10.1124/dmd.32.7.681 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 830AH UT WOS:000222093500001 PM 15205381 ER PT J AU Basu, NK Kole, L Kubota, S Owens, IS AF Basu, NK Kole, L Kubota, S Owens, IS TI Human UDP-glucuronosyltransferases show atypical metabolism of mycophenolic acid and inhibition by curcumin SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN LIVER; MOFETIL; IDENTIFICATION; GLUCURONIDE; LOCUS; PHARMACOKINETICS; EXPRESSION; GLUCOSIDE; MECHANISM; COMPLEX AB Although the promising immunosuppressant, mycophenolic acid (MPA), has many desirable properties and is widely prescribed for organ transplant recipients, its high oral dosage requirement is not understood. Whereas previous Northern blot analysis by Basu and colleagues ( 2004) located the mRNAs encoding MPA primary metabolizers, UDP-glucuronosyltransferases (UGTs) 1A7, 1A8, 1A9, and 1A10, in human gastrointestinal (GI) tissues, in situ hybridization analysis of mRNAs found that the isozymes were restricted to the mucosal layer of various GI organs. Concomitantly, MPA was glucuronidated by microsomes isolated from normal adjoining specimens. Microsomal studies showed the highest relative rates of metabolism in esophagus, ileum, duodenum, colon, and stomach at pH 6.4; only esophagus showed high pH 7.6 activity. Properties of the recombinant UGTs indicate that MPA is metabolized with pH 6.4 or 7.6 optimum. Activity for 1A7 and 1A9 increased with increasing concentrations up to 2.4 mM, with parallel production of both ether- and acylglucuronides; similarly, 1A8 and 1A10 reached plateaus at 1.6 mM, producing both glucuronides. K-m values were 250 to 550 muM. Between 400 and 1600 muM MPA, isozymes generated between 15 and 42% of the acylglucuronides. In effect, high K-m values (MPA) are associated with high concentrations to achieve saturation kinetics. Finally, transient inhibition of UGTs in human LS180 colon cells and mouse duodenum by the dietary agent, curcumin, has implications for in vivo pretreatment to reduce MPA glucuronidation to increase the therapeutic index. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Owens, IS (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. EM owensi@mail.nih.gov NR 26 TC 46 Z9 50 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL 1 PY 2004 VL 32 IS 7 BP 768 EP 773 DI 10.1124/dmd.32.7.768 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 830AH UT WOS:000222093500014 PM 15205394 ER PT J AU Janini, GM Chan, KC Conrads, TP Issaq, HJ Veenstra, TD AF Janini, GM Chan, KC Conrads, TP Issaq, HJ Veenstra, TD TI Two-dimensional liquid chromatography-capillary zone electrophoresis-sheathless electrospray ionization-mass spectrometry: Evaluation for peptide analysis and protein identification SO ELECTROPHORESIS LA English DT Article DE capillary electrophoresis; multidimensional separations; peptides; reversed-phase liquid chromatography; serum proteins; sheathless electrospray ionization; tandem mass spectrometry ID MULTIDIMENSIONAL SEPARATION; COMPLEX-MIXTURES; SERUM PROTEOME; PERFORMANCE; TECHNOLOGY; RESOLUTION; INTERFACE; EXTRACTS; UPDATE; MS AB A peptide separation strategy that combines two-dimensional (2-D) liquid chromatography (LC)-capillary zone electrophoresis (CZE) with tandem mass spectrometry (MS/MS) is described for the identification of proteins in complex mixtures. To test the effectiveness of this strategy, a serum sample was depleted of the high-abundance proteins by methanol precipitation, digested with trypsin to generate a complex peptide mixture, and separated into 96 fractions by reversed-phase (RP)-LC. Compared to ion-exchange LC separations, RPLC provides much higher resolution and peak capacity. Fractions were collected off-line from the RPLC separation, and subjected to short 20 min CZE separations. The separated zones were introduced to the mass spectrometer through a sheathless electrospray ionization interface that is integrated on the separation capillary. The ease of fabrication of the interface and its durability allowed for the analysis of all fractions on a single capillary in a relatively short. analysis time. A stable electrospray was produced at nanoliter flowrates by augmenting analyte electrophoretic and electroosmotic mobilities with pressure-assisted flow. Unlike first-dimensional ion-exchange LC fractionation, where there is a large degree of overlap, the CZE-MS results show less than 15% overlap between neighboring RPLC fractions. C1 NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Janini, GM (reprint author), NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. EM janini@ncifcrf.gov FU NCI NIH HHS [N01 CO-12400] NR 35 TC 25 Z9 27 U1 3 U2 15 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 2004 VL 25 IS 13 BP 1973 EP 1980 DI 10.1002/elps.200405948 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 840WM UT WOS:000222890600005 PM 15237396 ER PT J AU Zheng, J Jann, MW Hon, YY Shamsi, SA AF Zheng, J Jann, MW Hon, YY Shamsi, SA TI Development of capillary zone electrophoresis-electrospray ionization-mass spectrometry for the determination of lamotrigine in human plasma SO ELECTROPHORESIS LA English DT Article DE capillary zone electrophoresis; electrospray ionization-mass spectrometry Lamotrigine; therapeutic drug monitoring ID LIQUID-CHROMATOGRAPHIC METHOD; CE-ESI-MS; SERUM LAMOTRIGINE; PERFORMANCE; ASSAY; DRUGS; PHASE; ANTICONVULSANT; OPTIMIZATION; EXTRACTION AB A method of coupling capillary zone electrophoresis (CZE) with electrospray ionization-mass spectrometry (ESI-MS) detection has been developed for monitoring an antiepileptic drug, lamotrigine (LTG) in human plasma. The CZE-MS was developed in three stages: (i) CZE separation and ESI-MS detection of LTG and tyramine (TRM, internal standard) were simultaneously optimized by studying the influence of CZE background electrolyte (BGE) pH, BGE ionic strength, and nebulizer pressure of the MS sprayer; (ii) sheath liquid parameters, such as pH, ionic strength, organic modifier content, and flow rate of the sheath liquid, were systematically varied under optimum CZE-MS conditions developed in the first stage; (iii) MS sprayer chamber parameters (drying gas temperature and drying gas flow rate) were varied for the best MS detection of LTG. The developed assay was finally applied for the determination of LTG in plasma samples. The linear range of LTG in plasma sample assay was between 0.1-5.0 mug/mL with a limit of detection as low as 0.05 mug/mL and run time less than 6 min. Finally, the concentration-time profile of LTG in human plasma sample was found to correlate well when CZE-ESI-MS was compared to a more established method of high-performance liquid chromatography with ultraviolet detection. C1 Georgia State Univ, Ctr Biotechnol & Drug Design, Dept Chem, Atlanta, GA 30303 USA. Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, Atlanta, GA USA. NIH, Clin Ctr, Pharm Dept, Clin Pharmacokinet Res Lab, Bethesda, MD USA. RP Shamsi, SA (reprint author), Georgia State Univ, Ctr Biotechnol & Drug Design, Dept Chem, Atlanta, GA 30303 USA. EM chesas@panther.gsu.edu FU NIGMS NIH HHS [GM 62314-02] NR 32 TC 32 Z9 33 U1 1 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 2004 VL 25 IS 13 BP 2033 EP 2043 DI 10.1002/elps.20305823 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 840WM UT WOS:000222890600013 PM 15237404 ER PT J AU Aladjem, MI Fanning, E AF Aladjem, MI Fanning, E TI The replicon revisited: an old model learns new tricks in metazoan chromosomes SO EMBO REPORTS LA English DT Review DE chromatin domain; DNA replication; mammalian chromosomes; origins; replicators; replicon ID ORIGIN RECOGNITION COMPLEX; BETA-GLOBIN LOCUS; DNA-REPLICATION; GENE-EXPRESSION; MAMMALIAN CHROMOSOMES; CELL-CYCLE; INITIATION; SEQUENCE; ELEMENTS; BINDING AB The origins of DNA replication were proposed in the replicon model to be specified genetically by replicator elements that coordinate the initiation of DNA synthesis with gene expression and cell growth. Recent studies have identified DNA sequences in mammalian cells that fulfil the genetic criteria for replicators and are beginning to uncover the sequence requirements for the initiation of DNA replication. Mammalian replicators are composed of non-redundant modules that cooperate to direct initiation to specific chromosomal sites. Conversely, replicators do not show strong sequence similarity, and their ability to initiate replication depends on the chromosomal context and epigenetic factors, as well as their primary sequence. Here, we review the properties of metazoan replicators, and discuss the genetic and epigenetic factors that determine where and when DNA replication is initiated. C1 NCI, Mol Pharmacol Lab, DSB, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Vanderbilt Univ Stn B351634, Dept Biol Sci, Nashville, TN 37232 USA. Vanderbilt Univ, Vanderbilt Univ Stn B351634, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. RP Aladjem, MI (reprint author), NCI, Mol Pharmacol Lab, DSB, NIH, Bldg 37,Room 5056,37 Convent Dr, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov; ellen.fanning@vanderbilt.edu RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU NCI NIH HHS [CA09385, T32 CA009385]; NIGMS NIH HHS [GM52948, R01 GM052948] NR 53 TC 58 Z9 61 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUL PY 2004 VL 5 IS 7 BP 686 EP 691 DI 10.1038/sj.embor.7400185 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 842LH UT WOS:000223005100010 PM 15229645 ER PT J AU Kalish, ML Robbins, KE Pieniazek, D Schaefer, A Nzilambi, N Quinn, TC St Louis, ME Youngpairoj, AS Phillips, J Jaffe, HW Folks, TM AF Kalish, ML Robbins, KE Pieniazek, D Schaefer, A Nzilambi, N Quinn, TC St Louis, ME Youngpairoj, AS Phillips, J Jaffe, HW Folks, TM TI Recombinant viruses and early global HIV-1 epidemic SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 SUBTYPE; RISK-FACTORS; KINSHASA; ZAIRE; INFECTION; DIVERSITY; ORIGIN; CONGO; AIDS AB Central Africa was the epicenter of the HIV type 1 (HIV-1) pandemic. Understanding the early epidemic in the Democratic Republic of the Congo, formerly Zaire, could provide insight into how HIV evolved and assist vaccine design and intervention efforts. Using enzyme immunosorbent assays, we tested 3,988 serum samples collected in Kinshasa in the mid-1980s and confirmed seroreactivity by Western blot. Polymerase chain reaction of gag p17, env C2V3C3, and/or gp41; DNA sequencing; and genetic analyses were performed. Gene regions representing all the HIV-1 group M clades and unclassifiable sequences were found. From two or three short gene regions, 37% of the strains represented recombinant viruses, multiple infections, or both, which suggests that if whole genome sequences were available, most of these strains would have mosaic genomes. We propose that the HIV epidemic was well established in central Africa by the early 1980s and that some recombinant viruses most likely seeded the early global epidemic. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Project SIDA, Kinshasa, Zaire. NIH, Bethesda, MD 20892 USA. RP Kalish, ML (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,Mailstop G19, Atlanta, GA 30333 USA. EM mkalish@cdc.gov NR 35 TC 55 Z9 57 U1 1 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL PY 2004 VL 10 IS 7 BP 1227 EP 1234 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 835CF UT WOS:000222456800007 PM 15324542 ER PT J AU Abraham, IM Todman, MG Korach, KS Herbison, AE AF Abraham, IM Todman, MG Korach, KS Herbison, AE TI Critical in vivo roles for classical estrogen receptors in rapid estrogen actions on intracellular signaling in mouse brain SO ENDOCRINOLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; BETA MESSENGER-RNA; ER-ALPHA; HORMONE NEURONS; KNOCKOUT MOUSE; KINASE PATHWAY; RAT FOREBRAIN; ACTIVATION; MEMBRANE; CREB AB Estrogen exerts classical genomic as well as rapid nongenomic actions on neurons. The mechanisms involved in rapid estrogen signaling are poorly defined, and the roles of the classical estrogen receptors (ERs alpha and beta) are unclear. We examined here the in vivo role of classical ERs in rapid estrogen actions by evaluating the estrogen-induced effects on two major signaling pathways within the brains of alphaER-, betaER-, and double alphabetaER-knockout (ERKO) ovariectomized female mice. Estrogen significantly (P < 0.05) increased the numbers of phospho-cAMP response element binding protein (phospho-CREB)-immunoreactive cells in specific brain regions of wild-type mice in a time-dependent manner beginning within 15 min. In brain areas that express predominantly ER beta, this response was absent in beta ERKO mice, whereas brain regions that express mostly ER alpha displayed no change in alpha ERKO mice. the medial preoptic nucleus (MPN), an area that expresses both ERs, the estrogen-induced phosphorylation of CREB was normal in both alpha ERKO and beta ERKO mice. However, estrogen had no effect on CREB phosphorylation in the MPN, or any other brain region, in double alpha beta ERKO animals. Estrogen was also found to increase MAPK phosphorylation levels in a rapid (<15 min) manner within the MPN. In contrast to CREB signaling, this effect was lost in either alphaERKO or betaERKO mice. These data show that ERalpha and ERbeta play region- and pathway-specific roles in rapid estrogen actions throughout the brain. They further indicate an indispensable role for classical ERs in rapid estrogen actions in vivo and highlight the importance of ERs in coordinating both classical and rapid actions of estrogen. C1 Univ Otago, Sch Med Sci, Dept Physiol, Ctr Neuroendocrinol, Dunedin, New Zealand. Babraham Inst, Neuroendocrinol Lab, Cambridge CB2 4AT, England. Eotvos Lorand Univ, Hungarian Acad Sci, Neurobiol Res Grp, H-1117 Budapest, Hungary. NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Herbison, AE (reprint author), Univ Otago, Sch Med Sci, Dept Physiol, Ctr Neuroendocrinol, POB 913, Dunedin, New Zealand. EM allan.herbison@stonebow.otago.ac.nz OI Korach, Kenneth/0000-0002-7765-418X; Herbison, Allan/0000-0002-9615-3022 NR 42 TC 143 Z9 148 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2004 VL 145 IS 7 BP 3055 EP 3061 DI 10.1210/en.2003-1676 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900002 PM 14976146 ER PT J AU Richards, RG Klotz, DM Walker, MP Diaugustine, RP AF Richards, RG Klotz, DM Walker, MP Diaugustine, RP TI Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I SO ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER RISK; POSTNATAL-GROWTH; BONE-GROWTH; HORMONE; RECEPTOR; EXPRESSION; DENSITIES; MOUSE; RAT AB The development of the mouse mammary gland occurs postnatally. Hormonal activation of local growth factor pathways stimulates rapid elongation and branching of the rudimentary gland through the fatty stroma. Earlier studies showed that GH is required for mammary gland ductal morphogenesis and that IGF-I mediates this action of GH. In the present study we show that adult IGF-I-m/m mutant mice exhibit a marked reduction in levels of mammary gland and liver igf1 transcripts compared with controls. Whole mounts of the adult IGF-I(m/m)mammary glands revealed ducts that extended to the limits of the fat pad; however, the number of bifurcation branch points in the ductal tree of the mutants was reduced by half compared with that of wild-type glands. In contrast, adult mutant mice with a liver-specific deletion of the igf1 gene obtained by Cre/loxP recombination strategy maintained the normal levels of mammary gland igf1 transcripts and did not exhibit a branching deficit in this organ. It was previously reported that this specific loss of liver IGF-I causes serum levels of IGF-I (endocrine) to decrease by approximately 75%, whereas the levels of tissue igf1 transcripts remain unchanged. On the basis of these findings, we propose that paracrine, not endocrine, IGF-I is important for mammary branching morphogenesis. C1 NIEHS, Hormones & Canc Grp, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Diaugustine, RP (reprint author), NIEHS, Hormones & Canc Grp, Mol Carcinogenesis Lab, POB 12233,MD D4-04, Res Triangle Pk, NC 27709 USA. EM diaugus2@niehs.nih.gov NR 23 TC 48 Z9 50 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2004 VL 145 IS 7 BP 3106 EP 3110 DI 10.1210/en.2003-1112 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900011 PM 15059953 ER PT J AU Haluzik, M Colombo, C Gavrilova, O Chua, S Wolf, N Chen, M Stannard, B Dietz, KR Le Roith, D Reitman, ML AF Haluzik, M Colombo, C Gavrilova, O Chua, S Wolf, N Chen, M Stannard, B Dietz, KR Le Roith, D Reitman, ML TI Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice SO ENDOCRINOLOGY LA English DT Article ID ADIPOSE-TISSUE; LIPOATROPHIC MICE; OBESITY; PROTEIN; MUSCLE; EXPRESSION; MOUSE; SENSITIVITY; ADIPONECTIN; GLUCOSE AB We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency. Despite a comparable degree of obesity and hyperinsulinemia, C57BL/6J ob/ob mice had much milder hyperglycemia and, surprisingly, normal circulating adiponectin levels despite still-prominent signs of insulin resistance. Hyperinsulinemic-euglycemic clamp revealed relatively less whole-body and muscle insulin resistance in C57BL/6J ob/ob mice, whereas liver insulin resistance tended to be more severe than in FVB/N ob/ob mice. C57BL/6J ob/ob mice had also more rapid clearance of circulating triglycerides and more severe hepatic steatosis. We suggest that strain-related distinction in lipid handling is the most important player in the differences in diabetic phenotype and insulin sensitivity, whereas the impact of circulating adiponectin levels on the overall phenotype of ob/ob mice is less important. C1 Charles Univ, Fac Med 1, Dept Med 3, Prague 12808 2, Czech Republic. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Pediat, Div Mol Genet, New York, NY 10032 USA. Columbia Univ, Dept Pediat, New York Obes Res Ctr, New York, NY 10032 USA. NIDDKD, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Haluzik, M (reprint author), Charles Univ, Fac Med 1, Dept Med 3, U Nemocnice 1, Prague 12808 2, Czech Republic. EM mhalu@lf1.cuni.cz RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Dietz, Kelly/0000-0003-3670-2912 NR 36 TC 115 Z9 116 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2004 VL 145 IS 7 BP 3258 EP 3264 DI 10.1210/en.2004.0219 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 829JI UT WOS:000222043900031 PM 15059949 ER PT J AU Cooper, GS Martin, SA Longnecker, MP Sandler, DP Germolec, DR AF Cooper, GS Martin, SA Longnecker, MP Sandler, DP Germolec, DR TI Associations between plasma DDE levels and immunologic measures in African-American farmers in North Carolina SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID POLYCHLORINATED-BIPHENYLS; NEUTROPHIL FUNCTION; IMMUNE-RESPONSE; EXPOSURE; MICE; DISEASE; HEXACHLOROBENZENE; PESTICIDES; METABOLITE; HEALTH AB Experimental studies in rodents demonstrate evidence of immunosuppressive effects of dietary exposure to DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane], but human data pertaining to immunomodulating effects of DDT exposure are limited. In this study we examined the association between the persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p-chlorophenyl) ethylene (p,p'-DDE) and immunologic measures using blood samples in a relatively highly exposed population of farmers in the United States. Levels of serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies in relation to plasma p,p'-DDE levels were evaluated in samples from 137 African-American male farmers (30-88 years of age; median, 64 years). Participants were recruited through black churches in four rural counties in eastern North Carolina. Data collection included a telephone interview pertaining to farming practices and health history, and one blood sample was collected from each participant. Linear and logistic regression, adjusting for age, cholesterol, triglycerides, smoking status, and years of any kind of pesticide use, was used to assess the association between immunologic parameters and plasma levels of p,p'-DDE. The median plasma p,p'-DDE concentration was 7.7 mug/L (range, 0.6-77.4 mug/L). There was no association between p,p'-DDE and IgA in any of the models. IgG levels decreased with increasing p,p'-DDE levels, with a statistically significant decrease of approximately 50% in the highest two categories of exposure (greater than or equal to 6.0 mug/L) compared with values of < 3.0 mug/L. Sixteen (12%) were positive for antinuclear antibodies. The prevalence of antinuclear antibodies was somewhat elevated in the highest category of p,p'-DDE exposure (odds ratio, 1.9; 95% confidence interval, 0.32-11.3; for greater than or equal to 12.0 mug/L compared with < 3.0 mug/L p,p'-DDE), but this difference was not statistically significant. These analyses provide evidence that p,p'-DDE modulates immune responses in humans. C1 NIEHS, Mol Toxicol Lab, Epidemiol Branch, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Cook Cty Dept Publ Hlth, Chicago, IL USA. RP Germolec, DR (reprint author), NIEHS, Mol Toxicol Lab, Epidemiol Branch, Dept Hlth & Human Serv,NIH, MD C1-04,POB 12233, Res Triangle Pk, NC 27709 USA. EM germolec@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322; Sandler, Dale/0000-0002-6776-0018 NR 37 TC 38 Z9 38 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 JUL PY 2004 VL 112 IS 10 BP 1080 EP 1084 DI 10.1289/ehp.6892 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 835KR UT WOS:000222482300028 PM 15238281 ER PT J AU Daniels, JL Longnecker, MP Rowland, AS Golding, J AF Daniels, JL Longnecker, MP Rowland, AS Golding, J CA ALSPAC Study Team TI Fish intake during pregnancy and early cognitive development of offspring SO EPIDEMIOLOGY LA English DT Article ID SEYCHELLES CHILD-DEVELOPMENT; PRENATAL METHYLMERCURY EXPOSURE; POLYUNSATURATED FATTY-ACIDS; VISUAL RESOLUTION ACUITY; IN-UTERO EXPOSURE; MERCURY EXPOSURE; MINAMATA-DISEASE; UMBILICAL-CORD; FULL-TERM; CONSUMPTION AB Background: Fish is a source of many nutrients that can be beneficial during pregnancy, as well as a source of neurotoxicant contaminants such as methylmercury. Previous investigations of fish intake in relation to neurodevelopment have focused on possible damage from contaminants, whereas potential benefits of fish consumption have been relatively unexplored Methods: We evaluated the association between maternal fish intake during pregnancy and offspring's early development of language and communication skills in a cohort of 7421 British children born in 1991-1992. Fish intake by the mother and child was measured by questionnaire. The child's cognitive development was assessed using adaptations of the MacArthur Communicative Development Inventory at 15 months of age and the Denver Developmental Screening Test at 18 months of age. Mercury was measured in umbilical cord tissue for a subset of 1054 children Results: Total mercury concentrations were low and were not associated with neurodevelopment. Fish intake by the mother during pregnancy, and by the infant postnatally, was associated with higher mean developmental scores. For example, the adjusted mean MacArthur comprehension score for children whose mothers con- sumed fish 4 or more times per week was 72 (95% confidence interval = 71-74), compared with 68 (66-71) among those whose mothers did not consume fish. Conclusions: When fish is not contaminated, moderate fish intake during pregnancy and infancy may benefit development. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ New Mexico, Dept Family & Community Med, Albuquerque, NM 87131 USA. Univ Bristol, Inst Child Hlth, Bristol, Avon, England. RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM juliedaniels@unc.edu OI Longnecker, Matthew/0000-0001-6073-5322 NR 49 TC 179 Z9 183 U1 7 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP 394 EP 402 DI 10.1097/01.ede.0000129514.46451.ce PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800004 PM 15232398 ER PT J AU Parks, CG Cooper, GS Nylander-French, LA Hoppin, JA Sanderson, WT Dement, JM AF Parks, CG Cooper, GS Nylander-French, LA Hoppin, JA Sanderson, WT Dement, JM TI Comparing questionnaire-based methods to assess occupational silica exposure SO EPIDEMIOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CRYSTALLINE SILICA; UNITED-STATES; SCLERODERMA; SCLEROSIS; RISK; POPULATION; MORTALITY; CANCER; WOMEN AB Background: Epidemiologic assessment of occupational exposure to silica is typically limited to long-term work in the dusty trades, primarily in jobs held by men. We compared alternative questionnaire-based methods to assess silica exposure in a recent case-control study of 265 patients with systemic lupus erythematosus (mostly women) and 355 controls randomly selected from state driver's license registries and frequency-matched by age and sex. Methods: In-person interviews included a job history (all jobs held at least 12 months) and checklist of silica-related jobs and tasks (work of at least 2 weeks). Three industrial hygienists reviewed job descriptions without knowing case-control status. Potential high- or moderate-intensity exposures were confirmed or revised based on follow-up telephone interviews. Results: In the full assessment including all work of at least 2 weeks, 9% of cases and 4% of controls were classified as medium or high silica exposure (odds ratio of disease = 2.9; 95% confidence interval = 1.3-6.4). In contrast, only 4% of cases and 9% of controls were identified by the standardized code groups index as having worked in silica-related industries or occupations for at least 12 months, providing a much lower risk estimate for disease (0.4; 0.2-0.9). Conclusions: Specific task-based questions must be included to assess the full potential of occupational silica exposure. These findings highlight the limitations of using standardized code groups to define exposure or to select jobs for industrial hygienist review. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Univ Iowa, Iowa City, IA USA. Duke Univ, Ctr Med, Dept Community & Family Med, Durham, NC USA. RP Parks, CG (reprint author), NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, 1095 Willowdale Rd, Morgantown, WV 26505 USA. EM Cqp8@cdc.gov OI Parks, Christine/0000-0002-5734-3456 NR 40 TC 18 Z9 19 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP 433 EP 441 DI 10.1098/01.ede.0000129515.54074.b2 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800010 PM 15232404 ER PT J AU Alavanja, MCR Dosemeci, M Samanic, C Lubin, J Lynch, CF Knott, C Barker, J Hoppin, JA Sandler, DP Coble, J Thomas, K Blair, A AF Alavanja, MCR Dosemeci, M Samanic, C Lubin, J Lynch, CF Knott, C Barker, J Hoppin, JA Sandler, DP Coble, J Thomas, K Blair, A TI Use of agricultural pesticides and lung cancer risk in the agricultural health study cohort SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NCI, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. US EPA, NIEHS, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S178 EP S179 DI 10.1097/00001648-200407000-00473 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800472 ER PT J AU Bonner, M Lee, W Sandler, D Hoppin, J Dosemeci, M Alavanja, M Bonner, M AF Bonner, M Lee, W Sandler, D Hoppin, J Dosemeci, M Alavanja, M Bonner, M TI Cancer incidence associated with carbofuran use in the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NCI, Occupat & Environm Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S180 EP S180 DI 10.1097/00001648-200407000-00477 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800476 ER PT J AU De Roos, A Cooper, G Alavanja, M Sandler, D AF De Roos, A Cooper, G Alavanja, M Sandler, D TI Rheumatoid arthritis among women in the agricultural health study: Risk associated with farming history and occupational exposures SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S181 EP S182 DI 10.1097/00001648-200407000-00481 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800480 ER PT J AU Gray, K AF Gray, K TI NIEHS' environmental genome project SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S139 EP S140 DI 10.1097/00001648-200407000-00362 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800362 ER PT J AU Han, DW Rogerson, P Bonner, M Nie, J Vena, J Freudenheim, J AF Han, DW Rogerson, P Bonner, M Nie, J Vena, J Freudenheim, J TI Assessing the variability of risk surfaces using residential history data in a case control study of breast cancer SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 SUNY Buffalo, Buffalo, NY 14260 USA. NCI, Bethesda, MD 20892 USA. Univ S Carolina, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S208 EP S208 DI 10.1097/00001648-200407000-00552 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800551 ER PT J AU Jackson, L Correa-Villasenor, A Dominici, F Lees, PSJ Stewart, PA Breysse, PN Matanoski, G AF Jackson, L Correa-Villasenor, A Dominici, F Lees, PSJ Stewart, PA Breysse, PN Matanoski, G TI Paternal occupational lead exposure and total anomalous pulmonary venous return SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NICHHD, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. NCI, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S187 EP S188 DI 10.1097/00001648-200407000-00497 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800496 ER PT J AU Jackson, LW Schisterman, EF Dey-Rao, R Browne, RW Annstrong, D AF Jackson, LW Schisterman, EF Dey-Rao, R Browne, RW Annstrong, D TI Oxidative stress and endometriosis SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NICHHD, Bethesda, MD 20892 USA. SUNY Coll Buffalo, Buffalo, NY USA. Univ Florida, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S190 EP S190 DI 10.1097/00001648-200407000-00505 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800504 ER PT J AU Kamel, F Engel, L Gladen, B Hoppin, J Alavanja, M Sandler, D AF Kamel, F Engel, L Gladen, B Hoppin, J Alavanja, M Sandler, D TI Neurologic symptoms in licensed pesticide applicators in the agricultural health study (AHS) SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 Mem Sloan Kettering Canc Ctr, DHHS, NIH, NIEHS, Bronx, NY USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S181 EP S181 DI 10.1097/00001648-200407000-00480 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800479 ER PT J AU Lagorio, S Forastiere, F Pistelli, R Iavaronem, I Ostro, BD Michelozzi, P Fano, V AF Lagorio, S Forastiere, F Pistelli, R Iavaronem, I Ostro, BD Michelozzi, P Fano, V TI Air pollution and lung function among susceptible adult subjects: A panel study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NIH, Bethesda, MD 20892 USA. Univ Cattolica Sacro Cuore, I-20123 Milan, Italy. RI Forastiere, Francesco/J-9067-2016 OI Forastiere, Francesco/0000-0002-9162-5684 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S45 EP S46 DI 10.1097/00001648-200407000-00105 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800106 ER PT J AU Rusiecki, J Matthews, A Sturgeon, S Sinha, R Baris, D AF Rusiecki, J Matthews, A Sturgeon, S Sinha, R Baris, D TI A correlation study of organochlorine levels in serum, breast adipose and gluteal adipose tissue among breast cancer cases in India SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S75 EP S76 DI 10.1097/00001648-200407000-00186 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800187 ER PT J AU Schisterman, E Hu, J Whitcomb, B AF Schisterman, E Hu, J Whitcomb, B TI Limit of detection bias and the correction of variance estimates SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NICHD, DESPR, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S157 EP S157 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800413 ER PT J AU Schisterman, E Hernan, M Hernadez-Diaz, S AF Schisterman, E Hernan, M Hernadez-Diaz, S TI Does the Z-score method resolve the neonatal mortality paradox? SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NICHHD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S157 EP S157 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800411 ER PT J AU Shantakumar, S Gammon, MD Eng, SM Sagiv, SK Gaudet, MM Teitelbaum, SL Britton, JA Wang, LW Wang, Q Stellman, SD Beyea, J Hatch, M Camann, D Neugut, AI Santella, RM AF Shantakumar, S Gammon, MD Eng, SM Sagiv, SK Gaudet, MM Teitelbaum, SL Britton, JA Wang, LW Wang, Q Stellman, SD Beyea, J Hatch, M Camann, D Neugut, AI Santella, RM TI Environmental exposures and other characteristics associated with detectable PAH-DNA adducts among a population-based sample of healthy women SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10027 USA. NCI, Dept Populat & Genet, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S76 EP S77 DI 10.1097/00001648-200407000-00188 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800189 ER PT J AU Villanueva, CM Cantor, KP Grimalt, JO Dosemeci, M Malats, N Real, FX Silverman, D Tardon, A Garcia-Closas, R Serra, C Carrato, A Castano-Vinyals, G Rothman, N Kogevinas, M AF Villanueva, CM Cantor, KP Grimalt, JO Dosemeci, M Malats, N Real, FX Silverman, D Tardon, A Garcia-Closas, R Serra, C Carrato, A Castano-Vinyals, G Rothman, N Kogevinas, M TI Bladder cancer and exposure to disinfection byproducts in water through ingestion, bathing, showering and swimming in pools: Findings from the Spanish bladder cancer SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Oviedo, Dept Med Prevent & Salud Publ, Oviedo, Spain. RI Grimalt, Joan/E-2073-2011; Serra, C/E-6879-2014; Kogevinas, Manolis/C-3918-2017 OI Grimalt, Joan/0000-0002-7391-5768; Serra, C/0000-0001-8337-8356; NR 0 TC 2 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S105 EP S105 DI 10.1097/00001648-200407000-00264 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800264 ER PT J AU Ward, MH Cantor, KP Cerhan, J Lynch, CF Hartge, P AF Ward, MH Cantor, KP Cerhan, J Lynch, CF Hartge, P TI Nitrate in public water supplies and risk of cancer: Results from recent studies in the midwestern United States SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 NCI, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S214 EP S214 DI 10.1097/00001648-200407000-00568 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800567 ER PT J AU Wolff, MS Berkowitz, GS Wetmur, J Matte, T Landrigan, PJ AF Wolff, MS Berkowitz, GS Wetmur, J Matte, T Landrigan, PJ TI Gene-environment influences on neurologic and somatic development SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Conference of the International-Society-for-Environmental-Epidemiology CY AUG 01-04, 2004 CL New York, NY SP NYU Sch Med, UMDNJ Robert Wood Johnson Med Sch C1 Mt Sinai Sch Med, NIEHS EPA, Childrens Environm Hlth & Dis Prevent Res Ctr, Dept Community & Prevent Med, New York, NY USA. Mt Sinai Sch Med, NIEHS EPA, Childrens Environm Hlth & Dis Prevent Res Ctr, Dept Pediat, New York, NY USA. Mt Sinai Sch Med, NIEHS EPA, Childrens Environm Hlth & Dis Prevent Res Ctr, Dept Microbiol, New York, NY USA. NYC, Dept Hlth & Mental Hyg, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2004 VL 15 IS 4 BP S91 EP S91 DI 10.1097/00001648-200407000-00226 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 834GO UT WOS:000222399800227 ER PT J AU Kaminski, RM Livingood, MR Rogawski, MA AF Kaminski, RM Livingood, MR Rogawski, MA TI Allopregnanolone analogs that positively modulate GABA(A) receptors protect against partial seizures induced by 6-Hz electrical stimulation in mice SO EPILEPSIA LA English DT Article DE neuroactive steroid; ganaxolone; allopregnanolone; clonazepam; GABA(A)-receptor modulation; Seizure; 6-Hz model; mouse ID ANTICONVULSANT ACTIVITY; NEUROACTIVE STEROIDS; PROGESTERONE; GANAXOLONE AB Purpose: Low-frequency (6 Hz), long-duration (3 s) electrical stimulation in mice produces seizures characterized by immobility, focal clonus, and automatic behaviors reminiscent of human limbic epilepsy. Renewed interest has been expressed in this seizure model with the recognition that it is sensitive to a broad spectrum of anticonvulsants (AEDs) and may have distinct pharmacologic responsiveness from other in vivo tests of AED efficacy. Here we sought to determine whether the progesterone-derived neuroactive steroid allopregnanolone (5alpha,3alpha-P) and several structural analogues with varying degrees of activity as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors are protective in the 6-Hz seizure model. Methods: Mice were pretreated with neuroactive steroids (15 min before) or clonazepam (CZP; 30 min before) to 6-Hz corneal stimulation (32 mA). Animals that failed to exhibit immobility were considered protected. Results: The neuroactive steroids prevented 6-Hz seizures with rank order of potencies (ED50 values): ganaxolone (6.3 mg/kg) > 5alpha,3alpha-P (14.2 mg/kg) greater than or equal to 5beta,3alpha-P (14.4 mg/kg) > 5alpha,3beta-P (>100 mg/kg). CZP also was protective (ED50 value, 0.075 mg/kg). The potencies of the neuroactive steroids and CZP are similar to their previously reported activities in the pentylenetetrazol (PTZ) seizure model. Conclusions: Neuroactive steroids have comparable potencies in the 6-Hz and PTZ models. Their structural specificity in both models corresponds with their activities as positive allosteric modulators of GABA(A) receptors, although ganaxolone is more potent than expected, probably because it has greater bioavailability. The 6-Hz model may be a valuable toot in drug development for the identification of GABAergic AEDs. C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, NIH, Bldg 49,Room 5A75,49 Convent Dr MSC 4457, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 15 TC 102 Z9 103 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 2004 VL 45 IS 7 BP 864 EP 867 DI 10.1111/j.0013-9580.2004.04504.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 835VT UT WOS:000222514300022 PM 15230714 ER PT J AU Tornwall, ME Virtamo, J Korhonen, PA Virtanen, MJ Taylor, PR Albanes, D Huttunen, JK AF Tornwall, ME Virtamo, J Korhonen, PA Virtanen, MJ Taylor, PR Albanes, D Huttunen, JK TI Effect of alpha-tocopherol and beta-carotene supplementation on coronary heart disease during the 6-year post-trial follow-up in the ATBC study SO EUROPEAN HEART JOURNAL LA English DT Article DE alpha-tocopherol; beta-carotene; supplementation; coronary heart disease ID VITAMIN-E; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ANTIOXIDANT VITAMINS; RANDOMIZED-TRIAL; ATHEROSCLEROTIC PLAQUE; WOMENS HEALTH; LUNG-CANCER; RISK; PREVENTION AB Aims To evaluate the 6-year post-trial effects of alpha-tocopherol and P-carotene supplementation on coronary heart disease (CHD) in the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study. Methods and results 29 133 mate smokers, aged 50-69 years were randomised to receive alpha-tocopherol 50 mg, or beta-carotene 20 mg, or both, or placebo daily for 5-8 years. At the beginning of the post-trial follow-up, 23 144 men were still at risk for a first-ever major coronary event (MCE), and 1255 men with pre-trial history of myocardial infarction (MI) were at risk for MCE. Post-trial risk for MCE (n = 2059) was 0.95 (95% confidence interval 0.87-1.04) among alpha-tocopherol recipients compared with non-recipients, and 1.14 (1.04-1.24) among beta-carotene recipients compared with non-recipients. The risk for non-fatal MI (n = 993) was 0.96 (0.85-1.09) and 1.16 (1.03-1.32), and for fatal CHD (n = 1066) 0.94 (0.83-1.06) and 1.11 (0.99-1.25), respectively. Among men with pre-trial MI no effects were observed in post-trial risk of MCE (n = 257). Conclusion alphabeta-Carotene seemed to increase the post-trial. risk of first-ever non-fatal Ml but there is no plausible mechanism to support it. Our findings do not advocate the use of alpha-tocopherot or beta-carotene supplements in prevention of CHD among mate smokers. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki 00300, Finland. NCI, Bethesda, MD 20892 USA. RP Tornwall, ME (reprint author), Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Mannerheiminite 166, Helsinki 00300, Finland. EM markareetta.tornwall@ktl.fi; jarmo.virtamo@ktl.fi RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 33 TC 61 Z9 64 U1 1 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2004 VL 25 IS 13 BP 1171 EP 1178 DI 10.1016/j.ehj.2004.05.007 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 841DV UT WOS:000222910400013 PM 15231376 ER PT J AU Reese, TS AF Reese, TS TI My collaboration with John Heuser SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Editorial Material C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Reese, TS (reprint author), NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM treese@mbl.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUL PY 2004 VL 83 IS 6 BP 243 EP 244 DI 10.1078/0171-9335-00399 PG 2 WC Cell Biology SC Cell Biology GA 863AE UT WOS:000224531800002 PM 15511080 ER PT J AU Trovato, M Vitarelli, E Grosso, M Allesci, S Benvenga, S Trimarchi, E Barresi, G AF Trovato, M Vitarelli, E Grosso, M Allesci, S Benvenga, S Trimarchi, E Barresi, G TI Immunohistochemical expression of HGF, c-MET and transcription factor STAT3 in colorectal tumors SO EUROPEAN JOURNAL OF HISTOCHEMISTRY LA English DT Article DE HGF; c-met; STAT3; colorectal; adenomas; carcinomas; immunohistochemistry ID HEPATOCYTE GROWTH-FACTOR; SCATTER FACTOR; ULCERATIVE-COLITIS; FACTOR-RECEPTOR; CANCER; CELL; PROTOONCOGENE; ACTIVATION; CARCINOMA; HETEROZYGOSITY AB By immunohistochemistry, we have investigated the expression of hepatocyte growth factor (HGF), HGF-R or c-met and the transcritor factor STAT3 in a series of 80 colorectal tumours (40 adenomas and 40 adenocarcinomas). The expression of HGF, c-met and STAT3 was revealed in 40/40 (100%) of adenomas and in 26/40 (65%) of adenocarcinomas; the remaining 14/40 (35%) carcinomas expressed cmet but failed to express HGF and STAT3. Positive immunoreaction score was defined through the number of stained cells: low (1-10%), moderate (11-50%) and high (>51%). In adenomas, the HGF immunoreaction was high in 33 (82.5%) and moderate in 7 (17.5%); the c-met staining was high in 3 (7.5%) and moderate in 37 (92.5%); and the STAT3 reactivity was high in 25 (62.5%) and moderate in 15(37.5%). In carcinomas, the HGF immunoreaction was moderate in 21 (80.7%) and low in 5 (19.2%); the c-met staining was high in 14 (35%), moderate in 25 (62.5) and low in 1 (2.5%); and the STAT3 reactivity was moderate in 17 (65.3%) and low in 9 (34.6%). In both type of lesions, HGF and c-met showed a membranous and cytoplasmic location. In adenomas, STAT3 was detected in cytoplasm and nucleus and in carcinomas it was limited to cytoplasm. While the HGF/c-met/STAT3 expression in adenomas was significantly different from carcinomas (chi(2) = 17, p < 0.0001), no correlation was found among HGF, c-met, or STAT3 immunostaining with histotype or degree of dysplasia in adenomas and the same for histotype, grading or staging in carcinomas. These features, suggesting a role of the HGF/c-met/STAT3 signal in colon tumorigenesis, indicate that a reduced expression of HGF and c-met is associated to progression of adenoma into carcinoma. C1 Policlin Univ G Martino, Dipartimento Patol Umana, I-98125 Messina, Italy. Policlin Univ, Dipartimento Clin Sperimentale Med & Farmacol, Sez Endocrinol, Messina, Italy. NICHHD, NIH, Bethesda, MD 20892 USA. RP Trovato, M (reprint author), Policlin Univ G Martino, Dipartimento Patol Umana, Padig D,Via Consolare Valeria, I-98125 Messina, Italy. EM mariatrovato@tin.it NR 35 TC 15 Z9 19 U1 0 U2 2 PU LUIGI PONZIO E FIGLIO PI PAVIA PA VIA D DA CATALOGNA 1/3, 27100 PAVIA, ITALY SN 1121-760X J9 EUR J HISTOCHEM JI Eur. J. Histochem. PD JUL-SEP PY 2004 VL 48 IS 3 BP 291 EP 297 PG 7 WC Cell Biology SC Cell Biology GA 858YU UT WOS:000224229600010 PM 15590419 ER PT J AU Fogli, A Schiffmann, R Hugendubler, L Combes, P Bertini, E Rodriguez, D Kimball, SR Boespflug-Tanguy, O AF Fogli, A Schiffmann, R Hugendubler, L Combes, P Bertini, E Rodriguez, D Kimball, SR Boespflug-Tanguy, O TI Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE eIF2B; GEF activity; leukodystrophy; CACH/VWM syndrome; CREE encephalopathy; ovarioleukodystrophy ID VANISHING WHITE-MATTER; NERVOUS-SYSTEM HYPOMYELINATION; INITIATION-FACTOR EIF2B; CHILDHOOD ATAXIA; PROTEIN-SYNTHESIS; LEUKOENCEPHALOPATHY; MUTATIONS; SUBUNITS; CELLS AB Mutations in each of the five eucaryotic initiation factor 2B (eIF2B) subunits have been found in leukodystrophies of various severity: Cree leukoencephalopathy, childhood ataxia with central hypomyelination/leukodystrophy with vanishing white matter and ovarioleukodystrophy. A continuum was observed from fatal infantile forms to adult forms without neurological deterioration. Disease severity was found to correlate with the age at disease onset and the specific amino-acid substitution. In order to analyze the functional consequences of eIF2B mutations, we measured the guanine nucleotide exchange factor (GEF) activity of eIF2B in transformed lymphocytes from 30 affected patients carrying mutations in eIF2B compared to 10 unaffected heterozygotes and 22 controls without eIF2B mutations. A significant decrease of 20 - 70% in GEF activity was observed in all mutated cells. The severity of this decrement of GEF activity correlated with age at onset of the disease. These results suggest that a deficiency in GEF activity underlies the encephalopathy associated eIF2B-related disease. Our study demonstrates that the evaluation of the GEF activity in transformed lymphocytes represents an interesting alternative test to the systematic screening of the five EIF2B genes. This relevant cellular model may also be used to test the functional impact of different molecules on the GEF activity for future therapeutic strategies. C1 Fac Med, INSERM, UMR 384, F-63001 Clermont Ferrand, France. Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA. Bambino Gesu Pediat Hosp, Mol Med Unit, Rome, Italy. Hop Trousseau, AP HP, INSERM, U546,Serv Neuropediat, F-75571 Paris, France. RP Boespflug-Tanguy, O (reprint author), Fac Med, INSERM, UMR 384, 28 Pl Henri Dunant BP 38, F-63001 Clermont Ferrand, France. EM Odile.Boespflug@inserm.u-clermont1.fr OI Bertini, Enrico/0000-0001-9276-4590 FU NIDDK NIH HHS [DK13499] NR 21 TC 60 Z9 63 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JUL PY 2004 VL 12 IS 7 BP 561 EP 566 DI 10.1038/sj.ejhg.5201189 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 832NQ UT WOS:000222274600007 PM 15054402 ER PT J AU Lindvall, JM Blomberg, KEM Berglof, A Yang, O Smith, CIE Islam, TC AF Lindvall, JM Blomberg, KEM Berglof, A Yang, O Smith, CIE Islam, TC TI Gene expression profile of B cells from Xid mice and Btk knockout mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Btk; DNA microarray; Xid; Btk KO; real-time PCR ID BRUTONS TYROSINE KINASE; X-LINKED AGAMMAGLOBULINEMIA; FACTOR-KAPPA-B; TEC FAMILY; OLIGONUCLEOTIDE ARRAYS; RECEPTOR; ACTIVATION; CALCIUM; PROTEIN; ENGAGEMENT AB Bruton's tyrosine kinase (Btk) is important for B lymphocyte development. To identify genes that are differentially expressed in primary B cells lacking functional Btk, splenocytes from X-linked immunodeficiency (Xid), Btk knockout (Btk KO) and immunocompetent CBA mice were used in microarrays containing more than 12,000 genes and expressed-sequence tags. We found 4515 common transcripts expressed in duplicate experiments in the three strains. Out of these, 38 were differentially expressed genes (21 were up-regulated >2-fold and 17 were down-regulated <-2-fold) between CBA and Btk defective (Xid or Btk KO) mice. Ten out of these genes were selected and quantitative real-time PCR was conducted for validation and further investigation. Real-time experiments correlated nicely with the microarray data. No definitive phenotypic difference has previously been reported between Xid and Btk KO mice. We found 7 genes whose expression differed (>2-fold) between the two strains. Moreover, when the 38 genes that differed between immunocompetent CBA mice and Btk defective mice were ranked according to fold-increase, the levels in Btk KO mice were significantly more altered. This suggests that the defect in Btk KO mice is more severe and demonstrates that the mutant Btk protein in Xid mice does not generally function as dominant-negative form. C1 Karolinska Univ Hosp, Clin Res Ctr, Karolinska Inst, SE-14186 Huddinge, Sweden. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Smith, CIE (reprint author), Karolinska Inst, Clin Res Ctr, NOVUM, SE-14186 Huddinge, Sweden. EM edvard.smith@crc.ki.se OI Lindvall, Jessica/0000-0002-5042-8481; Smith, C. I. Edvard/0000-0003-1907-3392 NR 43 TC 20 Z9 20 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2004 VL 34 IS 7 BP 1981 EP 1991 DI 10.1002/eji.200324051 PG 11 WC Immunology SC Immunology GA 836NY UT WOS:000222563800022 PM 15214046 ER PT J AU Brown, PL Kiyatkin, EA AF Brown, PL Kiyatkin, EA TI Brain hyperthermia induced by MDMA ('ecstasy'): modulation by environmental conditions SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE brain hyperthermia; brain temperature; environmental stress; metabolic brain activation; neurotoxicity; rats ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; AMBIENT-TEMPERATURE; PROLONGED EXERCISE; RAT-BRAIN; HUMANS; PHARMACOLOGY; GLUCOSE; 3,4-METHYLENEDIOXYAMPHETAMINE; METHYLENEDIOXYMETHAMPHETAMINE; THERMOREGULATION AB Drugs of abuse, such as 3,4-methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one-fifth of the known LD50 in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 degreesC, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 degreesC, MDMA pushed temperatures in the brain to its biological limits (>41 degreesC; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under 'party' conditions may be much more dangerous than under standard laboratory conditions. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 48 TC 52 Z9 52 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2004 VL 20 IS 1 BP 51 EP 58 DI 10.1111/j.1460-9568.2004.03453.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 835YQ UT WOS:000222522000005 PM 15245478 ER PT J AU Hayes, RJ Gardner, EL AF Hayes, RJ Gardner, EL TI The basolateral complex of the amygdala mediates the modulation of intracranial self-stimulation threshold by drug-associated cues SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE addiction; cocaine; conditioning; craving; rat; reward ID CONDITIONED PLACE PREFERENCE; COCAINE-SEEKING BEHAVIOR; VENTRAL TEGMENTAL AREA; STIMULUS REWARD ASSOCIATIONS; RAT NUCLEUS-ACCUMBENS; BRAIN-STIMULATION; MESOLIMBIC DOPAMINE; EXCITOTOXIC LESIONS; PREFRONTAL CORTEX; MEMORY-SYSTEMS AB Learning and memory appear to be critical aspects of drug abuse; presumably playing an especially important role in craving and relapse. Thus, understanding the interaction of learning- and memory-related brain areas with the classical reward circuitry is of importance. Toward this goal, the effect of drug-associated contextual cues on intracranial self-stimulation (ICSS) behaviour was assessed in rats. We used a method that allows the establishment of baseline behaviour, the pairing of drug exposure with unique cues, and testing the effect of cue exposure within the same apparatus. ICSS thresholds were decreased by morphine (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired drug-cue training sessions. Subsequent presentation of the drug-associated cues decreased thresholds in the absence of drug. Cues associated with saline had no effect. These results suggest a Pavlovian conditioning phenomenon in which the functioning of brain reward circuitry is modulated by drug-associated cues. In a second experiment, we tested the hypothesis that the mechanism by which conditioning affects ICSS thresholds may include the basolateral complex of the amygdala (BLC) due to its known role in conditioning and anatomical linkage with classical reward circuitry. Lesions of the BLC abolished the ability of cocaine-associated cues to lower ICSS threshold. Lesions did not alter response capability or the unconditioned effect of cocaine. We conclude that the BLC is necessary for cues associated with previous drug exposure to modulate activity within or downstream from the classical reward circuitry of the medial forebrain bundle. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Behav Neurosci Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Hayes, RJ (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rhayes@intra.nida.nih.gov NR 72 TC 16 Z9 18 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2004 VL 20 IS 1 BP 273 EP 280 DI 10.1111/j.1460-9568.2004.03463.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 835YQ UT WOS:000222522000026 PM 15245499 ER PT J AU Tanaka, TS Ko, MSH AF Tanaka, TS Ko, MSH TI A global view of gene expression in the preimplantation mouse embryo: morula versus blastocyst SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article; Proceedings Paper CT Serono Symposium on Genesis and Fate of the Preimplantation Empryo CY SEP 29-OCT 01, 2002 CL Serono, ITALY DE preimplantation mouse embryos; cDNA microarray; morula; blastocyst ID STEM-CELLS; PROTEIN-SYNTHESIS; PATTERNS; PIWI; DIFFERENTIATION; ACTIVATION; MIWI; RNA AB As a first step to understand preimplantation development, we performed global gene-expression profiling of morula and blastocyst using the NIA 15k mouse cDNA microarray. Gene expression levels were measured four times for blastocyst and five times for morula. Student's t-test at the 5% significance level identified 428 genes upregulated and 748 downregulated in blastocyst compared to morula. This trend was consistent with semi-quantative RT-PCR analysis of sample genes. The upregulated genes known to be involved in critical regulatory processes, included Mist1, Id2, Hd1, and Requiem; the downregulated genes included CREB-binding protein, Per3, zinc finger protein 217, Krox-25, and miwi1. Such well-characterized genes and many novel genes provide markers for early stages in development and starting materials for further functional studies. Published by Elsevier Ireland Ltd. C1 NIA, Dev Gen & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Gen & Aging Sect, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM kom@grc.nia.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 30 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD JUL 1 PY 2004 VL 115 SU 1 BP S85 EP S91 DI 10.1016/j.ejogrb.2004.01.026 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 838YE UT WOS:000222748600018 PM 15196723 ER PT J AU Moyer, C Allen, D Basabe, A Maronpot, RR Nyska, A AF Moyer, C Allen, D Basabe, A Maronpot, RR Nyska, A TI Analysis of vascular endothelial growth factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE pyrrolizidine alkaloid; endothelium; hemangiosarcoma; cytotoxicity; vascular endothelial growth factor; VEGFR-2; KDR/flk-1; in situ hybridization; immunohistochemistry ID CELL-PROLIFERATION; TYROSINE RESIDUES; IN-VIVO; ANGIOGENESIS; EXPRESSION; MICE; KDR; CARCINOGENICITY; ACTIVATION; TOXICITY AB Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (NYSKA et al. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium. including, those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. A Charles River Co, Pathol Associates, Raleigh, NC USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov NR 34 TC 7 Z9 7 U1 0 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD JUL PY 2004 VL 55 IS 6 BP 455 EP 465 DI 10.1078/0940-2993-00344 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 850PF UT WOS:000223624200004 PM 15384251 ER PT J AU Kalehua, AN Nagel, JE Whelchel, LM Gides, JJ Pyle, RS Smith, RJ Kusiak, JW Taub, DD AF Kalehua, AN Nagel, JE Whelchel, LM Gides, JJ Pyle, RS Smith, RJ Kusiak, JW Taub, DD TI Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE chemokine; inflammation; astrocytes; CNS; kainic acid; apoptosis ID FIBROBLAST-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; RAT-BRAIN; KAINIC ACID; NEURONAL DEATH; CHEMOKINE RECEPTORS; MESSENGER-RNA; INDUCED APOPTOSIS AB Intrahippocamal injections of kainic acid (KA) significantly increase the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) in the ipsilateral hippocampus at 2-4 h and 21-45 days post-administration, suggesting the possible involvement of these chemokines in both neurodegenerative and regenerative processes. To examine the possible role of these chemokines on neuronal cell death, hippocampal neurons were incubated with either MCP-1 or MIP-2 in vitro and examined to assess the effects on neuronal cell viability. These treatments resulted in significant neuronal apoptosis that could be abrogated by prior treatment with the caspase-1 inhibitor, Z-VAD-FMK, the caspase-3 inhibitor, Z-DEVD-FMK, the Galphai inhibitor, pertussis toxin, or the MAO-B inhibitor, (-)deprenyl. Furthermore, this chemokine apoptotic effect could also be observed in vivo as intrahippocampal injections of MCP-1 or MIP-2 resulted in the apoptosis of hippocampal neurons, thus supporting a direct role of these chemokines in neuronal death. In contrast, immunohistological analysis of kainic acid lesions on days 21-45 revealed significant expression of MCP-1 and MIP-2 associated with reactive astrocytes and macrophages, respectively, with no apoptotic populations being observed. These results suggested that these chemokines might also mediate distinct biological effects on local microenvironmental cell populations at various stages post truama and during cellular repair. To address this possibility, astrocyte were cultured in the presence or absence of these chemokines and examined by microarray analysis for effects on astrocytes gene expression. A number of genes encoding proteins associated with inflammation, cellular signaling, differentiation, and repair were directly modulated by chemokine treatment. More specifically, the RNA and protein expression of the neurotrophic factor, basic fibroblast growth factor (bFGF), was found to be significantly increased upon culture with MCP-1 and MIP-2. Conditioned media derived from chemokine-stimulated astrocytes also facilitated bFGF-dependent neuronal cell differentiation and promoted survival of H19-7 neurons in vitro, suggesting a possible role for chemokine-activated astrocytes as a source of trophic support. Taken together, these data support possible autocrine and paracrine roles for MCP-1 and MIP-2 in both the "death and life" of hippocampal neurons following CNS injury. Published by Elsevier Inc. C1 NIA, Clin Immunol Sect, Mol Neurobiol Sect, Ctr Gerontol Res,Lab Immunol,NIH,Intraumal Res Pr, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, Mol Neurobiol Sect, NIH, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Clin Immunol Sect, Mol Neurobiol Sect, Ctr Gerontol Res,Lab Immunol,NIH,Intraumal Res Pr, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM Taubd@grc.nia.nih.gov NR 69 TC 66 Z9 70 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2004 VL 297 IS 1 BP 197 EP 211 DI 10.1016/j.yexer.2004.02.031 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 831DW UT WOS:000222174400017 PM 15194436 ER PT J AU Scoltock, AB Cidlowski, JA AF Scoltock, AB Cidlowski, JA TI Activation of intrinsic and extrinsic pathways in apoptotic signaling during UV-C-induced death of Jurkat cells: the role of caspase inhibition SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Jurkat cells; caspase inhibition; apoptosis ID CYTOCHROME-C; HUMAN KERATINOCYTES; LYMPHOCYTE APOPTOSIS; LEUKEMIA-CELLS; COMPLEX DISC; T-CELLS; MECHANISMS; RADIATION; INDUCTION; SHRINKAGE AB We have examined UV irradiation-induced cell death in Jurkat cells and evaluated the relationships that exist between inhibition of caspase activity and the signaling mechanisms and pathways of apoptosis. Jurkat cells were irradiated with UV-C light, either with or without pretreatment with the pan-caspase inhibitor, z-VAD-fmk (ZVAD), or the more selective caspase inhibitors z-IETD-fmk (IETD), z-LEHD-fmk (LEHD), and z-DEVD-fmk (DEVD). Flow cytometry was used to examine alterations in viability, cell size, plasma membrane potential (PMP), mitochondrial membrane potential (DeltaPsi(mito)), intracellular Na+ and K+ concentrations, and DNA degradation. Processing of pro-caspases 3, 8, and 9 and the pro-apoptotic protein Bid was determined by Western blotting. UV-C irradiation of Jurkat cells resulted in characteristic apoptosis within 6 h after treatment and pretreatment of cells with ZVAD blocked these features. In contrast, pretreatment of the cells with the more selective caspase inhibitors under conditions that effectively blocked DNA degradation and inhibited caspase 3 and 8 processing as well as Bid cleavage had little protective effect on the other apoptotic characteristics examined. Thus, both intrinsic and extrinsic pathways are activated during UV-induced apoptosis in Jurkat cells and this redundancy appears to assure cell death during selective caspase inhibition. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov NR 42 TC 41 Z9 43 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2004 VL 297 IS 1 BP 212 EP 223 DI 10.1016/j.yexer.2004.03.025 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 831DW UT WOS:000222174400018 PM 15194437 ER PT J AU Piatigorsky, J Zigler, JS Horwitz, J AF Piatigorsky, J Zigler, JS Horwitz, J TI Frederick Bettelheim (1923-2004) SO EXPERIMENTAL EYE RESEARCH LA English DT Biographical-Item C1 NEI, Lab Mol Dev Biol, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Lab Mol Dev Biol, NIH, Bldg 7,Room 100A, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 2004 VL 79 IS 1 BP 1 EP 2 DI 10.1016/j.exer.2004.03.011 PG 2 WC Ophthalmology SC Ophthalmology GA 831EK UT WOS:000222175900001 ER PT J AU Hejtmancik, JF Kantorow, M AF Hejtmancik, JF Kantorow, M TI Molecular genetics of age-related cataract SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE lens; cataract; genetics; gene expression ID ANTERIOR POLAR CATARACTS; ALDOSE REDUCTASE GENE; LENS EPITHELIAL-CELLS; CORTICAL CATARACT; RISK-FACTORS; CONGENITAL CATARACT; ITALIAN POPULATION; VISUAL IMPAIRMENT; ALPHA-CRYSTALLIN; JUVENILE-ONSET AB Advances in molecular biological and genetic technology have greatly accelerated elucidation of the genetic contribution to age-related cataract. Epidemiological studies have documented tendencies for cataracts to occur more frequently in relatives of cataract patients than in the general population, genetic studies have demonstrated contributory roles of some specific genes in age related cataract in small populations. and molecular studies have shown changes in expression of specific genes in cataractous lenses. Together, these studies are beginning to provide a conceptual framework for understanding age-related cataracts. (C) 2004 Elsevier Ltd. All rights reserved. C1 Florida Atlantic Univ, Dept Biomed Sci, Boca Raton, FL 33431 USA. NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Kantorow, M (reprint author), Florida Atlantic Univ, Dept Biomed Sci, 777 Glades Rd,POB 3091, Boca Raton, FL 33431 USA. EM mkantoro@fau.edu FU NEI NIH HHS [EY13022, R01 EY013022] NR 59 TC 72 Z9 74 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 2004 VL 79 IS 1 BP 3 EP 9 DI 10.1016/j.exer.2004.03.014 PG 7 WC Ophthalmology SC Ophthalmology GA 831EK UT WOS:000222175900002 PM 15183095 ER PT J AU Zhu, M Miura, J Lu, LX Bernier, M DeCabo, R Lane, MA Roth, GS Ingram, DK AF Zhu, M Miura, J Lu, LX Bernier, M DeCabo, R Lane, MA Roth, GS Ingram, DK TI Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE caloric restriction; insulin signaling; PTP-1B; lipid metabolism; adiponectin ID PROTEIN-TYROSINE PHOSPHATASE-1B; COMPLEMENT-RELATED PROTEIN; NECROSIS-FACTOR-ALPHA; FATTY-ACID OXIDATION; PPAR-GAMMA; DIABETES-MELLITUS; ADIPOSE-TISSUE; MICE LACKING; METABOLIC SYNDROME; RHESUS-MONKEYS AB Caloric restriction (CR) has a well-known insulin sensitizing effect in vivo. Although this effect has been confirmed in rodents and primates for many years, its precise molecular mechanisms remain unknown. Here we show a significant increase in plasma adiponectin and a decrease in blood glucose, plasma triglyceride and insulin levels in rats maintained on CR diet for 2, 10, 15, and 20 months. Long-term CR rats exhibited significantly higher insulin-stimulated insulin receptor tyrosine phosphorylation and lower PTP-1B activity both in liver and skeletal muscle than those observed in rats fed ad libitum (AL). In addition, the triglyceride levels in these tissues were significantly lower in long-term CR animals. Interestingly, concentrations of plasma adiponectin in long-term CR rats were associated with increased expression of the transcription factor mRNAs for the peroxisome proliferator-activated receptor (PPAR)alpha, gamma and delta, but decreased expression for SREBP-1c, resulting in a concerted modulation in the expression of key transcription target genes involved in fatty acid oxidation and energy combustion in liver. Taken together, our findings suggest an important role for adiponectin in the beneficial effects of long-term CR. (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, Lab Expt Gerontol, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. NIA, Diabet Sect, Clin Invest Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP NIA, Lab Expt Gerontol, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Bernier, Michel/0000-0002-5948-368X; , rafael/0000-0003-2830-5693 NR 46 TC 112 Z9 118 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL PY 2004 VL 39 IS 7 BP 1049 EP 1059 DI 10.1016/j.exger.2004.03.024 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 840YC UT WOS:000222895300008 PM 15236764 ER PT J AU Bendixen, MH Nexo, BA Bohrc, VA Frederiksen, H McGue, M Kolvraa, S Christensen, K AF Bendixen, MH Nexo, BA Bohrc, VA Frederiksen, H McGue, M Kolvraa, S Christensen, K TI A polymorphic marker in the first intron of the Werner gene associates with cognitive function in aged Danish twins SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Werner's syndrome; WRN gene; polymorphism and aging ID SINGLE NUCLEOTIDE POLYMORPHISMS; BASAL-CELL CARCINOMA; HAND GRIP STRENGTH; JAPANESE POPULATION; SYNDROME PROTEIN; HELICASE GENE; AGING PROCESS; DNA HELICASE; VARIANT; COHORTS AB Werner's syndrome is a premature aging syndrome with many features common to normal aging. The possible association between phenotypic markers for normal aging and SNP's in the WRN gene was investigated in 426 dizygotic, Danish twins age 70-90 years. All participants were scored every second year using a number of physical and cognitive tests. In addition their self-rated health was registered as well as self reported status with regards to nine diseases. Blood was drawn from all participants and purified DNA was typed for four SNP's in the WRN gene. The four SNP's were located in intron 1, exon 6, exon 9 and exon 34. In an unpaired analysis of this material a significant association between the intron 1 SNP and cognitive function was demonstrated. Our finding, which will need corroboration in independent samples, therefore may suggest that the t-allele of the intron 1 SNP is beneficial to cognitive function. However, since the t-allele of this SNP is very rare, we did not encounter any tt-homozygous individuals for this allele. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Aarhus, Inst Human Genet, DK-8000 Aarhus C, Denmark. Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. Univ So Denmark, Inst Publ Hlth, Odense C, Denmark. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP Kolvraa, S (reprint author), Univ Aarhus, Inst Human Genet, Wilh Meyers Alle, DK-8000 Aarhus C, Denmark. EM steen@humgen.au.dk RI Christensen, Kaare/C-2360-2009 OI Christensen, Kaare/0000-0002-5429-5292 FU PHS HHS [P01-08761] NR 30 TC 9 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL PY 2004 VL 39 IS 7 BP 1101 EP 1107 DI 10.1016/j.exger.2004.03.036 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 840YC UT WOS:000222895300014 PM 15236770 ER PT J AU Cairo, MS Cohen, G Wagner, E Fraser, J Jensen, L Carter, S Kernan, N Kurtzberg, J AF Cairo, MS Cohen, G Wagner, E Fraser, J Jensen, L Carter, S Kernan, N Kurtzberg, J TI Cord blood (CB) hematopoietic progenitor cell (HPC) characterization and correlation with ethnicity: A report from the COBLT/NHLBI program SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 Univ Calif Los Angeles, Los Angeles, CA USA. Georgetown Univ, Washington, DC USA. Emmes Corp, Rockville, MD USA. NHLBI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 112 BP 57 EP 57 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700099 ER PT J AU Chen, J Ellison, FM Young, NS AF Chen, J Ellison, FM Young, NS TI Minor histocompatibility antigen H60 disparity induces bone marrow failure in congenic C.B10 mice SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 121 BP 59 EP 59 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700108 ER PT J AU Gurevich, RM Aplan, PD Humphries, RK AF Gurevich, RM Aplan, PD Humphries, RK TI Functional dissection of the NUP98-TOP1 fusion gene: Overlapping and unique features with NUP98-HOX fusion genes SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 159 BP 69 EP 70 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700145 ER PT J AU Cairo, MS Cohen, G Wagner, E Fraser, J Jensen, L Carter, S Kernan, N Kurtzberg, J AF Cairo, MS Cohen, G Wagner, E Fraser, J Jensen, L Carter, S Kernan, N Kurtzberg, J TI Unrelated cord blood (CB) banking, immune lymphocyte subsets and nucleated RBC characterization and correlation with ethnicity, birthweight, sex and type of delivery: A report from the COBLT/NHLBI program SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 Georgetown Univ, Washington, DC USA. Emmes Corp, Rockville, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. NHLBI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 198 BP 80 EP 80 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700184 ER PT J AU Yuan, R Astle, CM Chen, J Harrison, DE AF Yuan, R Astle, CM Chen, J Harrison, DE TI Despite a large advantage in repopulation, B6 fetal liver shows no advantage over adult marrow in HSC expansion after serial transplantation; BALB fetal liver shows the expected advantage SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol C1 Jackson Lab, Bar Harbor, ME 04609 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 SU 1 MA 200 BP 80 EP 81 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 841FM UT WOS:000222914700186 ER PT J AU Cai, JL Weiss, ML Rao, MS AF Cai, JL Weiss, ML Rao, MS TI In search of "stemness" SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID HUMAN HEMATOPOIETIC PROGENITORS; CENTRAL-NERVOUS-SYSTEM; UMBILICAL-CORD BLOOD; NEURAL CREST CELLS; ALDEHYDE DEHYDROGENASE; GAP-JUNCTIONS; BONE-MARROW; DNA-DAMAGE; ES CELLS; MOLECULAR SIGNATURE AB Stem cells have been identified and characterized in a variety of tissues. In this review we examine possible shared properties of stem cells. We suggest that irrespective of their lineal origin, stem cells have to respond in similar ways to regulate self-renewal and differentiation and it is likely that cell-cycle control, asymmetry/differentiation controls, cellular protective and DNA repair mechanisms, and associated apoptosis/senescence signaling pathways all might be expected to be more highly regulated in stem cells, likely by similar mechanisms. We review the literature to suggest a set of candidate sternness genes that may serve as universal stem cell markers. While we predict many similarities, we also predict that differences will exist between stem cell populations and that when transdifferentiation is considered genes expected to be both similar and different need to be examined. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Stem Cell Biol Unit,NIH, Baltimore, MD 21224 USA. Kansas State Univ, Coll Vet Med, Dept Anat & Physiol, Manhattan, KS 66506 USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, Stem Cell Biol Unit,NIH, 333 Cassell Dr,Rm 406A, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov FU NINDS NIH HHS [R01 NS034160, R01 NS034160-05A2] NR 118 TC 87 Z9 96 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2004 VL 32 IS 7 BP 585 EP 598 DI 10.1016/j.exphem.2004.03.013 PG 14 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 838QB UT WOS:000222726900001 PM 15246154 ER PT J AU Kreitman, RJ AF Kreitman, RJ TI Recombinant immunotoxins for the treatment of haematological malignancies SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE CD3; CD7; CD22; CD25; CD30; CD64; CD87; diphtheria toxin; fusion protein; granulocyte-macrophage colony-stimulating factor; Hodgkin's disease; IL-2; IL-3; leukaemia; lymphoma; monoclonal antibody; pseudomonas exotoxin; urokinase ID HAIRY-CELL LEUKEMIA; SINGLE-CHAIN IMMUNOTOXIN; PLASMINOGEN-ACTIVATOR RECEPTOR; PHASE-I TRIAL; ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; TRUNCATED DIPHTHERIA-TOXIN; TOXIN-INTERLEUKIN-3 FUSION PROTEIN; REFRACTORY HODGKINS LYMPHOMA AB Recombinant immunotoxins are fusion proteins which contain a ligand derived from the immune system fused to a toxin. The protein toxin is truncated to delete its binding domain, allowing selective ligand-directed binding. Growth factor fusion toxins are often considered immunotoxins. One of these molecules, containing the truncated diphtheria toxin and human IL-2 (Ontak(R), Ligand Pharmaceuticals), has been approved for the treatment of cutaneous T-cell lymphoma. Recombinant immunotoxins have also been produced containing the variable domains (Fv fragment) of monoclonal antibodies fused to toxins. These agents are relatively versatile with respect to the range of antigens possible. Several of these recombinant immunotoxins have showed clinical effectiveness in Phase I testing against haematological malignancies. One of these molecules, BL22, targets CD22 on hairy-cell leukaemia and has enabled patients to achieve complete remissions despite previous treatment and resistance to chemotherapy. C1 NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 512B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov NR 160 TC 13 Z9 18 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUL PY 2004 VL 4 IS 7 BP 1115 EP 1128 DI 10.1517/14712598.4.7.1115 PG 14 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 839OO UT WOS:000222794600010 PM 15268678 ER PT J AU Gills, JJ Dennis, PA AF Gills, JJ Dennis, PA TI The development of phosphatidylinositol ether lipid analogues as inhibitors of the serine/threonine kinase, Akt SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE Akt; cancer; phosphatidylinositol ether lipid analogue; pleckstrin homology domain ID PLECKSTRIN HOMOLOGY DOMAIN; CANCER-CELL-GROWTH; INTEGRIN-LINKED KINASE; PROTEIN-KINASE; EPITHELIAL-CELLS; ACTIVATION; PATHWAY; BREAST; RESISTANCE; MECHANISM AB The serine/threonine kinase Akt is a component of the phosphatidylinositol 3'-kinase/Akt signal transduction pathway that is activated by receptor tyrosine kinases, -activated Ras and integrins. As Akt regulates many processes crucial to carcinogenesis, and Akt activation has been observed in human cancers, intense efforts are underway to develop Akt inhibitors as cancer therapeutics. Towards this aim, phosphatidylinositol ether lipid analogues (PlAs), which are structurally similar to the products of phosphatidylinositol 3'-kinase, have been synthesised. PlAs inhibit Akt translocation, phosphorylation and kinase activity. Furthermore, they selectively induce apoptosis in cancer cell lines that depend on Akt for survival. This review will trace the development of PlAs, cover the biological activities of PlAs and discuss future steps and challenges in their development. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Navy Med Oncol, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Navy Med Oncol, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 59 TC 49 Z9 53 U1 2 U2 6 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUL PY 2004 VL 13 IS 7 BP 787 EP 797 DI 10.1517/13543784.13.7.787 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 837JU UT WOS:000222626500005 PM 15212619 ER PT J AU Wagner, PD Maruvada, P Srivastava, S AF Wagner, PD Maruvada, P Srivastava, S TI Molecular diagnostics: a new frontier in cancer prevention SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE cancer biomarkers; early detection; screening; technology development; validation ID PROSTATE-CANCER; OVARIAN-CANCER; HEPATOCELLULAR-CARCINOMA; PROTEIN MICROARRAYS; PROTEOMIC PATTERNS; MASS-SPECTROMETRY; BREAST-CANCER; SERUM; IDENTIFICATION; CELLS AB The promise of molecular diagnostics for cancer prevention In terms of early detection rests on two premises: assays can be developed to measure proteins, DNA, RNA or metabolites that accurately and reproducibly detect Incipient neoplasias; and that this early detection will eventually result In a decrease In morbidity and mortality and therefore benefit patients. Novel molecular technologies, Including laser capture microdissection, time-of-flight mass spectrometry, DNA microarrays, tissue arrays, protein microarrays and antibody microarrays, are being developed to Investigate the molecular differences between disease and normal cells and detect cancer-specific alterations In proteins, DNA and RNA In body fluids. Although literally hundreds of articles are published each year describing alterations In genes or proteins that are associated with cancer, very few result In useful molecular diagnostics for early cancer detection. Thus, there remains a critical need for new biomarkers for use In early detection and for assay methods that allow the translation of these biomarkers from the laboratory to the clinic. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Execut Plaza N,Room 3142,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM ssla@nih.gov NR 41 TC 11 Z9 11 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD JUL PY 2004 VL 4 IS 4 BP 503 EP 511 DI 10.1586/14737159.4.4.503 PG 9 WC Pathology SC Pathology GA 835KP UT WOS:000222482100010 PM 15225098 ER PT J AU Tzavara, ET Bymaster, FP Davis, RJ Wade, MR Perry, KW Wess, J McKinzie, DL Felder, C Nomikos, GG AF Tzavara, ET Bymaster, FP Davis, RJ Wade, MR Perry, KW Wess, J McKinzie, DL Felder, C Nomikos, GG TI M-4 muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related central nervous system pathologies SO FASEB JOURNAL LA English DT Article DE acetylcholine; microdialysis; dopamine; psychostimulants ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; STRIATAL DOPAMINE; ACETYLCHOLINE-RECEPTORS; SUBSTANTIA-NIGRA; KNOCKOUT MICE; GLUTAMATE RECEPTORS; NUCLEUS-ACCUMBENS; MESSENGER-RNAS; BASAL GANGLIA AB Dopaminergic dysfunction is an important pathogenetic factor for brain pathologies such as Parkinson's disease, ADHD, schizophrenia, and addiction as well as for metabolic disorders and anorexia. Dopaminergic neurons projecting from the midbrain to forebrain regions, such as the nucleus accumbens and the prefrontal cortex, regulate motor and cognitive functions and coordinate the patterned response of the organism to sensory, affective, and rewarding stimuli. In this study, we showed that dopaminergic neurotransmission is highly dependent on M-4 cholinergic muscarinic receptor function. Using in vivo microdialysis, we found elevated dopamine (DA) basal values and enhanced DA response to psychostimulants in the nucleus accumbens of M-4 knockout mice. We also demonstrated impaired homeostatic control of cholinergic activity that leads to increased basal acetylcholine efflux in the midbrain of these animals. Thus, loss of M-4 muscarinic receptor control of cholinergic function effectuates a state of dopaminergic hyperexcitability. This may be responsible for pathological conditions, in which appetitive motivation as well as affective and cognitive processing is impaired. We propose that M-4 receptor agonists could represent an innovative strategy for the treatment of pathologies associated with hyperdopaminergia. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Nomikos, GG (reprint author), Eli Lilly & Co, Lilly Corp Ctr, DC0510, Indianapolis, IN 46285 USA. EM gnomikos@lilly.com NR 54 TC 80 Z9 84 U1 2 U2 8 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 JUL PY 2004 VL 18 IS 10 BP 1410 EP + DI 10.1096/fj.04-1575fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 842CB UT WOS:000222979200020 PM 15231726 ER PT J AU Matsusue, K Peters, JM Gonzalez, FJ AF Matsusue, K Peters, JM Gonzalez, FJ TI PPAR beta/delta potentiates PPAR gamma-stimulated adipocyte differentiation SO FASEB JOURNAL LA English DT Article DE peroxisome proliferator-activated receptor ID ACTIVATED-RECEPTOR-DELTA; ADIPOSE DIFFERENTIATION; BROWN ADIPOCYTES; GENE-EXPRESSION; PERILIPIN-A; INSULIN; ADIPOGENESIS; MACROPHAGES; PROTEIN; TRANSCRIPTION AB It is well established that peroxisome proliferator-activated receptor-gamma (PPARgamma) has a critical role in modulating adipocyte differentiation based on gain-of-function and loss-of-function experiments. However, recent gain-of-function experiments suggest that PPARbeta may also have a role in mediating adipocyte differentiation. Because ligands for PPARs can activate more than one receptor isoform, the specific role of PPARbeta in adipocyte differentiation was examined using PPARbeta-null adipocytes. Wild-type adipocytes accumulate lipids in response to differentiation signaling induced from standard differentiation medium, and this effect is significantly reduced in PPARbeta-null adipocytes. The addition of the PPARbeta ligand L165041 to the standard differentiation medium causes enhanced adipocyte differentiation and lipid accumulation, and this effect is diminished in adipocytes lacking expression of PPARbeta. Treatment of wild-type adipocytes with the PPARgamma ligand troglitazone causes accelerated adipocyte differentiation and lipid accumulation, and this effect is marginally reduced in PPARbeta-null adipocytes. Expression patterns of mRNA markers of early and late adipocyte differentiation are consistent with the morphological and biochemical differences observed. Results from these studies demonstrate that in the absence of PPARbeta expression, adipocyte differentiation is significantly impaired, providing loss-of-function evidence supporting a role for this receptor in adipocyte differentiation. These results also demonstrate that L165041-stimulated adipocyte differentiation and lipid accumulation is mediated by PPARbeta. In addition, as the ability of troglitazone to induce adipocyte differentiation is also impaired in PPARbeta null adipocytes, this suggests that both PPARbeta and PPARgamma isoforms are required to facilitate maximal lipid accumulation and differentiation during adipogenesis. C1 NCI, LAb Metab, Bethesda, MD 20892 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. RP Gonzalez, FJ (reprint author), NCI, LAb Metab, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Peters, Jeffrey/D-8847-2011 FU NCI NIH HHS [CA97999, R01 CA89607] NR 30 TC 63 Z9 71 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 JUL PY 2004 VL 18 IS 10 BP 1477 EP + DI 10.1096/fj.04-1944fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 842CB UT WOS:000222979200001 PM 15247146 ER PT J AU Potlog-Nahari, C Feldman, AL Stratton, P Koziol, DE Segars, J Merino, MJ Nieman, LK AF Potlog-Nahari, C Feldman, AL Stratton, P Koziol, DE Segars, J Merino, MJ Nieman, LK TI CD10 immunohistochemical staining enhances the histological detection of endometriosis SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WA SP Amer Soc Reproduct Med DE CD10; diagnostic test; endometriosis; hematoxylin and eosin; immunohistochemistry ID NEUTRAL METALLOENDOPEPTIDASE; LAPAROSCOPY; EXPRESSION; DIAGNOSIS; STROMA; CELLS; ENDOSALPINGIOSIS; CARCINOMA; NEOPLASMS; ANTIGEN AB Objective: To determine whether the use of CD10 immunohistochemistry in addition to hematoxylin and eosin (H&E) staining would increase the sensitivity of surgically suspected endometriosis lesions. Design: Retrospective cohort study. Setting: Tertiary care government research hospital. Patient(s): Thirty-one women with chronic pelvic pain. Intervention(s): Immunohistochemical analysis for CD10 was performed on 108 possible endometriotic lesions and in the corresponding endometrial biopsy samples obtained during laparoscopy. When CD10 immunohistochemistry results were positive, the corresponding H&E section was reviewed to determine if the initial diagnosis should be revised. Main Outcome Measure(s): Histologic diagnosis of endometriosis by adjunctive use of CD10 immunohistochemistry in conjunction with H&E-stained specimens. Result(s): In endometrial stroma, CD10 was consistently present. Of the 70 specimens judged negative initially by H&E staining, CD10 staining led to the diagnosis of endometriosis in 11. The addition of CD10 immunohistochemistry detected more positive endometriosis lesions than H&E staining alone (45% vs. 35%). In three women with minimal endometriosis at surgery but initially negative histopathology, CD10 immunohistochemistry changed the histologic diagnosis to endometriosis. Conclusion(s): The adjunctive use of CD10 immunohistochemistry improves diagnostic sensitivity for endometriosis, especially for women with minimal disease. (C) 2004 by American Society for Reproductive Medicine. C1 NICHHD, PREB, Bethesda, MD 20892 USA. NCI, Surg Pathol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. RP Potlog-Nahari, C (reprint author), NICHD, PREB, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM naharic@mail.nih.gov RI Feldman, Andrew/D-5028-2012 NR 22 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2004 VL 82 IS 1 BP 86 EP 92 DI 10.1016/j.fertnstert.2003.11.059 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 838XB UT WOS:000222745600017 PM 15236994 ER PT J AU Luellen, BA Unger, EL Lyons, WE Blue, ME Mamounas, LA Andrews, AM AF Luellen, B. A. Unger, E. L. Lyons, W. E. Blue, M. E. Mamounas, L. A. Andrews, A. M. TI Constitutive reductions in SERT ezpression alter age-dependent changes in serotonin innervation patterns SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Luellen, B. A.; Unger, E. L.; Andrews, A. M.] Penn State Univ, University Pk, PA 16802 USA. [Lyons, W. E.; Mamounas, L. A.] NINDS, NIH, Bethesda, MD 20892 USA. [Blue, M. E.] Kennedy Krieger Res Inst, Baltimore, MD USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2004 VL 18 SU 1 BP 43 EP 43 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V28EH UT WOS:000208663600220 ER PT J AU Sudweeks, SN Yakel, JL van Hooft, JA AF Sudweeks, S. N. Yakel, J. L. van Hooft, J. A. TI Serotonin 5-HT3 receptors in rat CA1 hippocampal interneurones: functional and molecular characterization SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Sudweeks, S. N.; Yakel, J. L.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [van Hooft, J. A.] Univ Amsterdam, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2004 VL 18 SU 1 BP 129 EP 129 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V28EH UT WOS:000208663600733 ER PT J AU Baumann, MH Clark, RD Rothman, RB Blough, BE AF Baumann, M. H. Clark, R. D. Rothman, R. B. Blough, B. E. TI Neurochemistry of ecstasy, metabolites of ecstasy and 'legal X' compounds SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Baumann, M. H.; Clark, R. D.; Rothman, R. B.] NIDA, IRP, NIH, Baltimore, MD 21224 USA. [Blough, B. E.] RTI, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2004 VL 18 SU 1 BP 132 EP 132 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V28EH UT WOS:000208663600755 ER PT J AU Nunez, MC Baumann, MH Rothman, RB AF Nunez, M. C. Baumann, M. H. Rothman, R. B. TI Substituted amphetamines increase the concentration of 'free' serotonin in the bloodstream of conscious rats SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Nunez, M. C.; Baumann, M. H.; Rothman, R. B.] NIDA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2004 VL 18 SU 1 BP 140 EP 140 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V28EH UT WOS:000208663600794 ER PT J AU Clark, RD Baumann, MH Rothman, RB Blough, BE AF Clark, R. D. Baumann, M. H. Rothman, R. B. Blough, B. E. TI In vivo evidence that extracellular serotonin inhibits dopaminergic effects of monoamine releasing agents in the rat SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Clark, R. D.; Baumann, M. H.; Rothman, R. B.] NIDA, IRP, NIH, Baltimore, MD USA. [Blough, B. E.] RTI, Res Triangle Inst, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD JUL PY 2004 VL 18 SU 1 BP 150 EP 150 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V28EH UT WOS:000208663600855 ER PT J AU Darling, RL Romero, JJ Dial, EJ Akunda, JK Langenbach, R Lichtenberger, LM AF Darling, RL Romero, JJ Dial, EJ Akunda, JK Langenbach, R Lichtenberger, LM TI The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice SO GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SELECTIVE CYCLO-OXYGENASE-2 INHIBITORS; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; RAT STOMACH; GENE DISRUPTION; DAMAGE; INJURY; COX-2; INDOMETHACIN AB Background & Aims: Insight into the role of the different cyclooxygenase isoforms in prostaglandin biosynthesis, surface hydrophobicity, and gastric mucosal barrier integrity can be gained by comparing the effects of luminal damaging agents in wild-type and cyclooxygenase knockout mice. Methods: Fasted wild-type, cyclooxygenase-1, and cyclooxygenase-2 knockout mice were intragastrically administered saline, 0.6N HCl, or aspirin (aspirin 20 mmol/L) in combination with 0.6N HCl and killed 1 hour later, at which time the gastric lesion score was assessed and biopsy samples were taken for surface, biochemical, and morphological analyses. Results: The gastric mucosa of cyclooxygenase-1 knockout mice was more severely injured by both HCl alone and aspirin/HCl than that of wild-type and cyclooxygenase-2 knockout mice. HCl alone and aspirin/HCl also induced a more profound decrease in surface hydrophobicity in cyclooxygenase-1 knockout mice than in wild-type mice, whereas this surface property was unaffected in cyclooxygenase-2 knockout mice. The gastric injury induced by aspirin/HCl in cyclooxygenase-1 knockout mice could be prevented if the animals were treated with phosphatidylcholine-associated aspirin. Aspirin/HCl, in comparison to saline or HCl alone, induced a 4-6-fold increase in gastric mucosal prostaglandin E-2 concentration in the cyclooxygenase-1 knockout mice, whereas it decreased prostaglandin E-2 levels in wild-type and cyclooxygenase-2 knockout mice. This paradoxical aspirin-induced increase in gastric prostaglandin E-2 in cyclooxygenase-1 knockout mice seemed to correspond to an increase in cyclooxygenase-2 messenger RNA and protein expression. The gastric lesion score seemed to be significantly associated with alterations in surface hydrophobicity but not with mucosal prostaglandin E-2 concentration. Conclusions: Our evidence on cyclooxygenase knockout mice suggests that aspirin predominantly causes gastric injury by a non-prostaglandin mechanism, perhaps by attenuating surface hydrophobicity, a possibility supported by the low gastric toxicity of phosphatidylcholine/aspirin. However, prostaglandins generated by cyclooxygenase-1 may play an important permissive role in maintaining gastric mucosal barrier integrity. Aspirin seems to paradoxically increase the gastric mucosal prostaglandin E-2 concentration in cyclooxygenase-1 knockout mice, possibly by the induction of cyclooxygenase-2. C1 Univ Texas, Sch Med, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. RP Lichtenberger, LM (reprint author), Univ Texas, Sch Med, Dept Integrat Biol & Pharmacol, 6431 Fannin St, Houston, TX 77030 USA. EM lenard.m.lichtenberger@uth.tmc.edu FU NIDDK NIH HHS [DK 53195, P30 DK56338] NR 51 TC 56 Z9 57 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2004 VL 127 IS 1 BP 94 EP 104 DI 10.1016/j.gastro.2004.04.003 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836HE UT WOS:000222545700016 PM 15236176 ER PT J AU El-Serag, HB Everhart, JE AF El-Serag, HB Everhart, JE TI Is diabetes a risk factor for hepatocellular carcinoma? - Reply SO GASTROENTEROLOGY LA English DT Letter ID LIVER-DISEASE; HEPATITIS-C; VIRUS C1 Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDKD, Bethesda, MD 20892 USA. RP El-Serag, HB (reprint author), Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. NR 5 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 JUL PY 2004 VL 127 IS 1 BP 361 EP 362 DI 10.1053/j.gastro.2004.05.046 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836HE UT WOS:000222545700050 ER PT J AU Bierie, B Edwin, M Melenhorst, JJ Hennighausen, L AF Bierie, B Edwin, M Melenhorst, JJ Hennighausen, L TI The proliferation associated nuclear element (PANE1) is conserved between mammals and fish and preferentially expressed in activated lymphoid cells SO GENE EXPRESSION PATTERNS LA English DT Article DE proliferation associated nuclear element; zebrafish; beta-catenin; leukemia; lymphoma; PANE1 ID HUMAN-TUMOR XENOGRAFTS; NUDE-MICE; LINES; ESTABLISHMENT; CHROMOSOME; PC-3 AB The proliferation associated nuclear element (PANE 1) had been identified in a screen for genes activated in mouse mammary epithelium transformed by stabilized beta-catenin. We have now cloned the human and zebratish orthologs, analyzed their expression and expressed them ectopically in tissue culture cell lines. PANE1 consists of 180 amino acids and displays 38% conservation between man and zebrafish. Expression of the human PANE1 gene was detected preferentially in immune cells including leukemias and lymphomas, tumor tissues and tumor derived cell lines. In B- and T-cells PANE1 RNA was only detected after the respective cell types were activated either in vivo or in vitro. (C) 2004 Elsevier B.V. All rights reserved. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. EM hennighausen@nih.gov NR 16 TC 7 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD JUL PY 2004 VL 4 IS 4 BP 389 EP 395 DI 10.1016/j.modgep.2004.01.008 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 834TM UT WOS:000222433800004 PM 15183305 ER PT J AU Catherino, WH Leppert, PC Stenmark, MH Payson, M Potlog-Nahari, C Nieman, LK Segars, JH AF Catherino, WH Leppert, PC Stenmark, MH Payson, M Potlog-Nahari, C Nieman, LK Segars, JH TI Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids SO GENES CHROMOSOMES & CANCER LA English DT Article ID GROWTH-FACTOR-BETA; DERMATAN SULFATE PROTEOGLYCAN; ACIDIC MATRIX PROTEIN; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; TRANSFORMING GROWTH-FACTOR-BETA-1; COLLAGEN FIBRILLOGENESIS; CELL-CANCER; TGF-BETA; DECORIN AB Uterine leiomyomas are prevalent estrogen-responsive clonal tumors, but the specific genetic alterations that contribute to their development have not been elucidated. To identify genes involved in the formation of leiomyomas, we used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. Genes encoding extracellular-matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas revealed a disordered collagen fibril orientation. Expression of the collagen-binding protein dermatopontin was found to be consistently decreased in leiomyoma by both reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR (mean underexpression = 9.41 -fold) regardless of leiomyoma size, leiomyoma location, patient race, and patient age. This expression pattern was observed in 11 subjects and a total of 23 leiomyoma: myometrium pairs. Decreased expression of dermatopontin was also associated with keloid formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor-beta3 (TGFB3) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. These findings suggest that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular-matrix proteins. In particular, decreased expression of dermatopontin represents a molecular link between the leiomyoma and keloid phenotypes. (C) 2004 Wiley-Liss, Inc. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Reprod Sci Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Segars, JH (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D-42, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [HD-008737-02, Z01 HD008737] NR 49 TC 111 Z9 112 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 2004 VL 40 IS 3 BP 204 EP 217 DI 10.1002/gcc.20035 PG 14 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 825FC UT WOS:000221740400005 PM 15139000 ER PT J AU Kusakabe, T Kawaguchi, A Kawaguchi, R Feigenbaum, L Kimura, S AF Kusakabe, T Kawaguchi, A Kawaguchi, R Feigenbaum, L Kimura, S TI Thyrocyte-specific expression of Cre recombinase in transgenic mice SO GENESIS LA English DT Article DE cre-mediated recombination; transgenic mouse; thyroid-specific ID THYMUS; CELLS; GENE AB A transgenic mouse line that expresses Cre recombinase under control of the human thyroid peroxidase (TPO) gene promoter was established. The activity and specificity of the TPO-driven Cre recombinase were examined by using Northern blotting and by crossing with the ROSA26 reporter transgenic mouse line. In the latter mice, Cre-mediated recombination occurred only in the thyrocytes, and recombination commenced around embryonic day 14.5, at the time during thyroid organogenesis when TPO expression begins. This study demonstrates that the TPO-Cre transgenic mouse is a powerful tool to specifically delete loxP-inserted (floxed) genes in thyrocytes and will be of great value in the study of thyrocyte-specific genes during development and/or in adult thyroids. (C) 2004 Wiley-Liss, Inc. C1 NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, SAIC, FCRDC, Transgen Mouse Model Lab, Frederick, MD USA. RP Kimura, S (reprint author), NCI, Lab Metab, Canc Res Ctr, NIH, Bldg 37,Rm 3112B, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov NR 18 TC 32 Z9 32 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD JUL PY 2004 VL 39 IS 3 BP 212 EP 216 DI 10.1002/gene.20043 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 845FB UT WOS:000223221500008 PM 15282748 ER PT J AU Kistner, EO Weinberg, CR AF Kistner, EO Weinberg, CR TI Method for using complete and incomplete trios to identify genes related to a quantitative trait SO GENETIC EPIDEMIOLOGY LA English DT Article DE linkage disequilibrium; association; polytomous logistic; missing parents; population admixture; TDT ID DISEQUILIBRIUM; ASSOCIATION; TESTS AB A number of tests for linkage and association with qualitative traits have been developed, with the most well-known being the transmission/disequilibrium test (TDT). For quantitative traits, varying extensions of the TDT have been suggested. The quantitative trait approach we propose is based on extending the log-linear model for case-parent trio data (Weinberg et al. [1998] Am. J. Hum. Genet. 62:969-978). Like the log-linear approach for qualitative traits, our proposed polytomous logistic approach for quantitative traits allows for population admixture by conditioning on parental genotypes. Compared to other methods, simulations demonstrate good power and robustness of the proposed test under various scenarios of the genotype effect, distribution of the quantitative trait, and population stratification. In addition, missing parental genotype data can be accommodated through an expectation-maximization (EM) algorithm approach. The EM approach allows recovery of most of the lost power due to incomplete trios. Published 2004 Wiley-Liss, Inc. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Kistner, EO (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM kistner@niehs.nih.gov NR 14 TC 38 Z9 39 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2004 VL 27 IS 1 BP 33 EP 42 DI 10.1002/gepi.20001 PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 831XX UT WOS:000222231300004 PM 15185401 ER PT J AU Friedman, R Drake, JW Hughes, AL AF Friedman, R Drake, JW Hughes, AL TI Genome-wide patterns of nucleotide substitution reveal stringent functional constraints on the protein sequences of thermophiles SO GENETICS LA English DT Article ID SYNONYMOUS CODON USAGE; SELECTION; ORGANISMS; MUTATION; BACTERIA; RATES; THERMOSTABILITY AB To test the hypothesis that the proteins of thermophilic prokaryotes are subject to unusually stringent functional constraints, we estimated the numbers of synonymous and nonsynonymous nucleotide substitutions per site between 17,957 pairs of orthologous genes from 22 pairs of closely related species of Archaea and Bacteria. The average ratio of nonsynonymous to synonymous substitutions was significantly lower in thermophiles than in nonthermophiles, and this effect was observed in both Archaea and Bacteria. There was no evidence that this difference could be explained by factors such as nucleotide content bias. Rather, the results support the hypothesis that proteins of thermophiles are subject to unusually strong purifying selection, leading to a reduced overall level of amino acid evolution per mutational event. The results show that genome-wide patterns of sequence evolution can be influenced by natural selection exerted by a species' environment and shed light on a previous observation that relatively few of the mutations arising in a thermophilic archaeon were nucleotide substitutions in contrast to indels. C1 Univ S Carolina, Dept Sci Biol, Columbia, SC 29208 USA. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Hughes, AL (reprint author), Univ S Carolina, Dept Sci Biol, 700 Sumter St, Columbia, SC 29208 USA. EM atistin@biol.sc.edu FU NIGMS NIH HHS [GM66710] NR 29 TC 38 Z9 38 U1 0 U2 6 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2004 VL 167 IS 3 BP 1507 EP 1512 DI 10.1534/genetics.104.026344 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 843TL UT WOS:000223109300038 PM 15280258 ER PT J AU Johnston, JJ Turner, J Biesecker, LG AF Johnston, JJ Turner, J Biesecker, LG TI Significant genotype phenotype correlation for GL13 mutations refutes prior assertions of a lack of correlation. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 15 BP 253 EP 253 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200027 ER PT J AU Porter, F Wassif, C Kratz, L Kelly, R Correa-Cerro, L AF Porter, F Wassif, C Kratz, L Kelly, R Correa-Cerro, L TI Development, characterization, and treatment of a hypomorphic Smith-Lemli-Opitz syndrome mouse model. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. Kennedy Krieger Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 47 BP 269 EP 269 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200059 ER PT J AU Kleta, R Varade, WS Bernardini, I Ueda, M Phornphutkul, C Krasnewich, D Gahl, WA AF Kleta, R Varade, WS Bernardini, I Ueda, M Phornphutkul, C Krasnewich, D Gahl, WA TI Long-term follow-up of early and well-treated nephropathic cystinosis patients. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 NHGRI, Sect Human Biochem Genet, MGB, NIH,DHHS, Bethesda, MD 20892 USA. NIH, Off Rare Dis, Intramural Program, DHHS, Bethesda, MD 20892 USA. NIH, Off Director, DHHS, Bethesda, MD 20892 USA. Univ Rochester, Dept Pediat, Golisano Childrens Hosp Strong, Med Ctr, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 60 BP 275 EP 275 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200072 ER PT J AU Ueda, M Yang, S Karkera, J Lacbawan, F AF Ueda, M Yang, S Karkera, J Lacbawan, F TI Partial monosomy 11q with partial trisomy 12q: rare or missed cases? SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 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 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 140 BP 312 EP 312 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200149 ER PT J AU Lewis, J Hagerty, K Lander, L DellaRocca, M Soper, E Weaver, S Cowan, A Lanier, L Hyatt-Knorr, H AF Lewis, J Hagerty, K Lander, L DellaRocca, M Soper, E Weaver, S Cowan, A Lanier, L Hyatt-Knorr, H TI The Genetic and Rare Diseases Information Center: A federal government resource. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 Aspen Syst, Rockville, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Off Rare Dis, 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 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 192 BP 338 EP 338 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200201 ER PT J AU Sommer, S Feng, J Shibayama, A Glanzmann, C Yan, J Cook, E Craddock, N Jones, I Goldman, D Heston, LL AF Sommer, S Feng, J Shibayama, A Glanzmann, C Yan, J Cook, E Craddock, N Jones, I Goldman, D Heston, LL TI MECP2 variants in psychiatric diseases: possible association with autism. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 City Hope Natl Med Ctr, Dept Mol Genet, Duarte, CA 91010 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Birmingham, Div Neurosci, Queen Elizabeth Psychiat Hosp, Birmingham, W Midlands, England. NIAAA, Dept Psychiat, NIH, Bethesda, MD USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RI Jones, Ian/B-4925-2009 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 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 239 BP 361 EP 361 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200246 ER PT J AU Muenke, M AF Muenke, M TI Gene-enviroment interactions in holoprosencephaly. SO GENETICS IN MEDICINE LA English DT Meeting Abstract CT Annual Clinical Meeting of the American-College-of-Medical-Genetics CY MAR 04, 2004 CL Orlando, FL SP Amer Coll Med Genet C1 NHGRI, Med Genet Branch, NIH, DHHS, 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 1098-3600 J9 GENET MED JI Genet. Med. PD JUL-AUG PY 2004 VL 6 IS 4 MA 285 BP 382 EP 382 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 838WX UT WOS:000222745200291 ER PT J AU Boissinot, S Entezam, A Young, L Munson, PJ Furano, AV AF Boissinot, S Entezam, A Young, L Munson, PJ Furano, AV TI The Insertional history of an active family of L1 retrotransposons in humans SO GENOME RESEARCH LA English DT Article ID LINE-1 RETROTRANSPOSONS; HUMAN GENOME; ELEMENT; RECOMBINATION; INTEGRATION; EVOLUTION; SEQUENCES; CAPACITY; SEARCH; REGION AB As humans contain a currently active L1 (LINE-1) non-LTR retrotransposon family (Ta-1), the human genome database likely provides only a partial Picture of Ta-1-generated diversity. We used a non-biased method to clone Ta-1 retrotransposon-containing loci from representatives of four ethnic populations. We obtained 277 distinct Ta-1 loci and identified an additional 67 loci in the human genome database. This collection represents similar to90% of the Ta-1 population in the individuals examined and is thus more representative of the insertional history of Ta-1 than the human genome database, which lacked similar to40% of our cloned Ta-1 elements. As both polymorphic and fixed Ta-1 elements are as abundant in the GC-poor genomic regions as in ancestral L1 elements, the enrichment of L1 elements in GC-poor areas is likely due to insertional bias rather than selection. Although the chromosomal distribution of Ta-1 inserts is generally a function of chromosomal length and gene density, chromosome 4 significantly deviates from this pattern and has been Much more hospitable to Ta-1 insertions than any other chromosome. Also, the intra-chromosomal distribution of Ta-1 elements is not uniform. Ta-1 elements tend to cluster, and the maximal gaps between Ta-1 inserts are larger than Would be expected from a model Of uniform random insertion. C1 NIDDKD, Mol & Cellular Biol Lab, Sect Genomic Struct & Funct, NIH, Bethesda, MD 20892 USA. NIH, Analyt Biostat Sect, Math & Stat Comp Lab, Div Computat Biosci,Ctr Informat Technol, Bethesda, MD 20892 USA. RP Furano, AV (reprint author), NIDDKD, Mol & Cellular Biol Lab, Sect Genomic Struct & Funct, NIH, Bethesda, MD 20892 USA. EM avf@helix.nih.gov NR 35 TC 59 Z9 63 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2004 VL 14 IS 7 BP 1221 EP 1231 DI 10.1101/gr.2326704 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 834TQ UT WOS:000222434200002 PM 15197167 ER PT J AU Annilo, T Dean, M AF Annilo, T Dean, M TI Degeneration of an ATP-binding cassette transporter gene, ABCC13, in different mammalian lineages SO GENOMICS LA English DT Article DE ATP-binding cassette transporter; transcribed pseudogene; mammalian comparative genomics; evolution of a gene family ID CYSTIC-FIBROSIS GENE; SUPERFAMILY; IDENTIFICATION; LACKING; TRANSCRIPTION; DUPLICATION; SEQUENCES; DISEASE; CANCER; HEALTH AB The ABC transporter gene family has evolved by a gene "birth-and-death" process; however, the number of ABC pseudogenes in the human genome is surprisingly small. On chromosome 21q11.2, spanning 90 kb, is an ABC gene-like sequence (recently annotated as ABCC13) with the highest similarity to ABCC2. Here we show that while comparative analysis and in silico prediction methods indicate the presence of at least 28 exons, the majorABCC13 transcript in humans consists of only 6 exons with a total length of 1.1 kb. The open reading frame of this transcript is capable of encoding a polypeptide of only 274 amino acids, compared to the more than 1500 amino acids of related ABC transporters. The truncated ABCC13 transcript shows tissue-specific expression, highest in fetal liver, bone marrow, and colon. Since the last exon of the ABCC13 transcript contains an apparent frameshift, we sequenced the respective region from several primates and found that the frameshift is due to an 11-bp deletion that is shared between human, chimpanzee, and gorilla, but is not found in monkeys. In addition, the human ABCC13 gene contains two other frameshift indels in the exons that encode the second nucleotide-binding domain, indicating that ABCC13 is not capable of encoding a functional ABC protein. In an attempt to identify an intact ABCC13 ortholog, we have sequenced the full-length cDNA from rhesus macaque, which contains an open reading frame of 1296 amino acids, producing an apparently functional ABC transporter. Although the mouse and rat genomes contain long-range similarity in the locus where Abcc13 is expected to reside, most of the Abcc13 exons in rodents are degraded below the threshold of sequence homology searches or have been deleted completely. (C) 2004 Elsevier Inc. All rights reserved. C1 Natl Canc Inst, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. RP Annilo, T (reprint author), Natl Canc Inst, Human Genet Sect, Lab Genom Divers, Bldg 560,Room 21-31, Frederick, MD 21702 USA. EM tannilo@ncifcrf.gov RI Dean, Michael/G-8172-2012; Annilo, Tarmo/J-2900-2013 OI Dean, Michael/0000-0003-2234-0631; Annilo, Tarmo/0000-0002-9588-3058 NR 35 TC 25 Z9 27 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2004 VL 84 IS 1 BP 34 EP 46 DI 10.1016/j.ygeno.2004.02.010 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 835CU UT WOS:000222458400004 PM 15203202 ER PT J AU Yang, HH Hu, Y Buetow, KH Lee, MP AF Yang, HH Hu, Y Buetow, KH Lee, MP TI A computational approach to measuring coherence of gene expression in pathways SO GENOMICS LA English DT Article ID OLIGONUCLEOTIDE ARRAYS; PATTERNS; CANCERS; TISSUE AB This study uses a computational approach to analyze coherence of expression of genes in pathways. Microarray data were analyzed with respect to coherent gene expression in a group of genes defined as a pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Our hypothesis is that genes in the same pathway are more likely to be coordinately regulated than a randomly selected gene set. A correlation coefficient for each pair of genes in a pathway was estimated based on gene expression in normal or tumor samples, and statistically significant correlation coefficients were identified. The coherence indicator was defined as the ratio of the number of gene pairs in the pathway whose correlation coefficients are significant, divided by the total number of gene pairs in the pathway. We defined all genes that appeared in the KEGG pathways as, a reference gene set. Our analysis indicated that the mean coherence indicator of pathways is significantly larger than the mean coherence indicator of random gene sets drawn from the reference gene set. Thus, the result supports our hypothesis. The significance of each individual pathway of n genes was evaluated by comparing its coherence indicator with coherence indicators of 1000 random permutation sets of n genes chosen from the reference gene set. We analyzed three data sets: two Affymetrix microarrays and one cDNA microarray. For each of the three data sets, statistically significant pathways were identified among all KEGG pathways. Seven of 96 pathways had a significant coherence indicator in normal tissue and 14 of 96 pathways had a significant coherence indicator in tumor tissue in all three data sets. The increase in the number of pathways with significant coherence indicators may reflect the fact that tumor cells have a higher rate of metabolism than normal cells. Five pathways involved in oxidative phosphorylation, ATP synthesis, protein synthesis, or RNA synthesis were coherent in both normal and tumor tissue, demonstrating that these are essential genes, a high level of expression of which is required regardless of cell type. Published by Elsevier Inc. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Lee, MP (reprint author), NCI, Lab Populat Genet, 41 Lib Dr, Bethesda, MD 20892 USA. EM leemax@mail.nih.gov NR 12 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2004 VL 84 IS 1 BP 211 EP 217 DI 10.1016/j.ygeno.2004.01.007 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 835CU UT WOS:000222458400021 PM 15203219 ER PT J AU Kelly, JM Marrero, DG Gallivan, J Leontos, C Perry, S AF Kelly, JM Marrero, DG Gallivan, J Leontos, C Perry, S TI Diabetes prevention - A GAMEPLAN for success SO GERIATRICS LA English DT Article DE diabetes; prevention; national diabetes education program; impaired glucose tolerance; impaired fasting glucose; pre-diabetes ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE AB Diabetes prevalence is growing at epidemic proportions, and the greatest increase in number of cases is anticipated to be among older adults. The Diabetes Prevention Program (DPP) showed that diabetes can be prevented or delayed among people with pre-diabetes (impaired glucose tolerance, impaired fasting glucose, or both). The National Diabetes Education Program has developed tools adapted from the DPP that primary care providers can use to counsel middle-age and older patients on diabetes prevention. C1 Ctr Dis Control & Prevent, Natl Diabet Educ Program, Atlanta, GA 30333 USA. Indiana Univ, Sch Med, Indiana Diabet Res & Training Ctr, Demonstrat & Educ Div, Bloomington, IN 47405 USA. Natl Diabet Educ Program, NIH, Bethesda, MD USA. RP Kelly, JM (reprint author), Ctr Dis Control & Prevent, Natl Diabet Educ Program, Atlanta, GA 30333 USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD JUL PY 2004 VL 59 IS 7 BP 26 EP 31 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 836HJ UT WOS:000222546200006 PM 15250193 ER PT J AU Diosdado, B Wapenaar, MC Franke, L Duran, KJ Goerres, MJ Hadithi, M Crusius, JBA Meijer, JWR Duggan, DJ Mulder, CJJ Holstege, FCP Wijmenga, C AF Diosdado, B Wapenaar, MC Franke, L Duran, KJ Goerres, MJ Hadithi, M Crusius, JBA Meijer, JWR Duggan, DJ Mulder, CJJ Holstege, FCP Wijmenga, C TI A microarray screen for novel candidate genes in coeliac disease pathogenesis SO GUT LA English DT Article ID T-CELL TOLERANCE; INTESTINAL EPITHELIUM; SCAVENGER RECEPTORS; INTERFERON-GAMMA; GLUTEN; EXPRESSION; ANTIGEN; LYMPHOCYTES; DISRUPTION; PEPTIDES AB Background and aims: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. Methods: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy ( Marsh III) and seven control individuals with normal biopsies ( Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. Results: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly ( p< 0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes ( p< 0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. Conclusions: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy. C1 Univ Med Ctr Utrecht, Dept Biomed Genet, Complex Genet Grp, NL-3508 TA Utrecht, Netherlands. Univ Med Ctr, Dept Biomed Genet, Genom Lab, Utrecht, Netherlands. Rijnstate Hosp, Dept Gastroenterol & Hepatol, Arnhem, Netherlands. Free Univ Amsterdam, Med Ctr, Dept Gastroenterol, Amsterdam, Netherlands. Free Univ Amsterdam, Med Ctr, Lab Gastrointestinal Immunogenet, Amsterdam, Netherlands. Rijnstate Hosp, Dept Pathol, Arnhem, Netherlands. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Med Ctr, Dept Physiol Chem, Genom Lab, Utrecht, Netherlands. RP Wijmenga, C (reprint author), Univ Med Ctr Utrecht, Dept Biomed Genet, Complex Genet Grp, Stratenum 2-117,POB 80030, NL-3508 TA Utrecht, Netherlands. EM t.n.wijmenga@med.uu.nl RI Wijmenga, Cisca/D-2173-2009; OI Wijmenga, Cisca/0000-0002-5635-1614 NR 25 TC 46 Z9 47 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUL PY 2004 VL 53 IS 7 BP 944 EP 951 DI 10.1136/gut.2003.018374 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829CS UT WOS:000222021800009 PM 15194641 ER PT J AU Cracchiolo, BM Heller, DS Clement, PMJ Wolff, EC Park, MH Hanauske-Abel, HM AF Cracchiolo, BM Heller, DS Clement, PMJ Wolff, EC Park, MH Hanauske-Abel, HM TI Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva SO GYNECOLOGIC ONCOLOGY LA English DT Article DE EIF5A-1; intraepithelial neoplasia; vulva ID SQUAMOUS-CELL CARCINOMA; HYPUSINE; PROTEIN; CYCLE; DEOXYHYPUSINE; INHIBITORS; EIF-5A; IDENTIFICATION; HYDROXYLATION; GROWTH AB Objective. The mature eukaryotic translation initiation factor 5A contains the unusual amino acid hypusine, formed post-translationally from a specific lysine residue and essential for proliferation of eukaryotic cells. We hypothesized that the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH-353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was used to test this proposal in biopsies of vulvar high-grade intraepithelial neoplasia (VIN), characterized by the presence of proliferating cells throughout the thickness of the epithelium. Methods. Formalin-fixed and paraffin-embedded archival samples with an independently established diagnosis of VIN 3 were stained immunohistochemically after antigen retrieval, employing NIH-353 and, for comparison, the standard Ki-67 antibody. Results. NIH-353 labeled neoplastic keratinocytes throughout the thickness of the epithelium in all VIN 3 samples. Malignant cells in a case of focally invasive squamous cell carcinoma also stained strongly for mature, hypusine-containing eIF5A-1. Epithelium adjacent to these lesions, though still of apparently normal morphology, was immunoreactive throughout its full thickness. At inflammatory foci of lesional sites, solitary reactive lymphocytes were positive, as were individual proliferating cells within dermal appendages. The submucosal stroma lacked reactive cells. Conclusion. NIH-353 identifies mature eIF5A-1 as an in situ biomarker for proliferation. Like Ki-67, this immunoreagent promises broad applicability in histopathological diagnosis and may be helpful in outcome prediction. In contrast to Ki-67, NIH-353 visualizes a molecular target for antineoplastic therapy, and thus may guide the development and clinical testing of drugs that, like the fungicide ciclopirox, inhibit hypusine formation and cell proliferation. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, Newark, NJ 07101 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07101 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. RP Heller, DS (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, UH-E158,185 S Orange Ave, Newark, NJ 07101 USA. EM hellerds@umdnj.edu FU NICHD NIH HHS [HD-1457] NR 32 TC 33 Z9 36 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2004 VL 94 IS 1 BP 217 EP 222 DI 10.1016/j.ygyno.2004.03.018 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 835ND UT WOS:000222489500035 PM 15262146 ER PT J AU Childress, JF Miller, FG AF Childress, JF Miller, FG TI In memoriam: John C. Fletcher SO HASTINGS CENTER REPORT LA English DT Biographical-Item C1 Univ Virginia, Charlottesville, VA 22903 USA. NIH, Bethesda, MD 20892 USA. RP Childress, JF (reprint author), Univ Virginia, Charlottesville, VA 22903 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JUL-AUG PY 2004 VL 34 IS 4 BP 49 EP 49 PG 1 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 846HE UT WOS:000223305700022 ER PT J AU Elnekave, E Gross, R AF Elnekave, E Gross, R TI The healthcare experiences of Arab Israeli women in a reformed healthcare system SO HEALTH POLICY LA English DT Article DE women's health; health care reform; Arabs; Israel; primary care; empowerment ID COMMUNITY EMPOWERMENT; BREAST-CANCER; EDUCATION; PROMOTION; PARTICIPATION; SATISFACTION; IDENTITY; SERVICES; ADVISERS; SOCIETY AB Arab Israeli women are subject to unique social stresses deriving from their status as part of an ethno-political minority and from their position as women in a patriarchal community. Collectively, their health profiles rate poorly in comparison to Jewish Israeli women or to women in the vast majority of developed countries. Objectives: To examine the experiences of Arab Israeli women in the contemporary Israeli healthcare system, following implementation of the National Health Insurance Law (NHIL). Methods: The study combined quantitative and qualitative research methodologies. A telephone survey utilizing a structured questionnaire was conducted during August-September 1998 among a random national sample of 849 women, with a response rate of 83%. Between the months of January and July of 2000, qualitative data was attained via participant-observation, long and short semi-structured interviews, and focus groups in one large Muslim Arab Israeli village. Findings: Arab Israeli women in the national survey reported poorer self-assessed health, lower rates of care by a woman primary care physician, lower satisfaction ratings for primary care physicians and more frequently foregoing medical care than did native or immigrant Jewish Israeli women. Three major factors contributing to Arab Israeli women's healthcare experiences were elucidated by the qualitative study: (1) the threat of physical and social exposure (2) difficulties in communicating with male physicians and (3) the stifling effect of family politics and surveillance on healthcare. Discussion: We discuss our findings in relation to structural changes associated with the recent reform of the Israeli health care system. We conclude by suggesting policy measures for better adapting primary care services to the needs of Arab Israeli women, and note the relevance to other systems that aim to provide service to cultural and ethno-political minorities, in which healthcare delivery is shaped by unique local circumstances. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Howard Hughes Med Inst, NIH, Bethesda, MD 20814 USA. Bar Ilan Univ, JDC, Brookdale Inst, IL-91130 Jerusalem, Israel. RP Elnekave, E (reprint author), Howard Hughes Med Inst, NIH, 1 Cloister Court, Bethesda, MD 20814 USA. EM eldad.elnekave@tufts.edu; revital@jdc.org.il NR 63 TC 27 Z9 29 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD JUL PY 2004 VL 69 IS 1 BP 101 EP 116 DI 10.1016/j.healthpol.2003.12.005 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 832VZ UT WOS:000222297000010 PM 15484611 ER PT J AU Rahman, F Heller, T Sobao, Y Mizukoshi, E Nascimbeni, M Alter, H Herrine, S Hoofnagle, J Liang, TJ Rehermann, B AF Rahman, F Heller, T Sobao, Y Mizukoshi, E Nascimbeni, M Alter, H Herrine, S Hoofnagle, J Liang, TJ Rehermann, B TI Effects of antiviral therapy on the cellular immune response in acute hepatitis C SO HEPATOLOGY LA English DT Article ID VIRUS ENVELOPE PROTEIN; CD8(+) T-CELLS; VIRAL CLEARANCE; PLUS RIBAVIRIN; HCV INFECTION; INTERFERON; DETERMINANTS; CD4(+); CHIMPANZEES; RECHALLENGE AB Spontaneous recovery occurs in a minority of patients with acute hepatitis C but is associated with vigorous and long-lasting cellular immune responses. Treatment-induced recovery can be achieved in the majority of patients who are treated in the acute phase, but the kinetics and mechanisms of viral clearance and immune responsiveness are not known. Both direct antiviral effects and indirect immune-mediated effects, such as immune modulation of Th2 to Th1 responses and prevention of exhaustion of cellular responses by rapid reduction of viral titer, have been proposed. To investigate how early antiviral therapy affects hepatitis C virus (HCV)-specific T cell responses, we performed detailed prospective clinical, virological, and immunological studies on 7 patients with acute hepatitis C who received antiviral therapy and were followed at 2 to 4 week intervals for 1 to 2 years. The total CD4(+) and CD8(+) cell response was analyzed with 600 overlapping HCV peptides and 6 proteins by ex vivo enzyme-linked immunospot (ELISpot), intracellular cytokine staining, and proliferation assays. In contrast to earlier studies with selected HCV epitopes, this extended analysis detected multispecific interferon gamma(+) (IFN-gamma(+)) responses in each patient, even in the absence of T-cell proliferation. After initiation of antiviral therapy (at a mean of 20 weeks after infection), all sustained responders demonstrated gradually decreasing, then nearly absent HCV-specific T-cell responses, whereas the sole patient who developed viral breakthrough after initial HCV control maintained cellular immune responses. In conclusion, a sustained response to antiviral therapy was not associated with a lasting enhancement of HCV-specific T-cell responsiveness in the blood. C1 NIDDK, Liver Dis Sect, Digest Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, Digest Dis Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov NR 46 TC 109 Z9 114 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2004 VL 40 IS 1 BP 87 EP 97 DI 10.1002/hep.20253 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 835SO UT WOS:000222506000015 PM 15239090 ER PT J AU Strader, DB Wright, TL Thomas, DL Seeff, LB AF Strader, DB Wright, TL Thomas, DL Seeff, LB TI HCV carriers with persistently normal aminotransferase levels - Reply SO HEPATOLOGY LA English DT Letter ID HEPATITIS-C; DIAGNOSIS C1 Fletcher Allen Hlth Care Univ Vermont, Coll Med, Burlington, VT USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NIDDKD, Bethesda, MD 20892 USA. RP Strader, DB (reprint author), Fletcher Allen Hlth Care Univ Vermont, Coll Med, Burlington, VT USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2004 VL 40 IS 1 BP 267 EP 268 DI 10.1002/hep.20315 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 835SO UT WOS:000222506000037 ER PT J AU Wilcox, AJ Baird, DD Dunson, DB McConnaughey, DR Kesner, JS Weinberg, CR AF Wilcox, AJ Baird, DD Dunson, DB McConnaughey, DR Kesner, JS Weinberg, CR TI On the frequency of intercourse around ovulation: evidence for biological influences SO HUMAN REPRODUCTION LA English DT Article DE intercourse; ovulation ID MENSTRUAL-CYCLE; PROGESTERONE METABOLITES; LUTEINIZING-HORMONE; URINARY ESTROGEN; WOMEN; PREGNANCY; CONTRACEPTIVES; CONCEPTION; FERTILITY; BEHAVIOR AB BACKGROUND: Intercourse in mammals is often coordinated with ovulation, for example through fluctuations in libido or by the acceleration of ovulation with intercourse. Such coordination has not been established in humans. We explored this possibility by examining patterns of sexual intercourse in relation to ovulation. METHODS: Sixty-eight sexually active North Carolina women with either an intrauterine device or tubal ligation provided data for up to three menstrual cycles. These women collected daily urine specimens and kept daily diaries of intercourse and menstrual bleeding. Major estrogen and progesterone metabolites excreted in urine were used to identify the day of ovulation. The fertile days of the cycle were defined as the 6 consecutive days ending with ovulation. Women contributed a total of 171 ovulatory cycles. Menstrual bleeding days were excluded from analysis. RESULTS: The frequency of intercourse rose during the follicular phase, peaking at ovulation and declining abruptly thereafter. The 6 consecutive days with most frequent intercourse corresponded with the 6 fertile days of the menstrual cycle. Intercourse was 24% more frequent during the 6 fertile days than during the remaining non-bleeding days (P < 0.001). CONCLUSIONS: There apparently are biological factors that promote intercourse during a woman's 6 fertile days. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Westat Corp, Durham, NC USA. NIOSH, Div Appl Res & Technol, Biomonitoring & Hlth Assessment Branch, Cincinnati, OH 45226 USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM wilcox@niehs.nih.gov OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 23 TC 66 Z9 66 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2004 VL 19 IS 7 BP 1539 EP 1543 DI 10.1093/humrep/deh305 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 834GR UT WOS:000222400100008 PM 15190016 ER PT J AU Davis, AR Robilotto, CM Westhoff, CL Forman, S Zhang, J AF Davis, AR Robilotto, CM Westhoff, CL Forman, S Zhang, J CA NICHD management Early Pregnancy F TI Bleeding patterns after vaginal misoprostol for treatment of early pregnancy failure SO HUMAN REPRODUCTION LA English DT Article DE bleeding; early pregnancy failure; misoprostol ID RANDOMIZED CLINICAL-TRIAL; SPONTANEOUS-ABORTION; MIFEPRISTONE RU-486; MEDICAL-MANAGEMENT; MISSED ABORTION; EVACUATION; CURETTAGE AB BACKGROUND: Dilatation and curettage (D&C) has been the usual treatment for early pregnancy failure (EPF). Medical management with misoprostol may be an effective alternative. Bleeding patterns during and after medical management of EPF are unknown. METHODS: A prospective cohort study was conducted at University-based clinics and physician offices. Eighty women <11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled. Treatment consisted of either 800 mug of moistened (2 ml of saline) or dry vaginal misoprostol. Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary. Haemoglobin was assessed at enrolment and 2 weeks later. RESULTS: After misoprostol treatment, patients reported bleeding or spotting every day for the 14 days observed. Self-assessed heavy bleeding days were few (median 3) and usually occurred immediately after treatment. Sanitary pad use was highly variable (mean 30.5, range 2-125 pads over the 2 week period) and not related to changes in haemoglobin. The mean decrease in haemoglobin was 0.5 g/dl (SD 1.2). Complete expulsion without D&C occurred in 85% of subjects. CONCLUSIONS: Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common. Heavy bleeding is usually limited to a few days after treatment. Clinically important changes in haemoglobin are rare. C1 Columbia Univ, Dept Obstet & Gynecol, New York, NY 10032 USA. Clin Trials & Surveys Corp, Baltimore, MD 21210 USA. NICHHD, Epidemiol Branch, NIH, Rockville, MD 20852 USA. RP Davis, AR (reprint author), Columbia Univ, Dept Obstet & Gynecol, 630 W 168th St, New York, NY 10032 USA. EM ard4@columbia.edu OI Nansel, Tonja/0000-0002-8298-7595 FU NICHD NIH HHS [N01-HD-3321-5] NR 11 TC 9 Z9 11 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2004 VL 19 IS 7 BP 1655 EP 1658 DI 10.1093/humrep/deh291 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 834GR UT WOS:000222400100029 PM 15178656 ER PT J AU Bagrov, AY Lakatta, EG AF Bagrov, AY Lakatta, EG TI The dietary sodium-blood pressure plot "stiffens" SO HYPERTENSION LA English DT Editorial Material ID SALT-SENSITIVE HYPERTENSION; RENIN-ANGIOTENSIN SYSTEM; SMOOTH-MUSCLE-CELLS; ENDOGENOUS LIGAND; LARGE ARTERIES; MARINOBUFAGENIN; INHIBITION; STIFFNESS; MORTALITY; WOMEN C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov NR 28 TC 23 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2004 VL 44 IS 1 BP 22 EP 24 DI 10.1161/01.HYP.0000132768.19056.33 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 832GU UT WOS:000222256200005 PM 15173129 ER PT J AU Korf, ESC White, LR Scheltens, P Launer, LJ AF Korf, ESC White, LR Scheltens, P Launer, LJ TI Midlife blood pressure and the risk of hippocampal atrophy - The Honolulu Asia Aging Study SO HYPERTENSION LA English DT Article DE blood pressure; magnetic resonance imaging; epidemiology; brain ID TEMPORAL-LOBE ATROPHY; MILD COGNITIVE IMPAIRMENT; HYPERTENSIVE BRAIN-DAMAGE; APOLIPOPROTEIN-E GENOTYPE; JAPANESE-AMERICAN MEN; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; MEMORY IMPAIRMENT; CARDIOVASCULAR-HEALTH; ENTORHINAL CORTEX AB Hippocampal atrophy ( HA) is usually attributed to the neurofibrillary tangles and neuritic plaques of Alzheimer disease. However, the hippocampus is vulnerable to global ischemia, which may lead to atrophy. We investigated the association of midlife blood pressure (BP) and late-life HA in a sample of Japanese-American men born between 1900 and 1919. BP was measured on 3 occasions between 1965 and 1971. In 1994 to 1996 a subsample underwent magnetic resonance imaging (MRI) of the brain. Hippocampal volume was estimated by manually drawing regions of interest on relevant scan slices; HA was defined as the lowest quartile of hippocampal volume. Also assessed on the MRI were cortical and subcortical infarcts, lacunes, and white matter hyperintensities. The risk ( OR, 95% CI) was estimated for HA associated with systolic (<140 versus &GE;140 mm Hg) and diastolic (<90 versus greater than or equal to90 mm Hg) BP and with antihypertensive treatment. Analyses were adjusted for sociodemographic factors, other cardiovascular risk factors, apolipoprotein E allele, and correlated brain pathology. Those never treated with antihypertensive medication had a significantly increased risk for HA (OR 1.7; CI = 1.12; 2.65). The nontreated subjects with high systolic BP had an increased risk (OR = 1.98; CI = 0.89; 4.39) for HA. Results were similar for untreated men with high diastolic BP (OR = 3.51; CI = 1.26; 9.74). In conclusion, treatment with antihypertensive treatment modifies the association of BP and HA, such that high levels of BP adversely affect the hippocampus in persons never treated with antihypertensives. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. Pacific Hlth Res Inst, Honolulu, HI USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 51 TC 152 Z9 157 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2004 VL 44 IS 1 BP 29 EP 34 DI 10.1161/01.HYP.0000132475.32317.bb PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 832GU UT WOS:000222256200008 PM 15159381 ER PT J AU Li, KCP AF Li, KCP TI Molecular imaging: Opportunities and challenges for bioengineers - Why is molecular imaging receiving so much attention? SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Li, KCP (reprint author), NIH, Ctr Clin, Bldg 10 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM kingli@nih.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2004 VL 23 IS 4 BP 26 EP 27 DI 10.1109/MEMB.2004.1337946 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 858FZ UT WOS:000224179000011 PM 15508382 ER PT J AU Koren, Y Carmel, L AF Koren, Y Carmel, L TI Robust linear dimensionality reduction SO IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS LA English DT Article; Proceedings Paper CT 9th Annual IEEE Symposium on Information Visualization (INFOVIS 2003) CY OCT 19-21, 2003 CL SEATTLE, WASHINGTON SP IEEE Comp Soc, TC Visualizat & Graph DE dimensionality reduction; visualization; classification; feature extraction; projection; linear transformation; principal component analysis; Fisher's linear discriminant analysis AB We present a novel family of data-driven linear transformations, aimed at finding low-dimensional embeddings of multivariate data, in a way that optimally preserves the structure of the data. The well-studied PCA and Fisher's LDA are shown to be special members in this family of transformations, and we demonstrate how to generalize these two methods such as to enhance their performance. Furthermore, our technique is the only one, to the best of our knowledge, that reflects in the resulting embedding both the data coordinates and pairwise relationships between the data elements. Even more so, when information on the clustering (labeling) decomposition of the data is known, this information can also be integrated in the linear transformation, resulting in embeddings that clearly show the separation between the clusters, as well as their internal structure. All of this makes our technique very flexible and powerful, and lets us cope with kinds of data that other techniques fail to describe properly. C1 AT&T Labs Res, Florham Pk, NJ 07932 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koren, Y (reprint author), AT&T Labs Res, 180 Pk Ave,Bldg 103, Florham Pk, NJ 07932 USA. EM yehuda@research.att.com; carmel@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 NR 12 TC 59 Z9 63 U1 0 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1077-2626 J9 IEEE T VIS COMPUT GR JI IEEE Trans. Vis. Comput. Graph. PD JUL-AUG PY 2004 VL 10 IS 4 BP 459 EP 470 DI 10.1109/TVCG.2004.17 PG 12 WC Computer Science, Software Engineering SC Computer Science GA 817XF UT WOS:000221209500010 PM 18579973 ER PT J AU Saleh, A Davies, GE Pascal, V Wright, PW Hodge, DL Cho, EH Lockett, SJ Abshari, M Anderson, SK AF Saleh, A Davies, GE Pascal, V Wright, PW Hodge, DL Cho, EH Lockett, SJ Abshari, M Anderson, SK TI Identification of probabilistic transcriptional switches in the Ly49 gene cluster: A eukaryotic mechanism for selective gene activation SO IMMUNITY LA English DT Article ID NK CELL-RECEPTOR; REGULATORY ELEMENT; C57BL/6 MICE; BONE-MARROW; IN-VITRO; EXPRESSION; FAMILY; REPERTOIRE; DNA; PROMOTER AB Murine natural killer cells selectively express members of the Ly49 family of class I MHC receptors; however, the molecular mechanism controlling probabilistic expression of Ly49 proteins has not been defined. A pair of overlapping, divergent promoters discovered in the Ly49g gene functions as a molecular switch that can produce a forward transcript containing the coding region of the gene (on position) or a noncoding transcript in the opposite direction (off position), and this element maintains transcription in the chosen direction. Competition of C/EBP and TBP transcription factors for overlapping binding sites determines the relative strength of the competing promoters and the probability of transcription in a given direction. Similar elements precede all Ly49 family members, and the relative strength of the forward promoter in each inhibitory Ly49 gene correlates with the percentage of natural killer cells that express a given receptor, supporting a promoter competition model of selective gene activation. C1 NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Image Anal Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. EM andersn@ncifcrf.gov RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-12400] NR 36 TC 72 Z9 72 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2004 VL 21 IS 1 BP 55 EP 66 DI 10.1016/j.immuni.2004.06.005 PG 12 WC Immunology SC Immunology GA 842AU UT WOS:000222975500008 PM 15345220 ER PT J AU Shaffer, AL Shapiro-Shelef, M Iwakoshi, NN Lee, AH Qian, SB Zhao, H Yu, X Yang, LM Tan, BK Rosenwald, A Hurt, EM Petroulakis, E Sonenberg, N Yewdell, JW Calame, K Glimcher, LH Staudt, LM AF Shaffer, AL Shapiro-Shelef, M Iwakoshi, NN Lee, AH Qian, SB Zhao, H Yu, X Yang, LM Tan, BK Rosenwald, A Hurt, EM Petroulakis, E Sonenberg, N Yewdell, JW Calame, K Glimcher, LH Staudt, LM TI XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation SO IMMUNITY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR XBP-1; 2 MESSENGER-RNAS; B-CELLS; GENE-EXPRESSION; TRANSMEMBRANE PROTEIN; ANTIBODY SECRETION; FLUORESCENT DYES; 3' ENDS; MEMBRANE AB The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific genes, including xbp1. Differentiating xbp1-deficient B cells induced Blimp-1 normally but failed to upregulate genes encoding many secretory pathway components. Conversely, ectopic expression of XBP1 induced a wide spectrum of secretory pathway genes and physically expanded the endoplasmic reticulum. In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis. Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Integrated Program Biophys Cellular & Mol Studies, New York, NY 10032 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Shelef, Miriam/0000-0002-8842-0303 FU NIAID NIH HHS [AI50659, AI32412, AI43576] NR 70 TC 486 Z9 500 U1 5 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2004 VL 21 IS 1 BP 81 EP 93 DI 10.1016/j.immuni.2004.06.010 PG 13 WC Immunology SC Immunology GA 842AU UT WOS:000222975500010 PM 15345222 ER PT J AU Takahashi, Y Yajima, A Cisar, JO Konishi, K AF Takahashi, Y Yajima, A Cisar, JO Konishi, K TI Functional analysis of the Streptococcus gordonii DL1 sialic acid-binding adhesin and its essential role in bacterial binding to platelets SO INFECTION AND IMMUNITY LA English DT Article ID SANGUIS C5; IDENTIFICATION; RECEPTORS; PARASANGUIS; GENE; ENDOCARDITIS; GLYCOPROTEIN; AGGREGATION; PELLICLES; PROTEINS AB Bacterial recognition of host sialic acid-containing receptors plays an important role in microbial colonization of the human oral cavity. The sialic acid-binding adhesin of Streptococcus gordonii DL1 was previously associated with the hsa gene encoding a 203-kDa protein. The predicted protein sequence consists of an N-terminal nonrepetitive region (NR1), including a signal sequence, a relatively short serine-rich region (SR1), a second nonrepetitive region (NR2), a long serine-rich region (SR2) containing 113 dodecapeptide repeats, and a C-terminal cell wall anchoring domain. In the present study, the contributions of SR1, NR2, and SR2 to Hsa-mediated adhesion were assessed by genetic complementation. Adhesion of an hsa chromosomal deletion mutant to sialic acid-containing receptors was restored by plasmids containing hsa constructs encoding Hsa that lacked either the N- or C-terminal portion of SR2. In contrast, hsa constructs that lacked the coding sequences for SR1, NR2, or the entire SR2 region failed to restore adhesion. Surface expression of recombinant Hsa was not affected by removal of SR1, NR2, or a portion of SR2 but was greatly reduced by complete removal of SR2. Wheat germ agglutinin, a probe for Hsa-specific glycosylation, reacted with recombinant Hsa lacking SR1, NR2, or SR2 but not with recombinant Hsa lacking both SR1 and SR2. Significantly, the aggregation of human platelets by S. gordonii DL1, an interaction implicated in the pathogenesis of infective endocarditis, required the expression of hsa. Moreover, neuraminidase treatment of the platelets eliminated this interaction, further supporting the hypothesis that Hsa plays an essential role in the bacterium-platelet interaction. C1 Nippon Dent Univ Tokyo, Sch Dent, Dept Microbiol, Chiyoda Ku, Tokyo 1028159, Japan. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Res, Bethesda, MD 20892 USA. RP Takahashi, Y (reprint author), Nippon Dent Univ Tokyo, Sch Dent, Dept Microbiol, Chiyoda Ku, 1-9-20 Fujimi, Tokyo 1028159, Japan. EM biseibut@tky.ndu.ac.jp NR 29 TC 51 Z9 51 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2004 VL 72 IS 7 BP 3876 EP 3882 DI 10.1128/IAI.72.7.3876-3882.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 832QU UT WOS:000222282800022 PM 15213130 ER PT J AU Meeks, MD Saksena, R Ma, XQ Wade, TK Taylor, RK Kovac, P Wade, WF AF Meeks, MD Saksena, R Ma, XQ Wade, TK Taylor, RK Kovac, P Wade, WF TI Synthetic fragments of Vibrio cholerae O1 inaba O-specific polysaccharide bound to a protein carrier are immunogenic in mice but do not induce protective antibodies SO INFECTION AND IMMUNITY LA English DT Article ID MONOCLONAL-ANTIBODIES; SEROTYPE INABA; LIPOPOLYSACCHARIDE; OGAWA; ANTIGENS; IDENTIFICATION; IMMUNITY; TOXIN; ACID; O-1 AB Development of Vibrio cholerae lipopolysaccharide (LPS) as a cholera vaccine immunogen is justified by the correlation of vibriocidal anti-LPS response with immunity. Two V. cholerae 01 LPS serotypes, Inaba and Ogawa, are associated with endemic and pandemic cholera. Both serotypes induce protective antibody following infection or vaccination. Structurally, the LPSs that define the serotypes are identical except for the terminal perosamine moiety, which has a methoxyl group at position 2 in Ogawa but a hydroxyl group in Inaba. The terminal sugar of the Ogawa LPS is a protective B-cell epitope. We chemically synthesized the terminal hexasaccharides of V. cholerae serotype Ogawa, which comprises in part the O-specific polysaccharide component of the native LPS, and coupled the oligosaccharide at different molar ratios to bovine serum albumin (BSA). Our initial studies with Ogawa immunogens showed that the conjugates induced protective antibody. We hypothesized that antibodies specific for the terminal sugar of Inaba LPS would also be protective. Neoglycoconjugates were prepared from synthetic Inaba oligosaccharides (disaccharide, tetrasaccharide, and hexasaccharide) and BSA at different levels of substitution. BALB/c mice responded to the Inaba carbohydrate (CHO)-BSA conjugates with levels of serum antibodies of comparable magnitude to those of mice immunized with Ogawa CHO-BSA conjugates, but the Inaba-specific antibodies (immunoglobulin M [IgM] and IgG1) were neither vibriocidal nor protective in the infant mouse cholera model. We hypothesize that the anti-Inaba antibodies induced by the Inaba CHO-BSA conjugates have enough affinity to be screened via enzyme-linked immunosorbent assay but not enough to be protective in vivo. C1 Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. NIDDKD, Lab Med Chem, NIH, Bethesda, MD 20892 USA. RP Wade, WF (reprint author), Dartmouth Coll Sch Med, Dept Microbiol & Immunol, 630 W Borwell Bldg, Lebanon, NH 03756 USA. EM william.wade@dartmouth.edu FU NIAID NIH HHS [AI 25096, AI 47373, R01 AI025096, R37 AI025096] NR 42 TC 36 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2004 VL 72 IS 7 BP 4090 EP 4101 DI 10.1128/IAI.72.7.4090-4101.2004 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 832QU UT WOS:000222282800046 PM 15213154 ER PT J AU Henderson, DK AF Henderson, DK TI How're we doin'? Preventing occupational infections with blood-borne pathogens in healthcare SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID POSTEXPOSURE PROPHYLAXIS; HIV; TRANSMISSION; EXPOSURE C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), Bldg 10,Room 2C146,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2004 VL 25 IS 7 BP 532 EP 535 DI 10.1086/502435 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 837KQ UT WOS:000222629100002 PM 15301023 ER PT J AU Weinstock, DM Boeckh, M Boulad, F Eagan, JA Fraser, VJ Henderson, DK Perl, TM Yokoe, D Sepkowitz, KA AF Weinstock, DM Boeckh, M Boulad, F Eagan, JA Fraser, VJ Henderson, DK Perl, TM Yokoe, D Sepkowitz, KA TI Postexposure prophylaxis against varicella-zoster virus infection among recipients of hematopoietic stem cell transplant: Unresolved issues SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; HERPES-ZOSTER; RISK-FACTORS; AIRBORNE TRANSMISSION; NOSOCOMIAL VARICELLA; VIRAL-INFECTIONS; IMMUNE GLOBULIN; ORAL ACYCLOVIR; CHILDREN AB Recent guidelines for the prevention of opportunistic infections have addressed a variety of issues germane to recipients of hematopoietic stem cell transplant. However, there are several issues regarding postexposure prophylaxis against varicella-zoster virus that remain unresolved. We address these questions and offer several consensus recommendations. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Washington Univ, Sch Med, St Louis, MO USA. Johns Hopkins Univ Hosp, Dept Hosp Epidemiol & Infect Control, Baltimore, MD USA. RP Weinstock, DM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave,Box 109, New York, NY 10021 USA. FU NCI NIH HHS [CA18029, CA009512]; NIAID NIH HHS [K24 AI52239-01] NR 58 TC 19 Z9 22 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2004 VL 25 IS 7 BP 603 EP 608 DI 10.1086/502447 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 837KQ UT WOS:000222629100014 PM 15301035 ER PT J AU Trotman, A AF Trotman, A TI Searching structured documents SO INFORMATION PROCESSING & MANAGEMENT LA English DT Article DE structured information retrieval; indexing and searching; vector space; Boolean searching; SGML and XML ID INVERTED FILES AB Structured document interchange formats such as XML and SGML are ubiquitous, however, information retrieval systems supporting structured searching are not. Structured searching can result in increased precision. A search for the author "Smith" in an unstructured corpus of documents specializing in iron-working could have a lower precision than a structured search for "Smith as author" in the same corpus. Analysis of XML retrieval languages identifies additional functionality that must be supported including searching at, and broken across multiple nodes in the document tree. A data structure is developed to support structured document searching. Application of this structure to information retrieval is then demonstrated. Document ranking is examined and adapted specifically for structured searching. Published by Elsevier Ltd. C1 Univ Otago, Dept Comp Sci, Dunedin, New Zealand. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Trotman, A (reprint author), Univ Otago, Dept Comp Sci, Dunedin, New Zealand. EM andrew@cs.otago.ac.nz RI Trotman, Andrew/A-4918-2008; OI Trotman, Andrew/0000-0003-1253-7123 NR 23 TC 11 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4573 J9 INFORM PROCESS MANAG JI Inf. Process. Manage. PD JUL PY 2004 VL 40 IS 4 BP 619 EP 632 DI 10.1016/S0306-4573(03)00041-4 PG 14 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 837AD UT WOS:000222597100003 ER PT J AU Cheng, DT Knight, DC Smith, CN Stein, EA Helmstetter, FJ AF Cheng, DT Knight, DC Smith, CN Stein, EA Helmstetter, FJ TI Autonomic fear responses and human amygdala activity: An event-related fMRI study SO INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Meeting Abstract C1 Univ Wisconsin, Milwaukee, WI 53201 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIMH, NIH, Bethesda, MD 20892 USA. NIDA, IRP, Baltimore, MD 21224 USA. UCSD, San Diego, CA USA. RI Stein, Elliot/C-7349-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU TRANSACTION PUBLISHERS PI PISCATAWAY PA RUTGERS UNIV, DEPT 8010, 35 BERRUE CIRCLE, PISCATAWAY, NJ 08854-8042 USA SN 1053-881X J9 INTEGR PHYS BEH SCI JI Integr. Physiol. Behav. Sci. PD JUL-SEP PY 2004 VL 39 IS 3 BP 216 EP 216 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 919WR UT WOS:000228648800009 ER PT J AU Creinin, MD Harwood, B Guido, RS Fox, MC Zhang, J AF Creinin, MD Harwood, B Guido, RS Fox, MC Zhang, J CA NICHD Manage Early Preg Fail Trial TI Endometrial thickness after misoprostol use for early pregnancy failure SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE misoprostol; early pregnancy failure; miscarriage; transvaginal ultrasound; endometrial thickness ID SPONTANEOUS-ABORTION; MISSED ABORTION; EXPECTANT MANAGEMENT; RANDOMIZED-TRIAL; TRANSVAGINAL SONOGRAPHY; TRIMESTER MISCARRIAGE; MEDICAL-MANAGEMENT; EVACUATION; CURETTAGE AB Objectives: To assess if there was any potential relationship between endometrial thickness and final treatment outcome in women successfully treated with misoprostol for a first trimester anembryonic gestation, embryonic demise or fetal demise. Methods: Eighty women were treated with up to two doses of misoprostol 800 mug vaginally for early pregnancy failure. Subjects were scheduled to return 2 (range 1-4), 7 (range 5-9) and 14 (range 12-17) days after treatment. Transvaginal ultrasonography was performed at each follow-up visit. Results: The median endometrial thickness at each of the follow-up visits for women who had expelled the gestational sac was 14 mm, 10 mm, and 7 mm, respectively. The endometrial thickness at the first follow-up visit exceeded 15 mm in 20 subjects (36%) and 30 mm in four subjects (7%). Only three women had a suction aspiration for bleeding after documented expulsion. The endometrial thickness for these women was 11, 13, and 14 mm at the first follow-up visit. Conclusions: There is no obvious relationship between increasing endometrial thickness and the need for surgical intervention in women treated with misoprostol for early pregnancy failure. (C) 2004 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. Magee Womens Res Inst, Pittsburgh, PA USA. NICHHD, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Creinin, MD (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. EM mcreinin@mail.magee.edu FU NCRR NIH HHS [M01 RR000056]; NICHD NIH HHS [N01-HD-1-3323, N01-HD-1-3324, N01-HD-1-3322, N01-HD-1-3325, N01-HD-1-3321] NR 20 TC 36 Z9 37 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD JUL PY 2004 VL 86 IS 1 BP 22 EP 26 DI 10.1016/j.ijgo.2004.02.004 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 835MG UT WOS:000222486900006 PM 15207665 ER PT J AU Obrosova, IG Minchenko, AG Frank, RN Seigel, GM Zsengeller, Z Pacher, P Stevens, MJ Szabo, C AF Obrosova, IG Minchenko, AG Frank, RN Seigel, GM Zsengeller, Z Pacher, P Stevens, MJ Szabo, C TI Poly(ADP-ribose) polymerase inhibitors counteract diabetes- and hypoxia-induced retinal vascular endothelial growth factor overexpression SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE 3-aminobenzamide; hypoxia; 1,5-isoquinolinediol; poly (ADP-ribose) polymerase; rat retina; retinal pigment epithelial cells; streptozotocin diabetes; vascular endothelial growth factor ID ALDOSE REDUCTASE INHIBITOR; ALPHA-LIPOIC ACID; OXIDATIVE STRESS; RAT RETINA; LIPID-PEROXIDATION; FACTOR EXPRESSION; POLYOL PATHWAY; UP-REGULATION; BLOOD-FLOW; RETINOPATHY AB We hypothesize that poly(ADP-ribose) polymerase (PARP) activation is an important mechanism in the oxidative stress-related development of diabetic retinopathy. In the experiments reported here, we evaluated if: a) PARP activation is present in the retina in short-term diabetes; and b) PARP inhibitors, 3-aminobenzamide and 1,5-isoquinolinediol, counteract diabetes- and hypoxia-induced retinal VEGF formation. In vivo studies were performed in control and streptozotocin-diabetic rats treated with/without 3-aminobenzamide or 1,5-isoquinolinediol (30 and 3 mg/kg per day, intraperitoneally, for 2 weeks after 2 weeks of diabetes). In vitro studies were performed in human retinal pigment epithelial cells exposed to normoxia or hypoxia with/without 3-aminobenzamide and 1,5-isoquinolinediol at 200 and 2 muM. Retinal immunostaining for poly(ADP-ribose) was increased and NAD concentration reduced in diabetic rats, and both variables were corrected by PARP inhibitors. Retinal VEGF protein (ELISA, immunohistochemistry), but not. mRNA (ribonuclease protection assay) abundance, was increased, in diabetic rats, and this increase was corrected by both 3-aminobenzamide and 1,5-isoquinolinediol. PARP inhibitors did not affect retinal glucose, sorbitol pathway intermediates or lipid peroxidation in diabetic rats. Hypoxia caused a several-fold increase in both VEGF-mRNA and protein in retinal pigment epithelial cells. VEGF mRNA overexpression was only slighly blunted by PARP inhibitors whereas VEGF protein was corrected. In conclusion, PARP is involved in diabetes- and hypoxia-induced VEGF production at post-transcriptional level, downstream from the sorbitol pathway activation and oxidative stress. The results justify studies of PARP inhibitors in models of retinopathy of prematurity and diabetic retinopathy. C1 Inotek Pharmaceut Corp, Cummings Ctr 100, Beverly, MA 01915 USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. Thomas Jefferson Univ, Dept Anesthesiol, Philadelphia, PA 19107 USA. Wayne State Univ, Sch Med, Kresge Eye Inst, Dept Ophthalmol, Detroit, MI 48202 USA. SUNY Buffalo, Dept Ophthalmol Physiol & Biophys, Buffalo, NY 14260 USA. NIAAA, DICBR, Lab Physiol Studies, Sect Neuroendocrinol, Rockville, MD 20852 USA. RP Szabo, C (reprint author), Inotek Pharmaceut Corp, Cummings Ctr 100, Suite 419E, Beverly, MA 01915 USA. EM szabocsaba@aol.com RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Minchenko, Oleksandr/0000-0002-7093-5173 FU NHLBI NIH HHS [HL/DK 71215-01]; NIDDK NIH HHS [DK 59809-01] NR 58 TC 48 Z9 53 U1 0 U2 5 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JUL PY 2004 VL 14 IS 1 BP 55 EP 64 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 830ZL UT WOS:000222162600005 PM 15202016 ER PT J AU Cassarino, DS Santi, M Arruda, A Patrocinio, R Tsokos, M Ghatak, N Quezado, M AF Cassarino, DS Santi, M Arruda, A Patrocinio, R Tsokos, M Ghatak, N Quezado, M TI Spinal adrenal cortical adenoma with oncocytic features: Report of the first intramedullary case and review of the literature SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Review DE oncocytoma; adrenal cortical adenoma; spinal cord; intramedullary tumor ID CAUDA-EQUINA; PARAGANGLIOMA; SYSTEM; GLAND; CORD AB Ectopic adrenal cortical neoplasms are extremely rare, and only a few have involved the CNS. We report the first case of an intramedullary oncocytic adrenal cortical neoplasm of the spinal cord with immunohistochemical (IMHC) confirmation. A 27-year-old man presented with progressive lower extremity weakness, spastic paraparesis, decreased reflexes, and hypoesthesia below T10. A spinal myelogram showed cauda equina blockade and obliteration of sacral nerve roots. This prompted emergent Surgical intervention. A well-circumscribed, approximately 3 x 2 cut, light brown to tan, intramedullary tumor was identified at the level of the conus medullaris. Histologically, the tumor showed sheets and nests of plump, cytologically bland polygonal cells with abundant eosinophilic cytoplasm. A single mitosis, but no necrosis, was identified. By IMHC, the cells were positive for inhibin, melan-A, and synaptophysin, and negative for GFAP, EMA, cytokeratins, S-100, HMB-45, and chromogranin. Electron microscopy study performed from paraffin-embedded tissues demonstrated abundant mitochondria, and lipid vacuoles. This case confirms the occurrence of adrenal cortical neoplasms in the CNS and is the first report of an intradural, intramedullary adrenal cortical adenoma of the spinal cord, and the first to occur in a male. This tumor should be considered in the differential diagnosis of tumors of the CNS. C1 NCI, Pathol Lab, NIH, Ctr Clin, Bethesda, MD 20892 USA. Washington Childrens Hosp, Dept Pathol, Washington, DC USA. Hosp Clin, Dept Surg, Fortaleza, Ceara, Brazil. Biopse Lab, Fortaleza, Ceara, Brazil. Virginia Commonwealth Univ, MCV Hosp, Neuropathol & Autopsy Serv, Richmond, VA USA. RP Quezado, M (reprint author), NCI, Pathol Lab, NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2N212, Bethesda, MD 20892 USA. OI Cassarino, David/0000-0001-8875-0858 NR 13 TC 9 Z9 10 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUL PY 2004 VL 12 IS 3 BP 259 EP 264 DI 10.1177/106689690401200309 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 846DH UT WOS:000223294800007 PM 15306940 ER PT J AU Gwiazda, JE Hyman, L Norton, TT Hussein, MEM Marsh-Tootle, W Manny, R Wang, Y Everett, D AF Gwiazda, JE Hyman, L Norton, TT Hussein, MEM Marsh-Tootle, W Manny, R Wang, Y Everett, D CA COMET Grp TI Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EVALUATION TRIAL COMET; LATE-ONSET MYOPIA; REFRACTIVE ERROR; NEAR-WORK; BIFOCAL LENSES; VISION; EMMETROPIZATION; SCHOOLCHILDREN; HETEROPHORIA; DESIGN AB To examine baseline measurements of accommodative lag, phoria, reading distance, amount of near work, and level of myopia as risk factors for progression of myopia and their interaction with treatment over 3 years, in children enrolled in the Correction of Myopia Evaluation Trial ( COMET). METHODS. COMET enrolled 469 ethnically diverse children (ages, 6-11 years) with myopia between -1.25 and -4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a + 2.00 addition (n = 235) or single vision lenses (SVLs; n = 234), the conventional spectacle treatment, and were observed for 3 years. The primary outcome measure was progression of myopia by autorefraction after cycloplegia with 2 drops of 1% tropicamide. Other measurements included accommodative response ( by an open field of view autorefractor), phoria ( by cover test), reading distance, and hours of near work. Independent and interaction analyses were based on the mean of the two eyes. Results were adjusted for important covariates with multiple linear regression. RESULTS. Children with larger accommodative lags (>0.43 D for a 33 cm target) wearing SVLs had the most progression at 3 years. PALs were effective in slowing progression in these children, with statistically significant 3-year treatment effects (mean +/- SE) for those with larger lags in combination with near esophoria (PAL-SVL progression = -1.08 D - [-1.72 D] = 0.64 +/- 0.21 D), shorter reading distances (0.44 +/- 0.20 D), or lower baseline myopia (0.48 +/- 0.15 D). The 3-year treatment effect for larger lags in combination with more hours of near work was 0.42 +/- 0.26 D, which did not reach statistical significance. Statistically significant treatment effects were observed in these four groups at 1 year and became larger from 1 to 3 years. CONCLUSIONS. The results support the COMET rationale (i.e., a role for retinal defocus in myopia progression). In clinical practice in the United States children with large lags of accommodation and near esophoria often are prescribed PALs or bifocals to improve visual performance. Results of this study suggest that such children, if myopic, may have an additional benefit of slowed progression of myopia. C1 New England Coll Optometry, Boston, MA 02115 USA. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. Univ Alabama, Sch Optometry, Birmingham, AL 35294 USA. Univ Houston, Coll Optometry, Houston, TX USA. NEI, NIH, Bethesda, MD 20892 USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. RP Gwiazda, JE (reprint author), New England Coll Optometry, 424 Beacon St, Boston, MA 02115 USA. EM gwiazdaj@ne-optometry.edu FU NEI NIH HHS [EY11755, EY11740, EY11752, EY11754, EY11756, EY11805] NR 46 TC 127 Z9 136 U1 3 U2 22 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2004 VL 45 IS 7 BP 2143 EP 2151 DI 10.1167/iovs.03-1306 PG 9 WC Ophthalmology SC Ophthalmology GA 833VH UT WOS:000222367900013 PM 15223788 ER PT J AU Tuo, JS Tuaillon, N Shen, DF Chan, CC AF Tuo, JS Tuaillon, N Shen, DF Chan, CC TI Endotoxin-induced uveitis in cyclooxygenase-2-deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CYTOKINE GENE-EXPRESSION; MESSENGER-RNA; INDUCIBLE CYCLOOXYGENASE; INFLAMMATORY RESPONSE; H SYNTHASE-1; LEUKOTRIENES; INTERLEUKIN-6; RAT; PROSTAGLANDINS; MEDIATORS AB PURPOSE. Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the role of COX-2 in acute ocular inflammation. METHODS. EIU was induced in wild-type (WT), heterozygotic (COX-2(+/-)) and COX-2 null (COX-2(-/-)) mice by injection of lipopolysaccharide (LPS). Other mice were coinjected with LPS and IFNgamma. Ocular histology, serum cytokines, and AA products determined by ELISA, and relevant ocular messengers determined by RT-PCR were compared among the different groups. RESULTS. Histology showed that the EIU score was significantly enhanced in COX-2(-/-) mice in comparison to WT and COX2(+/-). PGE(2) was increased in WT and COX-2(+/-) EIU but not in COX-2(-/-) EIU. LTB4 in serum and ocular 5-LO transcripts were increased in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-) EIU mice. IL-6 increased, whereas IFNgamma decreased both in serum and ocular transcripts in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-). Furthermore, EIU was suppressed in mice treated with recombinant IFNgamma, as shown by the decreased EIU scores, the presence of serum LTB4 and IL-6 and ocular 5-LO and IL-6 mRNA, and the increases in serum IFNgamma and ocular IFNgamma, particularly in COX-2(-/-) mice. CONCLUSIONS. These data suggest that disturbance of the AA pathway exacerbates EIU in COX- 2-deficient mice. IFNgamma moderately reverses this exacerbation and protects against EIU. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 49 TC 14 Z9 16 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2004 VL 45 IS 7 BP 2306 EP 2313 DI 10.1167/iovs.03-0756 PG 8 WC Ophthalmology SC Ophthalmology GA 833VH UT WOS:000222367900035 PM 15223810 ER PT J AU Bush, RA Lei, B Tao, W Raz, D Chan, CC Cox, TA Santos-Muffley, M Sieving, PA AF Bush, RA Lei, B Tao, W Raz, D Chan, CC Cox, TA Santos-Muffley, M Sieving, PA TI Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: Dose-dependent effects on ERG and retinal histology SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RHODOPSIN KNOCKOUT MOUSE; GANGLION-CELLS; ROD PHOTORECEPTORS; RETINITIS-PIGMENTOSA; GENE-EXPRESSION; ANIMAL-MODELS; INNER RETINA; MULLER CELLS; CNTFR-ALPHA; ELECTRORETINOGRAM AB PURPOSE. ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor ( CNTF). METHODS. Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days. RESULTS. Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas. CONCLUSIONS. CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities. C1 NIDCD, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. Neurotech USA, Lincoln, RI USA. Univ Missouri, Sch Med, Dept Ophthalmol, Columbia, MO USA. Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO USA. RP Bush, RA (reprint author), NIDCD, NIH, 50 S Dr MSC 8021,Room 4339, Bethesda, MD 20892 USA. EM bushr@nidcd.nih.gov FU NEI NIH HHS [EY06094] NR 45 TC 53 Z9 58 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2004 VL 45 IS 7 BP 2420 EP 2430 DI 10.1167/iovs.03-1342 PG 11 WC Ophthalmology SC Ophthalmology GA 833VH UT WOS:000222367900051 PM 15223826 ER PT J AU Sharabi, Y Zimlichman, R Mansouri, R Chun, J Goldstein, DS AF Sharabi, Y Zimlichman, R Mansouri, R Chun, J Goldstein, DS TI Does acetylcholinesterase inhibition affect catecholamine secretion by adrenomedullary cells? SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE acetylcholinesterase; catecholamine; adrenomedullary cells; edrophonium ID ADRENAL CHROMAFFIN CELLS; PHEOCHROMOCYTOMA CELLS; NEURONAL SECRETION; RELEASE; DIFFERENTIATION; CHLORPYRIFOS; POLYPEPTIDE; METABOLITES; RECEPTOR; CULTURE AB Background: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells. Objectives: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release. Methods: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48-72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin. II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10(-7) to 10(-1) M), for 1-20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether co-incubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed, in quadruplicate and repeated three times. Results: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect, Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+. Conclusion: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells. C1 Wolfson Med Ctr, Dept Med & Hypertens, IL-58100 Holon, Israel. Tel Aviv Univ, Sackler Fac Med, Brunner Inst Cardiovasc Res, Ramat Aviv, Israel. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Zimlichman, R (reprint author), Wolfson Med Ctr, Dept Med & Hypertens, IL-58100 Holon, Israel. EM zimlich@post.tau.ac.il NR 18 TC 2 Z9 2 U1 0 U2 0 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISRAEL MED ASSOC J JI Isr. Med. Assoc. J. PD JUL PY 2004 VL 6 IS 7 BP 396 EP 399 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 837KO UT WOS:000222628900003 PM 15274528 ER PT J AU Tansey, JT Sztalryd, C Hlavin, EM Kimmel, AR Londos, C AF Tansey, JT Sztalryd, C Hlavin, EM Kimmel, AR Londos, C TI The central role of perilipin A in lipid metabolism and adipocyte lipolysis SO IUBMB LIFE LA English DT Review DE adipocyte; lipolysis; perilipin; lipid droplets; ADRP; adipophilin ID HORMONE-SENSITIVE LIPASE; PROTEIN-KINASE-A; DIFFERENTIATION-RELATED PROTEIN; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; STORAGE DROPLET; STIMULATED LIPOLYSIS; MEDIATED LIPOLYSIS; 3T3-L1 ADIPOCYTES; DIABETES-MELLITUS AB The related disorders of obesity and diabetes are increasing to epidemic proportions. The role of neutral lipid storage and hydrolysis, and hence the adipocyte, is central to understanding this phenomenon. The adipocyte holds the major source of stored energy in the body in the form of triacylglycerols ( TAG). It has been known for over 35 years that the breakdown of TAG and release of free (unesterified) fatty acids and glycerol from fat tissue can be regulated by a cAMP-mediated process. However, beyond the initial signaling cascade, the mechanistic details of this lipolytic reaction have remained unclear. Work in recent years has revealed that both hormone-sensitive lipase (HSL), generally thought to be the rate-limiting enzyme, and perilipin, a lipid droplet surface protein, are required for optimal lipid storage and fatty acid release. There are multiple perilipin proteins encoded by mRNA splice variants of a single perilipin gene. The perilipin proteins are polyphosphorylated by protein kinase A and phosphorylation is necessary for translocation of HSL to the lipid droplet and enhanced lipolysis. Hence, the surface of the lipid storage droplet has emerged as a central site of regulation of lipolysis. This review will focus on adipocyte lipolysis with emphasis on hormone signal transduction, lipolytic enzymes, the lipid storage droplet, and fatty acid release from the adipocyte. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Otterbein Coll, Dept Chem, Westerville, OH 43081 USA. RP Londos, C (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3132, Bethesda, MD 20892 USA. EM DeanL@intra.niddk.nih.gov RI Bell, Erica/J-2950-2015 NR 39 TC 121 Z9 127 U1 2 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUL PY 2004 VL 56 IS 7 BP 379 EP 385 DI 10.1080/15216540400009968 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868EY UT WOS:000224898100001 PM 15545214 ER PT J AU Stadtman, TC AF Stadtman, TC TI Methanococcus vannielii selenium metabolism: Purification and N-terminal amino acid sequences of a novel selenium-binding protein and selenocysteine lyase SO IUBMB LIFE LA English DT Article DE selenium-binding protein; selenocysteine lyase; selenophosphate synthetase ID ESCHERICHIA-COLI; DELIVERY PROTEIN; SELENOPHOSPHATE; BIOSYNTHESIS; ENZYME; HYDROXYLASE; RHODANESE; CLONING; GENE; CSDB AB Selenium is an essential component of several enzymes and proteins in a number of methane-producing archae. Information concerning accessory proteins that function in selenium transport processes, however, is limited. A novel selenium-binding protein with a potential transport role and a selenocysteine lyase that serves as a selenium delivery protein are present in Methanococcus vannielii. The selenium-binding protein was purified from extracts of Se-75-labeled cells. Although there was gradual loss of Se-75 during purification, the isolated protein still could be detected as a radioactive 42 kDa species on native PAGE gels and as a 33 kDa species on SDS PAGE gels. The N-terminal amino acid sequence of residues 1 - 63 of the protein was determined by automated Edman degradative analysis. The only homologous sequence detected in the recorded data base was that of a gene encoding an unknown protein located in the genomic sequence of Methanococcus maripaludis. Cloning and expression of the corresponding gene from M. vannielii are described in a manuscript in press ( Self et al.). A 47 kDa selenocysteine lyase isolated from M. vannielii extracts exhibited sequence homology to the NIFS family of proteins that transport sulfur. The purified selenocysteine lyase catalyzed the elimination of an elemental form of selenium from free selenocysteine and delivered this selenium directly to selenophosphate synthetase. The synthetase converted the selenium to selenophosphate in an ATP-dependent reaction. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2120,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. NR 19 TC 7 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUL PY 2004 VL 56 IS 7 BP 427 EP 431 DI 10.1080/15216540400008911 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868EY UT WOS:000224898100007 PM 15545220 ER PT J AU Hitti, J Frenkel, LM Stek, AM Nachman, SA Baker, D Gonzalez-Garcia, A Provisor, A Thorpe, EM Paul, ME Foca, M Gandia, J Huang, S Wei, LJ Stevens, LM Watts, DH McNamara, J AF Hitti, J Frenkel, LM Stek, AM Nachman, SA Baker, D Gonzalez-Garcia, A Provisor, A Thorpe, EM Paul, ME Foca, M Gandia, J Huang, S Wei, LJ Stevens, LM Watts, DH McNamara, J CA PACTG 1022 Study Team TI Maternal toxicity with continuous nevirapine in pregnancy - Results from PACTG 1022 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE pregnancy; hepatic toxicity; cutaneous toxicity; nelfinavir; nevirapine ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; RANDOMIZED-TRIAL; INTRAPARTUM; ZIDOVUDINE; PATIENT AB Objective: To compare the safety of nelfinavir and nevirapine-based antiretroviral treatment in HIV-1-infected pregnant women. Methods: In Pediatric AIDS Clinical Trials Group Protocol 1022, 38 antiretroviral-naive pregnant women at 10-30 weeks' gestation were randomized to nelfinavir or nevirapine with zidovudine plus lamivudine. The study was suspended because of greater than expected toxicity and changes in nevirapine prescribing information. The incidence of treatment-limiting hepatic or cutaneous toxicity was compared between groups for all subjects and for the subset with CD4 cell counts greater than 250 cells/muL at study entry. Results: Toxicity was seen in 1 (5%) of 21 subjects randomized to nelfinavir and 5 (29%) of 17 subjects randomized to nevirapine (P = 0.07). Within the nevirapine group, I subject developed fulminant hepatic failure and died, and another developed Stevens-Johnson syndrome. The one adverse event associated with nelfinavir occurred in a subject with a CD4 cell count less than 250 cells/muL. All 5 events among subjects with a CD4 cell count greater than 250 cells/muL were associated with nevirapine (P = 0.04). Conclusions: Continuous nevirapine may be associated with increased toxicity among HIV-1-infected pregnant women with CD4 cell counts greater than 250 cells/muL, as has been observed in nonpregnant women. C1 Univ Washington, Med Ctr, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ So Calif, Los Angeles, CA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Miami, Miami, FL 33152 USA. Columbus Reg Healthcare Syst, Columbus, GA USA. Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Univ, New York, NY USA. City Hosp, San Juan, PR USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA. NIH, Bethesda, MD USA. RP Hitti, J (reprint author), Univ Washington, Med Ctr, Dept Obstet & Gynecol, Box 356460, Seattle, WA 98195 USA. EM jhitti@u.washington.edu NR 9 TC 93 Z9 96 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2004 VL 36 IS 3 BP 772 EP 776 DI 10.1097/00126334-200407010-00002 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 835KL UT WOS:000222481700001 PM 15213559 ER PT J AU Cunningham, CK Balasubramanian, R Delke, I Maupin, R Mofenson, L Dorenbaum, A Sullivan, JL Gonzalez-Garcia, A Thorpe, E Rathore, M Gelber, RD AF Cunningham, CK Balasubramanian, R Delke, I Maupin, R Mofenson, L Dorenbaum, A Sullivan, JL Gonzalez-Garcia, A Thorpe, E Rathore, M Gelber, RD TI The impact of race/ethnicity on mother-to-child HIV transmission in the united states in pediatric AIDS clinical trials group protocol 316 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE race/ethnicity; perinatal HIV transmission; clinical trials ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; RACIAL-DIFFERENCES; PREVENTION; WOMEN; CARE; DELIVERY; COHORT; RACE AB The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intrapartum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P less than or equal to 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery. C1 Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA USA. Univ Florida, Hlth Sci Ctr, Dept Obstet & Gynecol, Jacksonville, FL USA. Louisiana State Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, New Orleans, LA USA. Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD USA. Biomarin Pharmaceut Inc, Novato, CA USA. Univ Massachusetts, Sch Med, Dept Pediat & Mol Med, Worcester, MA USA. Univ Miami, Sch Med, Dept Obstet & Gynecol, Miami, FL 33101 USA. St Jude Childrens Res Hosp, Dept Obstet & Gynecol, Memphis, TN USA. Univ Florida, Hlth Sci Ctr, Dept Pediat, Jacksonville, FL USA. RP Cunningham, CK (reprint author), Duke Univ, Med Ctr, Dept Pediat, Box 3499, Durham, NC 27710 USA. EM Cunni016@mc.duke.edu OI Mofenson, Lynne/0000-0002-2818-9808 NR 17 TC 11 Z9 12 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2004 VL 36 IS 3 BP 800 EP 807 DI 10.1097/00126334-200407010-00006 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 835KL UT WOS:000222481700005 PM 15213563 ER PT J AU Biggar, RJ Kirby, KA Atkinson, T McNeel, TS Engels, E AF Biggar, RJ Kirby, KA Atkinson, T McNeel, TS Engels, E CA AIDS Cancer Match Study Grp TI Cancer risk in elderly persons with HIV/AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV/AIDS; cancer; Kaposi sarcoma; non-Hodgkin lymhoma; elderly persons ID NON-HODGKINS-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; KAPOSIS-SARCOMA; VIRUS-INFECTION; UNITED-STATES; AIDS; ADULTS AB Context: Cancer risks in persons with AIDS are increased, but risks in elderly persons with AIDS (EPWAs) have not been previously described. Objective: To determine the profile of cancer risks in EPWAs. Data Sources and Analysis: Using AIDS data from 1981-1996, 8828 EPWAs were identified (60+ years old) and their records were linked to data in local cancer registries, finding 1142 cases. Expected case numbers were derived from the cancer incidence in the population matched for age, sex, race, calendar year, and registry. Results: Compared with the general population, the relative risk (RR) for Kaposi sarcoma was 545 (95% CI, 406-717) in the 2 years after AIDS onset. For non-Hodgkin lymphoma, the RR was 24.6 (7.5-80.3). No cervical cancers were reported in this interval. From 60 months before to 27 months after AIDS onset, the RR of non-AIDS-defining cancers (n = 548) was 1.3 (1.2-1.4). The cancer types occurring at significant excess during this period were similar to those in younger adults with AIDS: Hodgkin lymphoma (RR: 13.1), anal cancer (8.2), liver cancer (3.9), multiple myeloma (2.7), leukemia (2.4), and lung cancer (1.9). However, none was significantly elevated in the 2 years after the AIDS onset. Prostate cancer risk was low overall (RR: 0.8; 0.6-0.9). Conclusions: The profile of cancer risks in EPWAs generally resembled that in younger adults with AIDS, although RRs were lower because of higher background incidence rates. We speculate that prostate cancer risk was low because of reduced screening for this cancer in EPWAs. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Ann Arbor, MI USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RP Biggar, RJ (reprint author), 6120 Execut Blvd,Room 8014, Rockville, MD 20852 USA. EM biggarb@mail.nih.gov NR 21 TC 45 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2004 VL 36 IS 3 BP 861 EP 868 DI 10.1097/00126334-200407010-00014 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 835KL UT WOS:000222481700013 PM 15213571 ER PT J AU Guralnik, J AF Guralnik, J TI Functional consequences of chronic disease and intervening to prevent disability SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD JUL PY 2004 VL 12 IS 3 BP 289 EP 290 PG 2 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 840OC UT WOS:000222867500073 ER PT J AU Guralnik, J AF Guralnik, J TI The LIFE study: A randomized clinical trial of exercise to prevent disability in high-risk older persons SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD JUL PY 2004 VL 12 IS 3 BP 343 EP 343 PG 1 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 840OC UT WOS:000222867500150 ER PT J AU Akin, C Metcalfe, DD AF Akin, C Metcalfe, DD TI The biology of Kit in disease and the application of pharmacogenetics SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Kit; c-kit; tyrosine kinase; mastocytosis; mast cells; mutations; pharmacogenetics; imatinib; tyrosine kinase inhibitors ID GASTROINTESTINAL STROMAL TUMORS; STEM-CELL FACTOR; KINASE INHIBITOR STI571; RECEPTOR TYROSINE KINASE; BLOOD MONONUCLEAR-CELLS; PROTOONCOGENE C-KIT; HUMAN MAST-CELLS; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; SYSTEMIC MASTOCYTOSIS; MOLECULAR-MECHANISMS AB C-kit encodes a transmembrane protein with intrinsic tyrosine kinase activity, which functions as the receptor for stem cell factor. It is expressed on a variety of cell types, including mast cells, hematopoietic progenitor cells, melanocytes, germ cells, and gastrointestinal pacemaker cells. Mutations resulting in alteration of Kit function are associated with diseases involving each of these cells. Recent development of tyrosine kinase inhibitors led to their evaluation as novel therapies for diseases associated with Kit activation. This review will discuss the pathobiology of Kit in human disease, with a particular emphasis on implications for potential targeted treatment strategies in mast cell disease. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Akin, C (reprint author), Univ Michigan, 4220-D MSRB III,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM cemakin@med.umich.edu OI Akin, Cem/0000-0001-6301-4520 NR 82 TC 86 Z9 87 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2004 VL 114 IS 1 BP 13 EP 19 DI 10.1016/j.jaci.2004.04.046 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 836DA UT WOS:000222534300002 PM 15241338 ER PT J AU Arbes, SJ Cohn, RD Yin, M Muilenberg, ML Friedman, W Zeldin, DC AF Arbes, SJ Cohn, RD Yin, M Muilenberg, ML Friedman, W Zeldin, DC TI Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: Results from the National Survey of Lead and Allergens in Housing SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergens; asthma; cat allergen; Can f 1; dog allergen; epidemiology; Fel d 1; survey ID DUST MITE; D-I; COCKROACH ALLERGENS; DOMESTIC ALLERGENS; PUBLIC PLACES; PARTICLE-SIZE; RISK-FACTORS; LOS-ALAMOS; NEW-MEXICO; F I AB Background: Exposures to dog and cat allergens are believed to play important roles in the etiology of asthma; however, the levels of these allergens have never been assessed in a representative sample of US homes. Objective: The objective of this study was to estimate and characterize exposures to Can f 1 (dog allergen) and Fell d 1 (cat allergen) in US homes. Methods: Data were obtained from the National Survey of Lead and Allergens in Housing, a nationally representative survey of 831 US homes. Vacuumed-collected dust samples from the bed, bedroom floor, living room floor, and living room sofa were analyzed for concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust). Results: Although a dog or cat had lived in only 49.1% of homes in the previous 6 months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes, respectively. Averaged over the sampled sites, geometric mean concentrations (mug/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and 200 for Fel d 1. Among homes without the indoor pet, geometric mean concentrations were above 1.0. The independent predictors of elevated concentrations in homes without pets were all demographic variables that were also linked to a higher prevalence of pet ownership. Conclusions: Can f 1 and Fel d 1 are universally present in US homes. Levels that have been associated with an increased risk of allergic sensitization were found even in homes without pets. Because of the transportability of these allergens on clothing, elevated levels in homes without pets, particularly among demographic groups in which pet ownership is more prevalent, implicate the community as an important source of these pet allergens. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Constella Grp Inc, Durham, NC USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. US Dept Housing & Urban Dev, Off Healthy Homes & Lead Hazard Control, Washington, DC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, POB 12233,Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. NR 32 TC 93 Z9 97 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2004 VL 114 IS 1 BP 111 EP 117 DI 10.1016/j.jaci.2004.04.036 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 836DA UT WOS:000222534300016 PM 15241352 ER PT J AU Kulka, M Alexopoulou, L Flavell, RA Metcalfe, DD AF Kulka, M Alexopoulou, L Flavell, RA Metcalfe, DD TI Activation of mast cells by double-stranded RNA: Evidence for activation through Toll-like receptor 3 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE mast cells; human; Toll-like receptors; innate immunity; type I interferons; double-stranded RNA; viruses ID DENDRITIC CELLS; VIRAL-INFECTION; INTERFERONS; PRECURSORS; LINES; PKR AB Background: Although mast cells (MCs) have been clearly implicated in innate immune responses involving bacteria, their ability to respond to viral infection is less clear. Objective: Given that MCs increase at sites of inflammation and are located at surfaces where exposure to invading viruses may occur, we explored the ability of MCs to produce cytokines including type I IFNs after exposure to viruses and to polyinosine-polycytidylic acid (polyI:C), a synthetic mimic of viral double-stranded RNA, and characterized the receptors involved, if any. Methods: Human peripheral blood-derived cultured MCs and 2 MC lines, Laboratory of Allergic Disease MC line and human MC line 1, were stimulated with viruses and polyI:C, and cytokine production, degranulation, and signaling pathway activation were examined. Because polyI:C is a ligand for Toll-like receptor (TLR)-3, human MCs were also analyzed for TLR expression. Results: Viruses and polyI:C induced IFN-alpha and IFN-beta production. PolyI:C did not induce TNF, IL-1beta, IL-5, or GMCSF production, in contrast with other TLR ligands (LPS, peptidoglycan, CpG-A, or flagellin). IFN-alpha production involved nuclear factor-kappaB, p38, and C-Jun NH2-terminal kinase and mitogen-activated protein kinase. RT-PCR and Western blot analysis confirmed expression of TLR-3 by all MCs. Human cultured MCs also expressed TLR-1, TLR-2, TLR-4, TLR-5, TLR-6, TLR-7 and TLR-9. Antibodies to TLR-3 significantly decreased IFN-a production. Bone marrow-derived MCs from TLR-3 knockout mice showed an ablated response to polyI:C. Conclusions: Murine and human MCs produce type I IFNs after exposure to double-stranded RNA and/or virus, the former via specific interactions with TLR-3. These data suggest that MCs contribute to innate immune responses to viral infection via the production of type I IFNs. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille, France. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,MSC 1881,Bldg 10,Room 11C209, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov RI Alexopoulou, Lena/A-5041-2017 OI Alexopoulou, Lena/0000-0003-4619-697X FU NIAID NIH HHS [P01AI36529] NR 32 TC 224 Z9 234 U1 1 U2 12 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2004 VL 114 IS 1 BP 174 EP 182 DI 10.1016/j.jaci.2004.03.049 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 836DA UT WOS:000222534300026 PM 15241362 ER PT J AU Holland, SM Shea, YR Kwon-Chung, J AF Holland, SM Shea, YR Kwon-Chung, J TI Regarding "Trichosporon pullulans infection in 2 patients with chronic granulomatous disease" SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 3 TC 11 Z9 11 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2004 VL 114 IS 1 BP 205 EP 206 DI 10.1016/j.jaci.2004.01.781 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 836DA UT WOS:000222534300034 PM 15282941 ER PT J AU Moylett, EH Chinen, J Wickes, B Shearer, WT AF Moylett, EH Chinen, J Wickes, B Shearer, WT TI Regarding "Trichosporon pullulans infection in 2 patients with chronic granulomatous disease" - Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA. NHGRI, Immunol Genet Sect, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol & Immunol, San Antonio, TX 78285 USA. RP Moylett, EH (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2004 VL 114 IS 1 BP 206 EP 206 DI 10.1016/j.jaci.2004.01.782 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 836DA UT WOS:000222534300035 ER PT J AU Bray, M Roy, CJ AF Bray, M Roy, CJ TI Antiviral prophylaxis of smallpox SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE monkeypox; airborne infections; antiviral therapy; aerosol therapy; cidofovir; vaccination; biodefence ID VACCINIA VIRUS-INFECTIONS; AEROSOLIZED CIDOFOVIR; PROTECTS MICE; COWPOX; METABOLISM; CHALLENGE; INFLUENZA; EFFICACY; MOUSEPOX; THERAPY AB Proof-of-concept studies suggest that current defences against smallpox could be strengthened by supplementing vaccination with antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication cidofovir. Delivery of aerosolized cidofovir to mice results in its prolonged retention in respiratory tissues and protection against lethal intranasal or aerosol poxviral challenge. Although cidofovir itself is not orally available, the addition of an alkoxyalkanol ether side-chain allows it to be absorbed from the gastrointestinal tract. This also markedly increases its antiviral activity and lengthens its intracellular half-life from roughly 3 to 8-10 days. Oral treatment also protected mice against lethal poxviral challenge. These results suggest that a single aerosol dose of cidofovir (or an alkoxyalkanol-ether derivative) could provide prolonged protection against initiation of smallpox infection, whereas oral treatment could prevent both initiation of infection and internal dissemination of virus. Both approaches may avoid the nephrotoxicity that occasionally results from intravenous cidofovir therapy. C1 NIAID, Biodef Clin Res Branch, Off Clin Res, NIH, Bethesda, MD 20892 USA. USA, Dept Aerobiol & Prod Evaluat, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Bray, M (reprint author), NIAID, Biodef Clin Res Branch, Off Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mbray@niaid.nih.gov NR 27 TC 23 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 2004 VL 54 IS 1 BP 1 EP 5 DI 10.1093/jac/dkh286 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 836LV UT WOS:000222558100001 PM 15163655 ER PT J AU Shukla, S Ambudkar, SV Prasad, R AF Shukla, S Ambudkar, SV Prasad, R TI Substitution of threonine-1351 in the multidrug transporter Cdr1p of Candida albicans results in hypersusceptibility to antifungal agents and threonine-1351 is essential for synergic effects of calcineurin inhibitor FK520 SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE C. albicans; azoles; synergy; multidrug resistance ID PROTEIN SECONDARY STRUCTURE; TRANSMEMBRANE DOMAIN; TOPOLOGY PREDICTION; DRUG-RESISTANCE; FLUCONAZOLE; MEMBRANE; EFFLUX; YEAST; GENE; SUSCEPTIBILITY AB Objectives: Functional characterization of a mutant Candida albicans drug resistance protein (Cdr1p) by overexpression in Saccharomyces cerevisiae. Methods: We overexpressed green fluorescent protein-tagged Cdr1p in S. cerevisiae AD1-8u(-) host and introduced a point mutation to substitute T1351 with F in Cdr1p. The cells expressing T1351F mutant Cdr1p were analysed for their functional activity using minimum inhibitory concentration, spot assay, and fluconazole efflux. The binding activity of photoaffinity analogues 8-azidoATP, iodoarylazidoprazosin and azidopine to the mutant T1351F Cdr1p was also characterized. Results: The T1351F mutant Cdr1p-expressing cells were susceptible to anisomycin, cycloheximide, fluconazole, miconazole and nystatin. The mutant protein was expressed to the same level as that of native Cdr1p in S. cerevisiae cells and was properly localized to the cell surface. There was also no difference between the mutant variant and the native protein's ability to bind a photoaffinity analogue of ATP, 8-azidoATP, or the radiolabelled photoaffinity agents iodoarylazidoprazosin and azidopine. However, the substitution of T1351 resulted in considerable reduction in its ability to export fluorescent substrate rhodamine 6G. The synergy between calcineurin inhibitors FK520 and azoles was abrogated in cells expressing the T1351F mutant variant of Cdr1p. Conclusions: The results from this study suggest that the T1351 in the predicted transmembrane domain (TMD) 11 of Cdr1p is not only important for drug-substrate transport but also has a role in governing synergy of FK520. C1 Jawaharlal Nehru Univ, Sch Life Sci, Membrane Biol Lab, New Delhi 110067, India. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Prasad, R (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, Membrane Biol Lab, New Delhi 110067, India. EM rp47@hotmail.com RI Ambudkar, Suresh/B-5964-2008 NR 40 TC 15 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 2004 VL 54 IS 1 BP 38 EP 45 DI 10.1093/jac/dkh308 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 836LV UT WOS:000222558100008 PM 15190023 ER PT J AU Adler, A Cieslewicz, G Irvin, CG AF Adler, A Cieslewicz, G Irvin, CG TI Unrestrained plethysmography is an unreliable measure of airway responsiveness in BALB/c and C57BL/6 mice SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE enhanced pause; airway resistance; lung mechanics ID BAROMETRIC METHOD; TIDAL VOLUME; NONINVASIVE MEASUREMENT; BREATHING PATTERN; SMALL ANIMALS; RESISTANCE MEASUREMENTS; THERMAL ARTIFACTS; CONSCIOUS DOGS; VENTILATION; RESPONSES AB There has been significant utilization of the technique described by Hamelmann et al. (Am J Respir Crit Care Med 156: 766-775, 1997) in which a parameter, enhanced pause (Penh), related to airways responsiveness is noninvasively measured by unrestrained plethysmography (IT). Investigating this technique, we sought to answer these questions: 1) How do changes in Penh compare with changes in traditional plethysmographic and lung mechanical parameters? 2) How do UP parameters perform in two different mouse strains? Awake immunized and control BALB/c (n = 16) and C57BL/6 (n = 14) mice were placed in the UP chamber and exposed to doses of acrosolized methacholine while the following parameters were measured at each concentration: inspiratory time (TI), expiratory time (TE), total time (Ttot), Ti/Ttot, peak inspiratory pressure, peak expiratory pressure, Pause, Penh, tidal Volume (VT), VT/Ti, VT/TF, and VT/Ttot. The next day, lung resistance (RL) and compliance (CL) were invasively measured in the same animals. For the BALB/c, the parameters with the highest magnitude of correlation coefficient vs. RL are (in order) 1) CL, 2) Pause and Penh, 3) parameters of breathing frequency (TE, Ttot, TH, and 4) parameters related to VT (inspiratory pressure, expiratory pressure). Flow parameters (VT/Ttot, VT/TE, VT/TI) and duty cycle parameters (Tifrtot) had insignificant correlations. This ordering is significantly different in C57BL/6 mice, in which the parameters with the largest correlations are 1) CL, 2) parameters of breathing frequency, and 3) flow parameters. Pause, Penh, VT, and duty cycle parameters had insignificant correlations. These data show that Penh is problematic in the sense that it is strain specific; it behaves very differently in BALB/c and C57BL/6 mice. We suggest that UP parameters largely originate as part of reflex control of breathing processes, rather than in the lung mechanics and conclude that it is inappropriate to use UP parameters in general, and Penh specifically, as substitute variables for invasive mechanical indexes such as RL. C1 Univ Ottawa, Sch Informat Technol & Engn, Ottawa, ON K1N 6N5, Canada. Univ Vermont, Vermont Lung Ctr, Burlington, VT 05405 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Adler, A (reprint author), Univ Ottawa, Sch Informat Technol & Engn, 800 King Edward Ave, Ottawa, ON K1N 6N5, Canada. EM aadler@uottawa.ca FU NCRR NIH HHS [P20 RR-15557]; NHLBI NIH HHS [HL-60793, HL-56638] NR 33 TC 137 Z9 139 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2004 VL 97 IS 1 BP 286 EP 292 DI 10.1152/japplphysiol.00821.2003 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 833BF UT WOS:000222310700036 PM 15033965 ER PT J AU Zheng, G AF Zheng, G TI Maximizing a family of optimal statistics over a nuisance parameter with applications to genetic data analysis SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE genetic analysis; maximal statistics; nuisance parameter; robust test ID EFFICIENCY ROBUST-TESTS; LINKAGE TESTS; AFFECTED SIBS; ASSOCIATION; SURVIVAL AB In this article, a simple algorithm is used to maximize a family of optimal statistics for hypothesis testing with a nuisance parameter not defined under the null hypothesis. This arises from genetic linkage and association studies and other hypothesis testing problems. The maximum of optimal statistics over the nuisance parameter space can be used as a robust test in this situation. Here, we use the maximum and minimum statistics to examine the sensitivity of testing results with respect to the unknown nuisance parameter Examples from genetic linkage analysis using affected sub pairs and a candidate-gene association study in case-parents trio design are studied. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 16 TC 4 Z9 4 U1 0 U2 0 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PD JUL PY 2004 VL 31 IS 6 BP 661 EP 671 DI 10.1080/1478881042000214640 PG 11 WC Statistics & Probability SC Mathematics GA 846IU UT WOS:000223310000004 ER PT J AU Miyata, M Petersen, JD AF Miyata, M Petersen, JD TI Spike structure at the interface between gliding Mycoplasma mobile cells and glass surfaces visualized by rapid-freeze-and-fracture electron microscopy SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SP-NOV; PNEUMONIAE; MOVEMENT; MOTILITY; PATHOGENICITY; CYTADHERENCE; ERYTHROCYTES; BACTERIUM; SEQUENCE; FEATURES AB Mycoplasma mobile is a flask-shaped bacteria that binds to a substrate and glides towards its tapered end, the so-called "head-like protrusion," by an unknown mechanism. To search for cellular structures underlying this motility, the cell-substrate interface of actively gliding cells was visualized by rapid-freeze-and-freeze-fracture rotary-shadow electron microscopy. Novel structures, called "spikes," were observed to protrude from the cell membrane and attach to the glass surface at their distal end. The spikes were on average 50 nm in length and 4 nm in diameter, most abundant around the head, and not observed in a nonbinding mutant. The spikes may be involved in the mechanism of binding, gliding, or both. C1 Osaka City Univ, Grad Sch Sci, Dept Biol, Sumiyoshi Ku, Osaka 5588585, Japan. JST, PRESTO, Sumiyoshi Ku, Osaka 5588585, Japan. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Miyata, M (reprint author), Osaka City Univ, Grad Sch Sci, Dept Biol, Sumiyoshi Ku, Osaka 5588585, Japan. EM miyata@sci.osaka-cu.ac.jp OI Petersen, Jennifer/0000-0003-1107-8535; MIYATA, Makoto/0000-0002-7478-7390 NR 32 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2004 VL 186 IS 13 BP 4382 EP 4386 DI 10.1128/JB.186.13.4382-4386.2004 PG 5 WC Microbiology SC Microbiology GA 831JA UT WOS:000222189500036 PM 15205441 ER PT J AU Kuban, W Jonczyk, P Gawel, D Malanowska, K Schaaper, RM Fijalkowska, WJ AF Kuban, W Jonczyk, P Gawel, D Malanowska, K Schaaper, RM Fijalkowska, WJ TI Role of Escherichia coli DNA polymerase IV in in vivo replication fidelity SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BASE SUBSTITUTION MUTATIONS; ALLOW RAPID DETECTION; ADAPTIVE MUTATION; INDUCED MUTAGENESIS; MISMATCH REPAIR; DINB GENE; POL-IV; FRAMESHIFT MUTATIONS; LACZ MUTATIONS; CHROMOSOME AB We have investigated whether DNA polymerase TV (Pol IV; the dinB gene product) contributes to the error rate of chromosomal DNA replication in Escherichia coli. We compared mutation frequencies in mismatch repair-defective strains that were either dinB positive or dinB deficient, using a series of mutational markers, including lac targets in both orientations on the chromosome. Virtually no contribution of Pol IV to the chromosomal mutation rate was observed. On the other hand, a significant effect of dinB was observed for reversion of a lac allele when the lac gene resided on an F'(pro-lac) episome. C1 Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Fijalkowska, WJ (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland. EM iwonaf@ibb.waw.pl RI Fijalkowska, Iwona/I-7796-2016 NR 41 TC 43 Z9 43 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2004 VL 186 IS 14 BP 4802 EP 4807 DI 10.1128/JB.186.4802-4807.2004 PG 6 WC Microbiology SC Microbiology GA 838QM UT WOS:000222728100040 PM 15231812 ER PT J AU Balagurunathan, Y Wang, NY Dougherty, ER Nguyen, D Chen, YD Bittner, ML Trent, J Carroll, R AF Balagurunathan, Y Wang, NY Dougherty, ER Nguyen, D Chen, YD Bittner, ML Trent, J Carroll, R TI Noise factor analysis for cDNA microarrays SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE cDNA microarray; experimental design; factorial experiment; image simulation; signal detection ID GENE-EXPRESSION PATTERNS; DNA MICROARRAY AB A microarray-image model is used that takes into account many factors, including spot morphology, signal strength, background fluorescent noise, and shape and surface degradation. The model yields synthetic images whose appearance and quality reflect that of real microarray images. The model is used to link noise factors to the fidelity of signal extraction with respect to a standard image-extraction algorithm. Of particular interest is the identification of the noise factors and their interactions that significantly degrade the ability to accurately detect the true gene-expression signal. This study uses statistical criteria in conjunction with the simulation of various noise conditions to better understand the noise influence on signal extraction for cDNA microarray images. It proposes a paradigm that is implemented in software. It specifically considers certain kinds of noise in the noise model and sets these at certain levels; however, one can choose other types of noise or use different noise levels. In sum, it develops a statistical package that can work in conjunction with the existing image simulation toolbox. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. Texas A&M Univ, Ctr Environm & Rural Hlth, College Stn, TX 77843 USA. Translat Genom Res Inst, TGEN, Phoenix, AZ USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. Univ Calif Davis, Sch Med, Div Biostat, Davis, CA 95616 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, 111D Zachry, College Stn, TX 77843 USA. EM yogab@ieee.org; e-dougherty@tamu.edu FU NCI NIH HHS [CA-90301, CA-74552, CA-57030, R01 CA074552-09, R01 CA074552]; NIEHS NIH HHS [P30-ES09106] NR 13 TC 17 Z9 18 U1 0 U2 3 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2004 VL 9 IS 4 BP 663 EP 678 DI 10.1117/1.1755232 PG 16 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 840NM UT WOS:000222865800001 PM 15250753 ER PT J AU Wu, YB Migliorini, M Walsh, J Yu, P Strickland, DK Wang, YX AF Wu, YB Migliorini, M Walsh, J Yu, P Strickland, DK Wang, YX TI NMR structural studies of domain 1 of receptor-associated protein SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alpha-helix; dipolar couplings; RAP; receptor-associated protein ID AMYLOID PRECURSOR PROTEIN; N-TERMINAL DOMAIN; DIPOLAR COUPLINGS; ALIGNMENT; MACROMOLECULES; REFINEMENT; MAGNITUDE; DATABASE; SYSTEM AB The 39 kDa receptor-associated protein (RAP) is an endoplasmic reticulum resident protein that binds tightly to the low-density lipoprotein receptor-related protein (LRP) as well as to other members of the low-density lipoprotein receptor superfamily. The association of RAP with LRP prevents this receptor from interacting with ligands. RAP is a three-domain protein that contains two independent LRP binding sites; one located within domains 1 and 2, and one located within domain 3. As the first step toward defining the structure of the full-length protein and understanding the interaction between RAP and this family of receptors, we have determined the 3D structure of domain 1 using constraints derived from heteronuclear multi-dimensional NMR spectra, including NOEs, dihedral angles, J-couplings and chemical shifts, as well as two sets of non-correlated residual dipolar couplings measured from the protein solutions in anisotropicmedia of Pf1 and 6% polyacrylamide gel. The backbone C-alpha rmsd between the current structure and a homo-nuclear NOE-based structure is about 2 Angstrom. The large rmsd mainly reflects the significant differences in helical orientation and in the structural details of the long helix (helix 2) between the two structures. C1 NCI, Prot Nucl Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Dept Vasc Biol, Rockville, MD 20855 USA. RP Strickland, DK (reprint author), NCI, Prot Nucl Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. EM strickla@usa.redcross.org; wangyu@ncifcrf.gov FU NHLBI NIH HHS [HL50784, HL54710, HL65939] NR 27 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 2004 VL 29 IS 3 BP 271 EP 279 DI 10.1023/B:JNMR.0000032507.96325.6d PG 9 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 831QX UT WOS:000222211200004 PM 15213425 ER PT J AU Chou, JJ Baber, JL Bax, A AF Chou, JJ Baber, JL Bax, A TI Characterization of phospholipid mixed micelles by translational diffusion SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE bicelle; detergent; DHPC; lysolipid; hydration; NMR; relaxation; self diffusion ID ANGLE NEUTRON-SCATTERING; INFLUENZA-A VIRUS; FIELD GRADIENT; SELF-DIFFUSION; NMR-SPECTROSCOPY; PROTEINS; BICELLES; DIPOLAR; DIHEXANOYLPHOSPHATIDYLCHOLINE; POLYPEPTIDES AB The concentration dependence of the translational self diffusion rate, D-s, has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions Phi (Phi less than or equal to 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D-s = D-o(1-3.2lambdaPhi) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D-s at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide N-15 relaxation data. C1 NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. EM bax@nih.gov RI Chou, James/N-9840-2013 NR 38 TC 85 Z9 85 U1 1 U2 16 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 2004 VL 29 IS 3 BP 299 EP 308 DI 10.1023/B:JNMR.0000032560.43738.6a PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 831QX UT WOS:000222211200007 PM 15213428 ER PT J AU Strotmeyer, ES Cauley, JA Schwartz, AV Nevitt, MC Resnick, HE Zmuda, JM Bauer, DC Tylavsky, FA de Rekeneire, N Harris, TB Newman, AB AF Strotmeyer, ES Cauley, JA Schwartz, AV Nevitt, MC Resnick, HE Zmuda, JM Bauer, DC Tylavsky, FA de Rekeneire, N Harris, TB Newman, AB CA Health ABC Study TI Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The health, aging, and body composition study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BMD; type 2 diabetes; insulin; muscle; fat; gender; race ID GROWTH FACTOR-I; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; ADIPOSE-TISSUE; INSULIN; MELLITUS; RISK; FRACTURE; GLUCOSE; ADULTS AB The association between type 2 diabetes, BMD, and bone volume was examined to determine the effect of lean and fat mass and fasting insulin in the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979). Diabetes predicted higher hip, whole body, and volumetric spine BMD, and lower spine bone volume, independent of body composition and fasting insulin. C1 Univ Pittsburgh, Hlth Aging Res Program, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. MedStar Res Inst, Dept Epidemiol, Hyattsville, MD USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Hlth Aging Res Program, Grad Sch Publ Hlth, Dept Epidemiol, 130 N Bellefield Ave,5th Floor, Pittsburgh, PA 15213 USA. EM Newmana@edc.pitt.edu RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Strotmeyer, Elsa/0000-0002-4093-6036 FU NIA NIH HHS [N01-AG-6-2103, 5-T32-AG00181, N01-AG-6-2102, N01-AG-6-2106] NR 36 TC 99 Z9 108 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2004 VL 19 IS 7 BP 1084 EP 1091 DI 10.1359/JBMR.040311 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 831JV UT WOS:000222191600005 PM 15176990 ER PT J AU Tsilou, E Rubin, BI Abraham, FA Kaiser-Kupfer, M AF Tsilou, E Rubin, BI Abraham, FA Kaiser-Kupfer, M TI Bilateral late posterior chamber intraocular lens dislocation with the capsular bag in a patient with gyrate atrophy SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID CONTRACTION AB A pseudophakic patient with gyrate atrophy of the choroid and retina presented with bilateral intraocular lens (IOL) dislocation with the capsular bag several years after uneventful cataract surgery. The patient had not performed strenuous physical activity. One IOL was initially repositioned by nonsurgical manipulations, while the other required surgical repositioning. Eventually, IOL exchange was performed successfully in both eyes. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Inst Eye, IL-52621 Tel Hashomer, Israel. RP Tsilou, E (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr,MSC-1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. EM tsiloue@nei.nih.gov NR 7 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 2004 VL 30 IS 7 BP 1593 EP 1594 AR PII S0886-3350(03)01107-6 DI 10.1016/j.jcrs.2003.10.033 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 846DT UT WOS:000223296000037 PM 15210246 ER PT J AU Motegi, A Fujimoto, J Kotani, M Sakuraba, H Yamamoto, T AF Motegi, A Fujimoto, J Kotani, M Sakuraba, H Yamamoto, T TI ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth SO JOURNAL OF CELL SCIENCE LA English DT Article DE ALK; agonist monoclonal antibody; neuroblastoma; MAP kinase; cell growth; neurite ID ANAPLASTIC LYMPHOMA KINASE; NON-HODGKINS-LYMPHOMA; ACTIVATED PROTEIN-KINASE; MOLECULE HB-GAM; MONOCLONAL-ANTIBODIES; PHOSPHATIDYLINOSITOL 3-KINASE; NERVOUS-SYSTEM; PHOSPHOINOSITIDE 3-KINASE; SIGNAL-TRANSDUCTION; ZETA/RPTP-BETA AB Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that is expressed preferentially in neurons of the central and peripheral nervous systems at late embryonic stages. To elucidate the role of ALK in neurons, we developed an agonist monoclonal antibody (mAb) against the extracellular domain of ALK. Here we show that mAb16-39 elicits tyrosine phosphorylation of endogenously expressed ALK in human neuroblastoma (SK-N-SH) cells. Stimulation of these cells with mAb16-39 markedly induces the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Shc, and c-Cbl and also their interaction with ALK and activation of ERK1/2. Furthermore, we show that continuous incubation with mAb16-39 induces the cell growth and neurite outgrowth of SK-N-SH cells. These responses are completely blocked by MEK inhibitor PD98059 but not by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, indicating an essential role of the mitogen-activated protein kinase (MAP kinase) signaling cascade in ALK-mediated growth and differentiation of neurons. C1 Univ Tokyo, Inst Med Sci, Div Oncol, Minato Ku, Tokyo 1088639, Japan. Tokyo Metropolitan Inst Med Sci, Dept Clin Genet, Tokyo 1138613, Japan. NHGRI, Gen Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Yamamoto, T (reprint author), Univ Tokyo, Inst Med Sci, Div Oncol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM tyamamot@ims.u-tokyo.ac.jp NR 63 TC 79 Z9 85 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL 1 PY 2004 VL 117 IS 15 BP 3319 EP 3329 DI 10.1242/jcs.01183 PG 11 WC Cell Biology SC Cell Biology GA 843VT UT WOS:000223115600023 PM 15226403 ER PT J AU Baksh, D Song, L Tuan, RS AF Baksh, D Song, L Tuan, RS TI Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Review DE mesenchymal stem cells; stem cell niche; differentiation; Wnt; gene therapy ID HUMAN-BONE-MARROW; EX-VIVO EXPANSION; PROGENITOR CELLS; STROMAL CELLS; CFU-F; IN-VITRO; HEMATOPOIETIC MICROENVIRONMENT; OSTEOGENESIS IMPERFECTA; TELOMERASE EXPRESSION; SELF-RENEWAL AB A considerable amount of retrospective data is available that describes putative mesenchyrnal stem cells (MSCs). However, there is still very little knowledge available that documents the properties of a MSC in its native environment. Although the precise identity of MSCs remains a challenge, further understanding of their biological properties will be greatly advanced by analyzing the mechanisms that govern their self-renewal and differentiation potential. This review begins with the current state of knowledge on the biology of MSCs, specifically with respect to their existence in the adult organism and postulation of their biological niche. While MSCs are considered suitable candidates for cell-based strategies owing to their intrinsic capacity to self-renew and differentiate, there is currently little information available regarding the molecular mechanisms that govern their stem cell potential. We propose here a model for the regulation of MSC differentiation, and recent findings regarding the regulation of MSC differentiation are discussed. Current research efforts focused on elucidating the mechanisms regulating MSC differentiation should facilitate the design of optimal in vitro culture conditions to enhance their clinical utility cell and gene therapy. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 S Dr,Room 1503,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov NR 103 TC 581 Z9 680 U1 13 U2 93 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JUL-SEP PY 2004 VL 8 IS 3 BP 301 EP 316 DI 10.1111/j.1582-4934.2004.tb00320.x PG 16 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 881GA UT WOS:000225850200003 PM 15491506 ER PT J AU Holmbeck, K Bianco, P Yamada, S Birkedal-Hansen, H AF Holmbeck, K Bianco, P Yamada, S Birkedal-Hansen, H TI MT1-MMP: A tethered collagenase SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MATRIX-METALLOPROTEINASE; EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; PROGELATINASE-A; TUMOR INVASION; KEY REGULATOR; GELATINASE-A; MICE LACKING; IN-VIVO; ACTIVATION AB Gene ablation in mice offers a powerful tool to assay in vivo the role of selected molecules. Numerous new mouse models of matrix metalloproteinases (MMP) deficiency have been developed in the past 5 years and have yielded a new understanding of the role of MMPs while also putting to rest assumptions based on data predating the days of mouse models. The phenotype of the MT1-MMP deficient mouse is one example which illustrates the sometimes rather surprising insights into extracellular matrix remodeling in development and growth that can begained with mouse genetics. While MT1-MMP appears to play little or no role in embryonic development, loss of this enzyme results in progressive impairment of postnatal growth and development affecting both the skeleton and the soft connective tissues. The underlying pathologic mechanism is loss of an indispensable collagenolytic activity, which remains essentially uncompensated. Our findings demonstrate that growth and maintenance of the skeleton requires coordinated and simultaneous MT1-MMP-dependent remodeling of all soft tissue attachments (ligaments, tendons, joint capsules). We note that the phenotype of the MT1-MMP deficient mouse bears no resemblance to those of mice deficient in MMP-2 and tissue inhibitors of metallo-proteinase (TIMP)-2 all but dispelling the view that activation of MMP-2 by the MT1-MMP/TIMP-2/proMMP-2 axis plays a significant role in growth and development throughout life. It is of interest to note that loss of a single catabolic function such as selective collagen degradation mediated by MT1-MMP gives rise to profound impairment of a number of both anabolic and catabolic functions. Published 2004 Wiley-Liss, Inc.(dagger) C1 NIDCR, Matrix Metalloprot Unit, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, I-00185 Rome, Italy. RP Birkedal-Hansen, H (reprint author), NIDCR, Matrix Metalloprot Unit, NIH, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. EM hbhansen@dir.nider.nih.gov NR 42 TC 121 Z9 124 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2004 VL 200 IS 1 BP 11 EP 19 DI 10.1002/jcp.20065 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 826PL UT WOS:000221840900003 PM 15137053 ER PT J AU LeRoith, D AF LeRoith, D TI Editorial: A blast from the past - Insulin does it again! SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CRITICALLY-ILL PATIENTS; ACUTE MYOCARDIAL-INFARCTION; GROWTH-HORMONE; GLYCEMIC CONTROL; MORTALITY; THERAPY; RESISTANCE; STATE C1 NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIH, Clin Endocrinol Branch, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3103 EP 3104 DI 10.1210/jc.2004-0740 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500005 PM 15240577 ER PT J AU Leschek, EW Rose, SR Yanovski, JA Troendle, JF Quigley, CA Chipman, JJ Crowe, BJ Ross, JL Cassorla, FG Blum, WF Cutler, GB Baron, J AF Leschek, EW Rose, SR Yanovski, JA Troendle, JF Quigley, CA Chipman, JJ Crowe, BJ Ross, JL Cassorla, FG Blum, WF Cutler, GB Baron, J CA Natl Inst Child Hlth Human Dev Eli Co Growth Hormone Collaborative Gr TI Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: A randomized, double-blind, placebo-controlled trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NATIONAL COOPERATIVE GROWTH; GH-DEFICIENT PATIENTS; FINAL HEIGHT; NORMAL GIRLS; THERAPY; PUBERTY; INSULIN; BOYS; SECRETION; DISADVANTAGE AB GH is often used to treat children with idiopathic short stature despite the lack of definitive, long-term studies of efficacy. We performed a randomized, double-blind, placebo-controlled trial to determine the effect of GH on adult height in peripubertal children. Subjects (n = 68; 53 males and 15 females), 9-16 yr old, with marked, idiopathic short stature [height or predicted height less than or equal to -2.5 SD score (SDS)] received either GH (0.074 mg/kg) or placebo sc three times per week until they were near adult height. At study termination, adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr. Adult height was greater in the GH-treated group (-1.81 +/- 0.11 SDS, least squares mean +/- SEM) than in the placebo-treated group (-2.32 +/- 0.17 SDS) by 0.51 SDS (3.7 cm; P < 0.02; 95% confidence interval, 0.10-0.92 SDS). A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS. Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS (0.52 SDS; 3.8 cm; P < 0.001; 95% confidence interval, 0.22-0.82 SDS) and no important dropout bias. In conclusion, GH treatment increases adult height in peripubertal children with marked idiopathic short stature. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Dept Endocrinol, Cincinnati, OH 45229 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Alfred I Dupont Hosp Children, Wilmington, DE 19899 USA. Univ Chile, Inst Invest Materno Infantil, Santiago, Chile. RP Baron, J (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM jeffrey_baron@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999] NR 51 TC 126 Z9 140 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3140 EP 3148 DI 10.1210/jc.2003-031457 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500012 PM 15240584 ER PT J AU Gunther, DF Bourdeau, I Matyakhina, L Cassarino, D Kleiner, DE Griffin, K Courkoutsakis, N Abu-Asab, M Tsokos, M Keil, M Carney, JA Stratakis, CA AF Gunther, DF Bourdeau, I Matyakhina, L Cassarino, D Kleiner, DE Griffin, K Courkoutsakis, N Abu-Asab, M Tsokos, M Keil, M Carney, JA Stratakis, CA TI Cyclical Cushing syndrome presenting in infancy: An early form of primary pigmented nodular adrenocortical disease, or a new entity? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; ALPHA REGULATORY SUBUNIT; SPOTTY SKIN PIGMENTATION; MCCUNE-ALBRIGHT-SYNDROME; CARNEY COMPLEX; ADRENAL-HYPERPLASIA; PITUITARY-ADENOMA; MUNCHAUSEN-SYNDROME; ENDOCRINE OVERACTIVITY; MICRONODULAR DYSPLASIA AB Cushing syndrome is uncommon in childhood and rare in infancy. We report the case of a 3-yr-old child who presented with symptoms of Cushing syndrome beginning shortly after birth. Her hypercortisolemia was cyclical, causing relapsing and remitting symptoms, which eventually led to suspicions of possible Munchausen syndrome by proxy. Investigation at the National Institutes of Health excluded exogenous administration of glucocorticoids and indicated ACTH-independent Cushing syndrome. Paradoxical response to dexamethasone stimulation (Liddle's test) suggested a diagnosis of primary pigmented nodular adrenocortical disease (PPNAD). After bilateral adrenalectomy, both glands showed micronodular adrenocortical hyperplasia, but histology was not consistent with typical PPNAD. DNA analysis of the coding sequences of the PRKAR1A gene (associated with PPNAD and Carney complex) and the GNAS gene (associated with McCune-Albright syndrome) showed no mutations. We conclude that hypercortisolemia in infancy may be caused by micronodular adrenocortical hyperplasia, which can be cyclical and confused with exogenous Cushing syndrome. A paradoxical rise of glucocorticoid excretion during Liddle's test may delineate these patients. Infantile micronodular disease has some features of PPNAD and may represent its early form; however, at least in the case of the patient reported here, micronodular hyperplasia was not caused by coding mutations of the PRKAR1A or GNAS genes or associated with typical histology or any other features of Carney complex or McCune-Albright syndrome and may represent a distinct entity. C1 Univ Washington, Childrens Hosp, Seattle, WA 98105 USA. Univ Washington, Reg Med Ctr, Seattle, WA 98105 USA. NICHHD, Dev Endocrinol Branch, Pathol Lab, Bethesda, MD 20892 USA. NCI, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NCI, Warren G Magnuson Clin Ctr, Pathol Lab, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Gunther, DF (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM dan.gunther@seattlechildrens.org; stratakc@mail.nih.gov RI Levesque, Isabelle/A-1899-2012; OI Abu-Asab, Mones/0000-0002-4047-1232; Kleiner, David/0000-0003-3442-4453 NR 76 TC 60 Z9 63 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3173 EP 3182 DI 10.1210/jc.2003-032247 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500018 PM 15240590 ER PT J AU Javor, ED Moran, SA Young, JR Cochran, EK Depaoli, AM Oral, EA Turman, MA Blackett, PR Savage, DB O'Rahilly, S Balow, JE Gorden, P AF Javor, ED Moran, SA Young, JR Cochran, EK Depaoli, AM Oral, EA Turman, MA Blackett, PR Savage, DB O'Rahilly, S Balow, JE Gorden, P TI Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: Baseline characteristics and course during recombinant leptin therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; REPLACEMENT THERAPY; RENAL-DISEASE; PATIENT; GLOMERULOSCLEROSIS; TRANSPLANTATION; DEFICIENCY; FAILURE; ONSET AB Generalized lipodystrophy is characterized by adipose tissue absence, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with recombinant leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with recombinant leptin, and we have followed 15 on leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macro-albuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73m(2)). Eleven of 15 patients (73%) treated with recombinant leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with recombinant leptin demonstrated reduction in proteinuria and hyperfiltration. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73104 USA. Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. RP Javor, ED (reprint author), 10 Ctr Dr,Room 8D20, Bethesda, MD 20892 USA. EM edwardj@intra.niddk.nih.gov OI Oral, Elif/0000-0002-9171-1144 NR 33 TC 48 Z9 52 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3199 EP 3207 DI 10.1210/jc.2003-032140 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500021 PM 15240593 ER PT J AU Bakalov, VK Cooley, MM Quon, MJ Luo, ML Yanovski, JA Nelson, LM Sullivan, G Bondy, CA AF Bakalov, VK Cooley, MM Quon, MJ Luo, ML Yanovski, JA Nelson, LM Sullivan, G Bondy, CA TI Impaired insulin secretion in the Turner metabolic syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE-TOLERANCE TEST; DIABETES-MELLITUS; GONADAL DYSGENESIS; RISK-FACTORS; ADULT WOMEN; SENSITIVITY; RESISTANCE; RELEASE; GROWTH; INDEX AB An increased prevalence of impaired glucose homeostasis (IGH) and diabetes mellitus is reported in monosomy X, or Turner syndrome (TS). To determine whether IGH is an intrinsic feature of this syndrome, independent of obesity or hypogonadism, we compared results of a standard oral glucose challenge in age- and body mass index-matched women with TS and with karyotypically normal premature ovarian failure (POF). Fasting glucose levels were normal in both groups, but glucose values after oral glucose challenge were higher in TS [2-h glucose, 135 +/- 36 mg/dl (7.5 +/- 2.0 mmol/liter) in TS and 97 +/- 18 mg/dl (5.4 +/- 1.0 mmol/liter) in POF; P < 0.0001]. Glucose-stimulated insulin secretion was lower in TS; e. g. the initial insulin response (Delta I/Delta G(30)) was decreased by 60% compared with POF ( P < 0.0001). We also compared responses to a standard iv glucose tolerance test in women with TS and in age- and body mass index-matched normal women and found that the insulin area under the curve was 50% lower in women with TS ( P = 0.003). Insulin sensitivity measured by the quantitative insulin sensitivity check index was higher in women with TS compared with both control groups. Thus, IGH is not secondary to obesity or hypogonadism in TS, but it is a distinct entity characterized by decreased insulin secretion, suggesting that haploinsufficiency for X-chromosome gene(s) impairs beta-cell function and predisposes to diabetes mellitus in TS. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary Med, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Yanovski, Jack/0000-0001-8542-1637; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999] NR 24 TC 57 Z9 63 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3516 EP 3520 DI 10.1210/jc.2004-0122 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500068 PM 15240640 ER PT J AU Scavo, LM Karas, M Murray, M Leroith, D AF Scavo, LM Karas, M Murray, M Leroith, D TI Insulin-like growth factor-I stimulates both cell growth and lipogenesis during differentiation of human mesenchymal stem cells into adipocytes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 3T3-L1 PREADIPOCYTE DIFFERENTIATION; RECEPTOR SUBSTRATE-1; ADIPOSE-TISSUE; PPAR-GAMMA; EXPRESSION; FUSION; PHOSPHORYLATION; INHIBITORS; RESISTANCE AB Insulin is known to regulate adipocyte differentiation and lipid accumulation, but the specific mechanism by which precursor cells differentiate into adipocytes is not clearly understood. This study evaluated the role of the IGF-I receptor in the process of adipocyte differentiation in bone marrow-derived human mesenchymal stem cells (HMSCs). The results demonstrated that nanomolar concentrations of IGF-I adequately replaced micromolar concentrations of insulin in supporting differentiation and lipid accumulation in HMSCs. The addition of IGF-I specifically increased cell proliferation and lipid accumulation in HMSCs, but a mixture of differentiation factors including dexamethasone, indomethacin, and 3-isobutyl-1-methylxanthine did not. These effects were blocked by the alphaIR-3 antibody, which inhibits IGF-I receptor activity. We also describe the pattern of differentiation with regard to cell growth, lipid accumulation, and morphologic changes and define the changes in these parameters that are influenced by IGF-I. Finally, peroxisome proliferator activating receptor-gamma immunoreactivity was also increased in response to IGF-I, and this effect was blocked in cells treated with the alphaIR-3 antibody. Taken together, these findings suggest that IGF-I plays a critical role in adipocyte differentiation and lipid accumulation. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Div Neonatol, Washington, DC 20010 USA. BioWhittaker Inc, Walkersville, MD 21793 USA. RP Leroith, D (reprint author), NIDDKD, Diabet Branch, NIH, Room 8D12,Bldg 10,MSC 1758, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 28 TC 75 Z9 80 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2004 VL 89 IS 7 BP 3543 EP 3553 DI 10.1210/jc.2003-031682 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835OG UT WOS:000222492500072 PM 15240644 ER PT J AU Andrieu, N Goldstein, AM AF Andrieu, N Goldstein, AM TI The case-combined-control design was efficient in detecting gene-environment interactions SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE case-control study; GxE interaction; population-based controls; sibling controls; study design ID BREAST-CANCER RISK; NESTED CASE-CONTROL; POPULATION STRATIFICATION; REPRODUCTIVE FACTORS; LOGISTIC-REGRESSION; BIAS; SELECTION; ASSOCIATION; FAMILY; QUANTIFICATION AB Objective: The interest in studying gene-environment (GxE) interaction is increasing for complex diseases. A design combining both related and unrelated controls (e.g., population-based and siblings) is proposed to increase the power to detect GxE interaction. Study Design and Setting: We used simulations to assess the efficiency of the case-combined-control design relative to a classical case-control study under a variety of assumptions. Results: The case-combined-control design appears more efficient and feasible than a classical case-control study for detecting interaction involving rare exposures and/or genetic factors. The number of available sibling controls per case and the frequencies of the risk factors are the most important parameters for determining relative efficiency. Relative efficiencies decrease as the frequency of the gene (G) increases. A positive correlation in exposure (E) between siblings decreases relative efficiency. Conclusions: Although the case-combined-control design may not be efficient for common genes with moderate effects, it appears to be a useful alternative in certain situations where classical approaches remain unrealistic. (C) 2004 Elsevier Inc. All rights reserved. C1 INSERM, F-91034 Evry, France. Inst Curie, Serv Biostat, F-75248 Paris 5, France. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Andrieu, N (reprint author), INSERM, EMI00-06,Tour Evry 2,523 Pl Terrasses Agora, F-91034 Evry, France. EM nadine.andrieu@curie.net RI ANDRIEU, Nadine/H-4255-2014 NR 45 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 2004 VL 57 IS 7 BP 662 EP 671 DI 10.1016/j.jclinepi.2003.11.014 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 856VB UT WOS:000224072200002 PM 15358394 ER PT J AU Dixit, VD Schaffer, EM Pyle, RS Collins, GD Sakthivel, SK Palaniappan, R Lillard, JW Taub, DD AF Dixit, VD Schaffer, EM Pyle, RS Collins, GD Sakthivel, SK Palaniappan, R Lillard, JW Taub, DD TI Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PLASMA GHRELIN; AUTOIMMUNE ENCEPHALOMYELITIS; CARDIAC CACHEXIA; ACYLATED PEPTIDE; CANCER ANOREXIA; HORMONE RELEASE; NEUROPEPTIDE-Y; SERUM LEPTIN; FOOD-INTAKE; GHS-R AB Ghrelin, a recently described endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is produced by stomach cells and is a potent circulating orexigen, controlling energy expenditure, adiposity, and growth hormone secretion. However, the functional role of ghrelin in regulation of immune responses remains undefined. Here we, report that GHS-R and ghrelin are expressed in human T lymphocytes and monocytes, where ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6,and TNF-alpha. Ghrelin led to a dose-dependent inhibition of leptin-induced cytokine expression, while leptin upregulated GHS-R expression on human T lymphocytes. These data suggest the existence of a reciprocal regulatory network by which ghrelin and leptin control immune cell activation and inflammation. Moreover, ghrelin also exerts potent anti-inflammatory effects and attenuates endotoxin-induced anorexia in a murine endotoxemia model. We believe this to be the first report demonstrating that ghrelin functions as a key signal, coupling the metabolic axis to the immune system, and supporting the potential use of ghrelin and GHS-R agonists in the management of disease-associated cachexia. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA USA. RP Taub, DD (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM TaubD@grc.nia.nih.gov NR 51 TC 498 Z9 547 U1 4 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2004 VL 114 IS 1 BP 57 EP 66 DI 10.1172/JC1200421134 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 834EG UT WOS:000222393800010 PM 15232612 ER PT J AU Masciarelli, S Horner, K Liu, CY Park, SH Hinckley, M Hockman, S Nedachi, T Jin, C Conti, M Manganiello, V AF Masciarelli, S Horner, K Liu, CY Park, SH Hinckley, M Hockman, S Nedachi, T Jin, C Conti, M Manganiello, V TI Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-KINASE-A; OOCYTE MEIOTIC MATURATION; GROWTH FACTOR-I; XENOPUS-OOCYTES; MOUSE OOCYTE; RAT OOCYTES; INSULIN-SECRETION; CAMP LEVELS; MEIOSIS; ARREST AB Since cAMP blocks meiotic maturation of mammalian and amphibian oocytes in vitro and cyclic nucleotide phosphodiesterase 3A (PDE3A) is primarily responsible for oocyte cAMP hydrolysis, we generated PDE3A-deficient mice by homologous recombination. The Pde3a(-/-) females were viable and ovulated a normal number of oocytes but were completely infertile, because ovulated oocytes were arrested at the germinal vesicle stage and, therefore, could not be fertilized. Pde3a(-/-) oocytes lacked cAMP-specific PDE activity, contained increased cAMP levels, and failed to undergo spontaneous maturation in vitro (up to 48 hours). Meiotic maturation in Pde3a(-/-) oocytes was restored by inhibiting protein kinase A (PKA) with adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS) or by injection of protein kinase inhibitor peptide (PKI) or mRNA coding for phosphatase CDC25, which confirms that increased cAMP-PKA signaling is responsible for the meiotic blockade. Pde3a(-/-) oocytes that underwent germinal vesicle breakdown showed activation of MPF and MAPK, completed the first meiotic division extruding a polar body, and became competent for fertilization by spermatozoa. We believe that these findings provide the first genetic evidence indicating that resumption of meiosis in vivo and in vitro requires PDE3A activity. Pde3a(-/-) mice represent an in vivo model where meiotic maturation and ovulation are dissociated, which underscores inhibition of oocyte maturation as a potential strategy for contraception. C1 NHLBI, Sect Biochem Physiol, PCCMB, NIH,Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Div Reprod Biol, Dept Obstet & Gynecol, Stanford, CA 94305 USA. NHLBI, Lab Res Program, NIH, Bethesda, MD 20892 USA. RP Manganiello, V (reprint author), NHLBI, Sect Biochem Physiol, PCCMB, NIH,Pulm Crit Care Med Branch, Bldg 10,Rm 5N307,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ManganiV@nhlbi.nih.gov OI MASCIARELLI, SILVIA/0000-0002-6738-6281 FU NICHD NIH HHS [U54 HD031398, U54-HD31398] NR 50 TC 130 Z9 139 U1 0 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2004 VL 114 IS 2 BP 196 EP 205 DI 10.1172/JCI2004210804 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 837UX UT WOS:000222667600010 PM 15254586 ER PT J AU Seifert, U Liermann, H Racanelli, V Halenius, A Wiese, M Wedemeyer, H Ruppert, T Rispeter, K Henklein, P Sijts, A Hengel, H Kloetzel, PM Rehermann, B AF Seifert, U Liermann, H Racanelli, V Halenius, A Wiese, M Wedemeyer, H Ruppert, T Rispeter, K Henklein, P Sijts, A Hengel, H Kloetzel, PM Rehermann, B TI Hepatitis C virus mutation affects proteasomal epitope processing SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MHC CLASS-I; CYTOTOXIC T-LYMPHOCYTES; DISTINCT PROTEOLYTIC PROCESSES; SINGLE-SOURCE OUTBREAK; INTERFERON-GAMMA; IMMUNE-RESPONSES; VIRAL CLEARANCE; ESCAPE-VARIANT; CTL EPITOPE; B-VIRUS AB The high incidence of hepatitis C virus (HCV) persistence raises the question of how HCV interferes with host immune responses. Studying a single-source HCV outbreak, we identified an HCV mutation that impaired correct carboxyterminal cleavage of an immunodominant HLA-A2-restricted CD8 cell epitope that is frequently recognized by recovered patients. The mutation, a conservative HCV nonstructural protein 3 (NS3) tyrosine to phenylalanine substitution, was absent in 54 clones of the infectious source, but present in 15/21 (71%) HLA-A2-positive and in 11/24 (46%) HLA-A2-negative patients with chronic hepatitis C. In order to analyze whether the mutation affected the processing of the HLA-A2-restricted CD8 cell epitope, mutant and wild-type NS3 polypeptides were digested in vitro with 20S constitutive proteasomes and with immunoproteasomes. The presence of the mutation resulted in impaired carboxyterminal cleavage of the epitope. In order to analyze whether impaired epitope processing affected T cell priming in vivo, HLA-A2-transgenic mice were infected with vaccinia viruses encoding either wild-type or mutant HCV NS3. The mutant induced fewer epitope-specific, IFN-gamma-producing and fewer tetramer(+) cells than the wild type. These data demonstrate how a conservative mutation in the flanking region of an HCV epitope impairs the induction of epitope-specific CD8(+) T cells and reveal a mechanism that may contribute to viral sequence evolution in infected patients. C1 NIDDK, Liver Dis Sect, NIH, DHHS,Digest Dis Branch, Bethesda, MD 20892 USA. Humboldt Univ, Inst Biochem, Charite, Berlin, Germany. MHH, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany. Stadt Klinikum St Georg, Klin Innere Med 2, Leipzig, Germany. Robert Koch Inst, D-1000 Berlin, Germany. Univ Giessen Klinikum, Inst Virol, Essen, Germany. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, DHHS,Digest Dis Branch, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov OI RACANELLI, Vito/0000-0002-8639-1940 NR 52 TC 96 Z9 99 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2004 VL 114 IS 2 BP 250 EP 259 DI 10.1172/JCI200420985 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 837UX UT WOS:000222667600016 PM 15254592 ER PT J AU Gaydos, CA Theodore, M Dalesio, N Wood, BJ Quinn, TC AF Gaydos, CA Theodore, M Dalesio, N Wood, BJ Quinn, TC TI Comparison of three nucleic acid amplification tests for detection of Chlamydia trachomatis in urine specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; SEXUALLY-TRANSMITTED-DISEASE; APTIMA COMBO-2 ASSAY; NEISSERIA-GONORRHOEAE; COBAS AMPLICOR; MULTICENTER EVALUATION; DNA AMPLIFICATION; FEMALE URINE; WOMEN; PCR AB Traditionally, culture and immunoassays have been performed for the detection of sexually transmitted diseases, including Chlamydia trachomatis. However, these assays may often require invasive specimen collection methods, such as female cervical and male urethral swabs. Recently, nucleic acid amplification tests (NAATs) have been approved for testing for the presence of C trachomatis in urine samples. Our objective was to compare the sensitivities and specificities of C trachomatis detection in urine samples with three NAATs: the Abbott LCx (LCx), BD ProbeTec ET (ProbeTec), and Gen-Probe APTIMA Combo 2 (AC2). Urine specimens (n = 506) were collected from both symptomatic and asymptomatic males and females from various high school health clinics. Specimens were tested for C. trachomatis with the three NAATs, and a true-positive result was defined as any two positive NAATs. The C. trachomatis prevalence was 14.8% (75 of 506 samples). Of the 75 urine samples defined as true positives, LCx detected 72, ProbeTec 72, and AC2 detected 75. The sensitivities of LCx, ProbeTec, and AC2 for C. trachomatis detection were 96.0, 96.0, and 100%, and the specificities were 99.1, 100, and 98.8%, respectively. Four of five samples that were positive with AC2 and negative with LCx and ProbeTec were found to be positive with an alternative target TMA-based NAAT, APTIMA C. trachomatis, suggesting that they may have been true positives. Two of four uniquely positive LCx samples available for subsequent testing were both found to be positive by Roche PCR. We found that the LCx, ProbeTec, and AC2 NAATs are highly sensitive and specific methods for the detection of C. trachomatis in urine specimens and can be recommended for noninvasive screening of C. trachomatis in urine. C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, 720 Rutland Ave,Ross 1159, Baltimore, MD 21205 USA. EM cgaydos@jhmi.edu RI Gaydos, Charlotte/E-9937-2010 NR 28 TC 94 Z9 95 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2004 VL 42 IS 7 BP 3041 EP 3045 DI 10.1128/JCM.42.7.3041-3045.2004 PG 5 WC Microbiology SC Microbiology GA 837WN UT WOS:000222672100026 PM 15243057 ER PT J AU Glatman-Freedman, A Casadevall, A Dai, ZD Jacobs, WR Li, AP Morris, SL Navoa, JAD Piperdi, S Robbins, JB Schneerson, R Schwebach, JR Shapiro, M AF Glatman-Freedman, A Casadevall, A Dai, ZD Jacobs, WR Li, AP Morris, SL Navoa, JAD Piperdi, S Robbins, JB Schneerson, R Schwebach, JR Shapiro, M TI Antigenic evidence of prevalence and diversity of Mycobacterium tuberculosis arabinomannan SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TUBERCLE-BACILLI; IN-VITRO; LIPOARABINOMANNAN; ANTIBODIES; VIRULENT; LIPOPOLYSACCHARIDE AB Arabinomannan (AM) is a polysaccharide of the mycobacterial capsule. The capsular polysaccharides of various microorganisms are diverse, and this diversity is important for classification of organisms into serotypes and vaccine development. In the present study we examined the prevalence and diversity of AM among Mycobacterium tuberculosis strains using four AM-binding monoclonal antibodies (MAbs). One of these MAbs, MAb 9d8, is known to bind to AM specifically. By whole-cell enzyme-linked immunosorbent assay (ELISA), the AM recognized by MAb 9d8 was detected on the surfaces of 9 of 11 strains, while 2 strains showed no reactivity with MAb 9d8. However, the AM recognized by MAb 9d8 was found in the culture supernatants of all 11 M. tuberculosis strains tested, as demonstrated by capture ELISA. Other AM-binding MAbs reacted both with the surfaces and with the culture supernatants of all 11 strains. Mice immunized with an experimental AM-recombinant Pseudomonas aeruginosa exoprotein A (rEPA) conjugate vaccine had an increased antibody response to AM and a moderate reduction in the numbers of CFU in their organs 7 days after challenge. Our results indicate that AM was detected in all M. tuberculosis strains tested, with differences in epitope distributions of certain strains. In addition, our results suggest that an experimental AM-rEPA vaccine has a moderate effect on the numbers of CFU in organs early after infection. C1 Yeshiva Univ Albert Einstein Coll Med, Childrens Hosp, Dept Pediat, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Glatman-Freedman, A (reprint author), Yeshiva Univ Albert Einstein Coll Med, Childrens Hosp, Dept Pediat, Golding Bldg,Room 702,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM afreedma@aecom.yu.edu FU NHLBI NIH HHS [R01 HL059842, HL059842]; NIAID NIH HHS [AI001691, AI026170, AI033142, AI033774, AI043268, AI052733, AI053192, K08 AI001691, R01 AI026170, R01 AI033142, R01 AI033774, R01 AI043268, R01 AI052733, R03 AI053192, R21 AI043268, R37 AI026170, R37 AI033142] NR 27 TC 25 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2004 VL 42 IS 7 BP 3225 EP 3231 DI 10.1128/JCM.42.7.3225-3231.2004 PG 7 WC Microbiology SC Microbiology GA 837WN UT WOS:000222672100055 PM 15243086 ER PT J AU Dalesio, N Marsiglia, V Quinn, A Quinn, TC Gaydos, CA AF Dalesio, N Marsiglia, V Quinn, A Quinn, TC Gaydos, CA TI Performance of the MagNA pure LC robot for extraction of Chlamydia trachomatis and Neisseria gonorrhoeae DNA from urine and swab specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; AMPLICOR CT/NG TESTS; FIRST-VOID URINE; MULTICENTER EVALUATION; UNITED-STATES; WOMEN; MEN; INFECTIONS; ASSAY; PREVALENCE AB DNA from uncentrifuged urines (n = 195 and n = 202) and cervical swabs (n = 221 and n = 601) was extracted by the MagNA Pure LC robot and the Amplicor method to validate the robot's extraction for Chlamydia trachomatis and Neisseria gonorrhoeae testing by Roche PCR. The robot provided a highly sensitive and specific method of DNA extraction. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Baltimore City Dept Hlth, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Gaydos, CA (reprint author), 1159 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@jhmi.edu RI Gaydos, Charlotte/E-9937-2010 NR 16 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2004 VL 42 IS 7 BP 3300 EP 3302 DI 10.1128/JCM.42.7.3300-3302.2004 PG 3 WC Microbiology SC Microbiology GA 837WN UT WOS:000222672100068 PM 15243099 ER PT J AU Dahut, WL Gulley, JL Arlen, PM Liu, Y Fedenko, KM Steinberg, SM Wright, JJ Parnes, H Chen, CC Jones, E Parker, CE Linehan, WM Figg, WD AF Dahut, WL Gulley, JL Arlen, PM Liu, Y Fedenko, KM Steinberg, SM Wright, JJ Parnes, H Chen, CC Jones, E Parker, CE Linehan, WM Figg, WD TI Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR ANGIOGENESIS; ESTRAMUSTINE; TAXOTERE; CARCINOMA; METASTASIS; INHIBITION; GUIDELINES; THERAPY; MYELOMA; UPDATE AB Purpose Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. Methods Seventy-five patients with chemotherapy-naive metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. Results After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P = .32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. Conclusion In this randomized phase II trial, the addition of thalicomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 5A-01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 42 TC 214 Z9 225 U1 3 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2004 VL 22 IS 13 BP 2532 EP 2539 DI 10.1200/JCO.2004.05.074 PG 8 WC Oncology SC Oncology GA 834JW UT WOS:000222408400005 PM 15226321 ER PT J AU Rich, JN Friedman, HS Powell, JB Dancey, JE AF Rich, JN Friedman, HS Powell, JB Dancey, JE TI Gefitinib in recurrent glioblastoma - In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TUMOR-CELLS C1 Duke Univ, Durham, NC 27710 USA. NCI, Bethesda, MD 20892 USA. RP Rich, JN (reprint author), Duke Univ, Durham, NC 27710 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2004 VL 22 IS 13 BP 2756 EP 2756 DI 10.1200/JCO.2004.99.044 PG 1 WC Oncology SC Oncology GA 834JW UT WOS:000222408400041 ER PT J AU Post, RM Chang, KD Findling, RL Geller, B Kowatch, RA Kutcher, SP Leverich, GS AF Post, RM Chang, KD Findling, RL Geller, B Kowatch, RA Kutcher, SP Leverich, GS TI Prepubertal bipolar I disorder and bipolar disorder NOS are separable from ADHD SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; DIVALPROEX SODIUM; REFERRED CHILDREN; MENTAL-DISORDERS; MANIC SYMPTOMS; PHENOTYPE; COMORBIDITY; ONSET; ADOLESCENTS; DEPRESSION C1 NIMH, BPB, Bethesda, MD 20892 USA. NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ Washington, Sch Med, St Louis, MO USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Dalhousie Univ, Halifax, NS, Canada. RP Post, RM (reprint author), NIMH, BPB, 10 Ctr Dr,MSC 1272,Bldg 10,Room 3S239, Bethesda, MD 20892 USA. EM postr@intra.nimh.nih.gov NR 58 TC 17 Z9 17 U1 5 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2004 VL 65 IS 7 BP 898 EP 902 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 845ZD UT WOS:000223283200003 PM 15291676 ER PT J AU Grant, BF Hasin, DS Stinson, FS Dawson, DA Chou, SP Ruan, WJ Pickering, RP AF Grant, BF Hasin, DS Stinson, FS Dawson, DA Chou, SP Ruan, WJ Pickering, RP TI Prevalence, correlates, and disability of personality disorders in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SUBSTANCE USE DISORDERS; AXIS-II COMORBIDITY; MENTAL-HEALTH; COMMUNITY AB Objective: To present nationally representative data on the prevalence, sociodemographic correlates, and disability of 7 of the 10 DSM-IV personality disorders. Method: The data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version, and associations between personality disorders and sociodemographic correlates were determined. The relationship between personality disorders and 3 emotional disability scores (Short-Form 12, version 2) was also examined. Results: Overall, 14.79% of adult Americans (95% CI = 14.08 to 15.50), or 30.8 million, had at least I personality disorder. The most prevalent personality disorder in the general population was obsessive-compulsive personality disorder, 7.88% (95% CI = 7.43 to 8.33), followed by paranoid personality disorder 4.41% (95% CI = 4.12 to 4.70), antisocial personality disorder 3.63% (95% CI = 3.34 to 3.92), schizoid personality disorder 3.13% (95% CI = 2.89 to 3.37), avoidant personality disorder 2.36% (95% CI = 2.14 to 2.58), histrionic personality disorder 1.84% (95% CI = 1.66 to 2.02), and dependent personality disorder 0.49% (95% CI = 0.40 to 0.58). The risk of avoidant, dependent, and paranoid personality disorders was significantly greater among women than men (p < .05); the risk of antisocial personality disorder was greater among men compared with women (p < .05); and no sex differences were observed in the risk of obsessive-compulsive, schizoid, or histrionic personality disorders. In general, risk factors for personality disorders included being Native American or black, being a young adult, having low socioeconomic status, and being divorced, separated, widowed, or never married. Avoidant, dependent, schizoid, paranoid, and antisocial personality disorders (p < .02 to p < .0001) were each statistically significant predictors of disability. Obsessive-compulsive personality disorder was inconsistently related to disability. In contrast, disability was not significantly different among individuals with histrionic personality disorder compared with those without the disorder. Conclusion: Personality disorders are prevalent in the general population and are generally highly associated with disability. This study highlights the need to develop more effective and targeted prevention and intervention initiatives for personality disorders. C1 US Dept Hlth & Human Serv, NIAAA, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry,NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY USA. RP Grant, BF (reprint author), US Dept Hlth & Human Serv, NIAAA, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry,NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 37 TC 399 Z9 403 U1 8 U2 41 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2004 VL 65 IS 7 BP 948 EP 958 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 845ZD UT WOS:000223283200011 PM 15291684 ER PT J AU Konig, P Giesow, K Schuldt, K Buchholz, UJ Keil, GM AF Konig, P Giesow, K Schuldt, K Buchholz, UJ Keil, GM TI A novel protein expression strategy using recombinant bovine respiratory syncytial virus (BRSV): modifications of the peptide sequence between the two furin cleavage sites of the BRSV fusion protein yield secreted proteins, but affect processing and function of the BRSV fusion protein SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID REPLICATION; GENE; TRANSCRIPTION; GENERATION; ACTIVATION; CULTURE; CDNA AB The bovine respiratory syncytial virus (BRSV) fusion (F) protein is cleaved at two furin cleavage sites, which results in generation of the disulfide-linked F-1 and F-2 subunits and release of an intervening peptide of 27 aa (pep27). A series of mutated open reading frames encoding F proteins that lacked the entire pep27, that contained an arbitrarily chosen 23 aa sequence instead of pep27 or in which pep27 was replaced by the amino acid sequences for the bovine cytokines interleukin 2 (bolL2), interleukin 4 (bolL4) or gamma interferon (boIFN-gamma) was constructed. Transient expression experiments revealed that the sequence of the intervening peptide influenced intracellular transport, maturation of the F protein and F-mediated syncytium formation. Expression of bolL2, bolL4 or boIFN-gamma in place of pep27 resulted in secretion of the cytokines into the culture medium. All mutated F proteins except the boIFN-gamma-containing variant could be expressed by and were functional for recombinant BRSV. Characterization of the cell culture properties of the recombinants demonstrated that the amino acid sequence between the two furin cleavage sites affected entry into target cells, direct spreading of virions from cell to cell and virus growth. Secretion of bolL2 and bolL4 into the medium of cells infected with the respective recombinants demonstrated that the F protein can be used to express secreted heterologous bioactive peptides or (glyco)proteins, which might be of interest for the development of novel RSV vaccines. C1 Fed Res Ctr Virus Dis Anim, Friedrich Loeffler Inst, Inst Mol Biol, D-17493 Greifswald, Germany. RP Keil, GM (reprint author), NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. EM Guenther.M.Keil@rie.bfav.de NR 18 TC 8 Z9 9 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 2004 VL 85 BP 1815 EP 1824 DI 10.1099/vir.0.80010-0 PN 7 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 837ML UT WOS:000222639500002 PM 15218165 ER PT J AU De Bault, LE Lu, S Angros, LH Benbrook, DM AF De Bault, LE Lu, S Angros, LH Benbrook, DM TI Retinoic acid effects on the expression of EGF-receptor mRNA and its protein in cervical cancer cells in vitro SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract CT 12th International Congress of Histochemistry and Cytochemistry CY JUL 24-29, 2004 CL La Jolla, CA SP Histochem Soc C1 Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2004 VL 52 SU 1 BP S36 EP S36 PG 1 WC Cell Biology SC Cell Biology GA 833QI UT WOS:000222352900143 ER PT J AU Gannot, G Tangrea, MA Gillespie, JW Wallis, BS Pohida, T Bonner, RF Linehan, MW Chuaqui, RF Emmert-Buck, MR AF Gannot, G Tangrea, MA Gillespie, JW Wallis, BS Pohida, T Bonner, RF Linehan, MW Chuaqui, RF Emmert-Buck, MR TI Histomathematics: Intersection of histopathology and bioinformatics SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract CT 12th International Congress of Histochemistry and Cytochemistry CY JUL 24-29, 2004 CL La Jolla, CA SP Histochem Soc C1 NIH, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2004 VL 52 SU 1 BP S12 EP S12 PG 1 WC Cell Biology SC Cell Biology GA 833QI UT WOS:000222352900046 ER PT J AU Hewitt, SM AF Hewitt, SM TI Driving forces in image analysis: Tissue microarrays and clinical trials SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract CT 12th International Congress of Histochemistry and Cytochemistry CY JUL 24-29, 2004 CL La Jolla, CA SP Histochem Soc C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2004 VL 52 SU 1 BP S15 EP S15 PG 1 WC Cell Biology SC Cell Biology GA 833QI UT WOS:000222352900059 ER PT J AU Espina, V Woodhouse, EC Wulfkuhle, J Asmussen, HD Petricoin, EF Liotta, LA AF Espina, V Woodhouse, EC Wulfkuhle, J Asmussen, HD Petricoin, EF Liotta, LA TI Protein microarray detection strategies: focus on direct detection technologies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE protein microarray; catalyzed reporter deposition; molecular profiling; fluorescence; chromogens ID CATALYZED REPORTER DEPOSITION; ATOMIC-FORCE MICROSCOPE; ALLERGEN-SPECIFIC IGE; TISSUE MICROARRAYS; SIGNAL AMPLIFICATION; MESSENGER-RNA; CLINICAL PROTEOMICS; CANCER SPECIMENS; CHIP TECHNOLOGY; ARRAYS AB Protein microarrays are being utilized for functional proteomic analysis, providing information not obtainable by gene arrays. Microarray technology is applicable for studying protein-protein, protein-ligand, kinase activity and posuranslational modifications of proteins. A precise and sensitive protein microarray, the direct detection or reverse-phase microarray, has been applied to ongoing clinical trials at the National Cancer Institute for studying phosphorylation events in EGF-receptor-mediated cell signaling pathways. The variety of microarray applications allows for multiple, creative microarray designs and detection strategies. Herein, we discuss detection strategies and challenges for protein microarray technology, focusing on direct detection of protein microarrays. Published by Elsevier B.V. C1 US FDA, NCI, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. Univ Colorado, Boulder, CO 80309 USA. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program, Bethesda, MD 20892 USA. RP Espina, V (reprint author), US FDA, NCI, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Room B1B53,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM espinav@mail.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 84 TC 123 Z9 140 U1 7 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL PY 2004 VL 290 IS 1-2 BP 121 EP 133 DI 10.1016/j.jim.2004.04.013 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 842QR UT WOS:000223019600009 PM 15261576 ER PT J AU Lukashev, D Ohta, A Apasov, S Chen, JF Sitkovsky, M AF Lukashev, D Ohta, A Apasov, S Chen, JF Sitkovsky, M TI Cutting edge: Physiologic attenuation of proinflammatory transcription by the Gs protein-coupled A2A adenosine receptor in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; KAPPA-B; A(2A) RECEPTORS; IMMUNE-RESPONSE; PROTECTION; INHIBITION; KINASE; CELLS; INFLAMMATION AB The A2A adenosine receptor plays a critical role in the physiologic immunosuppressive pathway that protects normal tissues from excessive collateral damage by overactive immune cells and their proinflammatory cytokines. In this study, we examine and clarify the mechanism of tissue protection by extracellular adenosine using A2AR-deficient mice and show that the A2AR inhibits TLR-induced transcription of proinflammatory cytokines in vivo. The observed increase in proinflammatory cytokines mRNA in A2AR-deficient mice was associated with enhanced activity of the NF-kappaB transcription factor. These observations provide the genetic in vivo evidence for attenuation of proinflammatory transcriptional activity of NF-kappaB by a "metabokine" adenosine and point to the need to re-evaluate the regulation of other transcription factors in hypoxic and adenosine-rich microenvironments of inflamed normal tissues and solid tumors. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Sitkovsky, M (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room IIN256, Bethesda, MD 20892 USA. EM mvsitkov@helix.nih.gov RI Lukashev, Dmitriy/F-8133-2010 NR 26 TC 112 Z9 118 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 JUL 1 PY 2004 VL 173 IS 1 BP 21 EP 24 PG 4 WC Immunology SC Immunology GA 831CQ UT WOS:000222170900007 PM 15210754 ER PT J AU Tumanov, AV Kuprash, DV Mach, JA Nedospasov, SA Chervonsky, AV AF Tumanov, AV Kuprash, DV Mach, JA Nedospasov, SA Chervonsky, AV TI Lymphotoxin and TNF produced by B cells are dispensable for maintenance of the follicle-associated epithelium but are required for development of lymphoid follicles in the Peyer's patches SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; BETA-DEFICIENT MICE; ABNORMAL-DEVELOPMENT; DISTINCT ROLES; T-CELL; ORGANOGENESIS; RECEPTOR; LYMPHOCYTES; NODES; ALPHA AB Organogenesis of Peyer's patches (PP), follicle-associated epithelium, and M cells is impaired in mice lacking B cells. At the same time, lymphotoxin (LT) and TNF are known to be critical for the development of PP. To directly address the function of LT and TNF expressed by B cells in the maintenance of PP structure, we studied the de novo formation of PP in B cell-deficient mice after the transfer of bone marrow from mice with targeted mutations in LT, TNF, or their combinations. We found that although the compartmentalization of T and B cell zones and development of follicular dendritic cells were affected by the lack of B cell-derived LT and TNF, the development of follicle-associated epithelium and M cells in PP was completely independent of LT/TNF production by B cells. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Chervonsky, AV (reprint author), 600 Main St, Bar Harbor, ME 04609 USA. EM avc@jax.org RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016; OI Kuprash, Dmitry/0000-0002-1488-4148; Chervonsky, Alexander/0000-0001-7547-871X FU NCI NIH HHS [N01 CO 12400]; NIDDK NIH HHS [DK 52210] NR 37 TC 40 Z9 40 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 JUL 1 PY 2004 VL 173 IS 1 BP 86 EP 91 PG 6 WC Immunology SC Immunology GA 831CQ UT WOS:000222170900015 PM 15210762 ER PT J AU Sun, RH Iribarren, P Zhang, N Zhou, Y Gong, WH Cho, EH Lockett, S Chertov, O Bednar, F Rogers, TJ Oppenheim, JJ Wang, JM AF Sun, RH Iribarren, P Zhang, N Zhou, Y Gong, WH Cho, EH Lockett, S Chertov, O Bednar, F Rogers, TJ Oppenheim, JJ Wang, JM TI Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID N-FORMYLPEPTIDE RECEPTOR; INNATE HOST DEFENSES; CHEMOATTRACTANT RECEPTOR; ACTIVATED RECEPTORS; CELL MOBILIZATION; SERINE PROTEASES; HUMAN PLATELETS; RESPONSES; THROMBIN; MONOCYTES AB The antimicrobial and proinflammatory neutrophil granule protein cathepsin G (CaG) has been reported as a chemoattractant for human phagocytic leukocytes by using a putative G protein coupled receptor. In an effort to identify potential CaG receptor(s), we found that CaG-induced phagocyte migration was specifically attenuated by the bacterial chemotactic peptide fMLP, suggesting these two chemoattractants might share a receptor. In fact, CaG chemoattracts rat basophilic leukemia cells (RBL cells) expressing the high affinity human fMLP receptor FPR, but not parental RBL cells or cells transfected with other chemoattractant receptors. In addition, a specific FPR Ab and a defined FPR antagonist, cyclosporin H, abolished the chemotactic response of phagocytes and FPR-transfected cells to CaG. Furthermore, CaG down-regulated the cell surface expression of FPR in association with receptor internalization. Unlike fMLP, CaG did not induce potent Ca2(+) flux and was a relatively weaker activator of MAPKs through FPR. Yet CaG activated an atypical protein kinase C,isozyme, protein kinase Q, which was essential for FPR to mediate the chemotactic activity of CaG. Thus, our studies identify CaG as a novel, host-derived chemotactic agonist for FPR and expand the functional scope of this receptor in inflammatory and immune responses. C1 Natl Canc Inst, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. Natl Canc Inst, Basi Res Program, Frederick, MD 21702 USA. Natl Canc Inst, Image Anal Lab, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA. RP Wang, JM (reprint author), Natl Canc Inst, Mol Immunoregulat Lab, Canc Res Ctr, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov FU NCI NIH HHS [N01 CO 12400]; NIDA NIH HHS [DA 06650, DA 11130, DA 14230] NR 49 TC 71 Z9 79 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2004 VL 173 IS 1 BP 428 EP 436 PG 9 WC Immunology SC Immunology GA 831CQ UT WOS:000222170900055 PM 15210802 ER PT J AU Zhang, N Rogers, TJ Caterina, M Oppenheim, JJ AF Zhang, N Rogers, TJ Caterina, M Oppenheim, JJ TI Proinflammatory chemokines, such as C-C chemokine ligand 3, desensitize mu-opioid receptors on dorsal root ganglia neurons SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MICE LACKING; PHARMACOLOGICAL CHARACTERIZATION; HETEROLOGOUS DESENSITIZATION; FUNCTIONAL EXPRESSION; CAPSAICIN RECEPTOR; ADENYLYL-CYCLASE; BINDING PROTEIN; PERTUSSIS TOXIN; RAT-BRAIN; PAIN AB Pain is one of the hallmarks of inflammation. Opioid receptors mediate antipain responses in both the peripheral nervous system and CNS. In the present study, pretreatment of CCR1:mu-opioid receptor/HEK293 cells with CCL3 (MIP-1alpha) induced internalization of mu-opioid receptors and severely impaired the mu-opioid receptor-mediated inhibition of cAMP accumulation. Immunohistochemical staining showed that CCR1 and mu-opioid receptors were coexpressed on small to medium diameter neurons in rat dorsal root ganglion. Analysis of ligand-induced calcium flux showed that both types of receptors were functional. Pretreatment of neurons with CCL3 exhibited an impaired [D-Ala(2),N-MePhe(4),Gly-o15]enkephalin-elicited calcium response, indicative of the heterologous desensitization of mu-opioid receptors. Other chemokines, such as CCL2, CCL5, and CXCL8, exhibited similar inhibitory effects. Our data indicate that proinflammatory chemokines are capable of desensitizing mu-opioid receptors on peripheral sensory neurons, providing a novel potential mechanism for peripheral inflammation-induced hyperalgesia. C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. Johns Hopkins Univ, Sch Med, Dept Biol Chem & Neurosci, Baltimore, MD 21287 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Room 21-89A, Frederick, MD 21702 USA. EM Oppenhei@ncifcrf.gov FU NIDA NIH HHS [DA 11130, DA 06650, DA 13429, DA 14230, DA 16544] NR 33 TC 70 Z9 74 U1 3 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2004 VL 173 IS 1 BP 594 EP 599 PG 6 WC Immunology SC Immunology GA 831CQ UT WOS:000222170900074 PM 15210821 ER PT J AU Elaraj, DM White, DE Steinberg, SM Haworth, K Rosenberg, SA Yang, JC AF Elaraj, DM White, DE Steinberg, SM Haworth, K Rosenberg, SA Yang, JC TI A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE angiogenesis; renal cancer; vascular endothelial growth factor (VEGF); bevacizumab; thalidomide ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; CANCER; SURVIVAL; INTERLEUKIN-2; ANGIOGENESIS; RECURRENT AB The use of antiangiogenic agents represents a promising strategy for the treatment of patients with metastatic renal cell carcinoma. Objective responses to single-agent thalidomide have been described, and a randomized study showed that bevacizumab (a neutralizing antibody against vascular endothelial growth factor) delayed time to progression of metastatic renal cancer. A pilot study combining these two agents was performed. Sequential cohorts of 10 and 12 patients (crossing over from placebo therapy in the aforementioned randomized bevacizuamab trial) were treated with low-dose bevacizumab alone or bevacizumab plus the maximum tolerated dose of thalidomide as determined by intrapatient escalation. Toxicity, objective responses, and time to progression were the endpoints of this study. Patients tolerated thalidomide and bevacizumab well, with more than 50% of patients escalating to at least 500 mg/d thalidomide. Grades I and 2 sensory neuropathy limited thalidomide dose escalation in 3 of 12 patients. The incidence of grades 3 and 4 toxicity was not different between patients treated with bevacizumab alone versus bevacizumab plus thalidomide. There were no objective responses and no difference in progression-free survival between the groups (2.4 months for bevacizumab alone, 3.0 months for bevacizumab plus thalidomide). Combination antiangiogenic therapy with bevacizumab plus thalidomide in patients with renal cell carcinoma is associated with similar toxicity and progression-free survival compared with bevacizumab alone. This study illustrates a clinical trial design for rapidly testing the feasibility and safety of combining antiangiogenic agents, an approach that will be necessary for rapidly evaluating the many potential combinations of antiangiogenic agents. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, NIH Bldg 10,Room 2B37,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jamesyang@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 18 TC 31 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2004 VL 27 IS 4 BP 259 EP 264 DI 10.1097/00002371-200407000-00001 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 833DP UT WOS:000222316900001 PM 15235386 ER PT J AU Mbulaiteye, SM Biggar, RJ AF Mbulaiteye, SM Biggar, RJ TI Saliva and the transmission of human herpesvirus 8: Potential role of promoter-arthropod bites - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID INFECTION C1 NCI, Viral Epidemiol Branch, NIH, DHHS, Rockville, MD 20852 USA. RP Mbulaiteye, SM (reprint author), NCI, Viral Epidemiol Branch, NIH, DHHS, 6120 Execut Plaza Blvd,Rm 8007,MSC 7248, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov NR 9 TC 0 Z9 0 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 JUL 1 PY 2004 VL 190 IS 1 BP 200 EP 201 DI 10.1086/420891 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 828VV UT WOS:000222002700026 ER PT J AU Riedl, E Tada, Y Udey, MC AF Riedl, E Tada, Y Udey, MC TI Identification and characterization of an alternatively spliced isoform of mouse Langerin/CD207 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE Birbeck granule; C-type lectin; dendritic cells; Langerhans cell ID EPIDERMAL LANGERHANS CELLS; C-TYPE LECTIN; CADHERIN-MEDIATED ADHESION; GRANULE-LIKE STRUCTURES; HUMAN DENDRITIC CELLS; ASIALOGLYCOPROTEIN RECEPTOR; CARBOHYDRATE-RECOGNITION; ANTIGEN PRESENTATION; BIRBECK GRANULES; CORED TUBULE AB The mouse homologue of human Langerin (CD207), a novel Langerhans cells (LC)-restricted C-type lectin that likely participates in antigen recognition and uptake, has been recently identified. In this study, we isolated the mouse Langerin cDNA from murine fetal skin-derived dendritic cells (FSDDC) by subtractive cloning and rapid amplification of cDNA ends (RACE). An alternatively spliced variant of mouse Langerin that lacked the extracellular neck domain (DeltaE3Langerin) was detected in RNA derived from FSDDC and epidermal LC by RT-PCR. In vitro-generated FSDDC and epidermal LC expressed both full-length and DeltaE3Langerin mRNA, but tissue expression was not restricted to skin. Mouse Langerin protein isoforms were readily detected in fibroblasts transfected with cDNAs encoding epitope-tagged Langerin and DeltaE3Langerin. Recombinant DeltaE3Langerin protein localized with transferrin-containing compartments in transfected fibroblasts. Full-length mouse Langerin-bound mannan, whereas DeltaE3Langerin and soluble bacterial recombinant Langerin protein lacking the neck domain did not. Fibroblasts transfected with mouse Langerin cDNA contained typical Birbeck granules (BG) and cored tubules, whereas DeltaE3Langerin cDNA did not induce BG or cored tubule formation in transfected fibroblasts. Developmentally regulated expression of Langerin isoforms provides a mechanism by which Langerin involvement in antigen uptake and processing could be regulated. C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Riedl, E (reprint author), Univ Vienna, Sch Med, Dept Dermatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM riedle@mail.nih.gov NR 52 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2004 VL 123 IS 1 BP 78 EP 86 DI 10.1111/j.0022-202X.2004.22718.x PG 9 WC Dermatology SC Dermatology GA 828LI UT WOS:000221974400014 PM 15191546 ER PT J AU Shibaki, A Sato, A Vogel, JC Miyagawa, F Katz, SI AF Shibaki, A Sato, A Vogel, JC Miyagawa, F Katz, SI TI Induction of GVHD-like skin disease by passively transferred CD8(+) T-cell receptor transgenic T cells into keratin 14-ovalbumin transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoimmune disease; GVHD; Langerhans cells; tolerance ID CLASS-II MHC; DEPENDENT DIABETES-MELLITUS; PANCREATIC BETA-CELLS; LANGERHANS CELLS; DENDRITIC CELLS; TOLERANCE INDUCTION; VIRUS-INFECTION; EPIDERMAL-CELLS; HOST-DISEASE; EXPRESSION AB To understand the mechanisms involved in immunological tolerance to skin-associated antigens, we have developed transgenic (Tg) mice that express a model self-antigen, membrane-bound chicken ovalbumin (OVA), under the control of a keratin 14 (K14) promoter. K14-mOVA Tg mice express OVA mRNA in the epidermis, and appear normal. K14-mOVA Tg mice failed to mount T cell and delayed type hypersensitivity reactions to OVA, suggesting that the Tg mice were tolerant to OVA. Skin dendritic cells, including Langerhans cells, may contribute to the tolerance induction because migratory skin DC derived from K14-mOVA efficiently activated CD8(+) T cells from OVA-specific T-cell receptor (Va2/Vb5) Tg (OT-I) mice. OT-I cells expanded and accumulated in skin-draining lymph nodes after intravenous injected into K14-mOVA mice and exhibited activation markers. Graft-versus-host disease-like skin lesions appeared in K14-mOVA mice by day 7 after injection of OT-I cells. These studies demonstrate that K14-mOVA Tg mice are susceptible to an autoimmunelike skin disease induced by passively transferred naive CD8(+) OVA T-cell receptor Tg T cells, and serve as a good model for understanding self-tolerance and for the investigation of the pathogenesis, treatment and potential prevention of cell-mediated autoimmune reactions in skin. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov NR 33 TC 54 Z9 55 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2004 VL 123 IS 1 BP 109 EP 115 DI 10.1111/j.0022-202X.2004.22701.x PG 7 WC Dermatology SC Dermatology GA 828LI UT WOS:000221974400018 PM 15191550 ER PT J AU Wahl, SM Swisher, J McCartney-Francis, N Chen, WJ AF Wahl, SM Swisher, J McCartney-Francis, N Chen, WJ TI TGF-beta: the perpetrator of immune suppression by regulatory T cells and suicidal T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 02-05, 2003 CL Philadelphia, PA SP Soc Leukocyte Bio DE immunoregulation.; apoptosis; leishmania ID GROWTH-FACTOR-BETA; IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; APOPTOTIC CELLS; LEISHMANIA-MAJOR; ORAL TOLERANCE; TRANSFORMING GROWTH-FACTOR-BETA-1; GENE-EXPRESSION; IFN-GAMMA; ANTIGEN 4 AB Innate and adaptive immunity function to eliminate foreign invaders and respond to injury while enabling coexistence with commensal microbes and tolerance against self and innocuous agents. Although most often effective in accomplishing these objectives, immunologic processes are not fail-safe and may underserve or be excessive in protecting the host. Checks and balances to maintain control of the immune system are in place and are becoming increasingly appreciated as targets for manipulating immunopathologic responses. One of the most recognized mediators of immune regulation is the cytokine transforming growth factor-beta (TGF-beta), a product of immune and nonimmune cells. Emerging data have unveiled a pivotal role for TGF-beta as a perpetrator of suppression by CD4(+)CD25(+) regulatory T (Treg) cells and in apoptotic. sequelae. Through its immunosuppressive prowess, TGF-beta effectively orchestrates resolution of inflammation and control of autoaggressive immune reactions by managing T cell anergy, defining unique populations of Treg cells, regulating T cell death, and influencing the host response to infections. C1 NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDCR, OIIB, NIH, Bldg 30,Rm 320,30 Convent Dr,MSC4352, Bethesda, MD 20892 USA. EM smwahl@dir.nider.nih.gov NR 128 TC 120 Z9 123 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2004 VL 76 IS 1 BP 15 EP 24 DI 10.1189/jlb.1103539 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 832RA UT WOS:000222283400003 PM 14966194 ER PT J AU Ruffini, PA Biragyn, A Coscia, M Harvey, LK Cha, SC Bogen, B Kwak, LW AF Ruffini, PA Biragyn, A Coscia, M Harvey, LK Cha, SC Bogen, B Kwak, LW TI Genetic fusions with viral chemokines target delivery of nonimmunogenic antigen to trigger antitumor immunity independent of chemotaxis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 02-05, 2003 CL Philadelphia, PA SP Soc Leukocyte Bio DE MC148; vMIP-1; viral chemokine antagonist; APC targeting; vaccine carrier; lymphoma ID T-CELL RESPONSES; DENDRITIC CELLS; BETA-CHEMOKINE; RECEPTOR CCR8; IN-VIVO; VMIP-I; EXPRESSION; ANTIBODY; I-309; TCA3 AB The ideal vaccine carrier should be able to tar-et antigen delivery and possibly recruit antigen-presenting cells (APC) and deliver an activation signal to promote adaptive immune responses. Ligands for chemokine receptors expressed on APC may be attractive candidates, as they can both target and attract APC. To investigate the requirement for APC recruitment, we used a pair of viral chemokines, agonist herpes simplex virus 8-derived macrophage inflammatory protein-I (vMIP-I) and antagonist MC148, which induce and suppress chemotaxis, respectively. Chemokine-antigen fusions efficiently delivered a model nonimmunogenic tumor antigen to APC for processing and presentation to antigen-specific T cells in vitro. Physical linkage of chemokine and antigen and specific binding of chemokine receptor by the fusion protein were required. Mice immunized with vMIP-I or MC148 fusion DNA vaccines elicited protection against tumor challenge. Therefore, vaccine efficacy depends primarily on the ability of the carrier to target antigen delivery to APC for subsequent processing and presentation, and chemotaxis directly induced by the chemokine moiety in the fusion may not be necessary. C1 NIA, Immunol Lab, Baltimore, MD 21224 USA. NCI, Expt Transplantat & Immunol Branch, Frederick, MD USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. Univ Oslo, Natl Hosp, Inst Immunol, Oslo, Norway. RP Biragyn, A (reprint author), NIA, Immunol Lab, Baltimore, MD 21224 USA. EM biragyna@grc.nia.hih.gov RI coscia, marta/K-4832-2016 OI coscia, marta/0000-0003-2123-7675 NR 40 TC 20 Z9 23 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2004 VL 76 IS 1 BP 77 EP 85 DI 10.1189/jlb.1003481 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 832RA UT WOS:000222283400011 PM 15075363 ER PT J AU Salvucci, O Basik, M Yao, L Bianchi, R Tosato, G AF Salvucci, O Basik, M Yao, L Bianchi, R Tosato, G TI Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-alpha- and IFN-gamma SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 02-05, 2003 CL Philadelphia, PA SP Soc Leukocyte Bio DE chemokine; cytokine; endothelium; inflammation ID INTERFERON-INDUCIBLE PROTEIN-10; TRANSFER-RNA SYNTHETASE; IN-VIVO; METALLOPROTEINASE INHIBITORS; TRANSCRIPTIONAL REGULATION; POTENT INHIBITOR; GROWTH-FACTOR; EXPRESSION; CHEMOKINE; RECEPTORS AB Vigorous inflammatory responses are associated with tissue damage, particularly when toxic levels of inflammatory cytokines are produced. Despite proangiogenic factors being present early at sites of inflammation, vascular repair occurs toward the end of the inflammatory response, suggesting modulation of the proangio-genic response. Endogenous inhibitors of angiogenesis induced during acute inflammation are poorly characterized. Here, we looked for endothelial cell-derived modulators of angiogenesis that may account for delayed neovascularization during inflammation. Gene profiling of endothelial cells showed that the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) selectively promote expression of the antiangiogenic molecules, IFN-inducible protein-10, monokine induced by IFN-gamma, tryptophanyl-tRNA synthetase, and tissue inhibitor of metalmetallo-proteinase-1, and inhibit expression of the proangiogenic molecules, platelet-endothelial cell adhesion molecule-I, vascular endothelial,"rowth factor receptor-2, stromal cell-derived factor-1 (SDF-1), collagen type IV, endothelial cell growth factor-1, and carcinoembryonic antigen-related cell adhesion molecule-1. Reduced endothelial cell expression of SDF-1 protein by TNF-alpha and IFN-gamma disrupts extracellular matrix-dependent endothelial cell tube formation, an in vitro morphogenic process that recapitulates critical steps in angiogenesis. Replacement of SDF-1 onto the endothelial cell surface reconstitutes this morphogenic process. In vivo, TNF-alpha and IFN-gamma inhibit growth factor-induced angio-genesis and SDF-1 expression in endothelial cells. These results demonstrate that SDF-1/CXC chemokine receptor-4 constitutes a TNF-alpha- and IFN-gamma-regulated signaling system that plays a critical role in inediatin- anodo-enesis inhibition by these inflammatory cytokines. C1 NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Brescia, Dept Biomed Sci & Biotechnol, Div Human Anat, I-25121 Brescia, Italy. Lab Canc Drug Dev, Translat Genom Res Inst, Phoenix, AZ USA. RP Tosato, G (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226,MSC 1907, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov NR 48 TC 39 Z9 46 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2004 VL 76 IS 1 BP 217 EP 226 DI 10.1189/jlb.1203609 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 832RA UT WOS:000222283400027 PM 15075355 ER PT J AU Ma, PL Cui, XL Wang, SB Zhang, JH Nishanian, EV Wang, WH Wesley, RA Danner, RL AF Ma, PL Cui, XL Wang, SB Zhang, JH Nishanian, EV Wang, WH Wesley, RA Danner, RL TI Nitric oxide post-transcriptionally up-regulates LPS-induced IL-8 expression through p38 MAPK activation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 02-05, 2003 CL Philadelphia, PA SP Soc Leukocyte Bio DE cytokines; protein kinases; gene regulation; mRNA; cAMP; cGMP ID INTERLEUKIN-8 GENE-EXPRESSION; VASCULAR ENDOTHELIAL-CELLS; MESSENGER-RNA STABILITY; SMOOTH-MUSCLE-CELLS; U937 CELLS; L-ARGININE; ISCHEMIA-REPERFUSION; LEUKOCYTE ADHESION; HUMAN NEUTROPHILS; ALPHA PRODUCTION AB Nitric oxide (NO.) contributes to vascular collapse in septic shock and regulates inflammation. Here, we demonstrate in lipopolysaccharide (LPS)-stimulated human THP-1 cells and monocytes that NO. regulates interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha) by distinct mechanisms. Dibutyryl-cyclic guanosine 5'-monophosphate (cGMP) failed to simulate NO.-induced increases in TNF-alpha or IL-8 production. In contrast, dibutyryl-cyclic adenosine monophosphate blocked NO.-induced production of TNF-alpha (P = 0.009) but not IL-8. NO. increased IL-8 (5.7-fold at 4 h; P = 0.04) and TNF-alpha mRNA levels (2.2-fold at 4 h; P = 0.037). However, nuclear run-on assays demonstrated that IL-8 transcription was slightly decreased by NO. (P=0.08), and TNF-alpha was increased (P = 0.012). Likewise, NO. had no effect on IL-8 promoter activity (P = 0.84) as measured by reporter gene assay. In THP-1 cells and human primary monocytes treated with actinomycin D, NO. had no effect on TNF-alpha mRNA stability (P > 0.3 for both cell types) but significantly stabilized IL-8 mRNA (P = 0.001 for both cell types). Because of its role in mRNA stabilization, the p38 mitogen-activated protein kinase (MAPK) pathway was examined and found to be activated by NO. in LPS-treated THP-1 cells and human monocytes. Further, SB202190, a p38 MAPK inhibitor, was shown to block NO-induced stabilization of IL-8 mRNA (P < 0.02 for both cell types). Thus, NO. regulates IL-8 but not TNF-alpha-post-transcriptionally. IL-8 mRNA stabilization by NO. is independent of cGMP and at least partially dependent on p38 MAPK activation. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Danner, RL (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. EM rdanner@nih.gov NR 69 TC 33 Z9 34 U1 2 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 2004 VL 76 IS 1 BP 278 EP 287 DI 10.1189/jlb.1203653 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 832RA UT WOS:000222283400034 PM 15178710 ER PT J AU Freeman, LA Kennedy, A Wu, J Bark, S Remaley, AT Santamarina-Fojo, S Brewer, HB AF Freeman, LA Kennedy, A Wu, J Bark, S Remaley, AT Santamarina-Fojo, S Brewer, HB TI The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ATP binding cassette transporter; CPF; liver receptor homolog-1; FTF; FXR; SHP; sitosterolemia cholesterol; bile acids ID LIVER-X-RECEPTOR; FETOPROTEIN TRANSCRIPTION FACTOR; BILIARY CHOLESTEROL SECRETION; NEGATIVE FEEDBACK-REGULATION; SMALL HETERODIMER PARTNER; BILE-ACID TRANSPORTER; HUMAN CETP GENE; STEROIDOGENIC FACTOR-1; DIETARY-CHOLESTEROL; HOMOLOG-1 CONTROLS AB The ATP binding cassette (ABC) half-transporters ABCG5 and ABCG8 facilitate biliary and intestinal removal of neutral sterols. Here, we identify a binding site for the orphan nuclear receptor liver receptor homolog-1 (LRH-1) at nt 134-142 of the ABCG5/ABCG8 intergenic region necessary for the activity of both the ABCG5 and ABCG8 promoters. Mutating this LRH-1 binding site reduced promoter activity of the human ABCG5/ABCG8 intergenic region more than 7-fold in HepG2 and Caco2 cells. Electrophoretic mobility shift assays with HepG2 nuclear extracts demonstrated specific binding of LRH-1 to the LRH-1 binding motif in the human ABCG5/ABCG8 intergenic region. LRH-1 overexpression increased promoter activity up to 1.6-fold and 3-fold in Caco2 and 293 cells, respectively. Finally, deoxycholic acid repressed the ABCG5 and ABCG8 promoters, consistent with bile acid regulation via the farnesoid X receptor-small heterodimeric partner-LRH-1 pathway. These results demonstrate that LRH-1 is a positive transcription factor for ABCG5 and ABCG8 and, in conjunction with studies on LRH-1 activation of other promoters, identify LRH-1 as a "master regulator" for genes involved in sterol and bile acid secretion from liver and intestine.-Freeman, L. A., A. Kennedy, J. Wit, S. Bark, A. T. Remaley, S. Santamarina-Fojo, and H. B. Brewer,Jr. The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter. C1 NHLBI, Mol Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Freeman, LA (reprint author), NHLBI, Mol Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM litaf@mail.nih.gov NR 55 TC 53 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 2004 VL 45 IS 7 BP 1197 EP 1206 DI 10.1194/jlr.C400002-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831HV UT WOS:000222186400002 PM 15121760 ER PT J AU Ikewaki, K Cain, W Thomas, F Shamburek, R Zech, LA Usher, D Brewer, HB Rader, DJ AF Ikewaki, K Cain, W Thomas, F Shamburek, R Zech, LA Usher, D Brewer, HB Rader, DJ TI Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoprotem B; apolipoprotcin E; kinetics; lipoprotein (a); stable isotopes ID APOLIPOPROTEIN-E DEFICIENCY; LOW-DENSITY-LIPOPROTEIN; VERY-LOW-DENSITY; TRANSFER PROTEIN-DEFICIENCY; III HYPERLIPOPROTEINEMIA; FAMILIAL HYPERCHOLESTEROLEMIA; MESSENGER-RNA; SECRETION; PLASMA; LP(A) AB The present study was undertaken to elucidate the metabolic basis for the increased remnants and lipoprotein(a) [Lp(a)] and decreased LDL apolipoprotein B (apoB) levels in human apoE deficiency. A primed constant infusion of C-13(6)-phenylalanine was administered to a homozygous apoE-deficient subject. apoB-100 and apoB-48 were isolated, and tracer enrichments were determined by gras chromatography-mass spectrometry, then kinetic paramters were calculated by multicompartmental modeling. In the apoE-deficient subject, fractional catabolic rates (FCRs) of apoB-100 in VLDL and intermediate density lipoprotein and apoB-48 in VLDL were 3 X, 12 X, and 12 x slower than those of controls. On the other hand, the LDL apoB-100 FCR was increased by 2.6 X. The production rate of VLDL apoB-100 was decreased by 45%. In the Lp(a) kinetic study, two types of Lp(a) were isolated from plasma with apoE deficiency: buoyant and normal Lp(a). I-125-buoyant Lp(a) was catabolized at a slower rate in the patient. However, I-125- buoyant Lp(a) was catabolized at twice as fast as I-131-normal Lp(a) in the control subjects. In summary, apoE deficiency results in: 1) a markedly impaired catabolism of VLDL/chylomicron and their remnants due to lack of direct removal and impaired lipolysis; 2) an increased rate of catabolism of LDL apoB-100, likely due to upregulation of LDL receptor activity; 3) reduced VLDL apoB production; and 4) a delayed catabolism of a portion of Lp(a).-Ikewaki, K., W. Cain, E Thomas, R. Shamburek, L. A. Zech, D. Usher, H. B. Brewer, Jr., and D. J. Rader. Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency. C1 NHLBI, Mol Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Delaware, Sch Life & Hlth Sci, Newark, DE 19716 USA. Jikei Univ, Sch Med, Div Cardiol, Dept Internal Med,Minato Ku, Tokyo 1058461, Japan. Univ Penn, Ctr Med, Philadelphia, PA 19104 USA. RP Ikewaki, K (reprint author), NHLBI, Mol Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM kikewaki@jikei.ac.jp NR 51 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 2004 VL 45 IS 7 BP 1302 EP 1311 DI 10.1194/jlr.M400020-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831HV UT WOS:000222186400012 PM 15102883 ER PT J AU Ziehe, A Laskov, P Nolte, G Muller, KR AF Ziehe, A Laskov, P Nolte, G Muller, KR TI A fast algorithm for joint diagonalization with non-orthogonal transformations and its application to blind source separation SO JOURNAL OF MACHINE LEARNING RESEARCH LA English DT Article DE joint diagonalization; common principle component analysis; independent component analysis; blind source separation; nonlinear least squares; Newton method; Levenberg-Marquardt algorithm ID INDEPENDENT COMPONENT ANALYSIS; SIGNALS; MATRICES AB A new efficient algorithm is presented for joint diagonalization of several matrices. The algorithm is based on the Frobenius-norm formulation of the joint diagonalization problem, and addresses diagonalization with a general, non-orthogonal transformation. The iterative scheme of the algorithm is based on a multiplicative update which ensures the invertibility of the diagonalizer. The algorithm's efficiency stems from the special approximation of the cost function resulting in a sparse, block-diagonal Hessian to be used in the computation of the quasi-Newton update step. Extensive numerical simulations illustrate the performance of the algorithm and provide a comparison to other leading diagonalization methods. The results of such comparison demonstrate that the proposed algorithm is a viable alternative to existing state-of-the-art joint diagonalization algorithms. The practical use of our algorithm is shown for blind source separation problems. C1 Fraunhofer FIST IDA, D-12489 Berlin, Germany. NIH, Bethesda, MD 20892 USA. Univ Potsdam, Dept Comp Sci, D-14482 Potsdam, Germany. RP Fraunhofer FIST IDA, Kekulestr 7, D-12489 Berlin, Germany. EM ZIEHE@FIRST.FHG.DE; LASKOV@FIRST.FHG.DE; NOLTEG@NINDS.NIH.GOV; KLAUS@FIRST.FHG.DE RI Muller, Klaus/C-3196-2013 NR 59 TC 113 Z9 126 U1 1 U2 5 PU MICROTOME PUBL PI BROOKLINE PA 31 GIBBS ST, BROOKLINE, MA 02446 USA SN 1532-4435 J9 J MACH LEARN RES JI J. Mach. Learn. Res. PD JUL PY 2004 VL 5 BP 777 EP 800 PG 24 WC Automation & Control Systems; Computer Science, Artificial Intelligence SC Automation & Control Systems; Computer Science GA 026GQ UT WOS:000236327800002 ER PT J AU Landi, MT Goldstein, AM Tsang, S Munroe, D Modi, W Ter-Minassian, M Steighner, R Dean, M Metheny, N Staats, B Agatep, R Hogg, D Calista, D AF Landi, MT Goldstein, AM Tsang, S Munroe, D Modi, W Ter-Minassian, M Steighner, R Dean, M Metheny, N Staats, B Agatep, R Hogg, D Calista, D TI Genetic susceptibility in familial melanoma from northeastern Italy SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MULTIPLE PRIMARY MELANOMAS; CDK4 MUTATION ANALYSIS; PRONE FAMILIES; LINKAGE ANALYSIS; MALIGNANT-MELANOMA; CDKN2A MUTATIONS; GERMLINE MUTATIONS; PANCREATIC-CANCER; PROTEIN INTERACTIONS; HEREDITARY MELANOMA C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Lab Mol Technol, SAIC, NIH,DHHS, Frederick, MD 21701 USA. NCI, Basic Res Program, SAIC, NIH,DHHS, Frederick, MD 21701 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, NIH,DHHS, Gaithersburg, MD USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS Room 7114, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 77 TC 28 Z9 29 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUL PY 2004 VL 41 IS 7 BP 557 EP 566 DI 10.1136/jmg.2003.016907 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 834US UT WOS:000222437000012 PM 15235029 ER PT J AU Fujita, Y Tsuda, Y Li, TY Motoyama, T Takahashi, M Shimizu, Y Yokoi, T Sasaki, Y Ambo, A Kita, A Jinsmaa, Y Bryant, SD Lazarus, LH Okada, Y AF Fujita, Y Tsuda, Y Li, TY Motoyama, T Takahashi, M Shimizu, Y Yokoi, T Sasaki, Y Ambo, A Kita, A Jinsmaa, Y Bryant, SD Lazarus, LH Okada, Y TI Development of potent bifunctional endomorphin-2 analogues with mixed mu-/delta-opioid agonist and delta-opioid antagonist properties SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DMT-TIC PHARMACOPHORE; MOUSE VAS-DEFERENS; HUMAN BRAIN CORTEX; PRO AMIDE BOND; RECEPTOR AGONISTS; MORPHINE-TOLERANCE; OPIATE RECEPTORS; PEPTIDES; ACID; DEPENDENCE AB The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism. C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Kobe, Hyogo 6512180, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan. Dainippon Pharmaceut Co Ltd, Discovery Res Labs, Dept Pharmacol 1, Suita, Osaka 5640053, Japan. NIEHS, Med Chem Grp, LCBRA, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM okada@pharm.kobegakuin.ac.jp NR 56 TC 49 Z9 52 U1 1 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 JUL 1 PY 2004 VL 47 IS 14 BP 3591 EP 3599 DI 10.1021/jm030649p PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 832LU UT WOS:000222269800014 PM 15214786 ER PT J AU Zicha, S Maltsev, VA Nattel, S Sabbah, HN Undrovinas, AI AF Zicha, S Maltsev, VA Nattel, S Sabbah, HN Undrovinas, AI TI Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE heart failure; Na+ channel; beta-subunits; patch-clamp; RT-PCR; Western blot ID ARRHYTHMIA SUPPRESSION TRIAL; ADRENAL CHROMAFFIN CELLS; DEPENDENT SODIUM-CHANNEL; PROTEIN-KINASE-A; DOWN-REGULATION; CANINE MODEL; VENTRICULAR MYOCYTES; AUXILIARY SUBUNIT; BRUGADA-SYNDROME; IONIC MECHANISM AB Clinical and experimental evidence has recently accumulated about the importance of alterations of Na+ channel (NaCh) function and slow myocardial conduction for arrhythmias in infarcted and failing hearts (i.e., heart failure, HF). The present study evaluated the molecular mechanisms of local alterations in the expression of NaCh subunits which underlie Na+ current (I-Na) density decrease in HE HF was induced in five dogs by sequential coronary microembolization and developed approximately 3 months after the last embolization (left ventricle (LV), ejection fraction = 27 +/- 7%). Five normal dogs served as a control group. Ventricular cardiomyocytes were isolated enzymatically from LV mid-myocardium and I-Na was measured by whole-cell patch-clamp. The mRNA encoding the cardiac-specific NaCh alpha-subunit Na(v)1.5, and one of its auxiliary subunits beta1 (NaChbeta1), were analyzed by competitive reverse transcription-polymerase chain reaction. Protein levels of Na(v)1.5, NaChbeta1 and NaChbeta2 were evaluated by western blotting. The maximum density of I-Na/C-m was decreased in HF (n = 5) compared to control hearts (33.2 +/- 4.4 vs. 50.0 +/- 4.9 pA/pF, mean +/- S.E.M., n = 5, P < 0.05). The steady-state inactivation and activation of I-Na remained unchanged in HF compared to control hearts. The levels of mRNA encoding Na(v)1.5, and NaCh beta 1 were unaltered in FH. However, Na(v)1.5 protein expression was reduced about 30% in HF, while NaCh beta 1 and NaCh beta 2 protein were unchanged. We conclude that experimental HF in dogs results in post-transcriptional changes in cardiac NaCh alpha-subunit expression. (C) 2004 Elsevier Ltd. All rights reserved. C1 Henry Ford Hosp, Inst Heart & Vasc, Div Cardiovasc Med, Dept Med, Detroit, MI 48202 USA. Montreal Heart Inst, Dept Med, Montreal, PQ H1T 1C8, Canada. Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. Univ Montreal, Montreal, PQ H1T 1C8, Canada. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H1T 1C8, Canada. NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Undrovinas, AI (reprint author), Henry Ford Hosp, Inst Heart & Vasc, Div Cardiovasc Med, Dept Med, Detroit, MI 48202 USA. EM aundrov1@hfhs.org FU NHLBI NIH HHS [HL-53819, R01 HL074328, HL-49090, R01 HL074328-01] NR 49 TC 32 Z9 33 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 91 EP 100 DI 10.1016/j.yjmcc.2004.04.003 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000012 PM 15242739 ER PT J AU Yamamura, K Steenbergen, C Murphy, E AF Yamamura, K Steenbergen, C Murphy, E TI PKC reduces sarcoplasmic reticulum calcium and induces cardioprotection SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 209 EP 209 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000193 ER PT J AU Pacher, P Bai, P Liaudet, L Mabley, JG Szabo, C AF Pacher, P Bai, P Liaudet, L Mabley, JG Szabo, C TI Doxorubicin-induced cardiac dysfunction: the nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase connection SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 NIAAA, NIH, Bethesda, MD USA. Inotek Pharmaceut, Beverly, MA USA. RI Liaudet, Lucas/E-1322-2017 OI Liaudet, Lucas/0000-0003-2670-4930 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 269 EP 269 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000368 ER PT J AU Pacher, P Benko, R Vaslin, A Mabley, JG Liaudet, L Hasko, G Kollai, M Szabo, C Marton, A AF Pacher, P Benko, R Vaslin, A Mabley, JG Liaudet, L Hasko, G Kollai, M Szabo, C Marton, A TI A novel ultrapotent poly(ADP-ribose) polymerase inhibitor improves cardiac and endothelial dysfunction associated with aging-induced heart failure SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 Inotek Pharmaceut, Beverly, MA USA. NIAAA, NIH, Bethesda, MD USA. RI Liaudet, Lucas/E-1322-2017 OI Liaudet, Lucas/0000-0003-2670-4930 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 269 EP 270 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000370 ER PT J AU Pacher, P Benko, R Vaslin, A Mabley, JG Liaudet, L Hasko, G Kollai, M Szabo, C Marton, A AF Pacher, P Benko, R Vaslin, A Mabley, JG Liaudet, L Hasko, G Kollai, M Szabo, C Marton, A TI A novel ultrapotent poly(ADP-ribose) polymerase inhibitor improves cardiac and endothelial dysfunction associated with aging-induced heart failure SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 NIAAA, NIH, Bethesda, MD USA. Inotek Pharmaceut, Beverly, MA USA. RI Liaudet, Lucas/E-1322-2017 OI Liaudet, Lucas/0000-0003-2670-4930 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 269 EP 269 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000369 ER PT J AU Pacher, P Batkai, S Kunos, G AF Pacher, P Batkai, S Kunos, G TI Blockade of anandamide hydrolysis reverses hypertension through activation of cardiac and vascular CB1 receptors SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 NIAAA, NIH, Bethesda, MD USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 273 EP 273 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000379 ER PT J AU Zhu, WZ Jo, SH Khalid, C Leblais, V Xiao, RP AF Zhu, WZ Jo, SH Khalid, C Leblais, V Xiao, RP TI beta-adrenoceptor subtype signaling SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 NIA, LCS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 314 EP 314 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000505 ER PT J AU Pacher, P AF Pacher, P TI Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase is a promising new approach for the therapy of various forms of heart failure SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 Inotek Pharmaceut, Beverly, MA USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 321 EP 322 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000526 ER PT J AU Lakatta, EG Maltsev, V Vinogradova, T AF Lakatta, EG Maltsev, V Vinogradova, T TI Calcium cycling in the heart is a general mechanism of chronotropy and inotropy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 18th World Congress of the International-Society-for-Heart-Research CY AUG 07-11, 2004 CL Brisbane, AUSTRALIA SP Int Soc Heart Res C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2004 VL 37 IS 1 BP 340 EP 340 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 841XH UT WOS:000222965000580 ER PT J AU Meragelman, KM McKee, TC McMahon, JB AF Meragelman, KM McKee, TC McMahon, JB TI Monanchorin, a bicyclic alkaloid from the sponge Monanchora ungiculata SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID POLYCYCLIC GUANIDINE ALKALOIDS; PTILOMYCALIN-A; NATURAL-PRODUCTS; CRAMBE-CRAMBE; CRAMBESCIDIN-800; ARBUSCULA; BINDING AB Monanchorin, a guanidine alkaloid with an unusual bicyclic skeleton, together with the known pentacyclic alkaloid crambescidin acid have been isolated from the aqueous extract of the sponge Monanchora ungiculata. C1 NCI, Canc Res Ctr, Mol Targets Dev Program, Frederick, MD 21702 USA. RP McKee, TC (reprint author), NCI, Canc Res Ctr, Mol Targets Dev Program, Frederick, MD 21702 USA. EM manuscripts@ncifcrf.gov NR 21 TC 16 Z9 17 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 2004 VL 67 IS 7 BP 1165 EP 1167 DI 10.1021/np030434i PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 841AF UT WOS:000222901000018 PM 15270573 ER PT J AU Tender, GC Butman, JA Oldfield, EH Lonser, RR AF Tender, GC Butman, JA Oldfield, EH Lonser, RR TI Thoracic spinal nerve hemangioblastoma - Case illustration SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE von Hippel-Lindau disease; thoracic spine; spinal nerve; hemangioblastoma ID HIPPEL-LINDAU-DISEASE; SURGICAL-MANAGEMENT; ROOT C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Louisiana State Univ, Dept Neurosurg, New Orleans, LA USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008 NR 5 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD JUL PY 2004 VL 1 IS 1 BP 142 EP 142 DI 10.3171/spi.2004.1.1.0142 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 879JL UT WOS:000225714000024 PM 15291036 ER PT J AU Ringger, NC Tolentino, PJ McKinsey, DM Pike, BR Wang, KKW Hayes, RL AF Ringger, NC Tolentino, PJ McKinsey, DM Pike, BR Wang, KKW Hayes, RL TI Effects of injury severity on regional and temporal mRNA expression levels of calpains and caspases after traumatic brain injury in rats SO JOURNAL OF NEUROTRAUMA LA English DT Article DE apoptosis; injury magnitude; neuronal death; proteases; RT-PCR ID CORTICAL IMPACT INJURY; FOCAL CEREBRAL-ISCHEMIA; NEURONAL CELL-DEATH; SEPTOHIPPOCAMPAL CULTURES; MITOCHONDRIAL DYSFUNCTION; DIFFERENTIAL EXPRESSION; DNA FRAGMENTATION; SPATIAL PROFILE; AXONAL INJURY; HEAD-INJURY AB Despite a preponderance of studies demonstrating gene expression and/or enzymatic activation of calpain and caspase proteases after traumatic brain injury (TBI), no studies have examined the effects of injury magnitude on expression levels of these cell death effectors after TBI. Determination of the degree to which injury severity affects specific expression profiles is critical to understanding the relevant pathways contributing to post-trauma pathology and for developing targeted therapeutics. This investigation tested the hypothesis that different injury magnitudes (1.0, 1.2, and 1.6 mm) cause alterations in the regional and temporal patterns of mRNA expression of calpain-related (calpain-1 and -2, calpastatin) and caspase-related (caspases -3, -8, -9, BID) gene products after cortical impact in rats. Quantitative RT-PCR was used to compare effects of injury severity on mRNA levels in ipsilateral (injured) cortex and hippocampus, 6 h to 5 days post-injury. TBI caused increases in mRNA expression of all proteins examined, with the highest expression detected in the cortex. Generally, injury magnitude and levels of gene expression were positively correlated. High levels of gene induction were observed with BID, caspase-3, and -8, while caspase-9 mRNA had the lowest level of induction. Interestingly, although calpains are activated within minutes of TBI, calpain mRNA expression was highest 72 h to 5 days post-TBI. This study is the first analysis of the regional and temporal expression of calpains and caspases after TBI. These data provide insight into the inter-relationship of these two protease families and on the distinct but overlapping cascades of cell death after TBI. C1 Univ Florida, Eyelyn F & William L McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32611 USA. Univ Florida, Eyelyn F & William L McKnight Brain Inst, Dept Neurosurg, Gainesville, FL 32611 USA. Univ Florida, Eyelyn F & William L McKnight Brain Inst, Dept Psychiat, Gainesville, FL 32611 USA. Univ Florida, Eyelyn F & William L McKnight Brain Inst, Ctr Traumat Brain Injuries, Gainesville, FL 32611 USA. NIGMS, NIH, Bethesda, MD USA. RP Ringger, NC (reprint author), 100 S Newell Dr,L1-100 POB, Gainesville, FL 32610 USA. EM ringger@ufbi.ufl.edu RI Pike, Bruce/K-5562-2014; OI Pike, Bruce/0000-0001-8924-683X; Wang, Kevin/0000-0002-9343-6473 NR 51 TC 20 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2004 VL 21 IS 7 BP 829 EP 841 DI 10.1089/0897715041526177 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 842AE UT WOS:000222973800001 PM 15307896 ER EF