FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Aguero, MF Facchinetti, MM Sheleg, Z Senderowicz, AM AF Aguero, MF Facchinetti, MM Sheleg, Z Senderowicz, AM TI Phenoxodiol, a novel isoflavone, induces G(1) arrest by specific loss in cyclin-dependent kinase 2 activity by p53-independent induction of p21(WAF1/CIP1) SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN CLINICAL-TRIALS; CANCER-CELLS; SOY ISOFLAVONES; CDK INHIBITORS; IN-VITRO; OVARIAN-CANCER; GENISTEIN; APOPTOSIS; FLAVOPIRIDOL AB Phenoxodiol, an isoflavone derivative of genistein with unknown mechanism of action, is currently being evaluated in early human cancer clinical trials. To determine the mechanism of antiproliferative effects of phenoxodiol, we examined its effects in a battery of human cell lines. Although we observed caspase-dependent apoptosis in HN12 cells as early as 24 hours after exposure, clonogenic death occurred only after 48-hour exposure despite caspase blockade by the general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (ZVAD)-fmk. Moreover, clear evidence of cell death as determined by nuclear morphology and plasmatic membrane damage occur despite ZVAD, suggesting that another mechanism besides caspase-dependent apoptosis is required for clonogenic death induced by phenoxodiol. In search for other potential antiproliferative effects, we assessed the effects of phenoxodiol in the cell cycle progression of human carcinoma cell lines. A significant G(1)-S arrest was observed by 12 hours of exposure in HN12 cell lines at concentrations >= 5 mu g/mL. Cell cycle arrest occurred several hours (similar to 12 hours) before induction of apoptosis. Analysis of in vitro purified cyclin-dependent kinase (cdk) activity showed that phenoxodiol did not inhibit cdk activity. In contrast, cellular cdk2 activity obtained from RN12 cell lines exposed to phenoxodiol for 12 hours decreased by 60%, whereas cdk6 activity remained unaltered, suggesting that the loss of cdk2 activity was specific. Loss in cdk2 activity was preceded by the accumulation of the endogenous cdk inhibitor p21(WAF1). To assess the role of p21(WAF1) induction by phenoxodiol, we used HCT116 isogenic cell lines and showed that phenoxodiol induced G, arrest together with p21(WAF1) expression in wild-type clones. In contrast, p21(-/-) variants failed to show G, arrest. Finally, induction of p21 by phenoxodiol is p53 independent, as phenoxodiol induced p21 in HCT116 lacking p53. These data therefore indicate that phenoxodiol promotes G(1)-S arrest by the specific loss in cdk2 activity due to p53-independent p21(WAF1) induction. This novel feature of phenoxodiol may have clinical implications, as the majority of human malignancies have aberrations in cell cycle progression regulation. C1 Natl Inst Dent & Craniofacial Res, Mol Theraoeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Senderowicz, AM (reprint author), Natl Inst Dent & Craniofacial Res, Mol Theraoeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sendero@helix.nih.gov NR 53 TC 51 Z9 54 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2005 VL 65 IS 8 BP 3364 EP 3373 PG 10 WC Oncology SC Oncology GA 916ZF UT WOS:000228424800052 PM 15833870 ER PT J AU Horn, TL Long, L Cwik, MJ Morrissey, RL Kapetanovic, IM McCormick, DL AF Horn, TL Long, L Cwik, MJ Morrissey, RL Kapetanovic, IM McCormick, DL TI Modulation of hepatic and renal drug metabolizing enzyme activities in rats by subchronic administration of farnesol SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 10th Symposium on Integration of Symbolic Computation Systems and Mechanized Reasoning CY JUL 01-05, 2002 CL Marseilles, FRANCE DE farnesol; cytochromes P450 (CYP); metabolism; toxicity; chemoprevention ID DT-DIAPHORASE ACTIVITY; FEMALE RATS; NUCLEAR RECEPTOR; LIVER-MICROSOMES; GROWTH-HORMONE; CYTOCHROME-P-450 ENZYMES; PHENOL SULFOTRANSFERASE; SUBSTRATE-SPECIFICITY; DEPENDENT EXPRESSION; OMEGA-HYDROXYLATION AB Farnesol demonstrates antitumor activity in several animal models for human cancer and was being considered for development as a cancer chemopreventive agent. This study was performer[ to characterize the effects of minimally toxic doses of famesol on the activity of phase I and II drug metabolizing enzymes. CD rats (20/sex/group) received daily gavage exposure to farnesol doses of 0, 500, or 1000 mg/kg/day for 28 days; 10 rats/sex/group were necropsied at the termination of farnesol exposure; remaining animals were necropsied after a 28-day recovery period. No deaths occurred during the study, and farnesol had no significant effects on body weight, food consumption, clinical signs, or hematology/coagulation parameters. Modest but statistically significant alterations in several clinical chemistry parameters were observed at the termination of farnesol exposure; all clinical pathology effects were reversed during the recovery period. At the termination of dosing, the activities of CYPIA, CYP2A1-3, CYP2B1/2, CYP2C11/12, CYP2E1, CYP3A1/2, CYP4A1-3, CYP19, glutathione reductase, NADPH/quinone oxidoreductase and UDP-glucuronosyltransferase were significantly increased in the livers of farnesol-treated rats; farnesol also increased the activity of glutathione S-transferase in the kidney. The effects of farnesol on hepatic and renal enzymes were reversed during the recovery period. At the end of the dosing period, increases in absolute and relative liver and kidney weights were in farnesol-treated rats. These increases may be secondary to induction of drug metabolizing enzymes. since organ weight increases were not associated with histopathologic alterations and were reversed upon discontinuation of farnesol exposure. Administration of farnesol at doses of up to 1000 mg/Kg/day induced reversible increases in the activities ofseveral hepatic and renal drug metabolizing enzymes in rats, while inducing only minimal toxicity. It is concluded that non-toxic or minimally toxic doses of farnesol could alter the metabolism, efficacy, and/or toxicity of drugs with which it is co-administered, (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. Pathol Associates Inc, Chicago, IL 60612 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. EM thorn@iitri.org FU NCI NIH HHS [N01-CN-25012] NR 62 TC 19 Z9 20 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 EI 1872-7786 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD APR 15 PY 2005 VL 152 IS 2-3 BP 79 EP 99 DI 10.1016/j.cbi.2005.02.006 PG 21 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 922PL UT WOS:000228849900002 PM 15840382 ER PT J AU Kelloff, G Hoffman, JM Johnson, B Scher, HI Siegel, BA Cheng, EY Cheson, BD O'Shaughnessy, J Guyton, KZ Mankoff, DA Shankar, L Larson, SM Sigman, CC Schilsky, RL Sullivan, DC AF Kelloff, G Hoffman, JM Johnson, B Scher, HI Siegel, BA Cheng, EY Cheson, BD O'Shaughnessy, J Guyton, KZ Mankoff, DA Shankar, L Larson, SM Sigman, CC Schilsky, RL Sullivan, DC TI Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMA; GROWTH-FACTOR-RECEPTOR; WHOLE-BODY PET; INDEPENDENT PROSTATE-CANCER; METASTATIC BREAST-CANCER; HYPOXIA-INDUCIBLE FACTOR; GASTROINTESTINAL STROMAL TUMORS AB 2- [F-18] Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PET also has significant potential for assessing therapy response. In this regard, it can improve patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile the apy. Moreover, a reduction in the FDG-PETsignal within days or weeks of initiating therapy (e.g., in lymphoma, non - small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now used in drug approvals. These findings suggest that FDGPETcould facilitate drug development an early surrogate of clinical benefit. This article reviews the scientific basis of FIDG-PETand its development and application as a valuable oncology imaging tool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/II trial end point to accelerate evaluation and approval of novel regimens and therapies. C1 NCI, Div Canc Treatment & Diagnost, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mallinckrodt Inst Radiol, Div Nucl Med, St Louis, MO USA. Fairview Univ, Med Ctr, Univ Minnesota & Orthopaed Surg Serv, Dept Orthopaed Surg, Minneapolis, MN USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. CCS Associates, Mountain View, CA USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Univ Chicago, Pritzker Sch Med, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Kelloff, G (reprint author), NCI, Div Canc Treatment & Diagnost, Canc Imaging Program, NIH, EPN 6130 Execut Blvd,Suite 6058, Bethesda, MD 20892 USA. EM kelloffg@mail.nih.gov RI Mankoff, David/F-9576-2010 NR 275 TC 307 Z9 318 U1 6 U2 40 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 APR 15 PY 2005 VL 11 IS 8 BP 2785 EP 2808 DI 10.1158/1078-0432.CCR-04-2626 PG 24 WC Oncology SC Oncology GA 916SM UT WOS:000228406300001 PM 15837727 ER PT J AU Bodaghi, S Yamanegi, K Xiao, SY Da Costa, M Palefsky, JM Zheng, ZM AF Bodaghi, S Yamanegi, K Xiao, SY Da Costa, M Palefsky, JM Zheng, ZM TI Colorectal papillomavirus infection in patients with colorectal cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; SQUAMOUS-CELL CARCINOMA; RISK; ASSOCIATION; AMPLIFICATION; NEOPLASIA; SEQUENCES; GENOTYPES; TYPE-16; LESIONS AB Purpose: Infection with human papillomaviruses (HPV) is associated with the development of cervical cancer, but whether HPVs have a role in colorectal cancer remains controversial. Experimental Designs: To determine the relationship between HPV and colorectal cancer, we did a retrospective, controlled study using tumor and tumor-adjacent colorectal tissues dissected from patients with colorectal cancer, as well as colorectal tissues from control individuals with no cancer. The samples were processed in a blinded fashion for nested PCR and in situ PCR detection of HPV DNAs. The PCR products were gel-purified and sequenced for HPV genotyping. Results: We found that colorectal tissues from 28 of 55 (51%) patients with colorectal cancer were positive for HPV DNA. Colorectal tissues from all 10 control individuals were negative for HPV DNA (P = 0.0034). Of the 107 usable (GAPDH(+)) samples collected as paired colorectal tissues (tumor and tumor-adjacent tissues) from the patients, 38 (36%) had HPV16 (n = 31), HPV18 (n = 5), or HPV45 (n = 2), with HPV DNA in both tumor and tumor-adjacent tissues of 10 paired samples, 13 in only the tumor, and 5 in only tumor-adjacent tissues. In situ PCR detection of the tumor tissues confirmed the presence of HPV DNA in tumor Cells. Conclusion: Our results suggest that colorectal HPV infection is common in patients with colorectal cancer, albeit at a low DNA copy number, with HPV16 being the most prevalent type. HPV infection may play a role in colorectal carcinogenesis. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 10 S255,MSC-1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI Xiao, Shu-Yuan/E-2215-2012 FU NCI NIH HHS [CA8340201, Z01 SC010357-06] NR 30 TC 69 Z9 74 U1 0 U2 5 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 APR 15 PY 2005 VL 11 IS 8 BP 2862 EP 2867 DI 10.1158/1078-0432.CCR-04-1680 PG 6 WC Oncology SC Oncology GA 916SM UT WOS:000228406300007 PM 15837733 ER PT J AU Morse, MA Clay, TM Hobeika, AC Osada, T Khan, S Chui, S Niedzwiecki, D Panicali, D Schlom, J Lyerly, HK AF Morse, MA Clay, TM Hobeika, AC Osada, T Khan, S Chui, S Niedzwiecki, D Panicali, D Schlom, J Lyerly, HK TI Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules SO CLINICAL CANCER RESEARCH LA English DT Article ID T-CELLS; ACTIVE IMMUNOTHERAPY; ENHANCED ACTIVATION; TRIAD; EXPRESSION; IMMATURE; PEPTIDE; VACCINE; VIRUS AB Purpose: To determine the safety and immunologic and clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules and tumor antigen. Experimental Design: In this phase I study, we administered one or two cycles of four triweekly s.c./intradermal injections of ex vivo generated dendritic cells modified with a recombinant fowl-pox vector encoding carcinoembryonic antigen (CEA) and a triad of costimulatory molecules [rF-CEA(6D)-TRICOM]. Controls consisted of immature dendritic cells loaded with tetanus toxoid and a HLA A2-restricted peptide derived from cytomegalovirus pp65 protein. Results:: Fourteen patients (11 with colorectal cancer and 3 with non-small cell lung cancer) were enrolled and 12 completed at least one cycle of immunization. There were no grade 3/4 toxicities directly referable to the immunizations. One patient had a decrease in the CEA level from 46 to 6.8 and a minor regression in adenopathy that occurred several months after completion of the immunizations. Five other patients were stable through at least one cycle of immunization (3 months). Direct analysis of peripheral blood mononuclear cells using the ELI-Spot assay showed an increase in the frequency of CEA-specific T cells in 10 patients (range, 10-541 CEA-specific cells/10(5) peripheral blood mononuclear cells). There was a trend for a greater peak frequency of CEA-specific T cells among those with either a minor response or a stable disease following at least one cycle of therapy. A second cycle was not associated with higher T-cell frequencies. Cytokine flow cytometry showed CEA-specific immune response among both CD4(+) and CD8(+) T cells in all immune responders. Conclusion: This immunization strategy is safe and activates potent CEA-specific immune responses. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Therion Biol, Cambridge, MA USA. NCI, Bethesda, MD 20892 USA. RP Morse, MA (reprint author), Duke Univ, Med Ctr, Box 3233, Durham, NC 27710 USA. EM michael.morse@duke.edu RI Lyerly, Herbert/B-6528-2014 OI Lyerly, Herbert/0000-0002-0063-4770 FU NCI NIH HHS [1-R21-CA94523] NR 24 TC 89 Z9 101 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2005 VL 11 IS 8 BP 3017 EP 3024 DI 10.1158/1078-0432.CCR-04-2172 PG 8 WC Oncology SC Oncology GA 916SM UT WOS:000228406300030 PM 15837756 ER PT J AU Edlin, BR Kresina, TF Raymond, DB Carden, MR Gourevitch, MN Rich, JD Cheever, LW Cargill, VA AF Edlin, BR Kresina, TF Raymond, DB Carden, MR Gourevitch, MN Rich, JD Cheever, LW Cargill, VA TI Overcoming barriers to prevention, care, and treatment of hepatitis C in illicit drug users SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Hepatitis C Virus Infection and Substance Abuse CY NOV 11-13, 2003 CL Washington, DC SP Off AIDS Res, NIAID, Natl Inst Diabetes & Dugest & Kidney Dus, Dept Vet Affairs, Hlth Resources & Serv Adm ID RANDOMIZED CONTROLLED-TRIAL; IMMUNODEFICIENCY-VIRUS-INFECTION; ALPHA-2A PLUS RIBAVIRIN; NEW-YORK-CITY; INTERFERON-ALPHA; SYRINGE EXCHANGE; B-VIRUS; NEEDLE EXCHANGE; METHADONE-MAINTENANCE; INJECTION EQUIPMENT AB Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities. C1 NIH, Off AIDS Res, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 10021 USA. NYU, Sch Med, Div Gen Internal Med, New York, NY USA. Harm Reduct Coalit, New York, NY USA. NIA, Ctr AIDS & Other Med Consequences Drug Abuse, Bethesda, MD 20892 USA. Hlth Resources & Serv Adm, HIV AIDS Bur, Dept Hlth & Human Serv, Washington, DC USA. Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02912 USA. RP Cargill, VA (reprint author), NIH, Off AIDS Res, 2 Ctr Dr,Rm 4E20,Mail Stop 0255, Bethesda, MD 20892 USA. EM vc52x@nih.gov RI Schofield, Joe/M-3516-2013; OI Schofield, Joe/0000-0002-1307-2375; Edlin, Brian/0000-0001-8172-8797 FU NIDA NIH HHS [R01 DA009532, R01 DA013245, R01 DA016159, R01-DA-09523, R01-DA-16159] NR 129 TC 120 Z9 122 U1 9 U2 13 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 APR 15 PY 2005 VL 40 SU 5 BP S276 EP S285 DI 10.1086/427441 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908WM UT WOS:000227820900004 PM 15768335 ER PT J AU Kresina, TF Khalsa, J Cesari, H Francis, H AF Kresina, TF Khalsa, J Cesari, H Francis, H TI Hepatitis C virus infection and substance abuse: Medical management and developing models of integrated care - An introduction SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abus, NIH, Ctr AIDS & Other Med Consequences Drug Abuse, Bethesda, MD 20892 USA. RP Kresina, TF (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abus, NIH, Ctr AIDS & Other Med Consequences Drug Abuse, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM tk13v@nih.gov NR 29 TC 13 Z9 13 U1 2 U2 2 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 APR 15 PY 2005 VL 40 SU 5 BP S259 EP S262 DI 10.1086/427438 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908WM UT WOS:000227820900001 PM 15768332 ER PT J AU Nam, JM Kim, J Lee, S AF Nam, JM Kim, J Lee, S TI Equivalence of two treatments and sample size determination under exponential survival model with censoring SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE censoring; equivalence trial; exponential model; score test; F test; power and sample size ID ESTABLISH EQUIVALENCE; RANDOMIZED TRIAL AB We present the likelihood score and F statistics for ascertaining equivalence of two treatments in survival under an exponential model with independent censoring. We provide explicit formulae for power and sample size requirement for trials using the score and F tests, and compare the score and F tests with the log rank test by Com-Nougue et al. (Statist. Med. 12 (1993) 1353). Simulation results show that empirical powers of the score, F and log rank tests are satisfactorily close to the corresponding asymptotic powers for small-to-moderate sample size. We find these three methods are essentially identical in terms of level and power. However, the score and F methods are very sensitive to departure from the exponential assumption while the log rank test is more robust. The methods are illustrated by application to data from a randomized trial of two treatments for B non-Hodgkin lymphoma. Published by Elsevier B.V. C1 Sejong Univ, Dept Appl Math, Seoul 143747, South Korea. Univ Suwon, Dept Appl Stat, Gyeonggi Do 445743, South Korea. NCI, Dept Hlth & Human Serv, Biostat Branch, DCEG,NIH, Rockville, MD 20852 USA. RP Lee, S (reprint author), Sejong Univ, Dept Appl Math, 98 Gunja Dong, Seoul 143747, South Korea. EM namj@mail.nih.gov; jinhkim@suwon.ac.kr; leesy@sejong.ac.kr NR 11 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD APR 15 PY 2005 VL 49 IS 1 BP 217 EP 226 DI 10.1016/j.csda.2004.05.009 PG 10 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 903YL UT WOS:000227461500015 ER PT J AU Lagziel, A Ahmed, ZM Schultz, JM Morell, RJ Belyantseva, IA Friedman, TB AF Lagziel, A Ahmed, ZM Schultz, JM Morell, RJ Belyantseva, IA Friedman, TB TI Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE cadherin 23; stereocilia; kinocilium; centrosomes; Reissner's membrane; Usher syndrome; deafness; Waltzer mice; adhesion proteins ID SYNDROME TYPE 1D; USHER-SYNDROME; HEARING-LOSS; TIP LINKS; VESTIBULAR ORGANS; CALCIUM CHELATION; KINOCILIAL LINKS; MUTANT ALLELES; STEREOCILIA; CDH23 AB Mutant alleles of the gene encoding cadherin 23 are associated with Usher syndrome type 1 (USH1D), isolated deafness (DFNB12) in humans, and deafness and circling behavior in waltzer (v) mice. Stereocilia of waltzer mice are disorganized and the kinocilia misplaced, indicating the importance of cadherin 23 for hair bundle development. Cadherin 23 was localized to developing stereocilia and proposed as a component of the tip link. We show that, during development of the inner ear, cadherin 23 is initially detected in centrosomes at E14.5, then along the length of emerging stereocilia, and later becomes concentrated at and subsequently disappears from the tops of stereocilia. In mature vestibular hair bundles, cadherin 23 is present along the kinocilium and in the region of stercocilia-kinocilium bonds, a pattern conserved in mammals, chicks, and frogs. Cadherin 23 is also present in Reissner's membrane (RM) throughout development. In homozygous v(6J) mice, a reported null allele, cadherin 23 was absent from stereocilia, but present in kinocilia, RM, and centrosomes. We reconciled these results by identifying two novel isoforms of Cdh23 unaffected in sequence and expression by the v(6J) allele. Our results suggest that Cdh23 participation in stereocilia links may be restricted to developing hair bundles. Published by Elsevier Inc. C1 Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [DC000048-06] NR 54 TC 100 Z9 103 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2005 VL 280 IS 2 BP 295 EP 306 DI 10.1016/j.ydbio.2005.01.015 PG 12 WC Developmental Biology SC Developmental Biology GA 916IC UT WOS:000228377600004 PM 15882574 ER PT J AU Broniec, A Pawlak, A Sarna, T Wielgus, A Roberts, JE Land, EJ Truscott, TG Edge, R Navaratnam, S AF Broniec, A Pawlak, A Sarna, T Wielgus, A Roberts, JE Land, EJ Truscott, TG Edge, R Navaratnam, S TI Spectroscopic properties and reactivity of free radical forms of A2E SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE A2E; A2E radicals; retinal lipofuscin; retinal pigment epithelium; phototoxicity; oxidative stress; pulse radiolysis; free radicals ID HUMAN RETINAL LIPOFUSCIN; PIGMENT EPITHELIAL-CELLS; ELECTRON REDUCTION POTENTIALS; SINGLET-OXYGEN GENERATION; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; HUMAN RPE; FUNDUS FLAVIMACULATUS; STARGARDTS-DISEASE; PULSE-RADIOLYSIS AB A pyridinium bisretinoid (A2E) is the only identified blue-absorbing chromophore of retinal lipofuscin that has been linked to its aerobic photoreactivity and phototoxicity. Pulse radiolysis has been used to Study both the one-electron oxidation and the one-electron reduction of A2E in aqueous micellar solutions. The reduction to the semireduced A2E (lambda(max) broad and between 500 and 540 nm) was achieved with formate radicals and the subsequent decay of A2E(.) was slow (over hundreds of milliseconds) via complex kinetics. The long lifetime of the A2E(.) should facilitate its reactions with other biomolecules. For example, with oxygen, the A2E(.) produced the superoxide radical anion with a rate constant of 3 X 10(8) M-1 s(-1). The A2E was also reduced by the NAD radical, the corresponding rate constant being 2.3 X 10(8) M-1 s(-1). Other experiments showed that the one-electron reduction potential of A2E lies in the range -640 to -940 mV. The semioxidized form of A2E (lambda(max) 590 nm) was formed via oxidation with the Br-2(.-) radical and had a much shorter lifetime than the semireduced form. With strongly oxidizing peroxyl radicals (CCl3O2.) our kinetic data suggest the formation of a radical adduct followed by dissociation to the semioxidized A2E. With milder oxidizing peroxyl radicals such as that from methanol, Our results were inconclusive. In benzene we observed an efficient oxidation of zeaxanthin to its radical cation by the A2E radical cation; this may be relevant to a detrimental effect of A2E in vision. (c) 2005 Elsevier Inc. All rights reserved. C1 Jagiellonian Univ, Fac Biotechnol, Dept Biophys, PL-30387 Krakow, Poland. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Fordham Univ, Dept Nat Sci, Bronx, NY 10458 USA. Univ Keele, Sch Chem & Phys, Keele, Staffs, England. Daresbury Lab, Free Radical Res Facil, Warrington, Cheshire, England. NE Wales Inst, Wrexham, Wales. Univ Salford, Biosci Res Inst, Salford M5 4WT, Lancs, England. RP Sarna, T (reprint author), Jagiellonian Univ, Fac Biotechnol, Dept Biophys, Gronostajowa 7, PL-30387 Krakow, Poland. EM tsarna@mol.uj.edu.pl RI Pawlak, Anna/A-7904-2016 NR 65 TC 10 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2005 VL 38 IS 8 BP 1037 EP 1046 DI 10.1016/j.freeradbiomed.2004.12.023 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 912DQ UT WOS:000228057700007 PM 15780762 ER PT J AU Lehti, K Allen, E Birkedal-Hansen, H Holmbeck, K Miyake, Y Chun, TH Weiss, SJ AF Lehti, K Allen, E Birkedal-Hansen, H Holmbeck, K Miyake, Y Chun, TH Weiss, SJ TI An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature SO GENES & DEVELOPMENT LA English DT Article DE PDGF-B; PDGF receptor; MT1-MMP; pericytes; vascular smooth muscle cells; mural cells ID MEMBRANE-TYPE-1 MATRIX-METALLOPROTEINASE; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; PDGF-B; SIGNALING PATHWAYS; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; MOLECULAR REGULATION; MURINE FIBROBLASTS; ANALYSIS REVEALS AB Platelet-derived growth factor (PDGF)/PDGFR beta-dependent investment of the vascular endothelium by mural cells (i.e., pericytes and vascular smooth muscle cells; VSMCs) is critical for normal vessel wall structure and function. In the developing vasculature, mural cell recruitment is associated with the functionally undefined expression of the type I transmembrane proteinase, membrane-type 1 matrix metalloproteinase (MT1-MMP). In this paper, using VSMCs and tissues isolated from gene-targeted mice, we identify MT1-MMP as a PDGF-B-selective regulator of PDGFR beta-dependent signal transduction and mural cell function. In VSMCs, catalytically active MT1-MMP associates with PDGFR beta in membrane complexes that support the efficient induction of mitogenic signaling by PDGF-B in a matrix metalloproteinase inhibitor-sensitive fashion. In contrast, MT1-MMP-deficient VSMCs display PDGF-B-selective defects in chemotaxis and proliferation as well as ERK1/2 and Akt activation that can be rescued in tandem fashion following retroviral transduction with the wild-type protease. Consistent with these in vitro findings, MT1-MMP-deficient brain tissues display a marked reduction in mural cell density as well as abnormal vessel wall morphology similar to that reported in mice expressing PDGF-B or PDGFR beta hypomorphic alleles. Together, these data identify MT1-MMP as a novel proteolytic modifier of PDGF-B/PDGFR beta signal transduction that cooperatively regulates vessel wall architecture in vivo. C1 Univ Michigan, Dept Internal Med, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Weiss, SJ (reprint author), Univ Michigan, Dept Internal Med, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. EM sjweiss@umich.edu OI Lehti, Kaisa/0000-0001-9110-8719 FU NCI NIH HHS [R01 CA071699, R01 CA71699] NR 66 TC 90 Z9 94 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2005 VL 19 IS 8 BP 979 EP 991 DI 10.1101/gad.1294605 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 917LM UT WOS:000228463300010 PM 15805464 ER PT J AU Maragakis, NJ Rao, MS Llado, J Wong, V Xue, HP Pardo, A Herring, J Kerr, D Coccia, C Rothstein, JD AF Maragakis, NJ Rao, MS Llado, J Wong, V Xue, HP Pardo, A Herring, J Kerr, D Coccia, C Rothstein, JD TI Glial restricted precursors protect against chronic glutamate neurotoxicity of motor neurons in vitro SO GLIA LA English DT Article DE astrocyte; motor neuron; glutamate transporter ID AMYOTROPHIC-LATERAL-SCLEROSIS; NEURAL STEM-CELLS; SPINAL-CORD; NEUROTROPHIC FACTORS; TRANSPORTER EAAT2; NERVOUS-SYSTEM; EXPRESSION; MODEL; BRAIN; ALS AB We have examined the expression of glutamate transporters in primary and immortalized glial precursors (GRIPs). We subsequently transduced these cells with the GLT1 glutamate transporter and examined the ability of these cells to protect motor neurons in an organotypic spinal cord culture. We show that glial restricted precursors and GRIP-derived astrocytes predominantly express glutamate transporters GLAST and GLT1. Oligodendrocyte differentiation of GRIPs results in downregulation of all glutamate transporter subtypes. Having identified these precursor cells as potential vectors for delivering glutamate transporters to regions of interest, we engineered a line of GRIPS that overexpress the glutamate transporter GLT1. These cells (G3 cells) have a nearly fourfold increase in glutamate transporter expression and at least a twofold increase in the V-max for glutamate transport. To assess whether G3 seeding can protect motor neurons from chronic glutamate neurotoxicity, G3s were seeded onto rat organotypic spinal cord cultures. These cultures have previously been used extensively to understand pathways involved in chronic glutamate neurotoxicity of motor neurons. After G3 seeding, cells integrated into the culture slice and resulted in levels of glutamate transport sufficient to enhance total glutamate uptake. To test whether neuroprotection was related to glutamate transporter overexpression, we isolated GRIPS from the GLT1 null mouse to serve as controls. The seeding of G3s resulted in a reduction of motor neuron cell death. Hence, we believe that these cells may potentially play a role in cell-based neuroprotection from glutamate excitotoxicity. 2005 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. NIA, Baltimore, MD 21224 USA. Neuronyx, Malvern, PA USA. RP Rothstein, JD (reprint author), Johns Hopkins Univ, Dept Neurol, Meyer 6-109,600 N Wolfe St, Baltimore, MD 21287 USA. EM jrothste@jhmi.edu RI KERR, Douglas /B-9270-2008; rothstein, jeffrey/C-9470-2013; OI Pardo, Andrea/0000-0001-7767-8539 FU NINDS NIH HHS [NS02131, NS33598] NR 53 TC 30 Z9 30 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD APR 15 PY 2005 VL 50 IS 2 BP 145 EP 159 DI 10.1002/glia.20161 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 915QC UT WOS:000228317900005 PM 15657939 ER PT J AU Maggio, MC Ferrucci, L Basaria, S Ceda, GP Ceresini, G Valenti, G AF Maggio, MC Ferrucci, L Basaria, S Ceda, GP Ceresini, G Valenti, G TI The role of soluble interleukin-6 receptor in inflammatory diseases SO IMMUNOLOGY LETTERS LA English DT Letter ID RHEUMATOID-ARTHRITIS; IL-6 RECEPTOR; COMPLEX C1 NIA, Clin Res Branch, Longitudinal Studies Sect, Harbor Hosp NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Endocrinol, Dept Med, Baltimore, MD USA. Univ Parma, Sect Geriat, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. RP Ferrucci, L (reprint author), NIA, Clin Res Branch, Longitudinal Studies Sect, Harbor Hosp NIH, 3001 S Hanover St, Baltimore, MD USA. EM ferruccilu@grc.nia.nih.gov OI Ceda, Gian Paolo/0000-0002-9648-8295 NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD APR 15 PY 2005 VL 98 IS 1 BP 171 EP 171 DI 10.1016/j.imlet.2004.10.024 PG 1 WC Immunology SC Immunology GA 916TS UT WOS:000228409700022 PM 15790523 ER PT J AU Duggal, P Winkler, CA An, P Yu, XF Farzadegan, H O'Brien, SJ Beaty, TH Vlahov, D AF Duggal, P Winkler, CA An, P Yu, XF Farzadegan, H O'Brien, SJ Beaty, TH Vlahov, D TI The effect of RANTES chemokine genetic variants on early HIV-1 plasma RNA among African American injection drug users SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE chemokines; RANTES; HIV-1 plasma RNA; HIV ID DISEASE PROGRESSION; VIRAL LOAD; CCR5 PROMOTER; ANTIRETROVIRAL THERAPY; CD4(+) LYMPHOCYTES; TYPE-1 INFECTION; AIDS PROGRESSION; DELETION ALLELE; BETA-CHEMOKINES; SEX-DIFFERENCES AB HIV-1 plasma RNA is a prognostic indicator of HIV-1, and increased levels of HIV-1 plasma RNA are associated with rapid progression to AIDS. Because chemokines and chemokine receptors are involved in the binding and entry of HIV-1, possible effects of host genetics on viral RNA levels should be visible in early infection. HIV-1 plasma RNA was measured within 2 years of seroconversion in 198 seroincident injection drug users followed in the AIDS Link to Intravenous Experience cohort. Genetic variants were identified in the chemokine receptors (CCR2, CCR5, and CCR5 promoter) and the chemokine RANTES using TaqMan and restriction fragment length polymorphism assays. Linear regression of RANTES haplotypes on early HIV-1 plasma RNA identified individuals homozygous for the RANTES RI haplotype as having a lower viral load by almost one-half log(10) unit compared with those bearing non-RANTES R1 haplotypes (-0.43, 95% confidence interval: -0.74, -0.12). Genetic variants in RANTES may downregulate RANTES gene expression and increase early HIV-1 plasma RNA. Because RANTES is a critical chemokine and competitively inhibits HIV-1 by binding to its receptor CCR5, treatment to enhance RANTES expression may assist in delaying the progression of AIDS by decreasing the initial viral load. C1 New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY 10029 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NCI, SAIC, Basic Res Program, Frederick, MD 21701 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Duggal, P (reprint author), New York Acad Med, Ctr Urban Epidemiol Studies, 1216 5th Ave, New York, NY 10029 USA. EM dvlahov@nyam.org FU NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [DA 04334] NR 35 TC 15 Z9 17 U1 0 U2 1 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 APR 15 PY 2005 VL 38 IS 5 BP 584 EP 589 DI 10.1097/01.qai.0000134741.49208.03 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 911QB UT WOS:000228018200012 PM 15793370 ER PT J AU Li, XH Zhang, R Luo, DH Park, SJ Wang, Q Kim, Y Min, W AF Li, XH Zhang, R Luo, DH Park, SJ Wang, Q Kim, Y Min, W TI Tumor necrosis factor alpha-induced desumoylation and cytoplasmic translocation of homeodomain-interacting protein kinase 1 are critical for apoptosis signal-regulating kinase 1-JNK/p38 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED ASK1 ACTIVATION; CELL-DEATH; ASK1-MEDIATED APOPTOSIS; SERINE/THREONINE KINASE; INDEPENDENT MANNER; PROTEIN KINASE-2; INHIBITOR 14-3-3; MAP KINASES; STRESS; SUMO-1 AB The apoptosis signal-regulating kinase 1 (ASK1)-JNK/ p38 signaling pathway is pivotal component in cell apoptosis and can be activated by a variety of death stimuli including tumor necrosis factor (TNF) alpha and oxidative stress ( reactive oxygen species). However, the mechanism for ASK1 activation is not fully understood. We have recently identified ASK1-interacting protein (AIP1) as novel signal transducer in TNF alpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3. In the present study, we employed yeast two-hybrid system using the N-terminal domain of AIP1 as bait and identified homeodomain-interacting protein kinase 1 (HIPK1) as an AIP1-associated protein. Interestingly, we showed that TNF alpha induced HIPK1 desumoylation concomitant with a translocation from nucleus to cytoplasm at 15 min followed by a return to nucleus by 60 min. The kinetics of HIPK1 translocation correlates with those of stress-induced ASK1-JNK/P38 activation. A specific JNK inhibitor blocked the reverse but not the initial translocation of HIPK1, suggesting that the initial translocation is an upstream event of ASK1-JNK/p38 signaling and JNK activation regulates the reverse translocation as a feedback mechanism. Consistently, expression of HIPK1 increased, whereas expression of a kinase-inactive form (HIPK1-D315N) or small interference RNA of HIPK1 decreased stress-induced ASK1-JNK/P38 activation without effects on IKK-NF-kappa B signaling. Moreover, a sumoylation-defective mutant of HIPK1 (KR5) localizes to the cytoplasm and is constitutively active in ASK1-JNK/P38 activation. Furthermore, HIPK1-KR5 induces dissociation of ASK1 from its inhibitors 14-3-3 and thioredoxin and synergizes with AIP1 to induce ASK1 activation. Our study suggests that TNF alpha-induced desumoylation and cytoplasmic translocation of HIPK1 are critical in TNF alpha-induced ASK1-JNK/p38 activation. C1 Yale Univ, Sch Med, Dept Pathol,Boyer Ctr Mol Med, Interdept Program Vasc Biol & Transplantat, New Haven, CT 06510 USA. NHLBI, Lab Res Program, NIH, Bethesda, MD 20892 USA. Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Guangzhou 510080, Peoples R China. RP Min, W (reprint author), Yale Univ, Sch Med, Dept Pathol,Boyer Ctr Mol Med, Interdept Program Vasc Biol & Transplantat, BCMM 454,295 Congress Ave, New Haven, CT 06510 USA. EM wang.min@yale.edu FU NHLBI NIH HHS [HL-65978] NR 44 TC 50 Z9 54 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 APR 15 PY 2005 VL 280 IS 15 BP 15061 EP 15070 DI 10.1074/jbc.M414262200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914OI UT WOS:000228236800089 PM 15701637 ER PT J AU Kovacs, M Wang, F Sellers, JR AF Kovacs, M Wang, F Sellers, JR TI Mechanism of action of myosin X, a membrane-associated molecular motor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; RABBIT SKELETAL-MUSCLE; DICTYOSTELIUM MYOSIN; KINETIC MECHANISM; NUCLEOTIDE-BINDING; SINGLE TRYPTOPHAN; FLUORESCENT-PROBE; HEAVY-MEROMYOSIN; V PROCESSIVITY; SMOOTH-MUSCLE AB We have performed a detailed biochemical kinetic and spectroscopic study on a recombinant myosin X head construct to establish a quantitative model of the enzymatic mechanism of this membrane-bound myosin. Our model shows that during steady-state ATP hydrolysis, myosin X exhibits a duty ratio (i.e. the fraction of the cycle time spent strongly bound to actin) of around 16%, but most of the remaining myosin heads are also actin-attached even at moderate actin concentrations in the so-called "weak" actin-binding states. Contrary to the high duty ratio motors myosin V and VI, the ADP release rate constant from actomyosin X is around five times greater than the maximal steady-state ATPase activity, and the kinetic partitioning between different weak actin-binding states is a major contributor to the rate limitation of the enzymatic cycle. Two different ADP states of myosin X are populated in the absence of actin, one of which shows very similar kinetic properties to actomyosin center dot ADP. The nucleotide-free complex of myosin X with actin shows unique spectral and biochemical characteristics, indicating a special mode of actomyosin interaction. C1 NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Kovacs, M (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM kovacsm@mail.nih.gov RI Kovacs, Mihaly/A-6841-2011 NR 50 TC 32 Z9 33 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 APR 15 PY 2005 VL 280 IS 15 BP 15071 EP 15083 DI 10.1074/jbc.M500616200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914OI UT WOS:000228236800090 PM 15705568 ER PT J AU Richard, JP Melikov, K Brooks, H Prevot, P Lebleu, B Chernomordik, LV AF Richard, JP Melikov, K Brooks, H Prevot, P Lebleu, B Chernomordik, LV TI Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN TRANSDUCTION DOMAINS; ARGININE-RICH PEPTIDES; HIV-1 TAT; PENETRATING PEPTIDES; FUSION PROTEINS; IN-VIVO; ANTENNAPEDIA HOMEODOMAIN; CAVEOLAR ENDOCYTOSIS; CRE RECOMBINASE; LIPID-BILAYERS AB Delivery of macromolecules mediated by protein transduction domains (PTDs) attracts a lot of interest due to its therapeutic and biotechnological potential. A major re-evaluation of the mechanism of PTD-mediated internalization and the role of endocytosis in this mechanism has been recently initiated. Here, we demonstrate that the entry of TAT peptide ( one of the most widely used PTDs) into different primary cells is ATP- and temperature-dependent, indicating the involvement of endocytosis. Specific inhibitors of clathrin-dependent endocytosis partially inhibit TAT peptide uptake, implicating this pathway in TAT peptide entry. In contrast, the caveolin-dependent pathway is not essential for the uptake of unconjugated TAT peptide as evidenced by the efficient internalization of TAT in the presence of the known inhibitors of raft/caveolin-dependent pathway and for cells lacking or deficient in caveolin-1 expression. Whereas a significant part of TAT peptide uptake involves heparan sulfate receptors, efficient internalization of peptide is observed even in their absence, indicating the involvement of other receptors. Our results suggest that unconjugated peptide might follow endocytic pathways different from those utilized by TAT peptide conjugated to different proteins. C1 NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Univ Montpellier 2, CNRS, UMR 5124, F-34095 Montpellier, France. RP Melikov, K (reprint author), NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, 10 Ctr Dr,Bldg 10,Rm 10D05, Bethesda, MD 20892 USA. EM melikovk@mail.nih.gov RI Melikov, Kamran/A-6604-2009 NR 40 TC 359 Z9 377 U1 3 U2 35 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 2005 VL 280 IS 15 BP 15300 EP 15306 DI 10.1074/jbc.M401604200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914OI UT WOS:000228236800115 PM 15687490 ER PT J AU Miltylk, W Surazynski, A Kasprzak, KS Fivash, MJ Buzard, GS Phang, JM AF Miltylk, W Surazynski, A Kasprzak, KS Fivash, MJ Buzard, GS Phang, JM TI Inhibition of prolidase activity by nickel causes decreased growth of proline auxotrophic CHO cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE prolidase; nickel; CHO cells; proline ID HAMSTER OVARY CELLS; OXIDATIVE DAMAGE; IMINODIPEPTIDURIA; CARCINOGENESIS; BIOSYNTHESIS; FIBROBLASTS; DEFICIENCY; DIPEPTIDES; EXPRESSION; APOPTOSIS AB Occupational exposure to nickel has been epidemiologically linked to increased cancer risk in the respiratory tract. Nickel-induced cell transformation is associated with both genotoxic and epigenetic mechanisms that are poorly understood. Prolidase [E.C.3.4.13.9] is a cytosolic Mn(II)-activated metalloproteinase that specifically hydrolyzes imidodipeptides with C-terminal proline or hydroxyproline and plays an important role in the recycling of proline for protein synthesis and cell growth. Prolidase also provides free proline as substrate for proline oxidase, whose gene is activated by p53 during apoptosis. The inhibition of prolidase activity by nickel has not yet been studied. We first showed that Ni(II) chloride specifically inhibited prolidase activity in CHO-K1 cells in situ. This interpretation was possible because CHO-K1 cells are proline auxotrophs requiring added free proline or proline released from added Gly-Pro by prolidase. In a dose-dependent fashion, Ni(II) inhibited growth on Gly-Pro but did not inhibit growth on proline, thereby showing inhibition of prolidase in situ in the absence of nonspecific toxicity. Studies using cell-free extracts showed that Ni(II) inhibited prolidase activity when present during prolidase activation with Mn(II) or during incubation with Gly-Pro. In kinetic studies, we found that Ni(II) inhibition of prolidase varied with respect to Mn(II) concentration. Analysis of these data suggested that increasing concentrations of Mn(II) stabilized the enzyme protein against Ni(II) inhibition. Because prolidase is an important enzyme in collagen metabolism, inhibition of the enzyme activity by nickel could alter the metabolism of collagen and other matrix proteins, and thereby alter cell-matrix and cell-cell interactions involved in gene expression, genomic stability, cellular differentiation, and cell proliferation. Published 2005 Wiley-Liss, lnc. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Metab Sect, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Data Management Serv Inc, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Bldg 538,Room 115, Frederick, MD 21702 USA. EM phang@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400]; PHS HHS [12401] NR 32 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2005 VL 94 IS 6 BP 1210 EP 1217 DI 10.1002/jcb.20384 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 912NW UT WOS:000228087000013 PM 15696600 ER PT J AU Maasho, K Opoku-Anane, J Marusina, AI Coligan, JE Borrego, F AF Maasho, K Opoku-Anane, J Marusina, AI Coligan, JE Borrego, F TI Cutting edge: NKG2D is a costimulatory receptor for human naive CD8(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID I-RELATED CHAIN; C VIRUS-INFECTION; NK CELLS; DENDRITIC CELLS; CELIAC-DISEASE; MIC LIGANDS; EXPRESSION; ACTIVATION; IMMUNORECEPTOR; DIFFERENTIATION AB In humans, all alpha beta CD8(+) T cells express NKG2D, but in mouse, it is only expressed by activated and memory CD8(+) Tcells. We purified human naive CD8+ Tcells to show that NKG2D serves as a costimulatory receptor for TCR induced Ca2+ mobilization and proliferation. The resulting effector cells are skewed toward a type 1 phenotype and produce high levels of IFN-gamma and TNF-alpha NKG2D ligands, MHC class I chain-related (MIC)A, MICB, and UL16-binding proteins are expressed on the proliferating cells and NKG2D is down-regulated, The addition of the homeostatic cytokines IL-7 and IL-15 to the culture medium not only enhances proliferation but also counteracts the down-regulation of NKG2D, more so than the addition of IL-2. These results indicate that NKG2D can regulate the priming of human naive CD8+ Tcells, which may provide an alternative mechanism for potentiating and channeling the immune response. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2 Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM Fborrego@niaid.nih.gov NR 28 TC 103 Z9 107 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4480 EP 4484 PG 5 WC Immunology SC Immunology GA 914NN UT WOS:000228234600008 PM 15814668 ER PT J AU Han, GC Li, Y Wang, JN Wang, RX Chen, GJ Song, L Xu, RN Yu, M Wu, XB Qian, JH Shen, BF AF Han, GC Li, Y Wang, JN Wang, RX Chen, GJ Song, L Xu, RN Yu, M Wu, XB Qian, JH Shen, BF TI Active tolerance induction and prevention of autoimmune diabetes by immunogene therapy using recombinant adenoassociated virus expressing glutamic acid decarboxylase 65 peptide GAD(500-585) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; GENE-TRANSFER; FACTOR-IX; NOD MICE; SKELETAL-MUSCLE; HEMOPHILIA-B; AAV VECTORS; TGF-BETA; INSULIN; RESPONSES AB Tolerance induction of autoreactive T cells against pancreatic 0 cell-specific autoantigens such as glutamic acid decarboxylase 65 (GAD65) and insulin has been attempted as a method to prevent autoimmune diabetes. In this study, we investigate whether adenoassociated virus (AAV) gene delivery of multiple immunodominant epitopes expressing GAD(500-585) could induce potent immune tolerance and persistently suppress autoimmune diabetes in NOD mice. A single muscle injection of 7-wk-old female NOD mice with rAAV/GAD(500-585) (3 X 10(11) IU/mouse) quantitatively reduced pancreatic insulitis and efficiently prevented the development of overt type I diabetes. This prevention was marked by the inactivation of GAD(500-585)-responsive T lymphocytes, the enhanced GAD(500-585)-specific Th2 response (characterized by increased IL-4, IL-10 production, and decreased IFN-gamma production; especially elevated anti-GAD(500-585) IgG1 titer; and relatively unchanged anti- GAD(500 -585) IgG2b titer), the increased secretion of TGF-beta and the production of protective regulatory cells. Our studies also revealed that peptides 509-528, 570-585, and 554-546 in the region of GAD(500-585) played important roles in rAAV/GAD(500-585) inummization-induced immune tolerance. These data indicate that using AAV, a vector with advantage for therapeutic gene delivery, to transfer autoantigen peptide GAD(500-585), can induce immunological tolerance through active suppression of effector T cells and prevent type I diabetes in NOD mice. C1 Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. Natl Lab Mol Virol & Genet Engn, Beijing, Peoples R China. NCI, Vaccine Branch, Bethesda, MD 20889 USA. RP Shen, BF (reprint author), Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd,27, Beijing 100850, Peoples R China. EM shenbf@mx.cei.gov.cn RI e-, a/F-9947-2012 NR 51 TC 37 Z9 39 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4516 EP 4524 PG 9 WC Immunology SC Immunology GA 914NN UT WOS:000228234600012 PM 15814672 ER PT J AU Vacchio, MS Hodes, RJ AF Vacchio, MS Hodes, RJ TI Fetal expression of Fas ligand is necessary and sufficient for induction of CD8 T cell tolerance to the fetal antigen H-Y during pregnancy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID (FASL)-INDUCED APOPTOSIS; DIFFERENTIATION; LYMPHOCYTES; ALLOGRAFT AB Interaction of Fas with Fas ligand (FasL) is known to play a role in peripheral tolerance mediated by clonal deletion of Ag-specific T cells. We have assessed the requirement for Fas/FasL interactions during induction of tolerance to the fetus. Using H-Y-specific TCR transgenic mice, we have previously demonstrated that exposure of maternal T cells to H-Y expressed by male fetuses results in deletion of 50% of H-Y-specific maternal T cells. The remaining H-Y-specific T cells were hyporesponsive to H-Y as assayed by decreased proliferative ability and CTL activity. To determine whether Fas/FasL interactions contribute to induction of maternal T cell tolerance, responsiveness to fetal H-Y was assessed in H-Y-specific TCR transgenic pregnant females that were deficient in functional Fas or FasL. Surprisingly, both deletion and nondeletion components of tolerance were abrogated in TCR transgenic H-Y-specific lpr (Fas-deficient) or gld (FasL-deficient) pregnant females. Experiments further revealed that expression of FasL by the fetus, but not by the mother, is necessary and sufficient for both components of maternal T cell tolerance to fetal Ags. Fas interaction with fetal FasL is thus critical for both deletion and hyporesponsiveness of H-Y-reactive CD8(+) T cells during pregnancy. The Journal of Immunology, 2005, 174: 4657-4661. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Vacchio, MS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM vacchio@nih.gov NR 21 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4657 EP 4661 PG 5 WC Immunology SC Immunology GA 914NN UT WOS:000228234600029 PM 15814689 ER PT J AU Sun, Y Schmitz, JE Acierno, PM Santra, S Subbramanian, RA Barouch, DH Gorgone, DA Lifton, MA Beaudry, KR Manson, K Philippon, V Xu, L Maecker, HT Mascola, JR Panicali, D Nabel, GJ Letvin, NL AF Sun, Y Schmitz, JE Acierno, PM Santra, S Subbramanian, RA Barouch, DH Gorgone, DA Lifton, MA Beaudry, KR Manson, K Philippon, V Xu, L Maecker, HT Mascola, JR Panicali, D Nabel, GJ Letvin, NL TI Dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced IL-2 expression by central memory CD4+ T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIV-1 INFECTION; CELL RESPONSES; CD8-T-CELL MEMORY; RHESUS MACAQUES; CD4-T-CELL HELP; SUBSETS; CD8; DIFFERENTIATION; INTERLEUKIN-2; VACCINATION AB Production of IL-2 and IFN-gamma by CD4(+) T lymphocytes is important for the maintenance of a functional immune system in infected individuals. In the present study, we assessed the cytokine production profiles of functionally distinct subsets of CD4(+) T lymphocytes in rhesus monkeys infected with pathogenic or attenuated SIV/simian human immunodeficiency virus (SHIV) isolates, and these responses were compared with those in vaccinated monkeys that were protected from immunodeficiency following pathogenic SHIV challenge. We observed that preserved central memory CD4(+) T lymphocyte production of SIV/SHIV-induced IL-2 was associated with disease protection following primate lentivirus infection. Persisting clinical protection in vaccinated and challenged monkeys is thus correlated with a preserved capacity of the peripheral blood central memory CD4(+) T cells to express this important immunomodulatory cytokine. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA. Therion Biol, Cambridge, MA 02142 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. BD Biosci, San Jose, CA 95131 USA. RP Letvin, NL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Res E Room 113,330 Brookline Ave, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu FU NIAID NIH HHS [R01 AI048394, AI30033, AI48394, R01 AI020729, AI20729, AI28691] NR 28 TC 23 Z9 24 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4753 EP 4760 PG 8 WC Immunology SC Immunology GA 914NN UT WOS:000228234600040 PM 15814700 ER PT J AU Rochman, I Paul, WE Ben-Sasson, SZ AF Rochman, I Paul, WE Ben-Sasson, SZ TI IL-6 increases primed cell expansion and survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; RECEPTOR MONOCLONAL-ANTIBODY; DENDRITIC CELLS; IL-6-DEFICIENT MICE; INTERLEUKIN-6-DEFICIENT MICE; IN-VIVO; INDUCED ARTHRITIS; B-LYMPHOCYTES AB Cytochrome c-specific CD4 T cells from transgenic donors transferred to syngeneic B10.A mice expand more vigorously upon immunization if exogenous IL-6 is provided during the initial phase of immunization. The resultant increase in the frequency and number of Ag-specific cells is observed in the blood, lymph nodes, spleen, liver, and lung and persists for at least 3 mo. Treatment of immunized recipients with anti-IL-6 or use of IL-6 knockout recipients reduced the frequency of Ag-specific CD4 T cells during a comparable period, indicating that IL-6 is physiologically involved in the expansion of memory and/or effector cells and thus in the persistence of memory. IL-6 did not alter the duration of Ag-presenting activity. Both USE dilution studies and labeling with BrdU indicated that IL-6 does not effect proliferative rates of responding CD4 T cells. By contrast, annexin V staining was diminished in responding cells from the IL-6-treated animals, particularly among those cells that had undergone five or more divisions. These results indicate that IL-6 reduces the level of apoptosis among Ag-stimulated cells; thus, it plays a central role in determining numbers of memory and/or effector CD4 T cells in response to immunization over extended periods. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumro Immunol, Jerusalem, Israel. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10-11N311, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov NR 63 TC 70 Z9 71 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4761 EP 4767 PG 7 WC Immunology SC Immunology GA 914NN UT WOS:000228234600041 PM 15814701 ER PT J AU Borbulevych, OY Baxter, TK Yu, ZY Restifo, NP Baker, BM AF Borbulevych, OY Baxter, TK Yu, ZY Restifo, NP Baker, BM TI Increased immunogenicity of an anchor-modified tumor-associated antigen is due to the enhanced stability of the peptide/MHC complex: Implications for vaccine design SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; METASTATIC MELANOMA; CRYSTAL-STRUCTURES; ELECTRON-DENSITY; BINDING-SITE; HLA-A2; RESIDUE; HLA-A-ASTERISK-0201; CONFORMATION; RECOGNITION AB The use of "anchor-fixed" altered peptide ligands is of considerable interest in the development of therapeutic vaccines for cancer and infectious diseases, but the mechanism by which successful altered peptide ligands elicit enhanced immunity is unclear. In this study, we have determined the crystallographic structure of a major tumor rejection Ag, gp100(209-217), in complex with the HLA-A*0201 (HLA-A2) molecule, as well as the structure of a modified version of the peptide which substitutes methionine for threonine at position 2 (T2M; gp100(211-2M)). The T2M-modified peptide, which is more immunogenic in vitro and in vivo, binds HLA-A2 with a similar to 9-fold greater affinity and has a similar to 7-fold slower dissociation rate at physiological temperature. Within the limit of the crystallographic data, the T2M substitution does not alter the structure of the peptide/HLA-A2 complex. Consistent with this finding, in peripheral blood from 95 human subjects, we were unable to identify higher frequencies of T cells specific for either the native or modified peptide. These data strongly support the conclusion that the greater immunogenicity of the gp100(201-2M) peptide is due to the enhanced stability of the peptide/MHC complex, validating the anchor-fixing approach for generating therapeutic vaccine candidates. Thermodynamic data suggest that the enhanced stability of the T2M-modified peptide/HLA-A2 complex is attributable to the increased hydrophobicity of the modified peptide, but the gain due to hydrophobicity is offset considerably by the loss of a hydrogen bond made by the native peptide to the HLA-A2 molecule. Our findings have broad implications for the optimization of current vaccine-design strategies. C1 Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Baker, BM (reprint author), Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA. EM bbaker2@nd.edu RI Restifo, Nicholas/A-5713-2008; Baker, Brian/B-4584-2009; OI Baker, Brian/0000-0002-0864-0964; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NIGMS NIH HHS [GM067079, R01 GM067079] NR 49 TC 58 Z9 60 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4812 EP 4820 PG 9 WC Immunology SC Immunology GA 914NN UT WOS:000228234600047 PM 15814707 ER PT J AU Foley, JF Yu, CR Solow, R Yacobucci, M Peden, KWC Farber, JM AF Foley, JF Yu, CR Solow, R Yacobucci, M Peden, KWC Farber, JM TI Roles for CXC chemokine ligands 10 and 11 in recruiting CD4(+) T cells to HIV-1-infected monocyte-derived macrophages, dendritic cells, and lymph nodes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IFN-GAMMA; INTERFERON-GAMMA; ALPHA-CHEMOATTRACTANT; INDUCIBLE PROTEIN-10; RECEPTOR EXPRESSION; HIV-1 INFECTION; RHESUS MACAQUES; GENE-EXPRESSION; IN-VITRO AB We investigated roles for chemoattractants; in dissemination of HIV-1 by examining the induction of T cell-active chemokines in HIV-1-infected human monocyte-derived macrophages and dendritic cells. Of the 12 chemokines analyzed, mRNAs for two, CXCL10 and CXCL11, ligands for the chemokine receptor CXCR3, were up-regulated in both cell types upon infection by HIV-1. Induction of these chemokine genes in infected cultures was dependent on both viral entry and reverse transcriptase activity, but not on the HIV-1 envelope glycoprotein. Conditioned medium from infected cells was chemotactic for freshly isolated human CD4(+) T cells, and chemotaxis was abolished by pretreatment with an Ab against CXCR3. A lymph node from an HIV-1-infected individual expressed CXCL10 and CXCL11 mRNAs in the paracortex, including venules, as detected by in situ hybridization, whereas neither mRNA was detected after highly active antiretroviral therapy. Because CCR5 on CD4(+) T cells is found predominantly on cells that also express CXCR3, these data implicate CXCL10 and CXCL11 in the recruitment of susceptible T cells to HIV-1-infected lymph nodes, macrophages, and dendritic cells. This recruitment might enhance the sequestration of T cells in infected lymphoid organs and the spread of infection between cells, contributing to the immunopathology of AIDS. C1 Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res Food & Durg Adm, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bldg 10,Room 11N288,MSC 1888, Bethesda, MD 20892 USA. EM peden@cber.fda.gov NR 62 TC 36 Z9 36 U1 4 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4892 EP 4900 PG 9 WC Immunology SC Immunology GA 914NN UT WOS:000228234600056 PM 15814716 ER PT J AU Kontoyiannis, DP Lionakis, MS Lewis, RE Chamilos, G Healy, M Perego, C Safdar, A Kantarjian, H Champlin, R Walsh, TJ Raad, II AF Kontoyiannis, DP Lionakis, MS Lewis, RE Chamilos, G Healy, M Perego, C Safdar, A Kantarjian, H Champlin, R Walsh, TJ Raad, II TI Zygomycosis in a Tertiary-Care Cancer Center in the era of Aspergillus-active antifungal therapy: A case-control observational study of 27 recent cases SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 44th Interscience Conference on Antimicrobial Agents and Chemotherapy CY OCT 30-NOV 02, 2004 CL Washington, DC ID INVASIVE FUNGAL-INFECTIONS; CELL TRANSPLANT RECIPIENTS; AMPHOTERICIN-B; RECEIVING VORICONAZOLE; MUCORMYCOSIS; DIAGNOSIS; AGENTS; SUSCEPTIBILITIES; EPIDEMIOLOGY; POSACONAZOLE AB Background. Anecdotal evidence suggests a rise in zygomycosis in association with voriconazole (VRC) use in immunosuppressed patients. Methods. We performed prospective surveillance of patients with zygomycosis ( group A;) and compared them with contemporaneous patients with invasive aspergillosis (group B; n = 54) and with matched contemporaneous high-risk patients without fungal infection (group C; n = 54). We also performed molecular typing and in vitro susceptibility testing of Zygomycetes isolates. Results. Nearly all patients with zygomycosis either had leukemia (n = 14) or were allogeneic bone marrow transplant recipients (n = 13). The Zygomycetes isolates (74% of which were of the genus Rhizopus) had different molecular fingerprinting profiles, and all were VRC resistant. In multivariate analysis of groups A and C, VRC prophylaxis (odds ratio [OR], 10.37 [95% confidence interval {CI}], 2.76-38.97]; P = .001), diabetes (OR, 8.39 [95% CI, 2.04-34.35]; P = .003), and malnutrition (OR, 3.70 [95% CI, 1.03-13.27]; P = .045) were found to be independent risk factors for zygomycosis. Between patients with zygomycosis ( after excluding 6 patients with mixed mold infections) and patients with aspergillosis, VRC prophylaxis (OR, 20.30 [95% CI, 3.85-108.15]; P = .0001) and sinusitis (OR, 76.72 [95% CI, 6.48-908.15]; P = .003) were the only factors that favored the diagnosis of zygomycosis. Conclusions. Zygomycosis should be considered in immunosuppressed patients who develop sinusitis while receiving VRC prophylaxis, especially those with diabetes and malnutrition. C1 Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Unit 402, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bone Marrow Transplantat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Houston, Coll Pharm, Houston, TX 77030 USA. Spectral Genom Inc, Houston, TX USA. NCI, NIH, Bethesda, MD 20892 USA. RP Kontoyiannis, DP (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Unit 402, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dkontoyi@mdanderson.org OI Lewis, Russell/0000-0002-2002-4339 NR 40 TC 372 Z9 387 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 APR 15 PY 2005 VL 191 IS 8 BP 1350 EP 1360 DI 10.1086/428780 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908QR UT WOS:000227804500021 PM 15776383 ER PT J AU Hisada, M Miley, WJ Biggar, RJ AF Hisada, M Miley, WJ Biggar, RJ TI Provirus load is lower in human T lymphotropic virus (HTLV)-II carriers than in HTLV-I carriers: A key difference in viral pathogenesis? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID CLONAL EXPANSION; HISTORY; DISEASE C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8008, Rockville, MD 20852 USA. EM hisadam@exchange.nih.gov NR 9 TC 6 Z9 6 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 APR 15 PY 2005 VL 191 IS 8 BP 1383 EP 1385 DI 10.1086/429094 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908QR UT WOS:000227804500030 PM 15776392 ER PT J AU Snyder, GA Colonna, M Sun, PD AF Snyder, GA Colonna, M Sun, PD TI The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DC-SIGN; HIV gp120; C-type lectin; dendritic cell; X-ray structure ID HEPATITIS-C VIRUS; MACROPHAGE MANNOSE RECEPTOR; HUMAN DENDRITIC CELLS; CARBOHYDRATE-RECOGNITION; ENDOTHELIAL-CELLS; LIGAND-BINDING; SELECTIVE RECOGNITION; ENVELOPE GLYCOPROTEIN; TRANS-INFECTION; PROTEIN AB The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative DC-SIGNR recognize various glycoproteins, both pathogenic and of cellular, through the receptor lectin domain-mediated carbohydrate recognition. While the carbohydrate-recognition domains (CRD) exist as monomers and bind individual carbohydrates with low affinity and are permissive in nature, the full-length receptors form tetramers through their repeat domain and recognize specific ligands with high affinity. To understand the tetramer-based ligand binding avidity, we determined the crystal structure of DC-SIGNR with its last repeat region. Compared to the carbohydrate-bound CRD structure, the structure revealed conformational changes in the calcium and carbohydrate coordination loops of CRD, an additional disulfide bond between the N and the C termini of the CRD, and a helical conformation for the last repeat. On the basis of the current crystal structure and other published structures with sequence homology to the repeat domain, we generated a tetramer model for DC-SlGN/R using homology modeling and propose a ligand-recognition index to identify potential receptor ligands. Published by Elsevier Ltd. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov OI Colonna, Marco/0000-0001-5222-4987 NR 42 TC 27 Z9 28 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 APR 15 PY 2005 VL 347 IS 5 BP 979 EP 989 DI 10.1016/j.jmb.2005.01.063 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912WY UT WOS:000228111800009 PM 15784257 ER PT J AU Akk, G Milescu, LS Heckmann, M AF Akk, G Milescu, LS Heckmann, M TI Activation of heteroliganded mouse muscle nicotinic receptors SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ACETYLCHOLINE-RECEPTOR; ALPHA-SUBUNIT; BINDING-SITE; NEUROMUSCULAR-JUNCTION; PARTIAL AGONIST; BLOCK CURRENTS; OPENING RATE; CHANNELS; CHOLINE; ADULT AB The activation of the mouse muscle-type nicotinic acetylcholine receptor was studied in the presence of carbachol, and in the simultaneous presence of carbachol and choline. The channel currents were recorded under steady-state conditions using cell-attached single-channel patch clamp, and during transient exposures to the agonists using a piezo-driven fast application system. The presence of choline resulted in inhibition of currents elicited by carbachol. The inhibitory effect of choline manifested as a reduction in the effective opening rate (increase in the mean intracluster closed time duration) in single-channel recordings. In the fast application experiments, the peak current amplitude was reduced and the current rise time increased when choline was co-applied with carbachol. The data were analysed according to a model in which receptor interactions with carbachol and choline resulted in three types of ligation: receptors occupied by two carbachol molecules, receptors occupied by two choline Molecules, and receptors in which one agonist binding site was occupied by carbachol and the other by choline, i.e. heteroliganded receptors. All three agonist-bound receptor populations could open albeit with different efficacies. The affinity of the resting receptor to choline was estimated to be 1-2 mm, and heteroliganded receptors opened with an opening rate constant of similar to 3000 s(-1). The results of the analysis suggest that the presence of choline in the neuromuscular junction in vivo has little effect on the time course of synaptic currents. Nevertheless, the contribution of heteroliganded receptors should be taken into consideration when the receptor is exposed simultaneously to two or more agonists. C1 Washington Univ, Dept Anesthesiol, St Louis, MO 63110 USA. NINDS, Neural Control Lab, Bethesda, MD 20892 USA. Univ Freiburg, Inst Physiol, D-7800 Freiburg, Germany. RP Akk, G (reprint author), Washington Univ, Dept Anesthesiol, Campus Box 8054,660 S Euclid Ave, St Louis, MO 63110 USA. EM akk@morpheus.wustl.edu OI Heckmann, Manfred/0000-0002-4874-1735 FU NINDS NIH HHS [R01 NS022356, NS-22356] NR 50 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 15 PY 2005 VL 564 IS 2 BP 359 EP 376 DI 10.1113/jphysiol.2004.078535 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 919FX UT WOS:000228604900003 PM 15718267 ER PT J AU Dever, TE Hinnebusch, AG AF Dever, TE Hinnebusch, AG TI GCN2 whets the appetite for amino acids SO MOLECULAR CELL LA English DT Editorial Material ID UNCHARGED TRANSFER-RNA; KINASE GCN2; MAMMALIAN-CELLS; GENE-EXPRESSION; PIRIFORM CORTEX; PHOSPHORYLATION; TRANSLATION; STARVATION; DEFICIENCY; STRESS AB In response to amino acid starvation, the kinase GCN2 in yeast activates amino acid biosynthesis. Two recent studies (Maurin et al., 2005; Hao et al., 2005) reveal that GCN2 in the brain of mice restricts intake of diets lacking essential amino acids. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. OI Dever, Thomas/0000-0001-7120-9678 NR 9 TC 23 Z9 27 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 15 PY 2005 VL 18 IS 2 BP 141 EP 142 DI 10.1016/j.molcel.2005.03.023 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 917EB UT WOS:000228437700001 PM 15837415 ER PT J AU Miller, GJ Wilson, MP Majerus, PW Hurley, JH AF Miller, GJ Wilson, MP Majerus, PW Hurley, JH TI Specificity determinants in inositol polyphosphate synthesis: Crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase SO MOLECULAR CELL LA English DT Article ID PROTEIN-KINASE-C; D-ALANINE LIGASE; ESCHERICHIA-COLI; 1,4,5-TRISPHOSPHATE 3-KINASE; DNA-PK; ATP; HEXAKISPHOSPHATE; PHOSPHATE; ENZYME; PYROPHOSPHATES AB Inositol hexakisphosphate and other inositol high polyphosphates have diverse and critical roles in eukaryotic regulatory pathways. Inositol 1,3,4-trisphosphate 5/6-kinase catalyzes the rate-limiting step in inositol high polyphosphate synthesis in animals. This multifunctional enzyme also has inositol 3,4,5,6-tetrakisphosphate 1-kinase and other activities. The structure of an archetypal family member, from Entamoeba histolytica, has been determined to 1.2 angstrom resolution in binary and ternary complexes with nucleotide, substrate, and product. The structure reveals an ATP-grasp fold. The inositol ring faces ATP edge-on such that the 5- and 6-hydroxyl groups are nearly equidistant from the ATP gamma-phosphate in catalytically productive phosphoacceptor positions and explains the unusual dual site specificity of this kinase. Inositol tris- and tetrakisphosphates interact via three phosphate binding subsites and one solvent-exposed site that could in principle be occupied by 18 different substrates, explaining the mechanisms for the multiple specificities and catalytic activities of this enzyme. C1 NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Div Hematol, St Louis, MO 63110 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM jh8e@nih.gov FU NHLBI NIH HHS [R01-HL016634-39, R01-HL55672-09] NR 54 TC 37 Z9 41 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 15 PY 2005 VL 18 IS 2 BP 201 EP 212 DI 10.1016/j.molcel.2005.03.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 917EB UT WOS:000228437700009 PM 15837423 ER PT J AU Xu, J Kemeny, S Park, G Frattali, C Braun, A AF Xu, J Kemeny, S Park, G Frattali, C Braun, A TI Language in context: emergent features of word, sentence, and narrative comprehension SO NEUROIMAGE LA English DT Article DE brain; human; functional magnetic resonance imaging; context; reading; narrative ID INFERIOR FRONTAL-CORTEX; RIGHT-HEMISPHERE; TEMPORAL CORTEX; FRONTOMEDIAN CORTEX; PREFRONTAL CORTEX; HUMAN BRAIN; FMRI; MEMORY; ORGANIZATION; ENGAGEMENT AB Context exerts a powerful effect on cognitive performance and is clearly important for language processing, where lexical, sentential, and narrative contexts should differentially engage neural systems that support lexical, compositional, and discourse level semantics. Equally important, but thus far unexplored, is the role of context within narrative, as cognitive demands evolve and brain activity changes dynamically as subjects process different narrative segments. In this study, we used fMRI to examine the impact of context, comparing responses to a single, linguistically matched set of texts when these were differentially presented as random word lists, unconnected sentences and coherent narratives. We found emergent, context-dependent patterns of brain activity in each condition. Perisylvian language areas were always active, consistent with their supporting core linguistic computations. Sentence processing was associated with expanded activation of the frontal operculum and temporal poles. The same stimuli presented as narrative evoked robust responses in extrasylvian areas within both hemispheres, including precuneus, medial prefrontal, and dorsal temporo-parieto-occipital cortices. The right hemisphere was increasingly active as contextual complexity increased, maximal at the narrative level. Furthermore, brain activity was dynamically modulated as subjects processed different narrative segments: left hemisphere activity was more prominent at the onset, and right hemisphere more prominent at the resolution of a story, at which point, it may support a coherent representation of the narrative as a whole. These results underscore the importance of studying language in an ecologically valid context, suggesting a neural model for the processing of discourse. Published by Elsevier Inc. C1 Natl Inst Deafness & Other Commun Disorders, Languages Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. NIH, WG Magnuson Clin Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Xu, J (reprint author), Natl Inst Deafness & Other Commun Disorders, Languages Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. EM xujiang@nidcd.nih.gov NR 62 TC 194 Z9 202 U1 4 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2005 VL 25 IS 3 BP 1002 EP 1015 DI 10.1016/j.neuroimage.2004.12.013 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 916KJ UT WOS:000228383500035 PM 15809000 ER PT J AU Jeang, KT AF Jeang, KT TI Life after 45 and before 60: the Retrovirology Prize SO RETROVIROLOGY LA English DT Editorial Material AB Retrovirology announces an annual prize to recognize one outstanding mid-career retrovirologist. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD APR 15 PY 2005 VL 2 AR 26 DI 10.1186/1742-4690-2-26 PG 2 WC Virology SC Virology GA 032RN UT WOS:000236792300001 PM 15833114 ER PT J AU Klein, RJ Zeiss, C Chew, EY Tsai, JY Sackler, RS Haynes, C Henning, AK SanGiovanni, JP Mane, SM Mayne, ST Bracken, MB Ferris, FL Ott, J Barnstable, C Hoh, J AF Klein, RJ Zeiss, C Chew, EY Tsai, JY Sackler, RS Haynes, C Henning, AK SanGiovanni, JP Mane, SM Mayne, ST Bracken, MB Ferris, FL Ott, J Barnstable, C Hoh, J TI Complement factor H polymorphism in age-related macular degeneration SO SCIENCE LA English DT Article ID GENOMEWIDE-SCAN; SUSCEPTIBILITY LOCI; EXTENDED FAMILIES; DISEASE; DRUSEN; ASSOCIATIONS; ACTIVATION; REGIONS; PROJECT; PROTEIN AB Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). in individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the Ask allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06520 USA. NEI, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD 20850 USA. Yale Univ, WM Keck Facil, New Haven, CT 06511 USA. RP Hoh, J (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM josephine.hoh@yale.edu RI SanGiovanni, John Paul/A-7605-2008; Klein, Robert/K-1888-2013; OI Klein, Robert/0000-0003-3539-5391; Barnstable, Colin/0000-0002-7011-4068 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000489-01]; NCRR NIH HHS [K01RR16090]; NEI NIH HHS [R01EY015771]; NHGRI NIH HHS [K25HG000060]; NIMH NIH HHS [R01MH44292] NR 30 TC 2346 Z9 2496 U1 28 U2 171 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 15 PY 2005 VL 308 IS 5720 BP 385 EP 389 DI 10.1126/science.1109557 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 917TL UT WOS:000228492000044 PM 15761122 ER PT J AU Liu, AY Wu, CQ Yu, KF Gehan, E AF Liu, AY Wu, CQ Yu, KF Gehan, E TI Supplementary analysis of probabilities at the termination of a group sequential phase II trial SO STATISTICS IN MEDICINE LA English DT Article DE bias-correction; estimation; response; toxicity; two-stage designs ID CLINICAL-TRIALS; CONFIDENCE-INTERVALS; DESIGNS; TESTS; BIAS AB We consider estimation of various probabilities after termination of a group sequential phase 11 trial. A motivating example is that the stopping rule of a phase 11 oncologic trial is determined solely based on response to a drug treatment, and at the end of the trial estimating the rate of toxicity and response is desirable. The conventional maximum likelihood estimator (sample proportion) of a probability is shown to be biased, and two alternative estimators are proposed to correct for bias, a bias-reduced estimator obtained by using Whitehead's bias-adjusted approach, and an unbiased estimator from the Rao-Blackwell method of conditioning. All three estimation procedures are shown to have certain invariance property in bias. Moreover, estimators of a probability and their bias and precision can be evaluated through the observed response rate and the stage at which the trial stops, thus avoiding extensive computation. Copyright (c) 2004 John Wiley W Sons, Ltd. C1 NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. USTC, Dept Stat & Finance, Hefei, Anhui, Peoples R China. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Div Biostat & Bioinformat, Washington, DC 20057 USA. RP Liu, AY (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 23 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 2005 VL 24 IS 7 BP 1009 EP 1027 DI 10.1002/sim.1990 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 907AO UT WOS:000227687100003 PM 15565737 ER PT J AU Ju, C Pohl, LR AF Ju, C Pohl, LR TI Tolerogenic role of Kupffer cells in immune-mediated adverse drug reactions SO TOXICOLOGY LA English DT Article; Proceedings Paper CT Drug Hypersensitivity Meeting 2004 CY MAY 05-08, 2004 CL Bern, SWITZERLAND DE tolerance mechanism; liver; Kupffer cells; T cells; animal model ID ALLOGRAFTS; INDUCTION; SURVIVAL; LIVER; RATS AB Immune-mediated adverse drug reactions (IADR) account for approximately 6-10% of all adverse drug reactions. Although IADR are often referred to as rare (afflicting 1/100 to 1/100,000 patients), their unpredictable and serious nature makes them a significant economic burden and safety concern to the health care community and the pharmaceutical industry. Current studies suggest that IADR are caused by immunogenic drug-protein adducts; however, it remains unclear why only a small percentage of patients are susceptible to developing these reactions. We hypothesized that most individuals may be resistant to IADR because they develop immunological tolerance to drug-protein adducts in the liver, an organ with tolerogenic properties. We tested this hypothesis using a murine model of T-cell-mediated reaction against a hapten, 2,4-dinitrochlorobenzene (DNCB). We showed that pre-treatment of mice with a protein adduct of DNCB led to its accumulation in Kupffer cells (KC) of the liver and induced tolerance to subsequent DNCB sensitization. KC depletion and adoptive transfer experiments further supported that KC may act as a primary inducer of immunological tolerance against protein adducts of haptens or drugs. Functional activities of KC, which are regulated by genetic and/or environmental factors, may play an important role in determining individual susceptibility to IADR. (c) 2005 Published by Elsevier Ireland Ltd. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ju, C (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, 4200 E 9th Ave, Denver, CO 80262 USA. EM cynthia.ju@uchsc.edu NR 8 TC 23 Z9 24 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 15 PY 2005 VL 209 IS 2 SI SI BP 109 EP 112 DI 10.1016/j.tox.2004.12.017 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 917BC UT WOS:000228429800004 PM 15767021 ER PT J AU Fowler, M Virostko, J Chen, ZY Poffenberger, G Radhika, A Brissova, M Shiota, M Nicholson, WE Shi, YB Hirshberg, B Harlan, DM Jansen, ED Powers, AC AF Fowler, M Virostko, J Chen, ZY Poffenberger, G Radhika, A Brissova, M Shiota, M Nicholson, WE Shi, YB Hirshberg, B Harlan, DM Jansen, ED Powers, AC TI Assessment of pancreatic islet mass after islet transplantation using in vivo bioluminescence imaging SO TRANSPLANTATION LA English DT Article DE bioluminescence; pancreatic islets; transplantation; insulin; imaging; diabetes ID BETA-CELL MASS; TYPE-1 DIABETES-MELLITUS; ANTIGEN EXPRESSION; FUNCTIONAL-STATE; GENE-EXPRESSION; LIVING MAMMALS; NUDE-MICE; INFECTION; REPORTER; VECTORS AB Background. Pancreatic islet transplantation is an emerging therapy for type 1 diabetes, but it is difficult to assess islets after transplantation and thus to design interventions to improve islet survival. Methods. To image and quantify islets, the authors transplanted luciferase- expressing murine or human islets (by adenovirus-mediated gene transfer) into the liver or beneath the renal capsule of immunodeficient mice and quantified the in vivo bioluminescence imaging (BLI) of mice using a cooled charge-coupled device camera and digital photon-counting image analysis. To account for variables that are independent of islet mass such as transplant site, animal positioning, and wound healing, the BLI of transplanted islets was calibrated against measurement of luminescence of an implanted bead emitting a constant light intensity. Results. BLI of mice bearing islet transplants was seen in the expected anatomic location, was stable for more than 8 weeks after transplantation, and correlated with the number of islets transplanted into the liver or kidney. BLI of the luminescent bead and of transplanted islets in the kidney was approximately four times greater than when transplanted in the liver, indicating that photon emission is dependent on optical absorption of generated light and thus light source location. Conclusion. In vivo BLI allows for quantitative, serial measurements of pancreatic islet mass after transplantation and should be useful in assessing interventions to sustain or increase islet survival of transplanted islets. C1 Vanderbilt Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Biomed Engn, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. NIDDK, Islet & Autoimmun Branch, NIH, Bethesda, MD USA. VA Tennessee Valley Healthcare Syst, Nashville, TN USA. RP Powers, AC (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, 715 PRB, Nashville, TN 37232 USA. EM al.powers@vanderbilt.edu RI Jansen, E. Duco/B-1894-2013 FU NIDDK NIH HHS [DK63439, DK55233, DK20593, DK62641] NR 38 TC 67 Z9 71 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2005 VL 79 IS 7 BP 768 EP 776 DI 10.1097/01.TP.0000152798.03204.5C PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 916GJ UT WOS:000228373100003 PM 15818318 ER PT J AU Murphy, TF Bakaletz, LO Kyd, JM Watson, B Klein, DL AF Murphy, TF Bakaletz, LO Kyd, JM Watson, B Klein, DL TI Vaccines for otitis media: proposals for overcoming obstacles to progress SO VACCINE LA English DT Article DE otitis media; vaccine; immunization ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; PNEUMOCOCCAL CONJUGATE VACCINE; MORAXELLA BRANHAMELLA CATARRHALIS; OUTER-MEMBRANE PROTEIN; DAY-CARE-CENTERS; MIDDLE-EAR; STREPTOCOCCUS-PNEUMONIAE; PULMONARY CLEARANCE; HEMOPHILUS-INFLUENZAE; RESPIRATORY VIRUSES AB Otitis media is a common problem with enormous morbidity worldwide. The development of vaccines to prevent otitis media would have an important human and economic impact. A striking lack of progress in the development, production and clinical testing of vaccines to prevent otitis media has occurred in the past decade. This review outlines a series of specific proposals intended to advance vaccine development for otitis media. (c) 2004 Elsevier Ltd, All rights reserved. C1 SUNY Buffalo, Dept Med, Div Infect Dis, Buffalo, NY 14260 USA. SUNY Buffalo, Dept Microbiol, Buffalo, NY 14260 USA. Western New York Vet Affairs Healthcare Syst, Buffalo, NY USA. Ohio State Univ, Coll Med & Publ Hlth, Ctr Microbial Pathogenesis, Columbus Childrens Res Inst,Dept Pediat, Columbus, OH 43210 USA. Univ Canberra, Gadi Res Ctr, Div Hlth Design & Sci, Canberra, ACT, Australia. NIDCD, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. RP Murphy, TF (reprint author), Buffalo Vet Affairs Med Ctr, Med Res 151,3495 Bailey Ave, Buffalo, NY 14215 USA. EM murphyt@buffalo.edu OI Kyd, Jennelle/0000-0002-3331-3658 NR 67 TC 25 Z9 25 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 15 PY 2005 VL 23 IS 21 BP 2696 EP 2702 DI 10.1016/j.vaccine.2004.12.014 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 914ST UT WOS:000228248700002 PM 15780715 ER PT J AU Sriraman, S Kevrekidis, LG Hummer, G AF Sriraman, S Kevrekidis, LG Hummer, G TI Coarse master equation from Bayesian analysis of replica molecular dynamics simulations SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PROTEIN-FOLDING KINETICS; RATE CONSTANTS; ISOMERIZATION DYNAMICS; MONTE-CARLO; PEPTIDE; SYSTEMS; ENERGY; WATER; OPTIMIZATION; MODELS AB We use Bayesian inference to derive the rate coefficients of a coarse master equation from molecular dynamics simulations. Results from multiple short simulation trajectories are used to estimate propagators. A likelihood function constructed as a product of the propagators provides a posterior distribution of the free coefficients in the rate matrix determining the Markovian master equation. Extensions to non-Markovian dynamics are discussed, using the trajectory "paths" as observations. The Markovian approach is illustrated for the filling and emptying transitions of short carbon nanotubes dissolved in water. We show that accurate thermodynamic and kinetic properties, such as free energy surfaces and kinetic rate coefficients, can be computed from coarse master equations obtained through Bayesian inference. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. Princeton Univ, Program Appl & Computat Math, Princeton, NJ 08544 USA. Princeton Univ, Dept Math, Princeton, NJ 08544 USA. RP Hummer, G (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 42 TC 84 Z9 87 U1 0 U2 20 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 APR 14 PY 2005 VL 109 IS 14 BP 6479 EP 6484 DI 10.1021/jp046448u PG 6 WC Chemistry, Physical SC Chemistry GA 914MF UT WOS:000228231200004 PM 16851726 ER PT J AU Gopich, I Szabo, A AF Gopich, I Szabo, A TI Fluorophore-quencher distance correlation functions from single-molecule photon arrival trajectories SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID RESONANCE ENERGY-TRANSFER; TRANSFER CONFOCAL MICROSCOPY; FLUORESCENCE SPECTROSCOPY; DYNAMICS PHOTON; PEPTIDES; PROTEINS; REVEALS AB We generalize and simplify the method of Yang and Xie (J. Chem. Phys. 2002, 117, 10965) to obtain distance correlation functions from photon arrival trajectories of single fluorophores whose lifetime, [k(r)](-1), depends on the distance to a quencher. It is assumed that this distance does not change during the fluorescence lifetime. The experimental trajectory is first transformed by replacing the delay time (i.e., the interval between the photon arrival and the nearest laser pulse) by a certain function of this delay time. This function is the inverse Laplace transform of r(k), which is the solution of k(r) = 1. The correlation function of the transformed data then directly gives the distance correlation function. Illustrative examples include Forster energy transfer and quenching due to electron transfer. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, I (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 21 TC 16 Z9 16 U1 0 U2 3 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 APR 14 PY 2005 VL 109 IS 14 BP 6845 EP 6848 DI 10.1021/jp045398q PG 4 WC Chemistry, Physical SC Chemistry GA 914MF UT WOS:000228231200048 PM 16851770 ER PT J AU Marincola, FM AF Marincola, FM TI A balanced review of the status T cell-based therapy against cancer SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material ID MELANOMA; IMMUNOTHERAPY; IMMUNIZATION; REGRESSION; VACCINES; PEPTIDE AB A recent commentary stirred intense controversy over the status of anti-cancer immunotherapy. The commentary suggested moving beyond current anti-cancer vaccines since active-specific immunization failed to match expectations toward a more aggressive approach involving the adoptive transfer of in vitro expanded tumor antigen-specific T cells. Although the same authors clarified their position in response to others' rebuttal more discussion needs to be devoted to the current status of T cell-based anti-cancer therapy. The accompanying publications review the status of adoptive transfer of cancer vaccines on one hand and active-specific immunization on the other. Hopefully, reading these articles will offer a balanced view of the current status of antigen-specific anti-cancer therapies and suggest future strategies to foster unified efforts to complement either approach with the other according to specific biological principles. C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. EM fmarincola@mail.cc.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 14 PY 2005 VL 3 DI 10.1186/1479-5876-3-16 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968KA UT WOS:000232160200002 ER PT J AU Sconocchia, G Provenzano, M Rezvani, K Li, JM Melenhorst, J Hensel, N Barrett, AJ AF Sconocchia, G Provenzano, M Rezvani, K Li, JM Melenhorst, J Hensel, N Barrett, AJ TI CD34+cells cultured in stem cell factor and interleukin-2 generate CD56+cells with antiproliferative effects on tumor cell lines SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; HEMATOPOIETIC PROGENITOR CELLS; NK CELLS; T-CELLS; DEFICIENT MICE; APOPTOSIS; DIFFERENTIATION; CYTOTOXICITY; EXPRESSION; RECEPTORS AB In vitro stimulation of CD34+ cells with IL-2 induces NK cell differentiation. In order to define the stages of NK cell development, which influence their generation from CD34 cells, we cultured G-CSF mobilized peripheral blood CD34+ cells in the presence of stem cell factor and IL-2. After three weeks culture we found a diversity of CD56+ subsets which possessed granzyme A, but lacked the cytotoxic apparatus required for classical NK-like cytotoxicity. However, these CD56+ cells had the unusual property of inhibiting proliferation of K562 and P815 cell lines in a cell-contact dependent fashion. C1 NHLBI, Hematol Branch, Stem Cell Allotransplant Sect, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, Stem Cell Allotransplant Sect, Bldg 10, Bethesda, MD 20892 USA. EM Giuseppe.Sconocchia@RoswellPark.org; mprovenzano@mail.cc.nih.gov; rezvanik@nhlbi.nih.gov; Lij@nhlbi.nih.gov; melenhoj@mail.nih.gov; Henseln@nhlbi.nih.gov; Barrettj@nhlbi.nih.gov NR 28 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 14 PY 2005 VL 3 DI 10.1186/1479-5876-3-15 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968KA UT WOS:000232160200001 ER PT J AU Emison, ES McCallion, AS Kashuk, CS Bush, RT Grice, E Lin, S Portnoy, ME Cutler, DJ Green, ED Chakravarti, A AF Emison, ES McCallion, AS Kashuk, CS Bush, RT Grice, E Lin, S Portnoy, ME Cutler, DJ Green, ED Chakravarti, A TI A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; DIABETES-MELLITUS; HIV-1 INFECTION; MOUSE MODEL; EXPRESSION; HAPLOTYPE; GENE; TRANSMISSION; DISEQUILIBRIUM; IDENTIFICATION AB The identification of common variants that contribute to the genesis of human inherited disorders remains a significant challenge. Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes. We have used family-based association studies to identify a disease interval, and integrated this with comparative and functional genomic analysis to prioritize conserved and functional elements within which mutations can be sought. We now show that a common non-coding RET variant within a conserved enhancer-like sequence in intron 1 is significantly associated with HSCR susceptibility and makes a 20-fold greater contribution to risk than rare alleles do. This mutation reduces in vitro enhancer activity markedly, has low penetrance, has different genetic effects in males and females, and explains several features of the complex inheritance pattern of HSCR. Thus, common low-penetrance variants, identified by association studies, can underlie both common and rare diseases. C1 Johns Hopkins Univ, Sch Med, KcKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, KcKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM aravinda@jhmi.edu OI Grice, Elizabeth/0000-0003-3939-2200 NR 42 TC 262 Z9 271 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 14 PY 2005 VL 434 IS 7035 BP 857 EP 863 DI 10.1038/nature03467 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915SV UT WOS:000228327600031 PM 15829955 ER PT J AU Schultz, JM Yang, Y Caride, AJ Filoteo, AG Penheiter, AR Lagziel, A Morell, RJ Mohiddin, SA Fananapazir, L Madeo, AC Penniston, JT Griffith, AJ AF Schultz, JM Yang, Y Caride, AJ Filoteo, AG Penheiter, AR Lagziel, A Morell, RJ Mohiddin, SA Fananapazir, L Madeo, AC Penniston, JT Griffith, AJ TI Modification of human hearing loss by plasma-membrane calcium pump PMCA2 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SENSORINEURAL DEAFNESS; MICE; ASSOCIATION; CADHERIN-23; MUTATION; DFNB12; MUTANT; CDH23; CELLS; 1D AB Five adult siblings presented with autosomal recessive sensorineural hearing loss: two had high-frequency loss, whereas the other three had severe-to-profound loss affecting all frequencies. Genetic evaluation revealed that a homozygous mutation in CDH23 (which encodes cadherin 23) caused the hearing loss in all five siblings and that a heterozygous, hypofunctional variant (V586M) in plasma-membrane calcium pump PMCA2, which is encoded by ATP2B2, was associated with increased loss in the three severely affected siblings. V586M was detected in two unrelated persons with increased sensorineural hearing loss, in the other caused by a mutation in MYO6 (which encodes myosin VI) in one and by noise exposure, suggesting that this variant may modify the severity of sensorineural hearing loss caused by a variety of factors. C1 NIDCD, Sect Gene Struct & Funct, NIH, Rockville, MD 20850 USA. NIDCD, Sect Human Genet, NIH, Rockville, MD 20850 USA. NIDCD, Hearing Sect, NIH, Rockville, MD 20850 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Griffith, AJ (reprint author), NIDCD, Sect Gene Struct & Funct, NIH, 5 Res Ct,Rm 2A-01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Madeo, Anne/K-2880-2012; OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [1 Z01 DC000064-02, 1 Z01 DC000039-05, 1 Z01 DC000060-02, DC04200]; NIGMS NIH HHS [GM28825] NR 24 TC 97 Z9 103 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 14 PY 2005 VL 352 IS 15 BP 1557 EP 1564 DI 10.1056/NEJMoa043899 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 915SH UT WOS:000228324200008 PM 15829536 ER PT J AU Paik, S Wolmark, N Shak, S AF Paik, S Wolmark, N Shak, S TI Molecular prediction of recurrence of breast cancer - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. Genom Hlth, Redwood City, CA 94063 USA. RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. EM spaik.nejm@nsabp.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 14 PY 2005 VL 352 IS 15 BP 1606 EP 1607 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 915SH UT WOS:000228324200026 ER PT J AU Sekine, I Sato, M Sunaga, N Toyooka, S Peyton, M Parsons, R Wang, WD Gazdar, AF Minna, JD AF Sekine, I Sato, M Sunaga, N Toyooka, S Peyton, M Parsons, R Wang, WD Gazdar, AF Minna, JD TI The 3p21 candidate tumor suppressor gene BAF180 is normally expressed in human lung cancer SO ONCOGENE LA English DT Article DE BAF180; lung cancer; tumor suppressor gene; chromatin remodeling factor ID DNA METHYLATION; ALLELE LOSS; COMPLEX; HSNF5/INI1; MUTATIONS; MULTIPLE; ARREST; BRG1; MICE AB BAF180 encoding a subunit of the human SWI/SNF chromatin remodeling complex maps to 3p21, in a region where frequent allele loss has been detected in lung cancer. BAF180 can be mutated and has tumor suppressing properties in breast cancer. In addition, another member of this complex, hSNF5/INI1, is a known tumor suppressor gene (TSG) for malignant rhabdoid and childhood central nervous system tumors. Thus, BAF180 is a strong candidate TSG for lung cancer. The objective of this study was to determine whether BAF180 mRNA or protein expression was inactivated or abnormal in lung cancers to prompt detailed DNA promoter methylation or mutational analyses. In 30 non-small-cell and 26 small-cell lung cancer cell lines, most of which had 3p21 allele loss, BAF180 mRNA and protein expression were evaluated by RT-PCR using three sets of primers and Western blotting using two anti-BAF180 antibodies. In all cases, BAF180 was expressed and no abnormal size BAF180 protein was detected. Finally, we found no amino-acid sequence coding mutations in five non-small-cell and five small-cell lung cancer cell lines, while we did find a new splicing isoform of BAF180 (AY281068). We conclude that abnormalities of BAF180 are not frequently involved in the pathogenesis of lung cancer. C1 Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Minna, JD (reprint author), Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. EM John.Minna@UTSouthwestern.edu RI Peyton, Michael/A-8728-2008; Sato, MITSUO/I-7280-2014 FU NCI NIH HHS [P50 CA70907, CA71618] NR 21 TC 9 Z9 10 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 14 PY 2005 VL 24 IS 16 BP 2735 EP 2738 DI 10.1038/sj.onc.1207694 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 916BC UT WOS:000228356700015 PM 15735765 ER PT J AU Orloff, MS Iyengar, SK Winkler, CA Goddard, KAB Dart, RA Ahuja, TS Mokrzycki, M Briggs, WA Korbet, SM Kimmel, PL Simon, EE Trachtman, H Vlahov, D Michel, DM Berns, JS Smith, MC Schelling, JR Sedor, JR Kopp, JB AF Orloff, MS Iyengar, SK Winkler, CA Goddard, KAB Dart, RA Ahuja, TS Mokrzycki, M Briggs, WA Korbet, SM Kimmel, PL Simon, EE Trachtman, H Vlahov, D Michel, DM Berns, JS Smith, MC Schelling, JR Sedor, JR Kopp, JB TI Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population SO PHYSIOLOGICAL GENOMICS LA English DT Article DE renal failure; single nucleotide polymorphism haplotype; polymorphism; African Americans ID DENYS-DRASH-SYNDROME; HAPLOTYPE FREQUENCY ESTIMATION; LINKAGE DISEQUILIBRIUM; WT1 MUTATIONS; TRANSCRIPTION FACTOR; NEPHROTIC SYNDROME; FUNCTIONAL SITES; FRASIER-SYNDROME; SUPPRESSOR GENE; PROTEIN P300 AB Wilms' tumor gene (WT1) is important for nephrogenesis and gonadal growth. WT1 mutations cause Denys-Drash and Frasier syndromes, which are characterized by glomerular scarring. To test whether genetic variations in WT1 and WIT1 (gene immediately 5' to WT1) associate with focal segmental glomerulosclerosis (FSGS), patients with biopsy-proven idiopathic and HIV-1-associated FSGS were enrolled in a multicenter study. We genotyped SNP rs6508 located in WIT1 exon 1, three SNPs (rs2301250, rs2301252, rs2301254) in the promoter shared by WT1 and WIT1, rs2234590 in exon 6, rs2234591 in intron 6, rs16754 in exon 7, and rs1799937 in intron 9 of WT1. Cases (n = 218) and controls (n = 281) were compared in the African American population. Stratification by HIV-1 infection status showed that SNPs rs6508, rs2301254, and rs1799937 were significantly associated with FSGS [rs6508 odds ratio (OR) 1.82, P = 0.006; rs2301254 OR 1.65, P = 0.049; rs1799937 OR 1.91, P = 0.005] in the non-HIV-1 group and rs2234591 (OR 0.234, P = 0.011) in the HIV-1 group. Haplotype analyses in the population revealed that seven SNPs were associated with FSGS; five SNPs had the highest contingency score [-log(10)(P value) = 13.57] in the HIV-1 group. This association could not be explained by population substructure. We conclude that SNPs in WT1 and WIT1 genes are significantly associated with FSGS, suggesting that variants in these genes may mediate pathogenesis by altering WT1 function. Furthermore, HIV-1 infection status interacts with genetic variations in both genes to influence this phenotype. We speculate that nephropathy liability alleles in WT1 pathway genes cause podocyte dysfunction and glomerular scarring. C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Basic Res Program, Sci Applicat Int Corp, NIH, Frederick, MD 21701 USA. Marshfield Clin Fdn Med Res & Educ, Dept Hypertens & Nephrol, Marshfield, WI 54449 USA. Univ Texas, Med Branch, Dept Med, Div Nephrol, Galveston, TX 77550 USA. Albert Einstein Coll Med, Div Nephrol, Bronx, NY 10467 USA. Johns Hopkins Univ, Sch Med, Div Nephrol, Baltimore, MD USA. Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. Tulane Univ, Sch Med, Nephrol Sect, New Orleans, LA 70112 USA. Schneider Childrens Hosp, Dept Pediat, Div Nephrol, New Hyde Pk, NY USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. W Virginia Univ, Dept Med, Morgantown, WV 26506 USA. Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. Univ Hosp Cleveland, Div Nephrol & Hypertens, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. MetroHlth Syst, Rammelkamp Ctr Res & Educ, Kidney Dis Res Ctr, Cleveland, OH USA. NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Iyengar, SK (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Wolstein Res Bldg 1315,10900 Euclid Ave, Cleveland, OH 44106 USA. EM ski@case.edu OI Trachtman, Howard/0000-0001-7447-9489; Kopp, Jeffrey/0000-0001-9052-186X FU NCI NIH HHS [N01-CO-12400, N01-CO-56000]; NIDDK NIH HHS [DK-38558, DK-54644, DK-57329, DK-54178, DK-51472, DK-02281] NR 58 TC 40 Z9 46 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 14 PY 2005 VL 21 IS 2 BP 212 EP 221 DI 10.1152/physiolgenomics.00201.2004 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 916LX UT WOS:000228387600009 PM 15687485 ER PT J AU Fox, CS Sorlie, PD Savage, PJ AF Fox, CS Sorlie, PD Savage, PJ TI Trends in cardiovascular complications of diabetes - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. NHLBI, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. EM foxca@nhlbi.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 13 PY 2005 VL 293 IS 14 BP 1723 EP 1724 DI 10.1001/jama.293.14.1723-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 915JS UT WOS:000228301100012 ER PT J AU Shlipak, MG Fried, LF Cushman, M Manolio, TA Peterson, D Stehman-Breen, C Bleyer, A Newman, A Siscovick, D Psaty, B AF Shlipak, MG Fried, LF Cushman, M Manolio, TA Peterson, D Stehman-Breen, C Bleyer, A Newman, A Siscovick, D Psaty, B TI Cardiovascular mortality risk in chronic kidney disease - Comparison of traditional and novel risk factors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ATHEROSCLEROSIS RISK; RENAL-INSUFFICIENCY; HEALTH; COMMUNITIES; EVENTS; ASSOCIATION; DYSFUNCTION; POPULATION; CREATININE AB Context Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown. Objective To compare traditional and novel risk factors as predictors of cardiovascular mortality. Design, Setting, and Patients A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years. Main Outcome Measures Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m(2). Results Among the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P=.05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference =. 15). Conclusions Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk. C1 Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Vermont, Coll Med, Dept Med, Colchester, VT USA. Univ Vermont, Coll Med, Dept Pathol, Colchester, VT USA. Univ Vermont, Coll Med, Dept Biochem, Colchester, VT USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Shlipak, MG (reprint author), Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85084, N01 HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85085, N01-HC-85086, R01 HL073208-01] NR 29 TC 355 Z9 374 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 13 PY 2005 VL 293 IS 14 BP 1737 EP 1745 DI 10.1001/jama.293.14.1737 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 915JS UT WOS:000228301100027 PM 15827312 ER PT J AU Voulalas, PJ Holtzclaw, L Wolstenholme, J Russell, JT Hyman, SE AF Voulalas, PJ Holtzclaw, L Wolstenholme, J Russell, JT Hyman, SE TI Metabotropic glutamate receptors and dopamine receptors cooperate to enhance extracellular signal-regulated kinase phosphorylation in striatal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE metabotropic glutamate receptor; dopamine receptor; ERK; PKC; striatum; signal transduction ID ACTIVATED PROTEIN-KINASE; MAP KINASE; B-RAF; SYNAPTIC PLASTICITY; CORTICAL-NEURONS; GENE-EXPRESSION; NMDA RESPONSES; IN-VITRO; PATHWAY; SYSTEM AB Striatal medium spiny neurons are an important site of convergence for signaling mediated by the neurotransmitters dopamine and glutamate. We report that in striatal neurons in primary culture, signaling through group I metabotropic glutamate receptors ( mGluRs) 1/5 and the D-1 class of dopamine receptors (DRs) 1/5 converges to increase phosphorylation of the mitogen-activated protein kinase ERK2 ( extracellular signal-regulated kinase 2). Induction of mitogen-activated protein kinase kinase-dependent signaling cascades by either mGluR1/5 or DR1/5 gave rise to increases in phosphorylation of ERK2. Coactivation of mGluR1/5 and DR1/5 with (S)- 3,5-dihydroxyphenylglycine and (+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride enhanced the phosphorylation of ERK2. This interaction between mGluR1/5 and DR1/5 required protein kinase C (PKC), because the PKC inhibitors calphostin C, bisindolylmaleimide I, and Go6976 blocked DR1/5-enhanced phosphorylation of ERK2. Use of the phosphatase inhibitors calyculin and okadaic acid indicated that inhibition of protein phosphatases 1 and 2A dramatically enhanced ERK2 phosphorylation by mGluR1/5. Coactivation of mGluR1/5 and DR1/5 also enhanced cAMP-response element binding protein ( CREB) phosphorylation ( compared with each receptor agonist alone) but did not enhance CREB-mediated transcriptional activity. Thus, signal transduction pathways activated by DR1/5 and mGluR5 interact to modify downstream events in striatal neurons while retaining numerous regulatory checkpoints. C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. NICHHD, Sect Cell Biol & Signal Transduct, NIH, Bethesda, MD 20892 USA. RP Voulalas, PJ (reprint author), Univ Maryland, Sch Med, Dept Physiol, 655 W Baltimore St, Baltimore, MD 21201 USA. EM pvoul001@umaryland.edu NR 67 TC 43 Z9 47 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 13 PY 2005 VL 25 IS 15 BP 3763 EP 3773 DI 10.1523/JNEUROSCI.4574-04.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 916BA UT WOS:000228356200003 PM 15829628 ER PT J AU Volkow, ND Wang, GJ Ma, YM Fowler, JS Wong, C Ding, YS Hitzemann, R Swanson, JM Kalivas, P AF Volkow, ND Wang, GJ Ma, YM Fowler, JS Wong, C Ding, YS Hitzemann, R Swanson, JM Kalivas, P TI Activation of orbital and medial prefrontal cortex by methylphenidate in cocaine-addicted subjects but not in controls: Relevance to addiction SO JOURNAL OF NEUROSCIENCE LA English DT Article DE thalamus; dopamine; motivation; orbitofrontal; cingulate gyrus; imaging ID BRAIN GLUCOSE-METABOLISM; TRANSPORTER-IMMUNOREACTIVE AXONS; OBSESSIVE-COMPULSIVE DISORDER; ORBITOFRONTAL CORTEX; DOPAMINE TRANSPORTER; MOLECULAR-MECHANISMS; MEDIODORSAL THALAMUS; C-11 RACLOPRIDE; MACAQUE MONKEY; BLOOD-FLOW AB Drugs of abuse are rewarding to addicted and nonaddicted subjects, but they trigger craving and compulsive intake only in addicted subjects. Here, we used positron emission tomography (PET) and [F-18] deoxyglucose to compare the brain metabolic responses ( marker of brain function) of cocaine-addicted subjects (n = 21) and controls (n = 15) to identify brain regions that are uniquely activated in addicted subjects by intravenous methylphenidate ( a drug that cocaine-addicted subjects report to be similar to cocaine). In parallel, we also measured the changes in dopamine (DA) induced by intravenous methylphenidate (using PET and [C-11] raclopride) in the striatum and in the thalamus. Metabolic responses between groups differed significantly only in the right medial orbital prefrontal cortex [Brodmann's area (BA) 25 and medial BA 11], where methylphenidate increased metabolism in addicted subjects but decreased metabolism in controls. These changes were associated in all subjects with increased "desire for methylphenidate" and in the addicted subjects with "cocaine craving." In addicted subjects, increases in BA 25 were also associated with mood elevation. Methylphenidate-induced increases in metabolism in the medial orbital prefrontal cortex were associated with its increase of DA in the thalamus but not in the striatum. These findings provide evidence that enhanced sensitivity of BA 25 (region involved with emotional reactivity) and BA 11 (region involved with salience attribution and motivation) in cocaine-addicted subjects may underlie the strong emotional response to the drug and the intense desire to procure it that results in craving and compulsive drug intake. It also suggests that the mesothalamic DA pathway may contribute to these processes. C1 NIDA, Rockville, MD 20857 USA. NIAAA, Rockville, MD 20852 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Oregon Hlth Sci Univ, Dept Behav Sci, Portland, OR 97201 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29465 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Rockville, MD 20857 USA. EM nvolkow@nida.nih.gov FU NIDA NIH HHS [R01DA06891] NR 72 TC 174 Z9 179 U1 5 U2 8 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 APR 13 PY 2005 VL 25 IS 15 BP 3932 EP 3939 DI 10.1523/JNEUROSCI.0433-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 916BA UT WOS:000228356200020 PM 15829645 ER PT J AU Choy, WY Zhou, Z Bai, YW Kay, LE AF Choy, WY Zhou, Z Bai, YW Kay, LE TI An N-15 NMR spin relaxation dispersion study of the folding of a pair of engineered mutants of apocytochrome b(562) SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TIME-SCALE DYNAMICS; 4-HELIX BUNDLE PROTEIN; HYDROGEN-EXCHANGE; CHEMICAL-EXCHANGE; CAVITY MUTANT; SLOW DYNAMICS; SIDE-CHAINS; T4 LYSOZYME; SPECTROSCOPY; QUANTUM AB N-15 relaxation dispersion NMR spectroscopy has been used to study exchange dynamics in a pair of mutants of Rd-apocyt b(562), a redesigned four-helix-bundle protein. An analysis of the relaxation data over a range of temperatures establishes that exchange in both proteins is best modeled as two-state and that it derives from the folding/unfolding transition. These results are in accord with predictions based on the reaction coordinate for the folding of the protein determined from native-state hydrogen exchange data [Chu, R.; Pei, W.; Takei, J.; Bai, Y. Biochemistry 2002, 41, 7998-8003]. The kinetics and thermodynamics of the folding transition have been characterized in detail. Although only a narrow range of temperatures could be examined, it is clear that the folding rate temperature profile is distinctly non-Arrhenius for both mutants, with the folding barrier for at least one of them entropic. C1 Univ Toronto, Prot Engn Network Ctr Excellence, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Microbiol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Biochem & Chem, Toronto, ON M5S 1A8, Canada. NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Kay, LE (reprint author), Univ Toronto, Prot Engn Network Ctr Excellence, 100 Coll St, Toronto, ON M5S 1A8, Canada. NR 38 TC 20 Z9 20 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 13 PY 2005 VL 127 IS 14 BP 5066 EP 5072 DI 10.1021/ja042560u PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 914LQ UT WOS:000228229600032 PM 15810841 ER PT J AU Levitsky, DA Obarzanek, E Mrdjenovic, G Strupp, BJ AF Levitsky, DA Obarzanek, E Mrdjenovic, G Strupp, BJ TI Imprecise control of energy intake: Absence of a reduction in food intake following overfeeding in young adults SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE overfeeding; control of food intake; regulation of body weight; luxusconsumption ID NONEXERCISE ACTIVITY THERMOGENESIS; OBESE PIMA-INDIANS; BODY-WEIGHT; SHORT-TERM; METABOLIC RESPONSE; OVERWEIGHT MEN; EXPENDITURE; FAT; CARBOHYDRATE; HUMANS AB The objective was to examine the extent to which overfeeding reduces spontaneous food intake in humans. Twelve normal-weight adults participated in the three stage study. During the 14 day baseline period and 21 day recovery period, food intake was consumed ad libitum, beyond a minimum 5 MJ (1200 kcal) basal diet. During the 13 day period of overfeeding, each subject consumed 35% more energy than they consumed at baseline. Overfeeding resulted in a weight gain of 2.3 +/- 0.37 kg, (p < 0.0001), approximately half the weight gain was determined to be fat (1.2 +/- 0.19 kg, p < 0.0001) by underwater densitometry. Following overfeeding, mean daily caloric intake was not significantly suppressed returning immediately to baseline values. Despite normal energy intake, participants lost 1.3 < 0.24 kg of body weight (p < 0.0001), of which 0.75 +/- 0.15 kg (p < 0.0001) was fat. These results indicated that (1) the physiological control of eating behavior in humans is not the major mechanism responsible for the recovery of body weight following a period of overfeeding and (2) an increase in energy expenditure of 1.28 MJ (307 kcal)/day or about 14% was required to account for the weight loss following overfeeding. 2005 Elsevier Inc. All rights reserved. C1 Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Cornell Univ, Dept Psychol, Ithaca, NY 14853 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Levitsky, DA (reprint author), Cornell Univ, Div Nutr Sci, 112 Savage hall, Ithaca, NY 14853 USA. EM dal4@cornell.edu OI Levitsky, David/0000-0002-2156-6893 NR 45 TC 32 Z9 34 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR 13 PY 2005 VL 84 IS 5 BP 669 EP 675 DI 10.1016/j.physbeh.2005.01.004 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 930LV UT WOS:000229418300001 PM 15885242 ER PT J AU Yamaguchi, H Minopoli, G Demidov, ON Chatterjee, DK Anderson, CW Durell, SR Appella, E AF Yamaguchi, H Minopoli, G Demidov, ON Chatterjee, DK Anderson, CW Durell, SR Appella, E TI Substrate specificity of the human protein phosphatase 2C delta Wip1 SO BIOCHEMISTRY LA English DT Article ID MAP KINASE; CELLULAR-REGULATION; KINETIC-ANALYSIS; OKADAIC ACID; UV-RADIATION; 2C; STRESS; PPM1D; P38; PATHWAY AB Wip1, the wild-type p53-induced phosphatase, selectively dephosphorylates a threonine residue on p38 MAPK and mediates a negative feedback loop of the p38 MAPK-p53 signaling pathway. To identify the substrate specificity of Wip1, we prepared a recombinant human Wip1 catalytic domain (rWip1) and measured kinetic parameters for phosphopeptides containing the dephosphorylation sites in p38 alpha and in a new substrate, UNG2. rWip1 showed properties that were comparable to those of PP2C alpha or full-length Wip1 in terms of affinity for Mg2+, insensitivity to okadaic acid, and threonine dephosphorylation. The substrate specificity constant k(cat)/K-m for a diphosphorylated peptide with a pTXpY sequence was 6-8-fold higher than that of a monophosphorylated peptide with a pTXY sequence, while PP2C alpha showed a preference for monophosphorylated peptides. Although individual side chains before and after the pTXpY sequence of the substrate did not have a significant effect on rWip1 activity, a chain length of at least five residues, including the pTXpY sequence, was important for substrate recognition by rWip1. Moreover, the X residue in the pTXpY sequence affected affinity for rWip1 and correlated with selectivity for MAPKs. These findings suggest that substrate recognition by Wip1 is centered toward a very narrow region around the pTXpY sequence. Three-dimension homology models of Wip1 with bound substrate peptides were constructed, and site-directed mutagenesis was performed to confirm the importance of specific residues for substrate recognition. The results of our study should be useful for predicting new physiological substrates and for designing specific Wip1 inhibitors. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, SAIC Frederick Inc, Prot Express Lab, Ft Detrick, MD 21702 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM appellae@pop.nci.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 43 TC 46 Z9 48 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 12 PY 2005 VL 44 IS 14 BP 5285 EP 5294 DI 10.1021/bi0476634 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914UC UT WOS:000228252300002 PM 15807522 ER PT J AU Ignatov, ME Berdis, AJ Le Grice, SFJ Barkley, MD AF Ignatov, ME Berdis, AJ Le Grice, SFJ Barkley, MD TI Attenuation of DNA replication by HIV-1 reverse transcriptase near the central termination sequence SO BIOCHEMISTRY LA English DT Article ID STEADY-STATE KINETICS; RNASE-H ACTIVITY; EXTINCTION COEFFICIENTS; FLUORESCENCE PROPERTIES; ANGSTROM RESOLUTION; POLYMERASE-ACTIVITY; DRUG-RESISTANCE; MECHANISM; POLYMERIZATION; BACTERIOPHAGE-T4 AB Previous pre-steady-state kinetic studies of equine infectious anemia virus-1 (EIAV) reverse transcriptase (RT) showed two effects of DNA substrates containing the central termination sequence (CTS) on the polymerization reaction: reduction of burst amplitude in single nucleotide addition experiments and accumulation of termination products during processive DNA synthesis [Berdis, A. J., Stetor, S. R., Le Grice, S. F. J., and Barkley, M. D. (2001) Biochemistry 40, 12140-12149]. The present study of HIV RT uses pre-steady-state kinetic techniques to evaluate the molecular mechanisms of the lower burst amplitudes using both random sequence and CTS-containing DNA substrates. The effects of various factors, including primer/template length, binding orientation, and protein concentration, on the burst amplitude were determined using random sequence DNA substrates. The percent active RT increases with total RT concentration, indicating that reversible dissociation of RT dimer is responsible for substoichiometric burst amplitudes with normal substrates. This finding was confirmed by gel mobility shift assays. Like EIAV RT, HIV RT showed lower burst amplitudes on CTS-containing DNA substrates compared to random sequences. The dissociation kinetics of RT-DNA complexes were monitored by enzyme activity and fluorescence. Biphasic kinetics were observed for both random sequence and CTS-containing DNA complexes, revealing two forms of the RT-DNA complex. A mechanism is proposed to account for reduction in burst amplitude of CTS-containing DNA that is consistent with the results of both single nucleotide addition and dissociation experiments. The two forms of the RT-DNA complex may represent partitioning of primer/template between the P- and N-sites on RT for the nucleic acid substrate. C1 Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Berdis, AJ (reprint author), Case Western Reserve Univ, Dept Pharmacol, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM ajb15@case.edu; mdb4@case.edu RI Barkley, Mary/C-6973-2011 FU NIGMS NIH HHS [GM52263] NR 55 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 12 PY 2005 VL 44 IS 14 BP 5346 EP 5356 DI 10.1021/bi048000p PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914UC UT WOS:000228252300008 PM 15807528 ER PT J AU Roy, S Dimitriadis, EK Kar, S Geanacopoulos, M Lewis, MS Adhya, S AF Roy, S Dimitriadis, EK Kar, S Geanacopoulos, M Lewis, MS Adhya, S TI Gal repressor-operator-HU temary complex: Pathway of repressosome formation SO BIOCHEMISTRY LA English DT Article ID INTEGRATION HOST FACTOR; SITE-SPECIFIC BINDING; ESCHERICHIA-COLI; RNA-POLYMERASE; DNA LOOP; TRANSCRIPTION; PROTEIN; CONTAINS; PROMOTER; HMG1 AB transaction reactions require formation of nucleoprotein complexes that involve multifaceted DNA-protein and protein-protein interactions. Genetic and biochemical studies suggested that the higher order Gal repressosome structure, which governs the transcription of two tandem gal promoters in Escherichia coli, involves sequence-specific binding of GalR repressor dimers to two operators, O-E and O-I, located 113 bp apart, binding of GalR to the sequence-nonspecific DNA binding protein HU, interaction of HU with an architecturally critical DNA site between the two operators, and interaction between two DNA-bound GalR dimers generating a loop of the intervening DNA segment. In this paper, we demonstrate and determine the thermodynamic parameters of several of these interactions, GalR dimer-O-E, GalR tetramerization, HU-GalR, and HU-GalR-O-E interactions, by analytical ultracentrifugation, fluorescence anisotropy, and fluorescence resonance energy transfer. The physiological significance of several of these interactions was confirmed by the finding that a mutant HU, which is unable to form the repressosome in vivo and in vitro, failed to show the HU-GalR interaction. The results help to construct a pathway of Gal repressosome assembly. C1 NCI, Mol Biol Lab, ORS OD, Bethesda, MD 20892 USA. NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Bose Inst, Dept Biophys, Kolkata 700019, W Bengal, India. RP Adhya, S (reprint author), NCI, Mol Biol Lab, ORS OD, 37 Convent Dr,Room 5138, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 30 TC 14 Z9 14 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 EI 1943-295X J9 BIOCHEMISTRY-US JI Biochemistry PD APR 12 PY 2005 VL 44 IS 14 BP 5373 EP 5380 DI 10.1021/bi047720t PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914UC UT WOS:000228252300010 PM 15807530 ER PT J AU Stone, PH Lloyd-Jones, DM Kinlay, S Frei, B Carlson, W Rubenstein, J Andrews, TC Johnstone, M Sopko, G Cole, H Orav, J Selwyn, AP Creager, MA AF Stone, PH Lloyd-Jones, DM Kinlay, S Frei, B Carlson, W Rubenstein, J Andrews, TC Johnstone, M Sopko, G Cole, H Orav, J Selwyn, AP Creager, MA CA Vascular Basis Study Grp TI Effect of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on myocardial ischemia in patients with stable coronary artery disease - The vascular basis for the treatment of myocardial ischemia study SO CIRCULATION LA English DT Article DE antioxidants; cholesterol; coronary disease; exercise; vasoconstriction ID ENDOTHELIUM-DEPENDENT VASODILATION; HYPERCHOLESTEROLEMIC HUMANS; CHOLESTEROL REDUCTION; ANGINA-PECTORIS; THERAPY; VASOMOTION; EXERCISE; IMPROVES; STATINS; ATHEROSCLEROSIS AB Background-Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia. Methods and Results-In a randomized, double-blind, placebo-controlled trial, 300 patients with stable coronary disease, a positive exercise treadmill test, 48-hour ambulatory ECG with >= 1 episode of ischemia, and fasting total cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) (n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL (n=103; control group). Ischemia end points, including ambulatory ECG monitoring and exercise treadmill testing, and endothelial assessment using brachial artery flow-mediated dilation were obtained at baseline and at 6 and 12 months. Baseline characteristics were similar in all groups. LDL decreased from approximate to 153 mg/dL at baseline in the 2 atorvastatin groups to approximate to 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in the control group (P<0.0001). During ambulatory ECG monitoring, mean number of ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; P = 0.15 across groups), without a change in daily heart rate activity. Mean duration of ischemia for 48 hours decreased 26% to 62% in each group (each P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment depression significantly increased in each group, but total exercise duration and mean sum of maximum ST depression were unchanged. Angina frequency decreased in each group. There was no incremental effect of supplemental vitamins C and E on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful changes. Conclusions-Intensive lipid lowering with atorvastatin to an LDL level of 80 mg/dL, with or without antioxidant vitamins, does not provide any further benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina frequency than moderate lipid lowering with diet and low-dose lovastatin to an LDL level of <120 mg/dL. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Newton Wellesley Hosp, Newton, MA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Oregon State Univ, Corvallis, OR 97331 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Stone, PH (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM pstone@partners.org RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [R01-HL38780] NR 37 TC 31 Z9 33 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 BP 1747 EP 1755 DI 10.1161/01.CIR.0000160866.90148.76 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900005 PM 15809368 ER PT J AU Cantrell, RA Howard, G Howard, VJ Prineas, RJ Cushman, M Gomez, CR Moy, CS Temple, E AF Cantrell, RA Howard, G Howard, VJ Prineas, RJ Cushman, M Gomez, CR Moy, CS Temple, E TI Differences in predicted 10-year risk of stroke by region and race SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Univ Vermont, Burlington, VT USA. Alabama Neurol Inst, Birmingham, AL USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P134 BP E212 EP E213 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900160 ER PT J AU Cao, JJ Arnold, AM Manolio, TA Psaty, BM Hirsch, CH Polak, JF Kuller, LH Cushman, M AF Cao, JJ Arnold, AM Manolio, TA Psaty, BM Hirsch, CH Polak, JF Kuller, LH Cushman, M TI Carotid atherosclerosis quality and quantity, C-reactive protein and future cardiovascular disease: The cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Davis, Davis, CA 95616 USA. Tufts Univ, Boston, MA 02111 USA. Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P27 BP E190 EP E190 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900053 ER PT J AU Carnethon, MR Bertoni, AG Shea, S Greenland, P Ni, HY Saad, M Liu, K AF Carnethon, MR Bertoni, AG Shea, S Greenland, P Ni, HY Saad, M Liu, K TI Racial/ethnic differences in subclinical atherosclerosis in diabetes: Multi Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Columbia, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P36 BP E192 EP E192 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900062 ER PT J AU Ebbesson, SO Carter, EA Resnick, HE Nobmann, ED Devereux, RB Dyke, B MacCluer, JW Fabsitz, RR Howard, BV AF Ebbesson, SO Carter, EA Resnick, HE Nobmann, ED Devereux, RB Dyke, B MacCluer, JW Fabsitz, RR Howard, BV TI Omega 3 fatty acid consumption and components of the metabolic syndrome in Eskimos: The Gocadan study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 MedStar Res Inst, Hyattsville, MD USA. IDM Consulting, Anchorage, AK USA. Cornell Med Ctr, New York, NY USA. SW Icon, San Antonio, TX USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P119 BP E209 EP E209 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900144 ER PT J AU Eilat-Adar, S Xu, JQ Resnick, HE Loria, C Mattil, C Howard, BV AF Eilat-Adar, S Xu, JQ Resnick, HE Loria, C Mattil, C Howard, BV TI Calcium intake is inversely associated with BMI in American Indians SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Medstar Res Inst, Hyattsville, MD USA. Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P116 BP E208 EP E209 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900141 ER PT J AU Eiriksdottir, G Aspelund, T Bjarnadottir, K Olafsdottir, E Launer, L Harris, T Gudnason, V AF Eiriksdottir, G Aspelund, T Bjarnadottir, K Olafsdottir, E Launer, L Harris, T Gudnason, V TI Apolipoprotein E genotype and statin use associated with C-reactive protein levels irrespective of coronary event: The AGES-Reykjavik Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Iceland Heart Assoc, Kopavogur, Iceland. NIA, NIH, Bethesda, MD 20892 USA. IHA, Kopavogur, Iceland. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA 5 BP E249 EP E250 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900338 ER PT J AU Elosua, R Ordovas, JM Cupples, LA Lai, CQ Demissie, S Fox, CS Polak, JF Wolf, PA D'Agostino, RA O'Donnell, CJ AF Elosua, R Ordovas, JM Cupples, LA Lai, CQ Demissie, S Fox, CS Polak, JF Wolf, PA D'Agostino, RA O'Donnell, CJ TI Variability at the Apoa5 locus is associated with common carotid intimal medial thickness with a modifying effect of obesity: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Inst Municipal Invest Med, E-08003 Barcelona, Spain. Tufts Univ, Sch Med, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P175 BP E221 EP E221 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900200 ER PT J AU Freitag, MH Petrovitch, H Masaki, KH Ross, GW White, LR Peila, R Launer, LJ AF Freitag, MH Petrovitch, H Masaki, KH Ross, GW White, LR Peila, R Launer, LJ TI Pulse pressure and the risk of dementia: The Honolulu Asia Aging Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Pacific Hlth Res Inst, Honolulu, HI USA. NIA, NIH, Bethesda, MD 20892 USA. RI Freitag, Michael/G-4887-2011 OI Freitag, Michael/0000-0002-7572-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P238 BP E233 EP E233 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900263 ER PT J AU Gudnason, V Aspelund, T Thorgeirsson, G Eiriksdottir, G Sigurdsson, S Karlsdottir, G Launer, L Detrano, R Harris, T AF Gudnason, V Aspelund, T Thorgeirsson, G Eiriksdottir, G Sigurdsson, S Karlsdottir, G Launer, L Detrano, R Harris, T TI Coronary and aortic calcium increase differently with age in those with and without history of coronary event (myocardial infarction, PCI and CABG): The AGES-Reykjavik Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Iceland Heart Assoc, Kopavogur, Iceland. NIA, Bethesda, MD 20892 USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P39 BP E193 EP E193 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900065 ER PT J AU Harris, TB Yanez, D Kuller, L Newman, A Cushman, M Chaves, PH Fried, LP Tracy, R AF Harris, TB Yanez, D Kuller, L Newman, A Cushman, M Chaves, PH Fried, LP Tracy, R TI Interleukin-6 as a predictor of cardiovascular and noncardiovascular mortality: The cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 NIA, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Vermont, Burlington, VT USA. Johns Hopkins Sch Med, Baltimore, MD USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P210 BP E227 EP E228 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900235 ER PT J AU Jaquish, CE Province, MA AF Jaquish, CE Province, MA CA NHLBI Genelink Investigators TI NHLBI GeneLink: A collaborative resource for gene localization SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 NIH, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P200 BP E226 EP E226 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900225 ER PT J AU Jonsdottir, B Lang, T Aspelund, T Detrano, R Sigurdsson, G Chen, HP Sigurdsson, S Garcia, M Eiriksdottir, G Launer, L Gudnason, V Harris, TB AF Jonsdottir, B Lang, T Aspelund, T Detrano, R Sigurdsson, G Chen, HP Sigurdsson, S Garcia, M Eiriksdottir, G Launer, L Gudnason, V Harris, TB TI Associations of vascular calcification and bone mineral from quantitative computerized tomography of the spine are explained by age and other risk factors: The Age, Gene/Evironment Susceptibility Reykjavik Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Iceland Heart Assoc, Reykjavik, Iceland. Univ Calif San Francisco, San Francisco, CA 94143 USA. Harbor Hosp Ctr, Los Angeles, CA USA. NIA, Bethesda, MD 20892 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P54 BP E196 EP E196 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900080 ER PT J AU Kanaya, AM Fyr, CW Cesari, M Nicklas, B Harris, T Satterfield, S Newman, A Cummings, S AF Kanaya, AM Fyr, CW Cesari, M Nicklas, B Harris, T Satterfield, S Newman, A Cummings, S TI Adiponectin and coronary heart disease: Differential association for whites and blacks SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. Univ Memphis, Memphis, TN 38152 USA. Univ Pittsburgh, Pittsburgh, PA USA. Calif Pacific Med Ctr, San Francisco, CA USA. RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013 OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P205 BP E226 EP E227 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900230 ER PT J AU Kaplan, RC Tirschwell, DL Longstreth, WT Manollo, TA Heckbert, SR Lefkowtiz, D El-Saed, A Psaty, BM AF Kaplan, RC Tirschwell, DL Longstreth, WT Manollo, TA Heckbert, SR Lefkowtiz, D El-Saed, A Psaty, BM TI High risk of vascular events and underutilization of preventive therapies following ischemic stroke among older adults: The Cardiovascular Health Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Washington, Seattle, WA 98195 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA USA. RI Kaplan, Robert/A-2526-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P296 BP E245 EP E245 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900320 ER PT J AU Kathiresan, S Yang, Q Larson, MG Lochner, A Tofler, GH Hirschhorn, JN Gabriel, SB O'Donnell, CJ AF Kathiresan, S Yang, Q Larson, MG Lochner, A Tofler, GH Hirschhorn, JN Gabriel, SB O'Donnell, CJ TI Relations of common haplotypes in five coagulation and fibrinolytic genes, plasma level of hemostatic factors, and risk of cardiovascular disease SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Royal N Shore Hosp, Sydney, NSW, Australia. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA 7 BP E250 EP E250 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900340 ER PT J AU McNeill, AM Katz, R Girman, CJ Rosamond, WD Wagenknecht, L Savage, PJ Barzilay, JI Tracy, RP Jackson, SA AF McNeill, AM Katz, R Girman, CJ Rosamond, WD Wagenknecht, L Savage, PJ Barzilay, JI Tracy, RP Jackson, SA TI Metabolic syndrome and incident cardiovascular disease in the elderly (The Cardiovascular Health Study) SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ N Carolina, Chapel Hill, NC USA. Univ Washington, Seattle, WA 98195 USA. Merck Res Labs, Blue Bell, PA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Kaiser Permanente Georgia, Tucker, GA USA. Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA 13 BP E251 EP E251 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900346 ER PT J AU Melenovsky, V Shetty, V Muller, DC Fleg, JL Andres, R Ferrucci, L Lakatta, EG Najjar, SS AF Melenovsky, V Shetty, V Muller, DC Fleg, JL Andres, R Ferrucci, L Lakatta, EG Najjar, SS TI Resting energy expenditure is an independent predictor of the metabolic syndrome: The Baltimore Longitudinal Study of Aging SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P65 BP E198 EP E198 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900091 ER PT J AU Mosher, MJ Howard, BV Lee, E Best, LG Fabsitz, R MacCluer, JW North, KE Lange, L AF Mosher, MJ Howard, BV Lee, E Best, LG Fabsitz, R MacCluer, JW North, KE Lange, L TI Evidence of sex-specific dietary and genetic effects on HDL and APOA-1 variation: The Strong Heart Family Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ N Carolina, Chapel Hill, NC USA. MedStar Res Inst, Hyattsville, MD USA. Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P160 BP E218 EP E218 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900185 ER PT J AU Newton-Cheh, C Larson, MG Guo, CY Musone, SL Drake, J Lochner, A Kathiresan, S Vasan, RS Levy, D Benjamin, EJ Hirschhorn, JN O'Donnell, CJ AF Newton-Cheh, C Larson, MG Guo, CY Musone, SL Drake, J Lochner, A Kathiresan, S Vasan, RS Levy, D Benjamin, EJ Hirschhorn, JN O'Donnell, CJ TI Association of genetic variants in KCNH2 with QT interval duration in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P170 BP E220 EP E220 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900195 ER PT J AU Obarzanek, E Vollmer, WM Appel, LJ Ard, JD Cooper, LS Elmer, PJ Harsha, DW Lin, PH Simons-Morton, DG Stevens, VJ Svetkey, LP Young, DR AF Obarzanek, E Vollmer, WM Appel, LJ Ard, JD Cooper, LS Elmer, PJ Harsha, DW Lin, PH Simons-Morton, DG Stevens, VJ Svetkey, LP Young, DR TI Weight loss best predicts systolic blood pressure at 6 months in multicomponent lifestyle interventions SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Alabama, Birmingham, AL USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Duke Hypertens Ctr, Durham, NC USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P245 BP E234 EP E235 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900270 ER PT J AU Pella, R Aspelund, T Sigurdsson, S Detrano, R van Buchem, MA Kjartansson, O Thorgelrsson, G Eiriksdottir, G Jonsson, PV Harris, T Gudnason, V Launer, LJ AF Pella, R Aspelund, T Sigurdsson, S Detrano, R van Buchem, MA Kjartansson, O Thorgelrsson, G Eiriksdottir, G Jonsson, PV Harris, T Gudnason, V Launer, LJ TI Association between vascular calcification and cerebral white matter lesions in a population based cohort: Age, Gene/Environment Susceptibility (AGES) Reykjavik Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 NIA, Bethesda, MD 20892 USA. Iceland Heart Assoc, Kopavogur, Iceland. Univ Calif Los Angeles, Torrance, CA USA. Leiden Univ, Med Ctr, Leiden, Netherlands. Landspitali Univ Hosp Hringbraut, Reykjavik, Iceland. Landspitali Univ Hosp Landakot, Reykjavik, Iceland. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P23 BP E189 EP E189 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900049 ER PT J AU Pletcher, MJ Hulley, BJ Houston, T Kiefe, CI Sidney, S AF Pletcher, MJ Hulley, BJ Houston, T Kiefe, CI Sidney, S TI Are mentholated cigarettes more addictive or more harmful than non-mentholated cigarettes? Results from CARDIA SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Kaiser Permanente, Div Res, Oakland, CA USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P271 BP E239 EP E240 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900295 ER PT J AU Pollitt, RA Beck, JD Offenbacher, S Rose, KM Sorlie, P Heiss, G AF Pollitt, RA Beck, JD Offenbacher, S Rose, KM Sorlie, P Heiss, G TI Adult and cumulative life-course socioeconomic status and inflammatory burden SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ N Carolina, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P208 BP E227 EP E227 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900233 ER PT J AU Rodondi, N Newman, AB Vittinghoff, E de Rekeneire, N Satterfield, S Harris, TB Bauer, DC AF Rodondi, N Newman, AB Vittinghoff, E de Rekeneire, N Satterfield, S Harris, TB Bauer, DC TI Subclinical hypothyroidism and the risk of cardiovascular events and death in older adults: The Health, Aging and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 UCSF, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Memphis, TN USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA 31 BP E255 EP E255 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900364 ER PT J AU Shea, S Barr, RG Ma, SG Crouse, JR Manolio, TA Saad, MA O'Leary, D AF Shea, S Barr, RG Ma, SG Crouse, JR Manolio, TA Saad, MA O'Leary, D TI Inflammatory factors and carotid intima-media thickness in the multi-ethnic study of atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Columbia Univ, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Tufts New England Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P231 BP E232 EP E232 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900256 ER PT J AU Sotoodehnia, N Vatta, M Lemaitre, RN Rautaharju, P Durda, P Towbin, JA Friedlander, Y Tracy, RP Manolio, T Burke, GL Kuller, LH Siscovick, DS AF Sotoodehnia, N Vatta, M Lemaitre, RN Rautaharju, P Durda, P Towbin, JA Friedlander, Y Tracy, RP Manolio, T Burke, GL Kuller, LH Siscovick, DS TI KCNE1 gene D85N variant, QT interval, and risk of mortality SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Washington, Seattle, WA 98195 USA. Baylor Coll Med, Houston, TX 77030 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Vermont, Burlington, VT USA. Hebrew Univ Jerusalem, Jerusalem, Israel. NHLBI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P189 BP E223 EP E223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900214 ER PT J AU Taylor, HA Han, H Adedeji, A Fox, ER Myerson, M Skelton, T Jones, DW AF Taylor, HA Han, H Adedeji, A Fox, ER Myerson, M Skelton, T Jones, DW TI Prognosis of left ventricular systolic dysfunction in African Americans without congestive heart failure: The ARIC Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P33 BP E191 EP E192 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900059 ER PT J AU Wang, XL Thayer, JF Treiber, FA AF Wang, XL Thayer, JF Treiber, FA TI Ethnic differences and heritability of heart rate variability in African and European American youth SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Med Coll Georgia, Augusta, GA 30912 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P181 BP E222 EP E222 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900206 ER PT J AU Xu, JQ Eilat-Adar, S Howard, BV Loria, C Mattil, C Fabsitz, RR Lee, ET AF Xu, JQ Eilat-Adar, S Howard, BV Loria, C Mattil, C Fabsitz, RR Lee, ET TI Association of macronutrient intake and risk of coronary heart disease: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Medstar Res Inst, Hyattsville, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P118 BP E209 EP E209 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900143 ER PT J AU Young, DR Simons-Morton, S Brown, AJ King, AC Stevens, VJ Elmer, PJ Craddick, S Larson, D Appel, LJ Vollmer, WM Aickin, M Harsha, DW AF Young, DR Simons-Morton, S Brown, AJ King, AC Stevens, VJ Elmer, PJ Craddick, S Larson, D Appel, LJ Vollmer, WM Aickin, M Harsha, DW TI Effects of lifestyle interventions on physical activity and fitness SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Univ Maryland, College Pk, MD 20742 USA. NHLBI, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Durham, NC USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA 2 BP E249 EP E249 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900335 ER PT J AU Zhang, L Kao, WHL Berthier-Schaad, Y Liu, YM Plantinga, L Jaar, B Fink, N Powe, N Klag, M Smith, MW Coresh, J AF Zhang, L Kao, WHL Berthier-Schaad, Y Liu, YM Plantinga, L Jaar, B Fink, N Powe, N Klag, M Smith, MW Coresh, J TI Haplotype of signal transducer and activator of transcription 3 (Stat3) gene is associated with cardiovascular disease (CVD) in dialysis patients SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RI Jaar, Bernard/B-1917-2009; Jaar, Bernard/B-5026-2011; Smith, Michael/B-5341-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P182 BP E222 EP E222 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900207 ER PT J AU Subramony, SH May, W Lynch, D Gomez, C Fischbeck, K Hallett, M Taylor, P Wilson, R Ashizawa, T AF Subramony, SH May, W Lynch, D Gomez, C Fischbeck, K Hallett, M Taylor, P Wilson, R Ashizawa, T CA Cooperative Ataxia Grp TI Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale SO NEUROLOGY LA English DT Article ID CEREBELLAR-ATAXIA; SYSTEM AB Measuring the severity of neurologic dysfunction in patients with inherited ataxias, including Friedreich ataxia (FA), is difficult because of the variable rate of progression, the variable age at onset and the variety of neural systems that may be affected. The authors discuss the problems related to rating scales in the ataxias, report a neurologic rating scale for FA, and demonstrate acceptable interrater reliability of the instrument. C1 Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Dept Prevent Med, Jackson, MS 39216 USA. Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Texas, Med Branch, Dept Neurol, Galveston, TX 77555 USA. RP Subramony, SH (reprint author), Univ Mississippi, Med Ctr, Dept Neurol, 2500 N State St, Jackson, MS 39216 USA. EM ssubramony@neurology.umsmed.edu NR 8 TC 128 Z9 131 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 12 PY 2005 VL 64 IS 7 BP 1261 EP 1262 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 915BO UT WOS:000228272800032 PM 15824358 ER PT J AU Liu, J Chen, M Deng, CX Bourc'his, D Nealon, JG Erlichman, B Bestor, TH Weinstein, LS AF Liu, J Chen, M Deng, CX Bourc'his, D Nealon, JG Erlichman, B Bestor, TH Weinstein, LS TI Identification of the control region for tissue-specific imprinting of the stimulatory G protein alpha-subunit SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genomic imprinting pseudohypoparathyroidism; DNA methylation; guanine nucleotide binding protein ID PSEUDOHYPOPARATHYROIDISM TYPE IB; MOUSE-CHROMOSOME 2; GNAS LOCUS; GENE; METHYLATION; CTCF; TRANSCRIPT; EXPRESSION; RESISTANCE; G(S)ALPHA AB Gnas is a complex gene with multiple imprinted promoters. The upstream Nesp and Nespas/Gnasxl promoters are paternally and maternally methylated, respectively. The downstream promoter for the stimulatory G protein alpha-subunit (G(s)alpha) is unmethylated, although in some tissues (e.g., renal proximal tubules), G(s)alpha is poorly expressed from the paternal allele. Just upstream of the G(s)alpha promoter is a primary imprint mark (1A region) where maternal-specific methylation is established during oogenesis. Pseudohypoparathyroidism type 1B, a disorder of renal parathyroid hormone resistance, is associated with loss of 1A methylation. Analysis of embryos of Dnmt3L(-/-) mothers (which cannot methylate maternal imprint marks) showed that Nesp, Nespas/Gnasxl, and 1A imprinting depend on one or more maternal primary imprint marks. We generated mice with deletion of the 1A differentially methylated region. These mice had normal Nesp-Nespas/Gnasxl imprinting, indicating that the Gnas locus contains two independent imprinting domains (Nespas-Nespas/Gnasxl and 1A-G(s)alpha) controlled by distinct maternal primary imprint marks. Paternal, but not maternal, 1A deletion resulted in G(s)alpha overexpression in proximal tubules and evidence for increased parathyroid hormone sensitivity but had no effect on G(s)alpha expression in other tissues where G(s)alpha is normally not imprinted. The 1A region is a maternal imprint mark that contains one or more methylation-sensitive cis-acting elements that suppress G(s)alpha expression from the paternal allele in a tissue-specific manner. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov RI deng, chuxia/N-6713-2016; OI Bourc'his, Deborah/0000-0001-9499-7291 NR 33 TC 79 Z9 81 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 2005 VL 102 IS 15 BP 5513 EP 5518 DI 10.1073/pnas.0408262102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 916HS UT WOS:000228376600041 PM 15811946 ER PT J AU Kato, K Mayer, DCG Singh, S Reid, M Miller, LH AF Kato, K Mayer, DCG Singh, S Reid, M Miller, LH TI Domain III of Plasmodium falciparum apical membrane antigen 1 binds to the erythrocyte membrane protein Kx SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE erythrocyte recognition; McLeod; merozoite; malaria; invasion ID MURINE MONOCLONAL-ANTIBODY; INVASION; RECEPTOR; INDUCTION; MALARIA; CELLS AB Plasmodium falciparum apical membrane antigen 1 (AMA1) is located in the merozoite micronemes, an organelle that contains receptors for invasion, suggesting that AMA1 may play a role in this process. However, direct evidence that A falciparum AMA1 binds to human erythrocytes is lacking. In this study, we determined that domain III of AMA1 binds to the erythrocyte membrane protein, Kx, and that the rate of invasion of Kx(null) erythrocytes is reduced, indicating a significant but not unique role of AMA1 and Kx in parasite invasion of erythrocytes. Domains domains I/II and domain III of AMA1 were expressed on the surface of CHO-K1 cells, and their ability to bind erythrocytes was determined. We observed that each of these domains failed to bind untreated human erythrocytes. In contrast, domain III, but not the other domains of AMA1, bound to trypsin-treated human erythrocytes. We tested the binding of AMA1 to trypsin-treated genetically mutant human erythrocytes, missing various erythrocyte membrane proteins. AMA1 failed to bind trypsin-treated Kx(null) (McLeod) erythrocytes, which lack the Kx protein. Furthermore, treatment of humanerythrocytes with trypsin, followed by alpha-chymotrypsin, cleaved Kx and destroyed the binding of AMA1 to human erythrocytes. Lastly, the rate of invasion of Kx null erythrocytes by A falciparum was significantly lower than Kx-expressing erythrocytes. Taken together, our data suggest that AMA1 plays an important, but not exclusive, role in invasion of human erythrocytes through a process that involves exposure or modification of the erythrocyte surface protein, Kx, by a trypsin-like enzyme. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. New York Blood Ctr, New York, NY 10021 USA. RP Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lmiller@niaid.nih.gov FU NHLBI NIH HHS [HL 54459, P50 HL054459] NR 26 TC 54 Z9 56 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 2005 VL 102 IS 15 BP 5552 EP 5557 DI 10.1073/pnas.0501594102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 916HS UT WOS:000228376600048 PM 15805191 ER PT J AU Esaki, T Cook, M Shimoji, K Murphy, DL Sokoloff, L Holmes, A AF Esaki, T Cook, M Shimoji, K Murphy, DL Sokoloff, L Holmes, A TI Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebral glucose utilization; cerebral metabolism; 2-deoxy[C-14]glucose ID PRIMARY SOMATOSENSORY CORTEX; KNOCK-OUT MICE; NORMAL ANXIETY-LIKE; MONOAMINE-OXIDASE; BRAIN-SEROTONIN; BARREL CORTEX; THALAMOCORTICAL AFFERENTS; TRANSIENT EXPRESSION; AGGRESSIVE-BEHAVIOR; THALAMIC AFFERENTS AB There is growing evidence that serotonin (5-hydroxtryptamine, 5-HT) has major influences on brain development in mammals. Genetic and pharmacological disruption of 5-HT signaling during early postnatal development in rodents causes neuroanatomical cortical abnormalities, including malformations in the somatosensory cortex. Possible functional consequences of this developmental perturbation by 5-HT are not yet understood. We have examined the effects of deletion of the 5-HT transporter (5-HTT) gene on somatosensory responses to sensory stimulation in mice. Local cerebral glucose utilization (1CMR(glc)) was measured by the quantitative 2-deoxy[C-14]glucose method during unilateral whisker stimulation in awake adult mice. 1CMR(glc) was increased by stimulation but to a markedly lesser extent in 5-HTT-/- mice than in 5-HTT+/+ controls in each of four major stations in the whisker-to-barrel cortex pathway (the spinal and principal sensory trigeminal nuclei, the ventral posteromedial thalamic nucleus, and the barrel region of the somatosensory cortex). Lowering brain 5-HT levels by administration of the selective tryptophan hydroxylase inhibitor p-chlorophenylalanine on postnatal days 0 and 1 restored the metabolic responses to functional activation in the whisker-to-barrel cortex pathway in adult 5-HTT-/- mice. These results indicate that functional deficits in this pathway in 5-HTT-/- mice may be due to excessive postnatal 5-HT activity. With or without postnatal p-chlorophenylalanine treatment, 5-HTT-/- mice exhibited lower resting (unstimulated) 1CMR(glc) than did 5-HTT+/+ controls in the whisker-to-barrel cortex pathway and throughout the brain. These findings have implications for understanding the potential long-term consequences of genetic and pharmacological disruption of 5-HT neurotransmission on cerebral functions during critical periods of postnatal development. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,1A-07,36 Convent Dr,MSC 4030, Bethesda, MD 20892 USA. EM louissokoloff@mail.nih.gov NR 54 TC 59 Z9 60 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 2005 VL 102 IS 15 BP 5582 EP 5587 DI 10.1073/pnas.0501509102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 916HS UT WOS:000228376600053 PM 15809439 ER PT J AU Stewart, KJ Bacher, A Turner, KL Fleg, JL Hees, PS Shapiro, EP Tayback, M Ouyang, P AF Stewart, KJ Bacher, A Turner, KL Fleg, JL Hees, PS Shapiro, EP Tayback, M Ouyang, P TI Effect of exercise on blood pressure in older persons - A randomized controlled trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID VISCERAL ADIPOSE-TISSUE; SYSTOLIC HYPERTENSION; MILD HYPERTENSION; PHYSICAL-ACTIVITY; BODY-FAT; WOMEN; PREVENTION; FITNESS AB Background: Because of age-related differences in the cause of hypertension, it is uncertain whether current exercise guidelines for reducing blood pressure (BP) are applicable to older persons. Few exercise studies in older persons have evaluated BP changes in relation to changes in body composition or fitness. Methods: This was a 6-month randomized controlled trial of combined aerobic and resistance training; controls followed usual care physical activity and diet advice. Participants (aged 55-75 years) had untreated systolic BP (SBP) of 130 to 159 mm Hg or diastolic BP (DBP) of 85 to 99 mm Hg. Results: Fifty-one exercisers and 53 controls completed the trial. Exercisers significantly improved aerobic and strength fitness, increased lean mass, and reduced general and abdominal obesity. Mean decreases in SBP and DBP, respectively, were 5.3 and 3.7 min Hg among exercisers and 4.5 and 1.5 mm Hg among controls (P <.001 for all). There were no significant group differences in mean SBP change from baseline (-0.8 mm Hg; P=.67). The mean DBP reduction was greater among exercisers (-2.2 mm Hg; P=.02). Aortic stiffness, indexed by aortofemoral pulse-wave velocity, was unchanged in both. groups. Body composition improvements explained 8% of the SBP reduction (P=.006) and 17% of the DBP reduction (P <.001). Conclusions: A 6-month program of aerobic and resistance training lowered DBP but not SBP in older adults with mild hypertension more than in controls. The concomitant lack of improvement in aortic stiffness in exercisers suggests that older persons may be resistant to exercise-induced reductions in SBP. Body composition improvements were associated with BP reductions and may be a pathway by which exercise training improves cardiovascular health in older men and women. C1 Johns Hopkins Bayview Med Ctr, Johns Hopkins Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21224 USA. NIA, Johns Hopkins Sch Med, Div Cardiol, NIH, Baltimore, MD USA. NIA, Johns Hopkins Sch Med, Div Geriatr Med, NIH, Baltimore, MD USA. NIA, Johns Hopkins Sch Med, Div Gerontol, NIH, Baltimore, MD USA. NIA, Johns Hopkins Sch Med, Dept Med, NIH, Baltimore, MD USA. NIA, Johns Hopkins Sch Med, Gerontol Res Ctr, NIH, Baltimore, MD USA. Natl Heart Lung & Blood Inst, NIH, Bethesda, MD USA. RP Stewart, KJ (reprint author), Johns Hopkins Bayview Med Ctr, Johns Hopkins Sch Med, Div Cardiol, Dept Med, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM kstewart@jhmi.edu FU NCRR NIH HHS [M01-RR-02719]; NHLBI NIH HHS [R01HL59164] NR 23 TC 91 Z9 102 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 11 PY 2005 VL 165 IS 7 BP 756 EP 762 DI 10.1001/archinte.165.7.756 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 915MR UT WOS:000228308800007 PM 15824294 ER PT J AU Goodpaster, BH Krishnaswami, S Harris, TB Katsiaras, A Kritchevsky, SB Simonsick, EM Nevitt, M Holvoet, P Newman, AB AF Goodpaster, BH Krishnaswami, S Harris, TB Katsiaras, A Kritchevsky, SB Simonsick, EM Nevitt, M Holvoet, P Newman, AB TI Obesity, regional body fat distribution, and the metabolic syndrome in older men and women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; ADIPOSE-TISSUE DISTRIBUTION; INSULIN-RESISTANCE SYNDROME; IMPAIRED GLUCOSE-TOLERANCE; SUBCUTANEOUS ABDOMINAL FAT; VISCERAL FAT; COMPUTED-TOMOGRAPHY; LIFE-STYLE; US ADULTS AB Background: The metabolic syndrome is a disorder that includes dyslipidemia, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cardiovascular disease. We determined whether patterns of regional fat deposition are associated with metabolic syndrome in older adults. Methods: A cross-sectional study was performed that included a random, population-based, volunteer sample of Medicare-eligible adults within the general communities of Pittsburgh, Pa, and Memphis, Tenn. The subjects consisted of 3035 men and women aged 70 to 79 years, of whom 41.7% were black. Metabolic syndrome was defined by Adult Treatment Panel III criteria, including serum triglyceride level, high-density lipoprotein cholesterol level, glucose level, blood pressure, and waist circumference. Visceral, subcutaneous abdominal, intermuscular, and subcutaneous thigh adipose tissue was measured by computed tomography. Results: Visceral adipose tissue was associated with the metabolic syndrome in men who were of normal weight (odds ratio, 95% confidence interval: 2.1, 1.6-2.9), overweight (1.8, 1.5-2.1), and obese (1.2, 1.0-1.5), and in women who were of normal weight (3.3, 2.4-4.6), overweight (2.4, 2.0-3.0), and obese (1.7, 1.4-2.1), adjusting for race. Subcutaneous abdominal adipose tissue was associated with the metabolic syndrome only in normal-weight men (13, 1.1-1.7). Intermuscular adipose tissue was associated with the metabolic syndrome in normal-weight (2.3, 1.6-3.5) and overweight (1.2, 1.1-1.4) men. In contrast, subcutaneous thigh adipose tissue was inversely associated with the metabolic syndrome in obese men (0.9, 0.8-1.0) and women (0.9, 0.9-1.0). Conclusion: In addition to general obesity, the distribution of body fat is independently associated with the metabolic syndrome in older men and women, particularly among those of normal body weight. C1 Univ Pittsburgh, Ctr Med, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. NIA, Res Program, Baltimore, MD USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA USA. Catholic Univ, Ctr Expt Surg & Anesthesiol, Louvain, Belgium. RP Goodpaster, BH (reprint author), Univ Pittsburgh, Ctr Med, Dept Med, 809 N MUH, Pittsburgh, PA 15213 USA. EM bgood@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [K01-AG-00851, N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 36 TC 284 Z9 303 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 11 PY 2005 VL 165 IS 7 BP 777 EP 783 DI 10.1001/archinte.165.7.777 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 915MR UT WOS:000228308800010 PM 15824297 ER PT J AU Venable, RM Delaglio, F Norris, SE Freedberg, DI AF Venable, RM Delaglio, F Norris, SE Freedberg, DI TI The utility of residual dipolar couplings in detecting motion in carbohydrates: application to sucrose SO CARBOHYDRATE RESEARCH LA English DT Article DE sucrose; residual dipolar coupling; carbohydrate structure; carbohydrate dynamics; heteronuclear NMR ID LIQUID-CRYSTALLINE MEDIUM; C-13 NMR RELAXATION; AQUEOUS-SOLUTION; CONFORMATIONAL-ANALYSIS; FORCE-FIELD; OPTICAL-ROTATION; HYDROXYL PROTONS; PROTEINS; OLIGOSACCHARIDES; MACROMOLECULES AB The solution structure and dynamics of sucrose are examined using a combination of NMR residual dipolar coupling and molecular mechanics force fields. It is found that the alignment tensors of the individual rings are different, and that fitting 35 measured residual dipolar couplings to structures with specific phi, psi values indicates the presence of three major conformations: 0, psi = (120 degrees, 270 degrees), (45 degrees, 300 degrees) and (90 degrees, 180 degrees). Furthermore, fitting two structures simultaneously to the 35 residual dipolar couplings results in a substantial improvement in the fits. The existence of multiple conformations having similar stabilities is a strong indication of motion, due to the interconversion among these states. Results from four molecular mechanics force fields are in general agreement with the experimental results. However, there are major disagreements between force fields. Because fits of residual dipolar couplings to structures are dependent on the force field used to calculate the structures, multiple force fields were used to interpret NMR data. It is demonstrated that the pucker of the fructofuranosyl ring affects the calculated potential energy surface, and the fit to the residual dipolar couplings data. Previously published C-13 nuclear relaxation results suggesting that sucrose is rigid are not inconsistent with the present results when motional timescales are considered. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Freedberg, DI (reprint author), US FDA, Ctr Biol Evaluat & Res, Biophys Lab, 1401 Rockville Pike, Rockville, MD 20852 USA. EM freedberg@cber.fda.gov NR 66 TC 27 Z9 27 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD APR 11 PY 2005 VL 340 IS 5 BP 863 EP 874 DI 10.1016/j.carres.2005.01.025 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 914ET UT WOS:000228208700008 PM 15780252 ER PT J AU Yamada, A Kimura, S AF Yamada, A Kimura, S TI Induction of uteroglobin-related protein 2 (Ugrp2) expression by EGF and TGF alpha SO FEBS LETTERS LA English DT Article DE uteroglobin-related protein 2; epidermal growth factor; transforming growth factor alpha; lung epithelial cells ID RECEPTOR TYROSINE KINASES; GROWTH FACTOR-ALPHA; SIGNAL-TRANSDUCTION; GENE; MOUSE; CYTOKINE; CASCADES; CLONING; FAMILY; HIN-1 AB Uteroglobin-related protein 2 (UGRP2) is thought to play a role in inflammation and/or epithelial cell differentiation in the lung. Induction of Ugrp2 mRNA expression by epidermal growth factor (EGF) and transforming growth factor a was examined using mouse transformed lung Clara cell-derived mtCC cells. The EGF-induced increase of Ugrp2 occurred at the transcriptional level that required the EGF receptor and the activation of the ERK-MAPK and phosphoinositide-3 kinase pathways. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3112B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov NR 25 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 11 PY 2005 VL 579 IS 10 BP 2221 EP 2225 DI 10.1016/j.febslet.2005.03.017 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 915NK UT WOS:000228310700034 PM 15811345 ER PT J AU Demidenko, ZN Fojo, T Blagosklonny, MV AF Demidenko, ZN Fojo, T Blagosklonny, MV TI Complementation of two mutant p53: Implications for loss of heterozygosity in cancer SO FEBS LETTERS LA English DT Article DE cancer; p53; tumor suppressor ID WILD-TYPE P53; GENE-EXPRESSION; IN-VITRO; CELLS; GAIN; APOPTOSIS; TRANSCRIPTION; RESISTANCE; MUTATIONS; DRUG AB Remarkably, a cancer cell rarely possesses two mutant p53 proteins. Instead, mutation of one allele is usually associated with loss of the second p53 allele. Why do not two mutant p53 co-exist? We hypothesize that two different p53 may complement each other, when expressed at equal levels. By titrating trans-deficient and DNA-binding-deficient p53 in cells with mutant p53 and by co-transfecting distinct mutant p53 in p53-null cells, we demonstrated activation of p53-dependent transcription. We suggest that, due to complementation of two mutant p53, cancer cells need to delete the second p53 allele rather than mutate it. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.Ni. All rights reserved. C1 New York Med Coll, Brander Canc Res Inst, Valhalla, NY 10595 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), Ordway Res Inst, Ctr Canc, 150 New Scotland Ave, Albany, NY 12208 USA. EM Blagosklonny@hotmail.com NR 42 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 11 PY 2005 VL 579 IS 10 BP 2231 EP 2235 DI 10.1016/j.febslet.2005.03.012 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 915NK UT WOS:000228310700036 PM 15811347 ER PT J AU Zaitseva, E Mittal, A Griffin, DE Chernomordik, LV AF Zaitseva, E Mittal, A Griffin, DE Chernomordik, LV TI Class II fusion protein of alphaviruses drives membrane fusion through the same pathway as class I proteins SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SEMLIKI-FOREST-VIRUS; PH-DEPENDENT FUSION; INFLUENZA HEMAGGLUTININ FUSION; BORNE ENCEPHALITIS-VIRUS; LIPOSOMAL MODEL SYSTEM; CONFORMATIONAL-CHANGE; TRANSMEMBRANE SEGMENTS; ENVELOPE GLYCOPROTEIN; BIOLOGICAL-MEMBRANES; BACULOVIRUS GP64 AB Viral fusion proteins of classes I and II differ radically in their initial structures but refold toward similar conformations upon activation. Do fusion pathways mediated by alphavirus E1 and influenza virus hemagglutinin (HA) that exemplify classes II and I differ to reflect the difference in their initial conformations, or concur to reflect the similarity in the final conformations ? Here, we dissected the pathway of low pH-triggered E1-mediated cell-cell fusion by reducing the numbers of activated E1 proteins and by blocking different fusion stages with specific inhibitors. The discovered progression from transient hemifusion to small, and then expanding, fusion pores upon an increase in the number of activated fusion proteins parallels that established for HA-mediated fusion. We conclude that proteins as different as E1 and HA drive fusion through strikingly similar membrane intermediates, with the most energy-intensive stages following rather than preceding hemifusion. We propose that fusion reactions catalyzed by all proteins of both classes follow a similar pathway. C1 NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Indian Inst Technol, Dept Biochem Engn & Biotechnol, New Delhi 110016, India. Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Chernomordik, LV (reprint author), NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 FU NINDS NIH HHS [R01 NS038932, R01 NS018596, NS18596] NR 64 TC 53 Z9 54 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 11 PY 2005 VL 169 IS 1 BP 167 EP 177 DI 10.1083/jcb.200412059 PG 11 WC Cell Biology SC Cell Biology GA 915SU UT WOS:000228327500015 PM 15809312 ER PT J AU Qu, W Diwan, BA Reece, JM Bortner, CD Pi, JB Liu, J Waalkes, MP AF Qu, W Diwan, BA Reece, JM Bortner, CD Pi, JB Liu, J Waalkes, MP TI Cadmium-induced malignant transformation in rat liver cells: role of aberrant oncogene expression and minimal role of oxidative stress SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cadmium; oncogene; transcription factors; malignant transformation; liver ID PROSTATE EPITHELIAL-CELLS; C-JUN; GENE-EXPRESSION; APOPTOSIS; MYC; DNA; CANCER; MICE; CARCINOGENESIS; ASSOCIATION AB Our study examined the role of oxidative stress and aberrant gene expression in malignant transformation induced by chronic, low-level cadmium exposure in non-tumorigenic rat liver epithelial cell line, TRL 1215. Cells were cultured in 1.0 muM cadmium (as CdCl2) for up to 28 weeks and compared to passage-matched control cells. The level of cadmium used for transformation produced no evidence of increased superoxide (O-2(-.)) or hydrogen peroxide (11202) levels in the early stages of exposure (less than or equal to24 hr). The chronic cadmium exposed liver epithelial cells (CCE-LE) were hyperproliferative with a growth rate about 3-fold higher than control cells. CCE-LE cells produced highly aggressive tumors upon inoculation into mice confirming malignant transformation. Analysis of cellular reactive oxygen species (ROS) showed that CCE-LE cells possessed markedly lower basal levels of intracellular O-2(-) and H2O2 and were very tolerant to high-dose (50 muM) cadmium-induced ROS. Time course studies showed the production of ROS by high-dose cadmium was abolished well in advance of malignant transformation. In contrast, marked overexpression of the oncogenes c-myc and c-jun occurred in transformed CCE-LE cells as evidenced by up to 10-fold increases in both transcript and protein. A significant increase in DNA-binding activity of the transcription factors AP-1 and NF-kappaB occurred in CCE-LE cells. Increases in oncogene expression and transcription factor activity occurred concurrently with malignant transformation. Thus, cadmium-induced ROS occurs as an early, high-dose event but is abolished well in advance of malignant transformation. Low-level chronic cadmium triggers oncogene overexpression possibly by altering critical transcription factor activity. Such changes in cellular gene expression likely culminate in the loss of growth control and cadmium-induced neoplastic transformation in CCE-LE cells, whereas generation of ROS by cadmium seemed to play a minimal role in this transformation. (C) 2004 Wiley-Liss, Inc. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NCI, SAIC, Basic Res Program, Frederick, MD 21701 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 41 TC 46 Z9 48 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 2005 VL 114 IS 3 BP 346 EP 355 DI 10.1002/ijc.20736 PG 10 WC Oncology SC Oncology GA 900OB UT WOS:000227223100003 PM 15551354 ER PT J AU Camphausen, K Cerna, D Scott, T Sproull, M Burgan, WE Cerra, MA Fine, H Tofilon, PJ AF Camphausen, K Cerna, D Scott, T Sproull, M Burgan, WE Cerra, MA Fine, H Tofilon, PJ TI Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE valproic acid; radiosensitization; historic deacetylase; in vivo; murine ID HISTONE-DEACETYLASE INHIBITORS; HUMAN NEUROBLASTOMA-CELLS; SODIUM VALPROATE; GAMMA-H2AX FOCI; EXPRESSION; BUTYRATE; CANCER; RADIATION; TARGET; DRUGS AB Valproic acid (VA) is a well-tolerated drug used to treat seizure disorders and has recently been shown to inhibit histone deacetylase (HDAC). Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radiorespouse, we investigated the effects of VA on the radiosensitivity of human brain tumor cells grown in vitro and in vivo. The human brain tumor cell lines SF539 and U251 were used in our study. Histone hyperacetylation served as an indicator of HDAC inhibition. The effects of VA on tumor cell radiosensitivity in vitro were assessed using a clonogenic survival assay and gammaH2AX expression was determined as a measure of radiation-induced DNA double strand breaks. The effect of VA on the in vivo radioresponse of brain tumor cells was evaluated according to tumor growth delay analysis carried out on U251 xenografts. Irradiation at the time of maximum VA-induced histone hyperacetylation resulted in significant increases in the radiosensitivity of both SF539 and U251 cells. The radiosensitization was accompanied by a prolonged expression of gammaH2AX. VA administration to mice resulted in a clearly detectable level of histone hyperacetylation in U251 xenografts. Irradiation of U251 tumors in mice treated with VA resulted in an increase in radiation-induced tumor growth delay. Valproic acid enhanced the radiosensitivity of both SF539 and U251 cell lines in vitro and U251 xenografts in vivo, which correlated with the induction of histone hyperacetylation. Moreover, the VA-mediated increase in radiation-induced cell killing seemed to involve the inhibition of DNA DSB repair. (C) 2004 Wiley-Liss, Inc. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NCI, Neuro Oncol Branch, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov NR 38 TC 143 Z9 145 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 2005 VL 114 IS 3 BP 380 EP 386 DI 10.1002/ijc.20774 PG 7 WC Oncology SC Oncology GA 900OB UT WOS:000227223100007 PM 15578701 ER PT J AU Moore, LE Gold, L Stewart, PA Gridley, G Prince, JR Zahm, SH AF Moore, LE Gold, L Stewart, PA Gridley, G Prince, JR Zahm, SH TI Parental occupational exposures and Ewing's sarcoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Ewing's sarcoma; organic dusts; pesticides; childhood cancer ID NATIONAL CASE-CONTROL; RECALL BIAS; MULTIMODAL THERAPY; CHILDHOOD-CANCER; BREAST-CANCER; PROXY RESPONDENTS; BONE CANCER; TUMORS; ETIOLOGY; RISK AB A case-control study of Ewing's sarcoma (ES) was conducted to search for occupational exposures associated with ES. The study consisted of 196 cases and 196 random-digit controls matched on geographical region, gender, ethnic origin and birth date. A questionnaire was administered to mothers of participants to obtain information on medical conditions, medications, and parental occupations during and after the index pregnancy. An occupational exposure expert coded jobs and industries for possible and probable exposure to selected occupational hazards. Risk of ES was increased with probable parental exposure to wood dusts during their usual occupation post pregnancy (odds ration [OR] = 3.2; 95% confidence interval [CI] = 1.1-9.2). Other exposures, including a priori suspected risk factors such as exposure to pesticides and farm animals, were not significantly associated with ES. A history of household pesticide extermination was associated with ES among boys aged 15 or younger (OR = 3.0; 95% CI = 1.1-8.1), but not among girls or older boys. Our results suggest that earlier reports of associations of ES with parental farm employment may have been describing risks associated with organic dusts encountered when working on a farm, rather than agricultural exposures or other farming related exposures. (C) 2004 Wiley-Liss, Inc. C1 NCI, Occupat & Environom Epidemiol Branch, DCEG, NIH,DHHS,Div Canc Epidemiol, Bethesda, MD 20892 USA. RP Moore, LE (reprint author), NCI, Occupat & Environom Epidemiol Branch, DCEG, NIH,DHHS,Div Canc Epidemiol, 6120 Execut Bvld,EPS 8118,MCS 7249, Bethesda, MD 20892 USA. EM moorele@mail.nih.gov RI Zahm, Shelia/B-5025-2015 NR 58 TC 15 Z9 15 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 2005 VL 114 IS 3 BP 472 EP 478 DI 10.1002/ijc.20734 PG 7 WC Oncology SC Oncology GA 900OB UT WOS:000227223100022 PM 15551353 ER PT J AU Bisht, H Roberts, A Vogel, L Subbarao, K Moss, B AF Bisht, H Roberts, A Vogel, L Subbarao, K Moss, B TI Neutralizing antibody and protective immunity to SARS coronavirus infection of mice induced by a soluble recombinant polypeptide containing an N-terminal segment of the spike glycoprotein SO VIROLOGY LA English DT Article DE polypeptide; glycoprotein; respiratory tract ID ACUTE RESPIRATORY SYNDROME; ANGIOTENSIN-CONVERTING ENZYME-2; MONOCLONAL-ANTIBODY; AFRICAN-GREEN; PROTEIN; RECEPTOR; VACCINE; IMMUNIZATION; FERRETS; REPLICATION AB A secreted, glycosylated polypeptide containing amino acids 14 to 762 of the SARS coronavirus (SARS-CoV) spike protein and a polyhistidine tag was expressed in recombinant baculovirus-infected insect cells. Mice received the affinity-purified protein with either a saponin (QS21) or a Ribi (MPL + TDM) adjuvant subcutaneously and were challenged intranasally with SARS-CoV. Both regimens induced binding and neutralizing antibodies and protection against SARS-CoV intranasal infection. However, the best results were obtained with QS21 and protein, which provided the highest antibody as well as complete protection of the upper and lower respiratory tract. Published by Elsevier Inc. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 24 TC 46 Z9 53 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 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2005 VL 334 IS 2 BP 160 EP 165 DI 10.1016/j.virol.2005.01.042 PG 6 WC Virology SC Virology GA 912WW UT WOS:000228111600003 PM 15780866 ER PT J AU Kouri, JG Oldfield, EH AF Kouri, JG Oldfield, EH TI A twin with Cushing's disease SO LANCET LA English DT Editorial Material C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Kouri, JG (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 9 PY 2005 VL 365 IS 9467 BP 1332 EP 1332 DI 10.1016/S0140-6736(05)61031-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 914HY UT WOS:000228219600029 PM 15823384 ER PT J AU Steingrimsson, E Copeland, NG Jenkins, NA AF Steingrimsson, E Copeland, NG Jenkins, NA TI Melanocyte stem cell maintenance and hair graying SO CELL LA English DT Review ID C-KIT ANTIBODY; NICHE; CYCLE; DIFFERENTIATION; ACTIVATION; EXPRESSION; FATE; PAX3; MICE C1 NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. Univ Iceland, Fac Med, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. RP Jenkins, NA (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM jenkins@ncifcrf.gov NR 20 TC 56 Z9 59 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 8 PY 2005 VL 121 IS 1 BP 9 EP 12 DI 10.1016/j.cell.2005.03.021 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 915YU UT WOS:000228348500005 PM 15820674 ER PT J AU Yamashita, M Ying, SX Zhang, GM Li, CL Cheng, SY Deng, CX Zhang, YE AF Yamashita, M Ying, SX Zhang, GM Li, CL Cheng, SY Deng, CX Zhang, YE TI Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation SO CELL LA English DT Article ID GROWTH-FACTOR-BETA; ACTIVATED PROTEIN-KINASE; C-JUN; TRANSCRIPTIONAL ACTIVATION; I RECEPTOR; DIFFERENTIATION; SMAD; EXPRESSION; PROMOTER; PATHWAY AB Bone is constantly resorbed and formed throughout life by coordinated actions of osteoclasts and osteoblasts. Here we show that Smurf1, a HECT domain ubiquitin ligase, has a specific physiological role in suppressing the osteogenic activity of osteoblasts. Smurf1-deficient mice are born normal but exhibit an age-dependent increase of bone mass. The cause of this increase can be traced to enhanced activities of osteoblasts, which become sensitized to bone morphogenesis protein (BMP) in the absence of Smurf1. However, loss of Smurf1 does not affect the canonical Smad-mediated intracellular TGF beta or BMP signaling; instead, it leads to accumulation of phosphorylated MEKK2 and activation of the downstream JNK signaling cascade. We demonstrate that Smurf1 physically interacts with MEKK2 and promotes the ubiquitination and turnover of MEKK2. These results indicate that Smurf1 negatively regulates osteoblast activity and response to BMP through controlling MEKK2 degradation. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Lab Anim Sci Program, Frederick, MD 21702 USA. NIDDKD, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM yingz@helix.nih.gov RI Zhang, Ying/G-3657-2015; deng, chuxia/N-6713-2016 OI Zhang, Ying/0000-0003-2753-7601; FU Intramural NIH HHS [Z01 BC010419-08, ZIA BC011168-01] NR 51 TC 178 Z9 192 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 8 PY 2005 VL 121 IS 1 BP 101 EP 113 DI 10.1016/j.cell.2005.01.035 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 915YU UT WOS:000228348500013 PM 15820682 ER PT J AU Park, H Adsit, FG Boyington, JC AF Park, H Adsit, FG Boyington, JC TI The 1.4 angstrom crystal structure of the human oxidized low density lipoprotein receptor Lox-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARTERY ENDOTHELIAL-CELLS; LECTIN-LIKE DOMAIN; MACROPHAGE SCAVENGER RECEPTOR; OX-LDL RECEPTOR-1; SUPPORTS ADHESION; UP-REGULATION; BINDING; PROTEIN; ATHEROSCLEROSIS; RECOGNITION AB The lectin-like oxidized low density lipoprotein receptor-1 (Lox-1) mediates the recognition and internalization of oxidatively modified low density lipoprotein by vascular endothelial cells. This interaction results in a number of pro-atherogenic cellular responses that probably play a significant role in the pathology of atherosclerosis. The 1.4 angstrom crystal structure of the extracellular C-type lectin-like domain of human Lox-1 reveals a heart-shaped homodimer with a ridge of six basic amino acids extending diagonally across the apolar top of Lox-1, a central hydrophobic tunnel that extends through the entire molecule, and an electrostatically neutral patch of 12 charged residues that resides next to the tunnel at each opening. Based on the arrangement of critical binding residues on the Lox-1 structure, we propose a binding mode for the recognition of modified low density lipoprotein and other Lox-1 ligands. C1 NIEHS, Biomol Crystallog Grp, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Boyington, JC (reprint author), NIEHS, Biomol Crystallog Grp, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM boyingt1@niehs.nih.gov NR 41 TC 48 Z9 49 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 APR 8 PY 2005 VL 280 IS 14 BP 13593 EP 13599 DI 10.1074/jbc.M500768200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500052 PM 15695803 ER PT J AU Hoffert, JD Chou, CL Fenton, RA Knepper, MA AF Hoffert, JD Chou, CL Fenton, RA Knepper, MA TI Calmodulin is required for vasopressin-stimulated increase in cyclic AMP production in inner medullary collecting duct SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OLFACTORY ADENYLYL-CYCLASE; WATER CHANNELS; UREA TRANSPORTER; RAT-KIDNEY; KINASE-II; CELLS; CALCIUM; PHOSPHORYLATION; MEMBRANE; AQUAPORIN-2 AB Calmodulin plays a critical role in regulation of renal collecting duct water permeability by vasopressin. However, specific targets for calmodulin action have not been thoroughly addressed. In the present study, we investigated whether Ca2+/calmodulin regulates adenylyl cyclase activity in the renal inner medullary collecting duct. Rat inner medullary collecting duct suspensions were incubated in the presence or absence of 0.1 nM vasopressin and the calmodulin inhibitors, monodansylcadaverine, W-7, and trifluoperazine, followed by measurement of cAMP. Vasopressin-stimulated cAMP elevation was significantly attenuated in the presence of calmodulin inhibitors. Analysis of transglutaminase 2 knock-out mice confirmed that these compounds were not acting through inhibition of transglutaminase 2 activity. Calmodulin inhibitors also blocked both cholera toxin- and forskolin-stimulated cAMP accumulation. In isolated perfused tubules, W-7 reversibly blocked vasopressin-stimulated urea permeability, a process that requires a rise in intracellular cAMP but does not appear to involve protein trafficking to the apical plasma membrane. These results suggest that calmodulin is required for vasopressin-stimulated adenylyl cyclase activity in the intact inner medullary collecting duct. Reverse transcription-PCR, immunoblotting, and immunohistochemistry revealed the presence of the calmodulin-sensitive adenylyl cyclase type 3 in the rat collecting duct, an isoform previously not known to be expressed in the collecting duct. Long-term treatment of Brattleboro rats with a vasopressin analog markedly decreased adenylyl cyclase type 3 protein abundance, providing an explanation for long-term down-regulation of vasopressin response in the collecting duct. These studies demonstrate the importance of calmodulin in the regulation of collecting duct adenylyl cyclase activity and transport function. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282-KE] NR 50 TC 46 Z9 48 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 13624 EP 13630 DI 10.1074/jbc.M500040200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500056 PM 15710610 ER PT J AU Hoashi, T Watabe, H Muller, J Yamaguchi, Y Vieira, WD Hearing, VJ AF Hoashi, T Watabe, H Muller, J Yamaguchi, Y Vieira, WD Hearing, VJ TI MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OCULOCUTANEOUS ALBINISM TYPE-1; SUBCELLULAR-LOCALIZATION; ENDOPLASMIC-RETICULUM; MELANOGENIC COMPLEX; MOUSE MELANOMA; TYROSINASE; BIOGENESIS; GP100; DIFFERENTIATION; TRAFFICKING AB More than 125 genes that regulate pigmentation have been identified to date. Of those, MART-1 has been widely studied as a melanoma-specific antigen and as a melanosome-specific marker. Whereas the functions of other melanosomal proteins, such as tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, and Pmel17, are known, the function of MART-1 in melanogenesis, is unclear. A role for MART-1 in pigmentation is expected because its expression pattern and subcellular distribution is quite similar to the other melanosomal proteins and usually correlates with melanin content. We investigated the function of MART-1 using a multi-disciplinary approach, including the use of siRNA to inhibit MART-1 function and the use of transfection to re-express MART-1 in MART-1-negative cells. We show that MART-1 forms a complex with Pmel17 and affects its expression, stability, trafficking, and the processing which is required for melanosome structure and maturation. We conclude that MART-1 is indispensable for Pmel17 function and thus plays an important role in regulating mammalian pigmentation. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Rockville, MD 20852 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 NR 34 TC 85 Z9 91 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 14006 EP 14016 DI 10.1074/jbc.M413692200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500103 PM 15695812 ER PT J AU Ma, XF Tian, WX Wu, LH Cao, XL Ito, Y AF Ma, XF Tian, WX Wu, LH Cao, XL Ito, Y TI Isolation of quercetin-3-O-L-rhamnoside from Acer truncatum Bunge by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Acer truncatum Bunge; high-speed counter-current chromatography; preparative chromatography; quercetin-3-O-L-rhamnoside ID MONGHOLICUS BGE. HSIAO; PREPARATIVE ISOLATION; PURIFICATION; SEPARATION; FLAVONOIDS; QUERCITRIN; GLYCOSIDES; EXTRACT AB Preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of quercetin-3-O-L-rhamnoside from the ethyl acetate extract of the leaves of Acer truncatum Bunge using a two-phase-system composed of ethyl acetate-ethanol-water at a volume ratio of 5:1:5 (v/v/v). In a single operation, 41.9 mg of quercetin-3-O-L-rhamnoside was obtained from 366 mg of the crude extract. High-performance liquid chromatography (HPLC) analyses of the CCC fraction revealed that the purity of quercetin-3-O-L-rhamnoside was over 96%. Its structure was identified by MS, H-1 NMR and C-13 NMR. Quercetin-3-O-L-rhamnoside was obtained from this plant for the first time. (c) 2005 Elsevier B.V. All rights reserved. C1 Chinese Acad Sci, Dept Biol, Grad Sch, Beijing 10049, Peoples R China. Beijing Technol & Business Univ, Beijing Key Lab Plant Resources Res & Dev, Beijing 100037, Peoples R China. NHLBI, NIH, Bethesda, MD 20892 USA. RP Tian, WX (reprint author), Chinese Acad Sci, Dept Biol, Grad Sch, Beijing 10049, Peoples R China. EM tianweixi@gscas.ac.cn NR 18 TC 34 Z9 42 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 8 PY 2005 VL 1070 IS 1-2 BP 211 EP 214 DI 10.1016/j.chroma.2005.02.052 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 915VK UT WOS:000228339200026 PM 15861807 ER PT J AU Garboczi, DN AF Garboczi, DN TI "D" is not for diversity SO SCIENCE LA English DT Editorial Material ID CELL ANTIGEN RECEPTOR; DELTA-T-CELLS C1 NIAID, Struct Biol Sect, Immunogenet Lab, Rockville, MD 20852 USA. RP Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov NR 9 TC 2 Z9 2 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 APR 8 PY 2005 VL 308 IS 5719 BP 209 EP 210 DI 10.1126/science.1111657 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915BX UT WOS:000228273700036 PM 15821077 ER PT J AU Vandepapeliere, P Rehermann, B Koutsoukos, M Moris, P Garcon, N Wettendorff, M Leroux-Roels, G AF Vandepapeliere, P Rehermann, B Koutsoukos, M Moris, P Garcon, N Wettendorff, M Leroux-Roels, G TI Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults SO VACCINE LA English DT Article DE Adjuvants; CTL; cytotoxicity; vaccination; AS02A; HBV ID PLASMODIUM-FALCIPARUM MALARIA; T-LYMPHOCYTE RESPONSES; PROTEIN VACCINE; IFN-GAMMA; VIRUS; IMMUNIZATION; CELLS; AIDS; IMMUNOGENICITY; TUBERCULOSIS AB Recombinant subunit protein vaccines generally elicit good humoral immune responses, weak helper T cell responses and no cytotoxic T cell responses. Certain adjuvants are known to enhance Immoral and cellular immune responses. This study evaluated the humoral, CD4+ T helper and CTL responses induced by the recombinant SL* protein adjuvanted with AS02A in comparison with non-adjuvanted SL* in PBS in two groups of 15 healthy adult volunteers. The AS02A adjuvant contains monophosphoryl lipid A (MPL), QS21 and an oil in water emulsion. The adjuvanted vaccine induced fast and vigorous humoral and helper T cell responses of the Th1 type. Using a pool of overlapping 20mer peptides a cytotoxic response was detected in 6 out of 14 HLA-A2-positive (+) and HLA-A2-negative (-) recipients of the adjuvanted vaccine. All HLA-A2-positive subjects in the adjuvanted group and up to 30% of the subjects in the SL* PBS group displayed a CTL response against selected HLA-A2-restricted CD8+ T cell epitopes. The non-adjuvanted vaccine induced a very weak antibody response and no helper T cell responses. Local and general reactions were more frequently reported by AS02A recipients than in the non-adjuvanted group but the safety profile was considered acceptable. AS02A can be considered as a useful adjuvant that strongly enhances the cellular and Immoral responses of subunit protein vaccines. (c) 2004 Elsevier Ltd. All rights reserved. C1 GlaxoSmithKline Biol, B-1330 Rixensart, Belgium. NIDDK, Liver Dis Sect, Digest Dis Branch, NIH,DHHS, Bethesda, MD USA. Ghent Univ & Hosp, Ctr Vaccinol, Ghent, Belgium. RP Vandepapeliere, P (reprint author), GlaxoSmithKline Biol, 89 Rue Inst, B-1330 Rixensart, Belgium. EM pierre.vandepapeliere@gskbio.com NR 43 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 8 PY 2005 VL 23 IS 20 BP 2591 EP 2601 DI 10.1016/j.vaccine.2004.11.034 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 914SQ UT WOS:000228248400006 PM 15780441 ER PT J AU Staker, BL Feese, MD Cushman, M Pommier, Y Zembower, D Stewart, L Burgin, AB AF Staker, BL Feese, MD Cushman, M Pommier, Y Zembower, D Stewart, L Burgin, AB TI Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CAMPTOTHECIN RESISTANCE; BIOLOGICAL EVALUATION; ELECTRON-DENSITY; ACTIVE-SITE; INHIBITORS; MECHANISM; CLEAVAGE; DRUGS; INDOLOCARBAZOLE; DERIVATIVES AB Human topoisomerase I (top1) is the molecular target of a diverse set of anticancer compounds, including the camptothecins, indolocarbazoles, and indenoisoquinolines. These compounds bind to a transient top1-DNA covalent complex and inhibit the resealing of a single-strand nick that the enzyme creates to relieve superhelical tension in duplex DNA. (Hertzberg, R. P.; et al. Biochem. 1989,28, 4629-4638. Hsiang, Y. H.; et al. J. Biol. Chem 1985,260,14873-14878. Champoux, J. J. Annu. Rev. Biochem. 2001, 70, 369-413. Stewart, L.; et al. Science 1998, 729, 1534-1541.) We report the X-ray crystal structures of the human top1-DNA complex bound with camptothecin and representative members of the indenoisoquinoline and indolocarbazole classes of top1 poisons. The planar nature of all three structurally diverse classes allows them to intercalate between DNA base pairs at the site of single-strand cleavage. All three classes of compounds have a free electron pair near Arg364, a residue that if mutated confers resistance to all three classes of drugs. The common intercalative binding mode is augmented by unexpected chemotype-specific contacts with amino acid residues Asn352 and Glu356, which adopt alternative side-chain conformations to accommodate the bound compounds. These new X-ray structures explain how very different molecules can stabilize top1-DNA covalent complexes and will aid the rational design of completely novel structural classes of anticancer drugs. C1 DeCODE BioStruct, Bainbridge Isl, WA 98110 USA. Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Burgin, AB (reprint author), DeCODE BioStruct, 7869 NE Day Rd W, Bainbridge Isl, WA 98110 USA. EM aburgin@decode.com FU NCI NIH HHS [R43 CA79439, R43 CA82694, U01 CA 89566]; NIGMS NIH HHS [R01 GM58596]; PHS HHS [C06 14499] NR 59 TC 245 Z9 254 U1 5 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 7 PY 2005 VL 48 IS 7 BP 2336 EP 2345 DI 10.1021/jm049146p PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 912WV UT WOS:000228111500013 PM 15801827 ER PT J AU Chadwick, RS AF Chadwick, RS TI Comment on 'Axisymmetric indentation of an incompressible elastic thin film' SO JOURNAL OF PHYSICS D-APPLIED PHYSICS LA English DT Editorial Material AB It is shown that a recent method based on the asymptotic inversion of Hankel transforms for indentation of thin films (Yang F Q 2003 J. Phys. D: Appl. Phys. 36 50) provides a non-unique solution for the case of frictionless contact between the film and the substrate. In addition to the solution given by Yang, another one exists having zero hydrostatic stress that results in half the force acting on the indenter for the same indentation. A more rigorous asymptotic method (Chadwick R S 2002 SIAM J Appl. Math. 62 1520) singles out the smaller force solution as the correct one. C1 Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. EM chadwick@helix.nih.gov NR 3 TC 1 Z9 1 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0022-3727 J9 J PHYS D APPL PHYS JI J. Phys. D-Appl. Phys. PD APR 7 PY 2005 VL 38 IS 7 BP 1104 EP 1104 DI 10.1088/0022-3727/38/7C01 PG 1 WC Physics, Applied SC Physics GA 920HL UT WOS:000228679900022 ER PT J AU Pelkey, KA Lavezzari, G Racca, C Roche, KW McBain, CJ AF Pelkey, KA Lavezzari, G Racca, C Roche, KW McBain, CJ TI MGluR7 is a metaplastic switch controlling bidirectional plasticity of feedforward inhibition SO NEURON LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM DEPRESSION; FIBER-INTERNEURON SYNAPSES; TARGET-SPECIFIC EXPRESSION; HIPPOCAMPAL INTERNEURONS; RAT HIPPOCAMPUS; SYNAPTIC PLASTICITY; TRANSMISSION; NEURONS; ACTIVATION AB Plasticity of feedforward inhibition in the hippocampal mossy fiber (MF) pathway can dramatically influence dentate gyrus-CA3 dialog. Interestingly, MF inputs to CA3 stratum lucidum interneurons (SLINs) undergo long-term depression (LTD) following high-frequency stimulation (HFS), in contrast to IVIF-pyramid (PYR) synapses, where long-term potentiation (LTP) occurs. Furthermore, activity-induced potentiation of IVIF-SLIN transmission has not previously been observed. Here we report that metabotropic glutamate receptor subtype 7 (mGluR7) is a metaplastic switch at MF-SLIN synapses, whose activation and surface expression governs the direction of plasticity. In naive slices, mGIuR7 activation during HFS generates MF-SLIN LTD, depressing presynaptic release through a PKC-dependent mechanism. Following agonist exposure, mGIuR7 undergoes internalization, unmasking the ability of IVIF-SLIN synapses to undergo presynaptic potentiation in response to the same HFS that induces LTD in naive slices. Thus, selective mGIuR7 targeting to MF terminals contacting SLINs and not PYRs provides cell target-specific plasticity and bidirectional control of feedforward inhibition. C1 NICHHD, Lab Cellular & Synaptic Neurophysiol, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. RP Pelkey, KA (reprint author), NICHHD, Lab Cellular & Synaptic Neurophysiol, NIH, Bldg 35, Bethesda, MD 20892 USA. EM pelkeyk2@mail.nih.gov; mcbainc@mail.nih.gov OI Roche, Katherine/0000-0001-7282-6539 NR 54 TC 112 Z9 115 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 7 PY 2005 VL 46 IS 1 BP 89 EP 102 DI 10.1016/j.neuron.2005.02.011 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 914LH UT WOS:000228228600011 PM 15820696 ER PT J AU Yamaguchi, H Calado, RT Ly, H Kajigaya, S Baerlocher, GM Chanock, SJ Lansdorp, PM Young, NS AF Yamaguchi, H Calado, RT Ly, H Kajigaya, S Baerlocher, GM Chanock, SJ Lansdorp, PM Young, NS TI Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LINKED DYSKERATOSIS-CONGENITA; CATALYTIC SUBUNIT; IN-VIVO; FUNCTIONAL MULTIMERIZATION; MYELODYSPLASTIC SYNDROME; ENZYME-ACTIVITY; RNA INTERACTION; DISEASE; HAPLOINSUFFICIENCY; DEFICIENT AB BACKGROUND: Mutations in TERC, the gene for the RNA component of telomerase, cause short telomeres in congenital aplastic anemia and in some cases of apparently acquired hematopoietic failure. We investigated whether mutations in genes for other components of telomerase also occur in aplastic anemia. METHODS: We screened blood or marrow cells from 124 patients with apparently acquired aplastic anemia and 282 control subjects for sequence variations in the TERT, DKC1, NHP2, and NOP10 genes; an additional 81 patients and 246 controls were examined for genetic variations in TERT. Telomere lengths and the telomerase activity of peripheral-blood leukocytes were evaluated in patients carrying genetic variants. Identified mutations were transfected into telomerase-deficient cell lines to examine their effects and their mechanism of action on telomerase function. RESULTS: Five heterozygous, nonsynonymous mutations (which cause an amino acid change in the corresponding protein) were identified in TERT, the gene for the telomerase reverse transcriptase catalytic enzyme, among seven unrelated patients. Leukocytes from these patients had short telomeres and low telomerase enzymatic activity. In three of these patients, the mutation was also detected in buccal mucosa cells. Family members carrying the mutations also had short telomeres and reduced telomerase activity but no evident hematologic abnormality. The results of coexpression of wild-type TERT and TERT with aplastic anemia-associated mutations in a telomerase-deficient cell line suggested that haploinsufficiency was the mechanism of telomere shortening due to TERT mutations. CONCLUSIONS: Heterozygous mutations in the TERT gene impair telomerase activity by haploinsufficiency and may be risk factors for marrow failure. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Emory Univ, Dept Pathol & Lab Med, Div Expt Pathol, Atlanta, GA 30322 USA. Univ British Columbia, Terry Fox Lab, BC Canc Res Ctr, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC,Rm 3E-5140, Bethesda, MD 20892 USA. EM youngns@mail.nih.gov RI Calado, Rodrigo/G-2619-2011 NR 53 TC 375 Z9 406 U1 1 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 2005 VL 352 IS 14 BP 1413 EP 1424 DI 10.1056/NEJMoa042980 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 913IP UT WOS:000228145200005 PM 15814878 ER PT J AU Staudt, LM Wright, G Dave, S AF Staudt, LM Wright, G Dave, S TI Immune signatures in follicular lymphoma - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 2005 VL 352 IS 14 BP 1496 EP 1497 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 913IP UT WOS:000228145200032 ER PT J AU Ross, PD Cheng, NQ Conway, JF Firek, BA Hendrix, RW Duda, RL Steven, AC AF Ross, PD Cheng, NQ Conway, JF Firek, BA Hendrix, RW Duda, RL Steven, AC TI Crosslinking renders bacteriophage HK97 capsid maturation irreversible and effects an essential stabilization SO EMBO JOURNAL LA English DT Article DE Brownian ratchet; conformational change; cryo-electron microscopy; differential scanning calorimetry; virus assembly ID CONFORMATIONAL-CHANGES; RNA VIRUS; PROTEIN; BINDING; STATES; TRANSFORMATIONS; RESOLUTION; STABILITY; SUBUNIT; PATHWAY AB In HK97 capsid maturation, structural change ('expansion') is accompanied by formation of covalent crosslinks, connecting residue K169 in the 'E-loop' of each subunit with N356 on another subunit. We show by complementation experiments with the K169Y mutant, which cannot crosslink, that crosslinking is an essential function. The precursor Prohead-II passes through three expansion intermediate (EI) states en route to the end state, Head-II. We investigated the effects of expansion and crosslinking on stability by differential scanning calorimetry of wild-type and K169Y capsids. After expansion, the denaturation temperature (Tp) of K169Y capsids is slightly reduced, indicating that their thermal stability is not enhanced, but crosslinking effects a major stabilization (DTp, +11 degrees C). EI-II is the earliest capsid to form crosslinks. Cryo-electron microscopy shows that for both wild-type and K169Y EI-II, most E-loops are in the 'up' position, 30 angstrom from the nearest N356: thus, crosslinking in EI-II represents capture of mobile E-loops in 'down' positions. At pH 4, most K169Y capsids remain as EI-II, whereas wild-type capsids proceed to EI-III, suggesting that crosslink formation drives maturation by a Brownian ratchet mechanism. C1 NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, CEA, Inst Biol Struct, Grenoble, France. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. RP Steven, AC (reprint author), NIH, Bldg 50,Room 1517,50 S Dr MSC 8025, Bethesda, MD 20892 USA. EM alasdair_steven@nih.gov RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 FU NIGMS NIH HHS [GM47795, R01 GM047795] NR 47 TC 40 Z9 40 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 6 PY 2005 VL 24 IS 7 BP 1352 EP 1363 DI 10.1038/sj.emboj.7600613 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 915SQ UT WOS:000228327100006 PM 15775971 ER PT J AU Yin, JH Sobeck, A Xu, C Meetei, AR Hoatlin, M Li, L Wang, WD AF Yin, JH Sobeck, A Xu, C Meetei, AR Hoatlin, M Li, L Wang, WD TI BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity SO EMBO JOURNAL LA English DT Article DE BLAP75; BLM; Bloom's syndrome; genomic instability; topoisomerase III alpha ID SYNDROME GENE-PRODUCT; TOPOISOMERASE III-ALPHA; SISTER-CHROMATID EXCHANGES; FANCONI-ANEMIA; SYNDROME HELICASE; DNA HELICASE; RECQ HELICASES; BLM; REPAIR; APOPTOSIS AB Bloom's syndrome (BS) is a rare human genetic disorder characterized by dwarfism, immunodeficiency, genomic instability and cancer predisposition. We have previously purified three complexes containing BLM, the helicase mutated in this disease. Here we demonstrate that BLAP75, a novel protein containing a putative OB-fold nucleic acid binding domain, is an integral component of BLM complexes, and is essential for their stability in vivo. Consistent with a role in BLM-mediated processes, BLAP75 colocalizes with BLM in subnuclear foci in response to DNA damage, and its depletion impairs the recruitment of BLM to these foci. Depletion of BLAP75 by siRNA also results in deficient phosphorylation of BLM during mitosis, as well as defective cell proliferation. Moreover, cells depleted of BLAP75 display an increased level of sister-chromatid exchange, similar to cells depleted of BLM by siRNA. Thus, BLAP75 is an essential component of the BLM-associated cellular machinery that maintains genome integrity. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,TRIAD Bldg,Rm 3000, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov FU NCI NIH HHS [R29 CA076172, CA112775, CA76172, CA91029, R01 CA076172, R01 CA091029, R01 CA112775] NR 44 TC 123 Z9 131 U1 0 U2 5 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 APR 6 PY 2005 VL 24 IS 7 BP 1465 EP 1476 DI 10.1038/sj.emboj.7600622 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 915SQ UT WOS:000228327100016 PM 15775963 ER PT J AU Wright, JT Dunn, JK Cutler, JA Davis, BR Cushman, WC Ford, CE Haywood, LJ Leenen, FHH Margolis, KL Papademetriou, V Probstfield, JL Whelton, PK Habib, GB AF Wright, JT Dunn, JK Cutler, JA Davis, BR Cushman, WC Ford, CE Haywood, LJ Leenen, FHH Margolis, KL Papademetriou, V Probstfield, JL Whelton, PK Habib, GB CA ALLHAT Collaborative Res Grp TI Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; CONVERTING-ENZYME-INHIBITOR; CALCIUM-CHANNEL BLOCKER; HIGH BLOOD-PRESSURE; ISOLATED SYSTOLIC HYPERTENSION; LEFT-VENTRICULAR DYSFUNCTION; MAJOR CARDIOVASCULAR EVENTS; JOINT NATIONAL COMMITTEE; RANDOMIZED-TRIAL AB Context Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs). Objective To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease (CVD) incidence in racial subgroups. Design, Setting, and Participants Prespecified subgroup analysis of ALLHAT, a randomized, double-blind, active-controlled, clinical outcome trial conducted between February 1994 and March 2002 in 33 357 hypertensive US and Canadian patients aged 55 years or older (35% black) with at least 1 other cardiovascular risk factor. Interventions Anti hypertensive regimens initiated with a CCB (amlodipine) or an ACE inhibitor (lisinopril) vs a thiazide-type diuretic (chlorthalidone). Other medications were added to achieve goal blood pressures (BPs) less than 140/90 mm Hg. Main Outcome Measures The primary outcome was combined fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined CVD (CND death, nonfatal MI, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. Results No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup. For amlodipine vs chlorthalidone only, HF was the only prespecified clinical outcome that differed significantly (overall: relative risk [RR], 1.37; 95% confidence interval [Cl], 1.24-1.51; blacks: RR, 1.46; 95% CI, 1.24-1.73; nonblacks: RR, 1.32; 95% CI, 1.17-1.49; P<.001 for each comparison) with no difference in treatment effects by race (P=.38 for interaction). For lisinopril vs chlorthalidone, results differed by race for systolic BP (greater decrease in blacks with chlorthalidone), stroke, and combined CVD outcomes (P<.001, P=.01, and P=.04, respectively, for interactions). In blacks and nonblacks, respectively, the RRs for stroke were 1.40 (95% CI, 1.17-1.68) and 1.00 (95% CI, 0.85-1.17) and for combined CVD were 1.19 (95% CI, 1.09-1.30) and 1.06(95% CI, 1.00-1.13). For HF, the RRs were 1.30 (95% CI, 1.10-1.54) and 1.13 (95% CI, 1.00-1.28), with no significant interaction by race. Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks. Conclusions In blacks and nonblack subgroups, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome, and diuretic-based treatment resulted in the lowest risk of heart failure. While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks, thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients. C1 Case Western Reserve Univ, Gen Clin Res Ctr, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Memphis Vet Affairs Med Ctr, Memphis, TN USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Univ Washington, Seattle, WA 98195 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Wright, JT (reprint author), Case Western Reserve Univ, Gen Clin Res Ctr, 11000 Euclid Ave,Bowell Bldg,5th Floor, Cleveland, OH 44106 USA. EM jackson.wright@case.edu OI Papademetriou, Vasilios/0000-0002-2882-2757 FU NHLBI NIH HHS [N01-HC-35130] NR 52 TC 187 Z9 193 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 6 PY 2005 VL 293 IS 13 BP 1595 EP 1607 DI 10.1001/jama.293.13.1595 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 913EV UT WOS:000228135300022 PM 15811979 ER PT J AU Rother, RP Bell, L Hillmen, P Gladwin, MT AF Rother, RP Bell, L Hillmen, P Gladwin, MT TI The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin - A novel mechanism of human disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; SICKLE-CELL-DISEASE; CROSS-LINKED HEMOGLOBIN; PRIMARY PULMONARY-HYPERTENSION; NITRIC-OXIDE BIOAVAILABILITY; RECOMBINANT HUMAN HEMOGLOBIN; LOWER ESOPHAGEAL SPHINCTER; BETA-THALASSEMIA MAJOR; REGIONAL BLOOD-FLOW; PIG-A GENE AB Context The efficient sequestration of hemoglobin by the red blood cell membrane and the presence of multiple hemoglobin clearance mechanisms suggest a critical need to prevent the buildup of this molecule in the plasma. A growing list of clinical manifestations attributed to hemoglobin release in a variety of acquired and iatrogenic hemolytic disorders suggests that hemolysis and hemoglobinemia should be considered as a novel mechanism of human disease. Evidence Acquisition Pertinent scientific literature databases and references were searched through October 2004 using terms that encompassed various aspects of hemolysis, hemoglobin preparations, clinical symptoms associated with plasma hemoglobin, nitric oxide in hemolysis, anemia, pulmonary hypertension, paroxysmal nocturnal hemoglobinuria, and sickle-cell disease. Evidence Synthesis Hemoglobin is released into the plasma from the erythrocyte during intravascular hemolysis in hereditary, acquired, and iatrogenic hemolytic conditions. When the capacity of protective hemoglobin-scavenging mechanisms has been saturated, levels of cell-free hemoglobin increase in the plasma, resulting in the consumption of nitric oxide and clinical sequelae. Nitric oxide plays a major role in vascular homeostasis and has been shown to be a critical regulator of basal and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial adhesion molecule expression, and platelet activation and aggregation. Thus, clinical consequences of excessive cell-free plasma hemoglobin levels during intravascular hemolysis or the administration of hemoglobin preparations include dystonias involving the gastrointestinal, cardiovascular, pulmonary, and urogenital systems, as well as clotting disorders. Many of the clinical sequelae of intravascular hemolysis in a prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria, are readily explained by hemoglobin-mediated nitric oxide scavenging. Conclusion A growing body of evidence supports the existence of a novel mechanism of human disease, namely, hemolysis-associated smooth muscle dystonia, vasculopathy, and endothelial dysfunction. C1 Alexion Pharmaceut, Res, Cheshire, CT 06410 USA. Leeds Teaching Hosp NHS Trust, Dept Haematol, Leeds, W Yorkshire, England. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Rother, RP (reprint author), Alexion Pharmaceut, Res, 352 Knotter Dr, Cheshire, CT 06410 USA. EM rotherr@alxn.com; mgladwin@nih.gov NR 127 TC 659 Z9 669 U1 7 U2 31 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 6 PY 2005 VL 293 IS 13 BP 1653 EP 1662 DI 10.1001/jama.293.13.1653 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 913EV UT WOS:000228135300028 PM 15811985 ER PT J AU Kang, SK Cho, KK Ahn, JK Bok, JD Kang, SH Woo, JH Lee, HG You, SK Choi, YJ AF Kang, SK Cho, KK Ahn, JK Bok, JD Kang, SH Woo, JH Lee, HG You, SK Choi, YJ TI Three forms of thermostable lactose-hydrolase from Thermus sp IB-21: cloning, expression, and enzyme characterization SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE lactose-hydrolase; beta-glycosidase; beta-galactosidase; lactose intolerance; low-lactose milk; Thermus sp.; thermostability ID BETA-GLYCOSIDASE GENE; EXTREME THERMOPHILE; ALPHA-GALACTOSIDASE; PURIFICATION; HYDROLYSIS; SEQUENCE; TEMPERATURE; ACID; A4 AB Three thermostable lactose-hydrolases, namely, two beta-glycosidases (bglA and bglB) and one beta-galactosidase (bgaA) genes were cloned from the genomic library of Thermus sp. IB-21. The bglA, bglB, and bgaA consisted of 1311 bp (436 amino acid residues), 1296 bp (431 aa), and 1938 bp (645 aa) of nucleotides with predicted molecular masses of 49,066, 48,679, and 72,714 Da. respectively. These enzymes were overexpressed in Escherichia coli BL21(DE3) using pET21b(+) vector system. The recombinant enzymes were purified to homogeneity by a heat precipitation (70 degrees C, 40 min) and a Ni2+-affinity chromatography. The molecular masses of the purified enzymes estimated by SDS-PAGE agreed with their predicted values. All the purified enzymes showed their optimal pH at around 5.0-6.0. In contrast, the temperature profiles for activity and thermostability patterns were different for each enzyme. BglB beta-glycosidase displayed the best lactose hydrolysis activity of the three enzymes without substrate inhibition up to 200mM lactose at 70 degrees C and pH 7.0. The specific activities (U/mg) of BglA, BglB, and BgaA on 138 mM lactose at 70 degrees C and pH 7.0 were 36.8, 160.3, and 8.5, respectively. (c) 2004 Elsevier B.V. All rights reserved. C1 NIMH, Sect Biophys Chem, Mol Biol Lab, Bethesda, MD 20892 USA. Choong Ang Biotech Co Ltd, R&D Ctr, Ansan, Kyunggi, South Korea. Korea Natl Open Univ, Dept Agr Sci, Seoul 110791, South Korea. Chinju Natl Univ, Dept Anim Resource Technol, Chinju 660758, Kyongnam, South Korea. Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151742, South Korea. RP You, SK (reprint author), Korea Univ, Coll Life & Environm Sci, Div Biotechnol & Genet Engn, Seoul 136701, South Korea. EM bioseung@korea.ac.kr; cyjcow@snu.ac.kr RI Kang, Phil Jun/F-4716-2013; Choi, Yunjaie /B-4697-2014; You, Seungkwon/H-3067-2015 NR 32 TC 29 Z9 33 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD APR 6 PY 2005 VL 116 IS 4 BP 337 EP 346 DI 10.1016/j.jbiotec.2004.07.019 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 907PU UT WOS:000227731100002 PM 15748760 ER PT J AU Marchetti, C Tabak, J Chub, N O'Donovan, MJ Rinzel, J AF Marchetti, C Tabak, J Chub, N O'Donovan, MJ Rinzel, J TI Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spontaneous activity; network; development; chloride; spinal cord; modeling ID RECEPTOR-MEDIATED CURRENTS; TEMPORAL-LOBE EPILEPSY; CHICK-EMBRYO; SYNAPTIC DEPRESSION; DEHYDROEPIANDROSTERONE-SULFATE; LUMBOSACRAL MOTONEURONS; PREGNENOLONE SULFATE; ELECTRICAL-ACTIVITY; NEONATAL-RAT; IN-VITRO AB We investigated how spontaneous activity is generated in developing, hyperexcitable networks. We focused our study on the embryonic chick spinal cord, a preparation that exhibits rhythmic discharge on multiple timescales: slow episodes (lasting minutes) and faster intraepisode cycling (similar to 1 Hz frequency). For this purpose, we developed a mean field model of a recurrent network with slow chloride dynamics and a fast depression variable. We showed that the model, in addition to providing a biophysical mechanism for the slow dynamics, was able to account for the experimentally observed activity. The model made predictions on how interval and duration of episodes are affected when changing chloride-mediated synaptic transmission or chloride flux across cell membrane. These predictions guided experiments, and the model results were compared with experimental data obtained with electrophysiological recordings. We found agreement when transmission was affected through changes in synaptic conductance and good qualitative agreement when chloride flux was varied through changes in external chloride concentration or in the rate of the Na+-K+-2Cl(-) cotransporter. Furthermore, the model made predictions about the time course of intracellular chloride concentration and chloride reversal potential and how these are affected by changes in synaptic conductance. Based on the comparison between modeling and experimental results, we propose that chloride dynamics could be an important mechanism in rhythm generation in the developing chick spinal cord. C1 NYU, Ctr Neural Sci, New York, NY 10003 USA. NYU, Courant Inst Math Sci, New York, NY 10003 USA. NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Rinzel, J (reprint author), NYU, Ctr Neural Sci, 4 Washington Pl,Room 809, New York, NY 10003 USA. EM rinzel@cns.nyu.edu RI Marchetti, Cristina/G-7220-2012; tabak, joel/K-1549-2013; o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Tabak, Joel/0000-0002-0588-957X NR 39 TC 33 Z9 33 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 6 PY 2005 VL 25 IS 14 BP 3601 EP 3612 DI 10.1523/JNEUROSCI.4290-04.2005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 913VQ UT WOS:000228184100014 PM 15814791 ER PT J AU Landgren, O Kerstann, KF Gridley, G Mellemkjaer, L Hemminki, K Linet, MS Goldin, LR AF Landgren, O Kerstann, KF Gridley, G Mellemkjaer, L Hemminki, K Linet, MS Goldin, LR TI Re: Familial clustering of Hodgkin lymphoma and multiple sclerosis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID AGGREGATION; DISEASE C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Novum, Dept Biosci, Stockholm, Sweden. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 7 TC 11 Z9 11 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 APR 6 PY 2005 VL 97 IS 7 BP 543 EP 544 DI 10.1093/jnci/dji092 PG 2 WC Oncology SC Oncology GA 953WT UT WOS:000231113100021 PM 15812083 ER PT J AU Bobb, AJ Addington, AM Sidransky, E Gornick, MC Lerch, JP Greenstein, DK Clasen, LS Sharp, WS Inoff-Germain, G Vrieze, FWD Arcos-Burgos, M Straub, RE Hardy, JA Castellanos, FX Rapoport, JL AF Bobb, AJ Addington, AM Sidransky, E Gornick, MC Lerch, JP Greenstein, DK Clasen, LS Sharp, WS Inoff-Germain, G Vrieze, FWD Arcos-Burgos, M Straub, RE Hardy, JA Castellanos, FX Rapoport, JL TI Support for association between ADHD and two candidate genes: NET1 and DRD1 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention deficit hyperactivity disorder (ADHD); norepinephrine transporter (NET1); dopamine D1 receptor (DRD1); association study; replication ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; CATECHOL-O-METHYLTRANSFERASE; RECEPTOR GENE; ALCOHOL DEPENDENCE; CEREBRAL-CORTEX; NO EVIDENCE; LINKAGE; PHENOTYPE AB Attention deficit hyperactivity disorder (ADHD) is a common, multifactorial disorder with significant genetic contribution. Multiple candidate genes have been studied in ADHD, including the norepinephrine transporter (NET1) and dopamine D1 receptor (DRD1). NET1 is implicated in ADHD because of the efficacy of atomoxetine, a selective noradrenergic reuptake inhibitor, in the treatment of ADHD. DRD1 is primarily implicated through mouse models of ADHD. DNA from 163 ADHD probands, 192 parents, and 129 healthy controls was used to investigate possible associations between ADHD and polymorphisms in 12 previously studied candidate genes (5-HTlB, 5-HT2A, 5-HT2C, ADRA2A, CHRNA4, COMT, DAT1, DRD1, DRD4, DRD5, NET1, and SNA-P-25). Analyses included case-control and family-based methods, and dimensional measures of behavior, cognition, and anatomic brain magnetic resonance imaging (MRI). Of the 12 genes examined, two showed a significant association with ADHD. Transmission disequilibrium. test (TDT) analysis revealed significant association of two NETI single nucleotide polymorphisms (SNPs) with ADRD (P < 0.009); case-control analysis revealed significant association of two DRD1 SNPs with ADHD (P < 0.008). No behavioral, cognitive, or brain MRI volume measurement significantly differed across NET1 or DRD1 genotypes at an alpha of 0.01. This study provides support for an association between ADHD and polymorphisms in both NET1 and DRD1; polymorphisms in ten other candidate genes were not associated with ADHD. Because family-based and case-control methods gave divergent results, both should be used in genetic studies of ADHD. Published 2005 Wiley-Liss, Inc.(dagger) C1 NIMH, Child Psychiat Branch, IRP, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NYU, Ctr Child Study, New York, NY USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, IRP, NIH, 10 Center Dr,Bldg 10,Room 3N-202, Bethesda, MD 20892 USA. EM rapoport@helix.nih.gov RI Hardy, John/C-2451-2009; OI Castellanos, Francisco/0000-0001-9192-9437 NR 65 TC 128 Z9 136 U1 1 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 5 PY 2005 VL 134B IS 1 BP 67 EP 72 DI 10.1002/ajmg.b.30142 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 910JK UT WOS:000227927100014 PM 15717291 ER PT J AU Liu, QR Walther, D Drgon, T Polesskaya, O Lesnick, TG Strain, KJ de Andrade, M Bower, JH Maraganore, DM Uhl, GR AF Liu, QR Walther, D Drgon, T Polesskaya, O Lesnick, TG Strain, KJ de Andrade, M Bower, JH Maraganore, DM Uhl, GR TI Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE polymorphism; haplotype; isoforms; promoters; translation mechanism ID MESSENGER-RNA EXPRESSION; FAMILY-BASED ASSOCIATION; AGE-OF-ONSET; CANDIDATE GENES; VAL66MET POLYMORPHISM; ALZHEIMERS-DISEASE; BIPOLAR DISORDER; SYNAPTIC SITES; MULTIPLE PROMOTERS; OLMSTED COUNTY AB Potential roles for variants in the human BDNF gene in human brain disorders are supported by findings that include: (a) influences that this trophic factor can exert on important neurons, brain regions, and neurotransmitter systems, (b) changes in BDNF expression that follow altered neuronal activity and drug treatments, and (c) linkages or associations between genetic markers in or near BDNF and human traits and disorders that include depression, schizophrenia, addictions, and Parkinson's disease. We now report assembly of more than 70 kb of BDNF genomic sequence, delineation of 7 noncoding and 1 coding human BDNF exons, elucidation of BDNF transcripts that are initiated at several alternative promoters, identification of BDNF mRNA splicing patterns, elucidation of novel sequences that could contribute to activity-dependent BDNF mRNA transcription, targeting and/or translation, elucidation of tissue-specific and brain-region-specific use of the alternative human BDNF promoters and splicing patterns, identification of single nucleotide polymorphism (SNP), and simple sequence length polymorphism (SSLP) BDNF genomic, variants and identification of patterns of restricted haplotype diversity at the BDNF locus. We also identified type 2 BDNF-locus transcripts that are coded by a novel gene that is overlapped with type I BDNF gene and transcribed in reverse orientation with several alternative splicing isoforms. Association studies of BDNF variants reveal no associations with Parkinson's disease. Comparisons between substance abusers and controls reveal modest associations. These findings increase interest in this diverse human gene. Published 2005 Wiley-Liss, Inc.(dagger) C1 NIDA IRP, Mol Neurobiol Branch, NIH, DHHS, Baltimore, MD USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. RP Uhl, GR (reprint author), Mol Neurobiol, Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012; OI Liu, Qing-Rong/0000-0001-8477-6452; de Andrade, Mariza/0000-0003-2329-2686 FU NIEHS NIH HHS [ES10751]; NINDS NIH HHS [NS33978] NR 60 TC 124 Z9 127 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 5 PY 2005 VL 134B IS 1 BP 93 EP 103 DI 10.1002/ajmg.b.30109 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 910JK UT WOS:000227927100020 PM 15666411 ER PT J AU Jeong, MY Kinugawa, K Vinson, C Long, CS AF Jeong, MY Kinugawa, K Vinson, C Long, CS TI AFos dissociates cardiac myocyte hypertrophy and expression of the pathological gene program SO CIRCULATION LA English DT Article DE hypertrophy; signal transduction; myocytes; molecular biology ID MYOSIN HEAVY-CHAIN; ACTIVATED PROTEIN-KINASE; SARCOPLASMIC-RETICULUM CA2+-ATPASE; C-FOS GENE; CARDIOMYOCYTE HYPERTROPHY; DNA-BINDING; RAT HEARTS; VENTRICULAR MYOCYTES; GROWTH-FACTORS; CELL-GROWTH AB Background - Although induction of activator protein-1 (AP-1) transcription factor activity has been observed in cardiac hypertrophy, a direct role for AP-1 in myocardial growth and gene expression remains obscure. Methods and Results - Hypertrophy was induced in cultured neonatal rat cardiomyocytes with phenylephrine or overexpression of a constitutively active MAP3K, MKK6. In both treatment groups, induction of the pathological gene profile was observed, ie, expression of beta-myosin heavy chain (beta MHC), atrial/brain natriuretic peptides (ANP/BNP), and skeletal alpha-actin (sACT) was increased, whereas expression for alpha-myosin heavy chain (alpha MHC) and the sarcoplasmic reticulum Ca2+-ATPase (SERCA) genes was repressed. The role of AP-1 in the hypertrophic phenotype was evaluated with the use of an adenoviral construct expressing a dominant negative mutant of the c-Fos proto-oncogene (AdAFos). Although AFos did not change the myocyte growth response, it abrogated the gene profile to both agonists, including the upregulation of both alpha MHC and SERCA expression. Conclusions - Although c-Fos/AP-1 is necessary for induction of the pathological/fetal gene program, it does not appear to be critical for cardiomyocyte hypertrophy. C1 Denver Hlth Med Ctr, Cardiol Sect, Denver, CO 80204 USA. Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan. Natl Canc Inst, Bethesda, MD USA. RP Long, CS (reprint author), Denver Hlth Med Ctr, Cardiol Sect, 777 Bannock St,Mailstop 0960, Denver, CO 80204 USA. EM clong@dhha.org FU NHLBI NIH HHS [R01 HL066399] NR 45 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1645 EP 1651 DI 10.1161/01.CIR.0000160367.99928.87 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900011 PM 15795322 ER PT J AU Sun, JH Steenbergen, C Murphy, E AF Sun, JH Steenbergen, C Murphy, E TI S-nitrosylation of the L-type calcium channel alpha 1 subunit contributes to male-female differences in ischemia-reperfusion injury under adrenergic stimulation SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1722 EP 1722 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900039 ER PT J AU Grayburn, PA Appleton, CP DeMaria, AN Greenberg, B Lowes, B Oh, J Plehn, JF Rahko, P Sutton, MS Eichhorn, EJ AF Grayburn, PA Appleton, CP DeMaria, AN Greenberg, B Lowes, B Oh, J Plehn, JF Rahko, P Sutton, MS Eichhorn, EJ CA BEST Trial Echocariographic Sub TI Echocardiographic predictors of morbidity and mortality in patients with advanced heart failure - The beta-blocker evaluation of survival trial (BEST) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; MITRAL REGURGITATION; DILATED CARDIOMYOPATHY; DOPPLER-ECHOCARDIOGRAPHY; HEMODYNAMIC CORRELATIONS; PROGNOSTIC IMPLICATIONS; DECELERATION TIME; TASK-FORCE; SEVERITY AB OBJECTIVES The aim of this study was to determine echocardiographic predictors of outcome in patients with advanced heart failure (HF) due to severe left ventricular (LV) systolic dysfunction in the Beta-blocker Evaluation of Survival Trial (BEST). BACKGROUND Previous studies indicate that echocardiographic measurements of LV size and function, mitral deceleration time, and mitral regurgitation (MR) predict adverse outcomes in HF. However, complete quantitative echocardiograms evaluating all of these parameters have not been reported in a prospective randomized clinical trial in the era of modern HF therapy. METHODS Complete echocardiograms were performed in 336 patients at 26 sites and analyzed by a core laboratory. A Cox proportional-hazards regression model was used to determine which echocardiographic variables predicted the primary end point of death or the secondary end point of death, HF hospitalization, or transplant. Significant variables were then entered into a multivariable model adjusted for clinical and demographic covariates. RESULTS On multivariable analysis adjusted for clinical covariates, only LV end-diastolic volume index predicted death (events = 75), with a cut point of 120 ml/m(2). Three echocardiographic variables predicted the combined end point of death (events = 75), HF hospitalization (events = 97), and transplant (events = 9): LV end-diastolic volume index, mitral deceleration time, and the vena contracta. width of MR. Optimal cut points for these variables were 120 ml/m(2), 150 ms, and 0.4 cm, respectively. CONCLUSIONS Echocardiographic predictors of outcome in advanced HF include LV end-diastolic volume index, mitral deceleration time, and vena contracta width. These variables indicate that LV remodeling, increased LV stiffiness, and MR are independent predictors of outcome in patients with advanced HF. (c) 2005 by the American College of Cardiology Foundation. C1 Mayo Clin Scottsdale, Scottsdale, AZ USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Colorado, Denver, CO 80202 USA. Mayo Clin Rochester, Rochester, MN USA. NHLBI, Washington, DC USA. Univ Wisconsin, Madison, WI USA. Univ Penn, Philadelphia, PA 19104 USA. RP Grayburn, PA (reprint author), Baylor Univ, Baylor Heart & Vasc Inst, Med Ctr, Echocardiog Core Lab, 621 N Hall St, Dallas, TX 75226 USA. EM paulgr@baylorhealth.edu OI Lowes, Brian/0000-0002-5919-2540 FU NHLBI NIH HHS [5K24 HL 03980-06] NR 41 TC 79 Z9 80 U1 1 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 APR 5 PY 2005 VL 45 IS 7 BP 1064 EP 1071 DI 10.1016/j.jacc.2004.12.069 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 912CU UT WOS:000228055500016 PM 15808765 ER PT J AU Lin-Gibson, S Jones, RL Washburn, NR Horkay, F AF Lin-Gibson, S Jones, RL Washburn, NR Horkay, F TI Structure-property relationships of photopolymerizable poly(ethylene glycol) dimethacrylate hydrogels SO MACROMOLECULES LA English DT Article ID ANGLE NEUTRON-SCATTERING; FUMARATE) HYDROGELS; CARTILAGE; NETWORKS; GELS AB Photopolymerized hydrogels from poly(ethylene glycol) dimethacrylate (PEGDM) and similar derivatives have been extensively used as scaffolds for tissue regeneration and other biological applications. A systematic investigation into the structure and mechanical properties of PEGDM hydrogels was performed to characterize the relationships between the network structure and gel properties. Gels were prepared from oligomers of different molecular masses (1000-8000 g/mol) at various concentrations. Small-angle neutron scattering was used to characterize the structural features of hydrogels with respect to their semidilute solution precursors. A well-defined structural length scale manifested as a maximum in the scattering intensity was observed for hydrogels derived from high molecular mass PEGDMs and/or high oligomer mass fractions. Mechanical testing showed that PEGDM hydrogels are mechanically robust, consistent with gel structures that contain reinforcing cross-linked clusters. Shear moduli were determined for hydrogels swollen to various degrees in water. The concentration dependence of shear modulus for these nonideal hydrogels exhibits a power law behavior with an exponent close to (1)/(3). C1 NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. EM slgibson@nist.gov NR 17 TC 71 Z9 71 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 EI 1520-5835 J9 MACROMOLECULES JI Macromolecules PD APR 5 PY 2005 VL 38 IS 7 BP 2897 EP 2902 DI 10.1021/ma0487002 PG 6 WC Polymer Science SC Polymer Science GA 912HG UT WOS:000228067600049 ER PT J AU Song, SW Pursell, ZF Copeland, WC Longley, MJ Kunkel, TA Mathews, CK AF Song, SW Pursell, ZF Copeland, WC Longley, MJ Kunkel, TA Mathews, CK TI DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; BASE EXCISION-REPAIR; RAT CARDIAC-MUSCLE; POLYMERASE-GAMMA; POINT MUTATIONS; HUMAN-CELLS; MTDNA; IDENTIFICATION; ACCUMULATION; MAINTENANCE AB The mutation rate of the mammalian mitochondrial genome is higher than that of the nuclear genome. Because mitochondrial and nuclear deoxyribonucleoside triphosphate (dNTP) pools are physically distinct and because dNTP concentrations influence replication fidelity, we asked whether mitochondrial dNTP pools are asymmetric with respect to each other. We report here that the concentrations of the four dNTPs are not equal in mitochondria isolated from several tissues of both young and old rats. In particular, in most tissues examined, mitochondrial dGTP concentrations are high relative to the other dNTPs. Moreover, in the presence of the biased dNTP concentrations measured in heart and skeletal muscle, the fidelity of DNA synthesis in vitro by normally highly accurate mtDNA polymerase gamma is reduced, with error frequencies increased by as much as 3-fold, due to increased formation of template T-dGTP mismatches that are inefficiently corrected by proofreading. These data, plus some published data on specific mitochondrial mutations seen in human diseases, are consistent with the hypothesis that normal intramitochondrial dNTP pool asymmetries may contribute to spontaneous mutagenesis in the mammalian mitochondrial genome. C1 Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Mathews, CK (reprint author), Oregon State Univ, Dept Biochem & Biophys, 2011 ALS, Corvallis, OR 97331 USA. EM mathewsc@onid.orst.edu OI Pursell, Zachary/0000-0001-5871-7192 FU NIEHS NIH HHS [ES00040, P01 ES000040] NR 45 TC 82 Z9 86 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 5 PY 2005 VL 102 IS 14 BP 4990 EP 4995 DI 10.1073/pnas.0500253102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 914AC UT WOS:000228195800015 PM 15784738 ER PT J AU Feng, HQ Zhou, Z Bai, YW AF Feng, HQ Zhou, Z Bai, YW TI A protein folding pathway with multiple folding intermediates at atomic resolution SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hidden folding intermediate; native-state hydrogen exchange; NMR structure; protein engineering; protein structure ID STATE HYDROGEN-EXCHANGE; NONNATIVE HYDROPHOBIC INTERACTIONS; 4-HELIX BUNDLE PROTEIN; CYTOCHROME-C; NATIVE-STATE; APOCYTOCHROME B(562); STRUCTURAL-CHARACTERIZATION; KINETIC EVIDENCE; PHAGE-DISPLAY; MECHANISM AB Using native-state hydrogen-exchange-directed protein engineering and multidimensional NMR, we determined the high-resolution structure (rms deviation, 1.1 angstrom) for an intermediate of the four-helix bundle protein: Rd-apocytochrome b(562). The intermediate has the N-terminal helix and a part of the C-terminal helix unfolded. In earlier studies, we also solved the structures of two other folding intermediates for the same protein: one with the N-terminal helix alone unfolded and the other with a reorganized hydrophobic core. Together, these structures provide a description of a protein folding pathway with multiple intermediates at atomic resolution. The two general features for the intermediates are (i) native-like backbone topology and (ii) nonnative side-chain interactions. These results have implications for important issues in protein folding studies, including large-scale conformation search, phi-value analysis, and computer simulations. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov NR 59 TC 85 Z9 88 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 5 PY 2005 VL 102 IS 14 BP 5026 EP 5031 DI 10.1073/pnas.0501372102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 914AC UT WOS:000228195800021 PM 15793003 ER PT J AU Yoon, BS Ovchinnikov, DA Yoshii, I Mishina, Y Behringer, RR Lyons, KM AF Yoon, BS Ovchinnikov, DA Yoshii, I Mishina, Y Behringer, RR Lyons, KM TI Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone morphogenetic protein; cartilage; endochondral ossification; Sox proteins; skeletal development ID MULTIPOTENTIAL MESENCHYMAL CELLS; BONE MORPHOGENETIC PROTEIN-2; SKELETAL DEVELOPMENT; LIMB CHONDROGENESIS; CARTILAGE FORMATION; SIGNALING PATHWAYS; MEDIATOR SMAD1; FACTOR SOX9; DIFFERENTIATION; RECEPTOR AB Previous studies have demonstrated the ability of bone morphogenetic proteins (BMPs) to promote chondrogenic differentiation in vitro. However, the in vivo role of BMP signaling during chondrogenesis has been unclear. We report here that BMP signaling is essential for multiple aspects of early chondrogenesis. Whereas mice deficient in type 1 receptors Bmpr1a or Bmpr1b in cartilage are able to form intact cartilaginous elements, double mutants develop a severe generalized chondrodysplasia. The majority of skeletal elements that form through endochondral ossification are absent, and the ones that form are rudimentary. The few cartilage condensations that form in double mutants are delayed in the prechondrocytic state and never form an organized growth plate. The reduced size of mutant condensations results from increased apoptosis and decreased proliferation. Moreover, the expression of cartilage-specific extracellular matrix proteins is severely reduced in mutant elements. We demonstrate that this defect in chondrocytic differentiation can be attributed to lack of Sox9, L-Sox5, and Sox6 expression in precartilaginous condensations in double mutants. In summary, our study demonstrates that BMPR1A and BMPR1B are functionally redundant during early chondrogenesis and that BMP signaling is required for chondrocyte proliferation, survival, and differentiation in vivo. C1 Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, MacDonald Res Labs 2641, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Lyons, KM (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, MacDonald Res Labs 2641, 675 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM klyons@mednet.ucla.edu RI Lyons, Karen/P-1843-2014; Ovchinnikov, Dmitry/J-7963-2014 OI Lyons, Karen/0000-0001-9420-5813; Ovchinnikov, Dmitry/0000-0001-9603-8385 FU NHLBI NIH HHS [NHLBI-T32-69766]; NIAMS NIH HHS [AR42919, AR44528, P01 AR042919, R01 AR044528] NR 35 TC 223 Z9 239 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 5 PY 2005 VL 102 IS 14 BP 5062 EP 5067 DI 10.1073/pnas.0500031102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 914AC UT WOS:000228195800027 PM 15781876 ER PT J AU Fisher, MA Grimm, D Henion, AK Elias, AF Stewart, PE Rosa, PA Gherardini, FC AF Fisher, MA Grimm, D Henion, AK Elias, AF Stewart, PE Rosa, PA Gherardini, FC TI Borrelia burgdorferi sigma(54) is required for mammalian infection and vector transmission but not for tick colonization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE infectivity; microarray; Lyme; transcription ID LYME-DISEASE SPIROCHETE; GENERAL STRESS-RESPONSE; IXODES-SCAPULARIS; PSEUDOMONAS-AERUGINOSA; SURFACE-PROTEINS; GLOBAL ANALYSIS; IN-VIVO; EXPRESSION; GENOME; VIRULENCE AB Previous studies have shown that a sigma(54)-sigma(S) cascade regulates the expression of a few key lipoproteins in Borrelia burgdorferi, the agent of Lyme disease. Here, we demonstrate that these sigma factors, both together and independently, regulate a much more extensive number of genes and cellular processes. Microarray analyses of sigma(54) and sigma(s) mutant strains identified 305 genes regulated by sigma(54) and 145 regulated by sigma(s), whereas the sigma(54)-sigma(s) regulatory cascade appears to control 48 genes in B. burgdorferi. In silico analyses revealed that nearly 80% of genes with altered expression in the sigma(54) mutant were linked to potential sigma(54)-dependent promoters. Many sigma(54)-regulated genes are expressed in vivo, and through genetic complementation of the mutant, we demonstrated that sigma(54) was required by B. burgdorferi to infect mammals. Surprisingly, sigma(54) mutants were able to infect Ixodes scapularis ticks and be maintained for at least 24 wk after infection, suggesting the sigma(54)-sigma(s) regulatory network was not involved in long-term survival in ticks. However, sigma(54) mutants did not enter the salivary glands during tick feeding, indicating that sigma(54)-regulated genes were involved in the transmission process. C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Gherardini, FC (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fgherardini@nih.gov NR 43 TC 144 Z9 147 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 5 PY 2005 VL 102 IS 14 BP 5162 EP 5167 DI 10.1073/pnas.0408536102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 914AC UT WOS:000228195800044 PM 15743918 ER PT J AU Kraemer, KH Bohr, VA AF Kraemer, KH Bohr, VA TI The DNA repair interest group: a global village SO DNA REPAIR LA English DT Editorial Material C1 NCI, Ctr Canc Res, Basic Res Lab, Bethesda, MD 20892 USA. NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Kraemer, KH (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Bldg 37,Room 4002, Bethesda, MD 20892 USA. EM kraemerk@nih.gov; vbohr@nih.gov FU Intramural NIH HHS [Z01 BC004517-31] NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 4 PY 2005 VL 4 IS 4 BP 405 EP 406 DI 10.1016/j.dnarep.2005.01.002 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 905AX UT WOS:000227540900001 PM 15725621 ER PT J AU Friedberg, EC Bohr, VA Fuchs, RPP AF Friedberg, EC Bohr, VA Fuchs, RPP TI Erling Christen Seeberg (1946-2004) - Obituary SO DNA REPAIR LA English DT Biographical-Item C1 Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, Dallas, TX 75390 USA. NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. CNRS, UPR 9003, Strasbourg, France. RP Friedberg, EC (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM friedberg.errol@pathology.swmed.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 4 PY 2005 VL 4 IS 4 BP 407 EP 408 DI 10.1016/j.dnarep.2004.12.007 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 905AX UT WOS:000227540900002 ER PT J AU Rajagopalan, S Long, EO AF Rajagopalan, S Long, EO TI Understanding how combinations of HLA and KIR genes influence disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID KILLER-CELL RECEPTORS; IMMUNOGLOBULIN-LIKE RECEPTOR; IG-LIKE RECEPTORS; COMPLEX CLASS-I; INHIBITORY RECEPTORS; RECOGNITION; LIGANDS; BINDING; ACTIVATION; MOLECULES AB Combinations of HLA and killer cell immunoglobulin-like receptor (KIR) genes have been associated with diseases as diverse as autoimmunity, viral infections, reproductive failure, and now cancer. Much as early observations of disease associations with HLA polymorphism preceded a detailed knowledge of HLA recognition by T cell receptors, the recently reported disease associations with HLA-KIR gene combinations beg for a better understanding of the underlying mechanisms. C1 NIAID, NIH, Rockville, MD 20852 USA. RP NIAID, NIH, Rockville, MD 20852 USA. EM elong@nih.gov RI Yang, Chen/G-1379-2010; Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 32 TC 121 Z9 129 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD APR 4 PY 2005 VL 201 IS 7 BP 1025 EP 1029 DI 10.1081/jem.20050199 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 913WW UT WOS:000228187300002 PM 15809348 ER PT J AU Marie, JC Letterio, JJ Gavin, M Rudensky, AY AF Marie, JC Letterio, JJ Gavin, M Rudensky, AY TI TGF-beta 1 maintains suppressor function and Foxp3 expression in CD4(+)CD25(+) regulatory T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; AUTOIMMUNE-DISEASE; MICE CAUSES; DISRUPTION; INDUCTION; TOLERANCE; MOUSE; ENTEROPATHY AB Transforming growth factor (TGF)-beta 1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-beta 1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4(+)CD25(+) regulatory T ( T reg) cells, but is not required for their thymic development. We found that in 8-10-d-old TGF-beta 1-deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-beta-mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-beta 1 signaling in peripheral T reg cells and T reg cell maintenance in vivo. C1 Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. NCI, Lab Cell Regulat & Carcinogensis, Bethesda, MD 20892 USA. RP Rudensky, AY (reprint author), Univ Washington, Dept Immunol, Seattle, WA 98195 USA. EM aruden@u.washington.edu RI Marie, Julien/I-5084-2016 FU NIAID NIH HHS [AI34206, R01 AI034206, R01 AI061816, AI061816, R37 AI034206] NR 30 TC 607 Z9 675 U1 1 U2 16 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 APR 4 PY 2005 VL 201 IS 7 BP 1061 EP 1067 DI 10.1084/jem.20042276 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 913WW UT WOS:000228187300007 PM 15809351 ER PT J AU Carrington, M Wang, S Martin, MP Gao, XJ Schiffman, M Cheng, J Herrero, R Rodriguez, AC Kurman, R Mortel, R Schwartz, P Glass, A Hildesheim, A AF Carrington, M Wang, S Martin, MP Gao, XJ Schiffman, M Cheng, J Herrero, R Rodriguez, AC Kurman, R Mortel, R Schwartz, P Glass, A Hildesheim, A TI Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID 3 ETHNIC-GROUPS; CLASS-I; HUMAN-PAPILLOMAVIRUS; C ALLELES; NK CELLS; HLA; GENES; RISK; RECOGNITION; MOLECULES AB Killer immunoglobulin-like receptor (KIR) recognition of specific human histocompatibility leukocyte antigen (HLA) class I allotypes contributes to the array of receptor-ligand interactions that determine natural killer (NK) cell response to its target. Contrasting genetic effects of KIR/HLA combinations have been observed in infectious and autoimmune diseases, where genotypes associated with NK cell activation seem to be protective or to confer susceptibility, respectively. We show here that combinations of KIR and HLA loci also affect the risk of developing cervical neoplasia. Specific inhibitory KIR/HLA ligand pairs decrease the risk of developing neoplasia, whereas the presence of the activating receptor KIR3DS1 results in increased risk of disease, particularly when the protective inhibitory combinations are missing. These data suggest a continuum of resistance conferred by NK cell inhibition to susceptibility involving NK cell activation in the development of cervical neoplasia and underscore the pervasive influence of KIR/HLA genetic variation in human disease pathogenesis. C1 Sci Applicat Int Corp, Natl Canc Inst, Lab Genom Divers, Basic Res Program, Ft Detrick, MD 21702 USA. NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. Proyecto Epidemiol Guanacaste, San Jose 3016151, Costa Rica. Johns Hopkins Med Inst, Div Gynecol Pathol, Baltimore, MD 21231 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. RP Carrington, M (reprint author), Sci Applicat Int Corp, Natl Canc Inst, Lab Genom Divers, Basic Res Program, Ft Detrick, MD 21702 USA. EM carringt@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 30 TC 149 Z9 157 U1 0 U2 1 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 APR 4 PY 2005 VL 201 IS 7 BP 1069 EP 1075 DI 10.1081/jem.20042158 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 913WW UT WOS:000228187300008 PM 15809352 ER PT J AU Sommers, CL Lee, J Steiner, KL Gurson, JM DePersis, CL El-Khoury, D Fuller, CL Shores, EW Love, PE Samelson, LE AF Sommers, CL Lee, J Steiner, KL Gurson, JM DePersis, CL El-Khoury, D Fuller, CL Shores, EW Love, PE Samelson, LE TI Mutation of the phospholipase C-gamma 1-binding site of LAT affects both positive and negative thymocyte selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; TEC FAMILY KINASES; ANTIGEN RECEPTOR; TYROSINE RESIDUES; THYMIC EMIGRANTS; ADAPTER PROTEIN; TRANSGENIC MICE; POINT MUTATION; ACTIVATION; SIGNAL AB Linker for activation of T cells (LAT) is a scaffolding adaptor protein that is critical for T cell development and function. A mutation of LAT (Y136F) that disrupts phospholipase C-gamma 1 activation and subsequent calcium influx causes a partial block in T cell development and leads to a severe lymphoproliferative disease in homozygous knock-in mice. One possible contribution to the fatal disease of LAT Y136F knock-in mice could be from autoreactive T cells generated in these mice because of altered thymocyte selection. To examine the impact of the LAT Y136F mutation on thymocyte positive and negative selection, we bred this mutation onto the HY T cell receptor (TCR) transgenic, recombination activating gene-2 knockout background. Female mice with this genotype showed a severe defect in positive selection, whereas male mice exhibited a phenotype resembling positive selection (i.e.,development and survival of CD8(hi) HY TCR-specific T cells) instead of negative selection. These results support the hypothesis that in non-TCR transgenic, LAT Y136F knock-in mice, altered thymocyte selection leads to the survival and proliferation of autoreactive T cells that would otherwise be negatively selected in the thymus. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU NCI NIH HHS [Z01 BC010304-07] NR 43 TC 57 Z9 58 U1 0 U2 1 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 APR 4 PY 2005 VL 201 IS 7 BP 1125 EP 1134 DI 10.1081/jem.20011869 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 913WW UT WOS:000228187300013 PM 15795236 ER PT J AU Chen, J Lee, CT Errico, S Deng, XL Cadet, JL Freed, WJ AF Chen, J Lee, CT Errico, S Deng, XL Cadet, JL Freed, WJ TI Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-D-aspartate-induced AF5 cell death SO MOLECULAR BRAIN RESEARCH LA English DT Article DE cannabinoids; NMDA; excitotoxicity; neuroprotection; antioxidant ID RECEPTOR-INDEPENDENT MECHANISM; IN-VIVO EXCITOTOXICITY; SV40 LARGE T; RUTHENIUM RED; CANNABINOID RECEPTORS; ANTIOXIDANT ACTIVITY; NEURONAL INJURY; NEUROPROTECTION; CAPSAICIN; NEUROTOXICITY AB The neuroprotective effects of Delta(9)-tetrahydrocannabinol (THC) were examined using an in vitro model in which the AF5 CNS cell line was exposed to toxic levels of N-methyl-D-aspartate (NMDA), an agonist of the NMDA glutamate receptor. NMDA toxicity was reduced by THC, but not by the more specific cannabinoid receptor agonist, WIN55,212-2. Addition of dibutyryl cAMP (dbcAMP) to the culture medium did not alter the neuroprotective effect of THC and did not unmask a neuroprotective effect of WIN55,212-2. The cannabinoid antagonist SR141716A did not inhibit the neuroprotection induced by THC or alter the response to WIN55,212-2, even in the presence of dbcAMP, indicating that the neuroprotective effect of THC was cannabinoid receptor-independent. On the other hand, both THC and WIN55,212-2 produced cellular toxicology at higher dosages, an effect which was blocked in part by SR141716A. Capsaicin, an antioxidant and vanilloid receptor agonist, also produced a protective effect against NMDA toxicology. The protective effect of capsaicin was blocked by co-application of ruthenium red, but was not blocked by the specific vanilloid receptor antagonist capsazepine, and the transient receptor potential vanilloid type 1 (TRPV1) and ANKTM1 transcripts were not detected in AF5 cells. Thus, the neuroprotective effects of THC and capsaicin did not appear to be mediated by TRP ion channel family receptors. The antioxidant alpha-tocopherol prevented neurotoxicity in a dose-dependent manner. Therefore, THC may function as an antioxidant to increase cell survival in NMDA-induced neurotoxicity in the AF5 cell model, while higher dosages produce toxicity mediated by CB1 receptor stimulation. Published by Elsevier B.V. C1 Dev & Plast Sect, Cell Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, Dept Hlth & Human Serv,Mol Neuropsychiat Sect,NIH, Baltimore, MD 21224 USA. RP Chen, J (reprint author), Dev & Plast Sect, Cell Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. EM jchen@intra.nida.nih.gov; serrico@intra.nida.nih.gov; xdeng@intra.nida.nih.gov; jcadet@intra.nida.nih.gov; wfreed@intra.nida.nih.gov NR 34 TC 9 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 4 PY 2005 VL 134 IS 2 BP 215 EP 225 DI 10.1016/j.molbrainres.2004.10.044 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 922NL UT WOS:000228844500005 ER PT J AU Moran, CM Donnelly, M Ortiz, D Pant, HC Mandelkow, EM Shea, TB AF Moran, CM Donnelly, M Ortiz, D Pant, HC Mandelkow, EM Shea, TB TI Cdk5 inhibits anterograde axonal transport of neurofilaments but not that of tau by inhibition of mitogen-activated protein kinase activity SO MOLECULAR BRAIN RESEARCH LA English DT Article DE cyclin-dependent kinase 5; mitogen-activated protein kinase; neurofilaments; Tau; axonal transport; phosphorylation; cytoskeleton; signal transduction ID CYCLIN-DEPENDENT KINASE-5; AMYOTROPHIC-LATERAL-SCLEROSIS; SUBUNITS UNDERGO; IN-VIVO; SIGNALING MECHANISMS; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; OXIDATIVE STRESS; SIDE-ARMS AB Cyclin-dependent kinase 5 (cdk5) inhibits neurofilament (NF) anterograde axonal transport while p42/44 mitogen-activated protein kinase (MAPk) promotes it. Since cdk5 is known to inhibit MAP kinase activity, we examined whether or not cdk5 inhibits anterograde NF transport via inhibition of MAPk activity. To accomplish this, we manipulated the activity of these kinases in differentiated NB2a/dl cells, and monitored anterograde axonal transport of green fluorescent protein-conjugated-NF-M (GFP-M) and cyan fluorescent protein-conjugated (CFP)-tau. The cdk5 inhibitor roscovitine increased anterograde axonal transport of GFP-M and CFP-tau; transfection with cdk5/p25 inhibited transport of both. Inhibition of MAPk activity by PD98059 or expression of dominant-negative MAPk inhibited anterograde GFPM transport, while expression of constitutively active MAR enhanced it; these treatments did not affect CFP-tau transport. PD98059 prevented roscovitine-mediated enhancement of GFP-M transport, but did not prevent enhancement of CFP-tau transport. Co-transfection with constitutively activated MAPk prevented the inhibition of GFP-M transport that normally accompanied transfection with cdk5/p25, but did not prevent inhibition of tau transport by cdk5/p25. Finally, the extent of inhibition of GFP-M axonal transport by PD98059 was not additive to that derived from transfection with cdk5/p35, and the increase in NF transport that accompanies roscovitine treatment was not additive to that derived from transfection with constitutively activated MAR, suggesting that the influence of these kinases on NF transport was within the same, rather than distinct, pathways. These findings suggest that axonal transport of tau and NFs is under the control of distinct kinase cascades, and that cdk5 inhibits NF transport at least in part by inhibiting MAPk. (c) 2004 Published by Elsevier B.V. C1 Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. Univ Massachusetts, Ctr Cell Neurobiol & Neurodegenerat Res, Lowell, MA 01854 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. DESY, Max Planck Unit Struct Mol Biol, D-22603 Hamburg, Germany. RP Shea, TB (reprint author), Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. EM Thomas_Shea@uml.edu NR 94 TC 18 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 4 PY 2005 VL 134 IS 2 BP 338 EP 344 DI 10.1016/j.molbrainres.2004.10.035 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 922NL UT WOS:000228844500015 ER PT J AU Bonner, MR Rothman, N Mumford, JL He, XZ Shen, M Welch, R Yeager, M Chanock, S Caporaso, N Lan, Q AF Bonner, MR Rothman, N Mumford, JL He, XZ Shen, M Welch, R Yeager, M Chanock, S Caporaso, N Lan, Q TI Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE green tea; smoky coal; lung cancer; OGG1; AKR1C3; GSTM1 ID HOGG1 SER326CYS POLYMORPHISM; ALDO-KETO REDUCTASE; XUAN-WEI; DIHYDRODIOL DEHYDROGENASE; COMBUSTION EMISSIONS; OXIDATIVE STRESS; O-QUINONES; CELL-LINES; POLYPHENOLS; MECHANISMS AB Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epiderniologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1). glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase IC3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR) = 4.93; 95% confidence interval (95%CI) = 1.27-19.13) than for drinkers (OR= 1.88-.95% CI = 1.01-3.48). Further, among individuals with the OGG1 Cys(326) allele, daily consumption was associated with a 72% reduction (95% CI=0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Set- 326 homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage. (c) 2004 Elsevier B.V. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Chinese Acad Prevent Med, Beijing, Peoples R China. RP Bonner, MR (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, 6120 Execut Blvd,EPS 8121,MSC 7240, Bethesda, MD 20892 USA. EM bonnerm@mail.nih.gov NR 41 TC 28 Z9 32 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD APR 4 PY 2005 VL 582 IS 1-2 BP 53 EP 60 DI 10.1016/j.mrgentox.2004.12.008 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 913XV UT WOS:000228189800007 PM 15781210 ER PT J AU Jerebko, AK Malley, JD Franaszek, M Summers, RM AF Jerebko, AK Malley, JD Franaszek, M Summers, RM TI Support vector machines committee classification method for computer-aided polyp detection in CT colonography SO ACADEMIC RADIOLOGY LA English DT Article DE computer-aided diagnosis (CAD); virtual colonoscopy; colon polyp; support vector machine (SVM); validation ID COLONIC POLYPS AB Rationale and Objectives. A new classification scheme for the computer-aided detection of colonic polyps in computed tomographic colonography is proposed. Materials and Methods. The scheme involves an ensemble of support vector machines (SVMs) for classification, a smoothed leave-one-out (SLOO) cross-validation method for obtaining error estimates, and use of a bootstrap aggregation method for training and model selection. Our use of an ensemble of SVM classifiers with bagging (bootstrap aggregation), built on different feature subsets, is intended to improve classification performance compared with single SVMs and reduce the number of false-positive detections. The bootstrap-based model-selection technique is used for tuning SVM parameters. In our first experiment, two independent data sets were used: the first, for feature and model selection, and the second, for testing to evaluate the generalizability of our model. In the second experiment, the test set that contained higher resolution data was used for training and testing (using the SLOO method) to compare SVM committee and single SVM performance. Results. The overall sensitivity on independent test set was 75%, with 1.5 false-positive detections/study, compared with 76%-78% sensitivity and 4.5 false-positive detections/study estimated using the SLOO method on the training set. The sensitivity of the SVM ensemble retrained on the former test set estimated using the SLOO method was 81%, which is 7%-10% greater than the sensitivity of a single SVM. The number of false-positive detections per study was 2.6, a 1.5 times reduction compared with a single SVM. Conclusion. Training an SVM ensemble on one data set and testing it on the independent data has shown that the SVM committee classification method has good generalizability and achieves high sensitivity and a low false-positive rate. The model selection and improved error estimation method are effective for computer-aided polyp detection. C1 Diagnost Radiol Dept, Bethesda, MD 20892 USA. Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. RP Jerebko, AK (reprint author), Diagnost Radiol Dept, Bethesda, MD 20892 USA. EM anna.jerebko@siemens.com NR 19 TC 39 Z9 41 U1 0 U2 3 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2005 VL 12 IS 4 BP 479 EP 486 DI 10.1016/j.acra.2004.04.024 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916VT UT WOS:000228415300012 PM 15831422 ER PT J AU Daldrup-Link, HE Rudelius, M Oostendorp, RAJ Jacobs, VR Simon, GH Gooding, C Rummeny, EJ AF Daldrup-Link, HE Rudelius, M Oostendorp, RAJ Jacobs, VR Simon, GH Gooding, C Rummeny, EJ TI Hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking in a xenotransplant mouse model XXX SO ACADEMIC RADIOLOGY LA English DT Article DE MR imaging; molecular imaging; contrast medium; cell targeting ID SUPERPARAMAGNETIC IRON-OXIDE; MR CONTRAST AGENTS; STEM-CELLS; BONE-MARROW; MICE; TRANSPLANTATION; FERUMOXIDES; PLASTICITY; PARTICLES; EXPANSION AB Rationale and Objectives. To compare and optimize ferumoxides labeling of human hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking with a clinical 1.5 T MR scanner. Materials and Methods. Human hematopoietic progenitor cells, derived from umbilical cord blood or peripheral blood, were labeled with Ferumoxides by simple incubation or lipofection. Cellular iron uptake was quantified with spectrometry. Then, 3 x 10(7)-labeled cells were injected into the tail vein of 12 female nude Balb/c mice. The mice underwent magnetic resonance imaging before and 24 hours after injection. Precontrast and postcontrast signal intensities of liver, spleen, and bone marrow were measured and tested for significant differences with the t-test. Immunostains served as a histopathologic standard of reference. Results. After labeling by simple incubation, only umbilical cord blood cells, but not peripheral blood cells, showed a significant iron uptake and could be tracked in vivo with magnetic resonance imaging. Using lipofection, both cell types could be tracked in vivo. A significant decline in signal intensity was observed in liver, spleen, and bone marrow at 24 hours after injection of efficiently labeled ferumoxides cells (P < .05). Histopathology proved the distribution of iron oxide-labeled cells to these organs. Conclusion. Hematopoietic progenitor cells from umbilical cord blood can be labeled by simple incubation with an Food and Drug Administration-approved magnetic resonance contrast agent with sufficient efficiency to provide an in vivo cell tracking at 1.5 T. Progenitor cells from peripheral blood need to be labeled with adjunctive transfection techniques to be depicted in vivo at 1.5 T. C1 Univ Calif San Francisco, Ctr Med, Dept Radiol, San Francisco, CA 94143 USA. Tech Univ, Dept Radiol, Munich, Germany. Tech Univ, Dept Gynaecol, Clin Internal Med 3, Munich, Germany. NIH, Washington, DC USA. Tech Univ, Lab Stem Cell Physiol, Munich, Germany. RP Daldrup-Link, HE (reprint author), Univ Calif San Francisco, Ctr Med, Dept Radiol, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM daldrup@radiology.ucsf.edu RI Daldrup-Link, Heike/D-9829-2012; Jacobs, Volker/A-2451-2009 OI Daldrup-Link, Heike/0000-0002-4929-819X; Jacobs, Volker/0000-0003-1202-0482 NR 31 TC 39 Z9 44 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 APR PY 2005 VL 12 IS 4 BP 502 EP 510 DI 10.1016/j.acra.2004.12.021 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916VT UT WOS:000228415300015 PM 15831425 ER PT J AU Vrabie, A Goldfarb, LG Shatunov, A Nagele, A Fritz, P Kaczmarek, I Goebel, HH AF Vrabie, A Goldfarb, LG Shatunov, A Nagele, A Fritz, P Kaczmarek, I Goebel, HH TI The enlarging spectrum of desminopathies: new morphological findings, eastward geographic spread, novel exon 3 desmin mutation SO ACTA NEUROPATHOLOGICA LA English DT Article; Proceedings Paper CT 29th Symposium on Muscle Diseases CY JUL, 2004 CL Oxford, ENGLAND DE desminopathy; desmin mutation; granulofilamentous material; cardiomyopathy; skeletal myopathy ID BODY-LIKE INCLUSIONS; SKELETAL MYOPATHY; FAMILIAL CARDIOMYOPATHY; DISTAL MYOPATHY; RESTRICTIVE CARDIOMYOPATHY; ATRIOVENTRICULAR-BLOCK; INTERMEDIATE-FILAMENTS; MYOFIBRILLAR MYOPATHY; HEREDITARY MYOPATHY; MISSENSE MUTATION AB A 52-year-old man, who had developed distal muscle weakness in legs and arms, was found to have distal muscle atrophy as well as cardiac arrhythmia. His 10-year younger brother developed restrictive cardiomyopathy at the age of 20 years, which required cardiac transplantation at the age of 41 years. Skeletal muscle biopsy specimens of the older brother revealed granulofilamentous material and plaques containing numerous proteins, foremost desmin, as did cardiac biopsy tissue. The explanted heart of the younger brother showed similar protein-rich plaques and granulofilamentous material within cardiac myocytes. A novel heterozygous Glu245Asp (E245D) missense mutation in exon 3 of the desmin gene (DES) at 2q35 was found in the older brother. While clinical data and muscle biopsy pathology of the older brother conform to the nosological spectrum of desminopathies, the early-onset cardiomyopathy, a similar cardiac pathology as in skeletal muscle tissues and a novel missense mutation in the DES gene, enlarge the nosological spectrum of desminopathies. C1 Univ Mainz, Med Ctr, Dept Neuropathol, D-55101 Mainz, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Dept Neurol, Christophsbad, Goppingen, Germany. Robert Bosch Krankenhaus, Dept Pathol, Stuttgart, Germany. Univ Munich, Dept Cardiac & Thorac Surg, Munich, Germany. RP Goebel, HH (reprint author), Univ Mainz, Med Ctr, Dept Neuropathol, Langenbeckstr 1, D-55101 Mainz, Germany. EM goebel@neuropatho.klinik.uni-mainz.de RI Shatunov, Aleksey/E-6946-2011 NR 34 TC 24 Z9 25 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2005 VL 109 IS 4 BP 411 EP 417 DI 10.1007/s00401-005-0980-1 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 924SK UT WOS:000229000400009 PM 15759133 ER PT J AU Merikangas, KR AF Merikangas, KR TI The significance of social connectedness: Comment on Slomkowski et al. 2005 SO ADDICTION LA English DT Editorial Material ID ADOLESCENT SUBSTANCE USE; SMOKING; BEHAVIOR C1 NIMH, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIMH, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov NR 8 TC 3 Z9 3 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2005 VL 100 IS 4 BP 442 EP 443 DI 10.1111/j.1360-0443.2005.01085.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 909NR UT WOS:000227867100008 PM 15784056 ER PT J AU Gray, CM Williamson, C Bredell, H Puren, A Xia, XH Filter, R Zijenah, L Cao, HY Morris, L Vardas, E Colvin, M Gray, G McIntyre, J Musonda, R Allen, S Katzenstein, D Mbizo, M Kumwenda, N Taha, T Karim, SA Flores, J Sheppard, HW AF Gray, CM Williamson, C Bredell, H Puren, A Xia, XH Filter, R Zijenah, L Cao, HY Morris, L Vardas, E Colvin, M Gray, G McIntyre, J Musonda, R Allen, S Katzenstein, D Mbizo, M Kumwenda, N Taha, T Karim, SA Flores, J Sheppard, HW TI Viral dynamics and CD4(+) T cell counts in subtype C human immunodeficiency virus type 1-infected individuals from southern Africa SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID FEMALE SEX WORKERS; HIV-1 INFECTION; DISEASE PROGRESSION; RNA LEVELS; LYMPHOCYTE COUNT; NATURAL-HISTORY; COTE-DIVOIRE; LARGE COHORT; LOAD; PLASMA AB Defining viral dynamics in natural infection is prognostic of disease progression and could prove to be important for vaccine trial design as viremia may be a likely secondary end point in phase III HIV efficacy trials. There are limited data available on the early course of plasma viral load in subtype C HIV-1 infection in Africa. Plasma viral load and CD4(+) T cell counts were monitored in 51 recently infected subjects for 9 months. Individuals were recruited from four southern African countries: Zambia, Malawi, Zimbabwe, and South Africa and the median estimated time from seroconversion was 8.9 months (interquartile range, 5.7-14 months). All were infected with subtype C HIV-1 and median viral loads, measured using branched DNA, ranged from 3.82-4.02 log(10) RNA copies/ml from 2-24 months after seroconversion. Viral loads significantly correlated with CD4(+) cell counts (r = -0.5, p < 0.0001; range, 376 - 364 cells/mm(3)) and mathematical modeling defined a median set point of 4.08 log(10) ( 12 143 RNA copies/ml), which was attained approximately 17 months after seroconversion. Comparative measurements using three different viral load platforms (bDNA, Amplicor, and NucliSens) confirmed that viremia in subtype C HIV-1-infected individuals within the first 2 years of infection did not significantly differ from that found in early subtype B infection. In conclusion, the course of plasma viremia, as described in this study, will allow a useful baseline comparator for understanding disease progression in an African setting and may be useful in the design of HIV-1 vaccine trials in southern Africa. C1 Natl Inst Communicable Dis, HIV Immunol Lab, AIDS Unit, ZA-2131 Johannesburg, South Africa. Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. Univ Pretoria, Dept Elect Engn, ZA-0002 Pretoria, South Africa. Univ Zimbabwe, Dept Immunol, Harare, Zimbabwe. Dept Hlth Serv, Richmond, CA USA. MRC, HIV Vaccine & Prevent Trials Unit, Durban, South Africa. Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa. Zambia UAB, HIV Res Project, Lusaka, Zambia. Stanford Univ, Med Ctr, Ctr AIDS Res, Stanford, CA 94305 USA. John Hopkins Res Project, Blantyre, Malawi. Natl Inst Hlth, Div Aids, Washington, DC USA. RP Gray, CM (reprint author), Natl Inst Communicable Dis, HIV Immunol Lab, AIDS Unit, ZA-2131 Johannesburg, South Africa. EM cgray@nicd.ac.za OI , Carolyn/0000-0003-0125-1226; , Lynn/0000-0003-3961-7828 FU NIAID NIH HHS [N01-AI-45202] NR 36 TC 17 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2005 VL 21 IS 4 BP 285 EP 291 DI 10.1089/aid.2005.21.285 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 926GK UT WOS:000229111000005 PM 15943570 ER PT J AU Purohit, V Khalsa, J Serrano, J AF Purohit, V Khalsa, J Serrano, J TI Mechanisms of alcohol-associated cancers: introduction and summary of the symposium SO ALCOHOL LA English DT Article DE alcohol-associated cancer; acetaldehyde; CYP2E1; oxidative stress ID DRINKING; RISK AB Chronic alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, and esophagus; breast; liver; ovary; colon; rectum; stomach; and pancreas. An understanding of the underlying mechanisms by which chronic alcohol consumption promotes carcinogenesis is important for development of appropriate strategies for prevention and treatment of alcohol-associated cancers. The National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, Office of Rare Diseases, National Cancer Institute, National Institute on Drug Abuse, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, sponsored an international symposium on Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, USA, October 2004. The following is a summary of the symposium. Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens; (3) depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; (4) induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase-mitogen-activated protein kinase signaling; (5) accumulation of iron and associated oxidative stress; (6) inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast); and (7) impairment of retinoic acid metabolism. Nicotine may promote carcinogenesis through activation of extracellular signal-regulated kinase/cyclooxygenase-2/vascular endothelial growth factor signaling pathway. (c) 2005 Elsevier Inc. All rights reserved. C1 NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. NIDA, Med Consequences Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Purohit, V (reprint author), NIAAA, Div Metab & Hlth Effects, NIH, 5635 Fishers Lane,Room 2035, Bethesda, MD 20892 USA. EM vpurohit@mail.nih.gov NR 6 TC 50 Z9 54 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD APR PY 2005 VL 35 IS 3 SI SI BP 155 EP 160 DI 10.1016/j.alcohol.2005.05.001 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 958HS UT WOS:000231435900001 PM 16054976 ER PT J AU Brown, LM AF Brown, LM TI Epidemiology of alcohol-associated cancers SO ALCOHOL LA English DT Article DE alcohol; breast cancer; cancer; colorectal cancer; esophageal cancer; laryngeal cancer; oral cancer; pancreatic cancer; pharyngeal cancer; tobacco; trends ID CELL ESOPHAGEAL CANCER; UNITED-STATES; ORAL-CAVITY; PUERTO-RICO; RISK; DRINKING; TOBACCO; BLACKS; WHITES; TRENDS AB Alcohol, especially in combination with smoking, is a well-established risk factor for cancers of the oral cavity and pharynx, esophagus, and larynx, with 25% to 80% of these cancers being attributable to alcohol. Rates of these cancers in the United States have been decreasing in recent years, possibly because of reductions in cigarette smoking and alcohol use. Chronic alcohol consumption has been linked with increased risk of liver cancer in epidemiologic studies. However, the rising rates of this cancer in the United States are most likely due to the increasing prevalence of chronic hepatitis B and C infections. Epidemiologic evidence has linked light to moderate intake of alcohol to cancers of the colorectum and female breast. These cancers are common in developed countries, so even small increases in risk can have important public health implications. Although results of most epidemiologic studies have provided little or no support for a causal relation between light and moderate alcohol use and risk of pancreatic cancer, a possible role of heavy alcohol consumption cannot be ruled out. Further studies of these cancers are needed to clarify the role of type of alcoholic beverage, the role of alcohol concentration, and the dose-response curve at low concentrations of alcohol. Future research also should be designed to promote the use of uniform ways to report alcohol intake and uniform measures for analysis, to include the investigation of alcohol-associated cancer risks in U.S. minority populations, to enhance experimental work to better understand the underlying mechanisms through which alcohol promotes carcinogenesis, and to develop preventive strategies. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,Room 8026,MSC 7244, Bethesda, MD 20892 USA. EM brownl@mail.nih.gov NR 25 TC 26 Z9 31 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD APR PY 2005 VL 35 IS 3 SI SI BP 161 EP 168 DI 10.1016/j.alcohol.2005.03.008 PG 8 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 958HS UT WOS:000231435900002 PM 16054977 ER PT J AU Brooks, PJ Theruvathu, JA AF Brooks, PJ Theruvathu, JA TI DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis SO ALCOHOL LA English DT Article DE crotonaldehyde; acetaidehyde; DNA-protein cross-links; DNA interstrand cross-links; DNA repair; Fanconi anemia; Xeroderma pigmentosum ID DEOXYGUANOSINE ADDUCT; POLYMERASE-ETA; VINYL-ACETATE; CROSS-LINKS; ESCHERICHIA-COLI; CANCER-RISK; HUMAN-BLOOD; HUMAN-CELLS; ACROLEIN; ETHANOL AB Alcoholic beverage consumption is classified as a known human carcinogen, causally related to an increased risk of cancer of the upper gastrointestinal tract. The formation of acetaldehyde from ethanol metabolism seems to be the major mechanism underlying this effect. Acetaldehyde is carcinogenic in rodents and causes sister chromatid exchanges and chromosomal aberrations in human cells. The best-studied DNA adduct from acetaldehyde is N-2-ethyl-2'-deoxyguanosine, which is increased in liver DNA obtained from ethanol-treated rodents and in white blood cells obtained from human alcohol abusers. However, the carcinogenic relevance of this adduct is unclear in view of the lack of evidence that it is mutagenic in mammalian cells. A different DNA adduct, 1,N-2-propano-2'-deoxyguanosine (PdG), can also be formed from acetaldehyde in the presence of histones and other basic molecules. PdG has been shown to be responsible for the genotoxic and mutagenic effects of crotonaldehyde. The PdG adduct can exist in either of two forms: a ring-closed form or a ring-opened aldehyde form. Whereas the ring-closed form is mutagenic, the aldehyde form can participate in the formation of secondary lesions, including DNA-protein cross-links and DNA interstrand cross-links. The formation of these types of complex secondary DNA lesions resulting from PdG may explain many of the observed genotoxic effects of acetaldehyde described above. Repair of PdG and its associated adducts is complex, involving multiple pathways. Inherited variation in the genes encoding the proteins involved in the repair of PdG and its secondary adducts may contribute to susceptibility to alcoholic beverage-related carcinogenesis. (c) 2005 Elsevier Inc. All rights reserved. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, 5626 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM pjbrooks@mail.nih.gov NR 49 TC 154 Z9 157 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD APR PY 2005 VL 35 IS 3 SI SI BP 187 EP 193 DI 10.1016/j.alcohol.2005.03.009 PG 7 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 958HS UT WOS:000231435900005 PM 16054980 ER PT J AU Rice, E Milburn, NG Rotheram-Borus, MJ Mallett, S Rosenthal, D AF Rice, E Milburn, NG Rotheram-Borus, MJ Mallett, S Rosenthal, D TI The effects of peer group network properties on drug use among homeless youth SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article DE peer influence; networks; drug use ID SUBSTANCE USE; SOCIAL RELATIONSHIPS; RUNAWAY ADOLESCENTS; ALCOHOL-USE; PREDICTORS; DISORDERS; ADULTHOOD; BEHAVIOR; PEOPLE AB The authors examine how the properties of peer networks affect amphetamine, cocaine, and injection drug use over 3 months among newly homeless adolescents, aged 12 to 20 in Los Angeles (n = 217; 83% retention at 3 months) and Melbourne (n = 119; 72% retention at 3 months). Several hypotheses regarding the effects of social network properties on the peer influence process are developed. Multivariate logistic regression analyses show that higher concentrations of homeless peers in networks at recruitment were associated with increased likelihood of amphetamine and cocaine use at 3-month follow-up. Higher concentrations of injecting peers were associated with increased risk of injection drug use 3 months later Change in network structure over time toward increased concentrations of homeless peers was associated with increased risk of cocaine use and injecting. Higher density networks at baseline were positively associated with increased likelihood of cocaine and amphetamine use at 3 months. C1 Univ Calif Los Angeles, Ctr Community Hlth, Los Angeles, CA 90024 USA. Univ Melbourne, Melbourne, Vic, Australia. Univ Calif Los Angeles, Treatment Serv Core, Los Angeles, CA USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA USA. NIMH, Ctr HIV Identificat Prevent & Treatment Serv, Bethesda, MD 20892 USA. RP Rice, E (reprint author), Univ Calif Los Angeles, Ctr Community Hlth, Los Angeles, CA 90024 USA. EM erice@ucla.edu FU NIMH NIH HHS [P30 MH058107, P30 MH058107-11, R01 MH049958, R01 MH049958-09, R01 MH061185, R01 MH061185-03] NR 41 TC 56 Z9 56 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 J9 AM BEHAV SCI JI Am. Behav. Sci. PD APR PY 2005 VL 48 IS 8 BP 1102 EP 1123 DI 10.1177/0002764204274194 PG 22 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 014LW UT WOS:000235482700009 PM 20539820 ER PT J AU Curtis, AB Gersh, BJ Corley, SD DiMarco, JP Domanski, MJ Geller, N Greene, HL Kellen, JC Mickel, M Dalquist, J Rosenberg, Y Schron, E Shemanski, L Waldo, AL Wyse, DG AF Curtis, AB Gersh, BJ Corley, SD DiMarco, JP Domanski, MJ Geller, N Greene, HL Kellen, JC Mickel, M Dalquist, J Rosenberg, Y Schron, E Shemanski, L Waldo, AL Wyse, DG CA AFFIRM Investigators TI Clinical factors that influence response to treatment strategies in atrial fibrillation: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; SINUS RHYTHM; ATRIOVENTRICULAR NODE; RISK-FACTORS; DOFETILIDE; MORTALITY; TRIAL; CARDIOMYOPATHY; PREDICTORS AB Background The AFFIRM Study was a randomized multicenter comparison of 2 treatment strategies, rate-control versus rhythm-control, in high-risk patients with atrial fibrillation (AF). The primary outcome of the trial showed no overall difference in survival between strategies. However, there may be important patient subgroups for which there are identifiable differences in outcome with 1 of the 2 strategies. Methods and Results Subgroups that were prespecified for analysis from the main AFFIRM Study were age, sex, coronary artery disease (CAD), hypertension, congestive heart failure (CHF), left ventricular ejection fraction (LVEF), rhythm at randomization, first episode of AF, and duration of the qualifying episode of AF. Baseline characteristics were analyzed for each subgroup. Adjusted hazard ratios for each subgroup and for each stratum were generated using Cox models, and these models were used to determine whether treatment strategy affected overall survival differentially by subgroup. Adjusted survival was worse for patients >= 65 years and for patients with a history of CHF, CAD, or an abnormal LVEF. In the adjusted analyses, the effect of treatment strategy was similar within all of the prespecified subgroups. When each subgroup stratum was analyzed separately, patients >= 65 years and patients without a history of CHF had significantly better outcome with rate-control therapy (each P < .01). Conclusions Overall, treatment effect for rate control versus rhythm control was the same within each subgroup. However, certain selected patient categories may have better survival with one particular strategy for management of AF. C1 Univ Florida, Gainesville, FL 32610 USA. Mayo Clin Fdn, Rochester, MN USA. Axio Res Corp, Seattle, WA USA. Univ Virginia, Charlottesville, VA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calgary, Calgary, AB, Canada. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Curtis, AB (reprint author), Univ Florida, Box 100277,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM curtisa@meclicine.ufl.edu NR 26 TC 41 Z9 47 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 APR PY 2005 VL 149 IS 4 BP 645 EP 649 DI 10.1016/j.ahj.2004.09.038 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 920VF UT WOS:000228717600013 PM 15990747 ER PT J AU Sachdev, V Shizukuda, Y Brenneman, CL Birdsall, CW Waclawiw, MA Arai, AE Mohiddin, SA Tripodi, D Fananapazir, L Plehn, JF AF Sachdev, V Shizukuda, Y Brenneman, CL Birdsall, CW Waclawiw, MA Arai, AE Mohiddin, SA Tripodi, D Fananapazir, L Plehn, JF TI Left atrial volumetric remodeling is predictive of functional capacity in nonobstructive hypertrophic cardiomyopathy SO AMERICAN HEART JOURNAL LA English DT Article ID VENTRICULAR DIASTOLIC FUNCTION; EXERCISE CAPACITY; HEART-FAILURE; VENTILATORY EFFICIENCY; FILLING PRESSURES; SYSTOLIC FUNCTION; RISK; ECHOCARDIOGRAPHY; DETERMINANTS; DYSFUNCTION AB Background The left atrium is afterload sensitive, responding to immediate changes in left ventricular (LV) diastolic pressure, and left atrial volumetric remodeling has been reported in conditions associated with abnormal diastolic function. We examined the relationship between left atrial volumetric remodeling and objective measures of exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Methods We compared LA volume indices, other 2-dimensional and Doppler echocardiographic parameters, invasive hemodynamic measures, and magnetic resonance imaging (MRI)-derived LV mass with exercise duration, maximal oxygen uptake (MVo(2)), anaerobic threshold (AT), and ventilatory efficiency (VE/V*(Co2) slope) in 43 patients with nonobstructive HCM. Patients underwent cardiac catheterization within 48 hours and metabolic stress testing within 1 week of their echocardiogram and MRI examinations. Results Left atrial volume at end-ventricular systole (LA(max)) and end-atrial emptying (LA(min)) correlated with MVo(2) (r -0.39, P <.01 for both), AT (r = -0.42, r = -0.39, respectively, P <.01 for both), and VE/V*(Co2) slope (r = 0.45, P =.003; r = 0.41, P =.008). Patients with an LA(max) >= 33 mL/m(2) had significantly lower MVo(2) V =.025) and AT levels (P =.017) and higher VE/V*(Co2) slope levels (P =.004),as compared with patients with a smaller LA size.-In multivariate analysis, MRI-determined LV mass, which was not a univariate correlate of exercise tolerance, provided additional effect when combined with LA volume index. Conclusions Left atrial volumetric remodeling predicts exercise capacity in nonobstructive HCM and may reflect chronic LV diastolic burden. This simple noninvasive measure of LA size may provide a long-term indication of the effects of chronically elevated filling pressures in patients with HCM and further studies testing its prognostic value are necessary. C1 NHLBI, Echocardiog Lab, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Sachdev, V (reprint author), NHLBI, Echocardiog Lab, Cardiovasc Branch, NIH, 10 Ctr Dr,MSC-1650, Bethesda, MD 20892 USA. EM sachdevv@nhibi.nih.gov FU Intramural NIH HHS NR 34 TC 54 Z9 54 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 APR PY 2005 VL 149 IS 4 BP 730 EP 736 DI 10.1016/j.ahj.2004.07.017 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 920VF UT WOS:000228717600026 PM 15990760 ER PT J AU Fox, CS Evans, JC Larson, MG Lloyd-Jones, DM O'Donnell, CJ Sorlie, PD Manolio, TA Kannel, WB Levy, D AF Fox, CS Evans, JC Larson, MG Lloyd-Jones, DM O'Donnell, CJ Sorlie, PD Manolio, TA Kannel, WB Levy, D TI A comparison of death certificate out-of-hospital coronary heart disease death with physician-adjudicated sudden cardiac death SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AUTOMATED EXTERNAL DEFIBRILLATORS; FRAMINGHAM; RISK AB The number of deaths due to out-of-hospital coronary heart disease as determined by death certificates was compared with the number physician-adjudicated sudden cardiac deaths in the Framingham Heart Study from 1950 to 1999. Out-of-hospital coronary heart disease deaths overestimated sudden cardiac death by 47%, suggesting that out-of-hospital coronary heart disease death rates derived from death certificates should be interpreted with caution. (c) 2005 by Excerpta Medica Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009; OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01-HC-25195] NR 14 TC 39 Z9 39 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2005 VL 95 IS 7 BP 856 EP 859 DI 10.1016/j.amjcard.2004.12.011 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 914MA UT WOS:000228230600008 PM 15781015 ER PT J AU Gallagher, D Kuznia, P Heshka, S Albu, J Heymsfield, SB Goodpaster, B Visser, M Harris, TB AF Gallagher, D Kuznia, P Heshka, S Albu, J Heymsfield, SB Goodpaster, B Visser, M Harris, TB TI Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE muscle; adipose tissue; race; aging; body composition; fatness ID REGIONAL FAT DISTRIBUTION; AFRICAN-AMERICAN WOMEN; METABOLIC RISK-FACTORS; INSULIN-RESISTANCE; RACIAL-DIFFERENCES; CARDIOVASCULAR-DISEASE; SKELETAL-MUSCLE; ABDOMINAL FAT; HEALTH; OBESITY AB Background: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. Objective: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and total-body skeletal muscle mass in healthy sedentary African American (AA), Asian, and white adults by whole-body magnetic resonance imaging. IMAT is the AT between muscles and within the boundary of the muscle fascia. Design: Analyses were conducted on 227 women [AA (n = 79): body mass index (BMI; in kg/m(2)), 29.0 +/- 5.5; age, 45.7 +/- 16.9 y; Asian (n = 38): BMI, 21.7 +/- 2.9; age, 47.2 +/- 19.9 y; whites (n = 110): BMI, 24.9 +/- 5.4; age, 43.7 +/- 16.2 y]) and Ill men [AA (n = 39): BMI, 25.6 +/- 3.2; age, 45.5 +/- 18.8 y; Asian (n = 13): BMI, 24.9 +/- 2.5; age, 45.6 +/- 25.0 y; white (n = 59): BMI, 25.8 +/- 3.8; age 44.5 +/- 16.3 y]. Results: IMAT depots were not significantly different in size between race groups at low levels of adiposity; however, with increasing adiposity, AAs had a significantly greater increment in the proportion of total AT (TAT) than did the whites and Asians (58,46, and 44 g IMAT/kg TAT, respectively; P = 0.001). VAT depots were not significantly different in size at low levels of adiposity but, with increasing adiposity, VAT accumulation was greater than IMAT accumulation in the Asians and whites; no significant differences were observed in AAs. Conclusion: Race differences in AT distribution extend to IMAT, a depot that may influence race-ethnicity differences in dysglycemia. C1 St Lukes Roosevelt Hosp, Obes Res Ctr, Dept Med, New York, NY USA. Columbia Univ, Inst Human Nutr, New York, NY USA. NIA, Geriatr Epidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands. RP Gallagher, D (reprint author), Obes Res Ctr, 1090 Amsterdam Ave, New York, NY 10025 USA. EM dg108@columbia.edu OI Gallagher, Dympna/0000-0003-1769-9754 FU NCRR NIH HHS [M01 RR000645, RR00645]; NIA NIH HHS [R29 AG014715, AG14715]; NIDDK NIH HHS [DK40414, DK42618, P01 DK042618, R01 DK040414] NR 35 TC 143 Z9 146 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2005 VL 81 IS 4 BP 903 EP 910 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 915CO UT WOS:000228275400027 PM 15817870 ER PT J AU Althuis, MD Moghissi, KS Westhoff, CL Scoccia, B Lamb, EJ Lubin, JH Brinton, LA AF Althuis, MD Moghissi, KS Westhoff, CL Scoccia, B Lamb, EJ Lubin, JH Brinton, LA TI Uterine cancer after use of clomiphene citrate to induce ovulation SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE clomiphene; fertility agents; gonadotropins; infertility; ovulation; uterine neoplasms ID ESTROGEN-RECEPTOR MODULATORS; IN-VITRO FERTILIZATION; ENDOMETRIAL CANCER; BREAST-CANCER; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; STIMULATING DRUGS; FERTILITY DRUGS; INFERTILE WOMEN; UNITED-STATES AB Clomiphene citrate, a selective estrogen receptor modulator, increases estradiol levels and consequently may increase risk of cancer of the uterine corpus. The authors conducted a retrospective cohort study of 8,431 US women (145,876 woman-years) evaluated for infertility during 1965-1988. Through 1999, 39 uterine cancers were ascertained by questionnaire or cancer and death registries. Poisson regression estimated adjusted rate ratios. Study results suggest that clomiphene may increase uterine cancer risk (rate ratio (RR) = 1.79, 95% confidence interval (CI): 0.9, 3.4) and present evidence of a dose response (p(trend) = 0.07) and latency effect (p(trend) = 0.04). Uterine cancer risk increased with clomiphene dose (RR = 1.93, 95% CI: 0.9, 4.0 for > 900 mg), menstrual cycles of use (RR = 2.16, 95% CI: 0.9, 5.2 for > 6 cycles), and time elapsed since initial use (RR = 2.50, 95% CI: 0.9, 7.2 for women followed for > 20 years). Risk was more strongly associated with clomiphene among nulligravid (RR = 3.49, 95% CI: 1.3, 9.3) and obese (RR = 6.02, 95% CI: 1.2, 30.0) women, with risk substantially elevated among women who were both obese and nulligravid (RR = 12.52, 95% CI: 1.5, 108.0). Clomiphene may increase uterine cancer risk, with higher doses leading to higher risk. Long-term follow-up of infertility cohorts is necessary to clarify the association between clomiphene use and uterine cancer. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA. RP Althuis, MD (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7084, Bethesda, MD 20892 USA. EM m.althuis@verizon.net RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 31 TC 54 Z9 60 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2005 VL 161 IS 7 BP 607 EP 615 DI 10.1093/aje/kwi084 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 910TH UT WOS:000227954600001 PM 15781949 ER PT J AU Mason, A Theal, J Bain, V Adams, E Perrillo, R AF Mason, A Theal, J Bain, V Adams, E Perrillo, R TI Hepatitis B virus replication in damaged endothelial tissues of patients with extrahepatic disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC ACTIVE HEPATITIS; CHRONIC VIRAL-HEPATITIS; IMMUNE-COMPLEX DISEASE; SURFACE-ANTIGEN; POLYARTERITIS-NODOSA; PERIARTERITIS-NODOSA; INFECTION; GLOMERULONEPHRITIS; MANIFESTATIONS; PATHOGENESIS AB Hepatitis B virus (HBV) infection may be complicated by extrahepatic manifestations such as polyarteritis nodosa (PAN), glomerulonephritis, polymyositis, and dermatitis, but the etiology of these processes is not yet clear. HBV replication has been demonstrated in a variety of extrahepatic tissues and cell types, but the possible pathogenetic role of extrahepatic HBV replication has not been fully explored in patients with extrahepatic manifestations of HBV infection. In this case series, immunohistochemistry and in situ hybridization studies were performed on extrahepatic tissues from one HBsAg-positive patient with PAN and another HBsAg-positive patient with polymyositis, using HBsAg-seronegative control subjects with the same vasculitic disorders as controls. Tissue samples from the two study patients had detectable HBV RNA, replicative intermediates of HBV DNA, as well as HBsAg and HBcAg localized to vascular endothelium. In contrast, HBsAg-negative control patients had no tissue reactivity. Our results suggest that patients with HBV-related extrahepatic disease have evidence of viral replication in damaged extrahepatic endothelial tissues. While further studies would be required to support a hypothesis of causality, these findings suggest a role for both immune complex deposition and viral replication within diseased endothelial tissue in the pathogenesis of these poorly understood extrahepatic disorders. C1 Univ Alberta, Div Gastroenterol, Edmonton, AB, Canada. Natl Inst Infect Allergy & Infect Dis, NIH, Bethesda, MD USA. Alton Ochsner Med Fdn & Ochsner Clin, Div Gastroenterol, New Orleans, LA USA. RP Perrillo, R (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Sect Gastroenterol & Hepatol, 1514 Jefferson Highway, New Orleans, LA 70121 USA. OI Mason, Andrew/0000-0002-0470-9522 NR 30 TC 25 Z9 28 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2005 VL 100 IS 4 BP 972 EP 976 DI 10.1111/j.1572-0241.2005.41308.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 907LU UT WOS:000227720400035 PM 15784044 ER PT J AU Cannon-Spoor, HE Levy, JA Zubenko, GS Zubenko, WW Cohen, RM Mirza, N Putnam, K Sunderland, T AF Cannon-Spoor, HE Levy, JA Zubenko, GS Zubenko, WW Cohen, RM Mirza, N Putnam, K Sunderland, T TI Effects of previous major depressive illness on cognition in Alzheimer disease patients SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 58th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CA SP Soc Biol Psychiat ID HIPPOCAMPAL VOLUME LOSS; AFFECTIVE-DISORDER; NEUROPSYCHOLOGICAL FUNCTION; EXECUTIVE DYSFUNCTION; GERIATRIC DEPRESSION; UNIPOLAR DEPRESSION; EUTHYMIC PATIENTS; DEMENTIA; IMPAIRMENT; MEMORY AB Objective: Major Depressive Disorder (MDD) may be a risk factor for subsequent development of irreversible dementia; however, the influence of a premorbid history of MDD on the clinical course of patients diagnosed with probable Alzheimer disease (AD) has not been fully explored. Methods: Forty-three AD patients with mild-to-moderate cognitive impairment were screened for a life-long history of MDD with the Clinical Assessment of Depression in Dementia Scale. Twenty-two subjects had a history of MDD before onset of cognitive impairment but none was suffering from an MDD episode at time of cognitive assessment Results: After controlling for age, education, duration of illness, gender, and medication status, subjects with a history of MDD had significantly lower scores, as a group, on cognitive performance tests, including the Mini-Mental State Exam, WAIS Full-Scale and Verbal Scale I.Q., and the Initiation/Perseveration subscale of the Mattis Dementia Rating Scale. These subjects also developed symptoms of dementia at a significantly earlier age than the subjects who bad no premorbid history of MDD. Conclusions: Although previous studies have shown that late-onset MDD may increase risk for subsequent dementia, the current results suggest that premorbid MDD is associated with more severe cognitive deficits during the actual course of dementia. C1 Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Cannon-Spoor, HE (reprint author), Geriatr Psychiat Branch, NIMH Bldg,10-CRC-2E-2-5330,MSC 1274, Bethesda, MD 20892 USA. EM spoorh@mail.nih.gov NR 57 TC 12 Z9 13 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2005 VL 13 IS 4 BP 312 EP 318 DI 10.1176/appi.ajgp.13.4.312 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 916BM UT WOS:000228360400007 PM 15845757 ER PT J AU Pavletic, SZ Smith, LM Bishop, MR Lynch, JC Tarantolo, SR Vose, JM Bierman, PJ Hadi, A Armitage, JO Kessinger, A AF Pavletic, SZ Smith, LM Bishop, MR Lynch, JC Tarantolo, SR Vose, JM Bierman, PJ Hadi, A Armitage, JO Kessinger, A TI Prognostic factors of chronic graft-versus-host disease after allogeneic blood stem-cell transplantation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE graft-versus-host; chronic; stem-cell transplantation; allogeneic ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; TERM FOLLOW-UP; PERIPHERAL-BLOOD; HEMATOLOGIC MALIGNANCIES; IMMUNE RECONSTITUTION; RANDOMIZED TRIAL; RISK; ALLOTRANSPLANTATION; PROLIFERATION AB Allogeneic hematopoietic stem cells in peripheral blood transplantation (alloPBSCT) or bone marrow transplantation (alloBMT) have different biological characteristics which may affect differently prognostic factors for incidence and severity of chronic graft-versus-host disease (cGVHD). To determine the prognostic factors of cGVHD in patients receiving alloPBSCT, data on 87 patients who survived at least 100 days after matched related donor myeloablative transplantation were analyzed. Factors significantly associated with higher incidence of cGVHD after alloPBSCT included CMV-positive donor, acute skin GVHD, and diagnoses other than lymphoma. Factors predictive for poor survival following cGVHD diagnosis included platelet count < 100,000/mm(3) and history of acute liver GVHD. Acute liver GVHD and etoposide in the preparative regimen significantly increased risk of death due to cGVHD after alloPBSCT. All alloPBSCT multivariate models were fit to an independent cohort of comparable matched related donor alloBMT patients (n = 75). After alloBMT, only acute skin GVHD and diagnoses other than lymphoma retained prognostic significance for predicting cGVHD. Low platelet count was the only variable predictive for poor survival in cGVHD patients after alloBMT. Acute liver GVHD was the only factor that retained prognostic significance for risk of death due to cGVHD after alloBMT. These data suggest there are some cGVHD prognostic factors that may be unique to recipients of alloPBSCT. More studies are needed to determine whether cGVHD prognostic systems should be used interchangeably in patient populations receiving different stem-cell products. (c) 2005 Wiley-Liss. C1 NCI, Head Graft Versus Host & Autoinmmun Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Univ Nebraska, Ctr Med, Dept Internal Med, Hematol Oncol Sect, Omaha, NE 68182 USA. Univ Nebraska, Ctr Med, Dept Prevent & Societal Med, Omaha, NE 68182 USA. RP Pavletic, SZ (reprint author), NCI, Head Graft Versus Host & Autoinmmun Unit, Expt Transplantat & Immunol Branch, 9000 Rockville Pike,Bldg 10,Room CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov NR 33 TC 44 Z9 45 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2005 VL 78 IS 4 BP 265 EP 274 DI 10.1002/ajh.20275 PG 10 WC Hematology SC Hematology GA 913GQ UT WOS:000228140000004 PM 15795914 ER PT J AU Johnston, JJ Olivos-Glander, I Killoran, C Elson, E Turner, JT Peters, KF Abbott, MH Aughton, DJ Aylsworth, AS Bamshad, MJ Booth, C Curry, CJ David, A Dinulos, MB Flannery, DB Fox, MA Graham, JM Grange, DK Guttmacher, AE Hannibal, MC Henn, W Hennekam, RCM Holmes, LB Hoyme, HE Leppig, KA Lin, AE MacLeod, P Manchester, DK Marcelis, C Mazzanti, L McCann, E McDonald, MT Mendelsohn, NJ Moeschler, JB Moghaddam, B Neri, G Newbury-Ecob, R Pagon, RA Phillips, JA Sadler, LS Stoler, JM Tilstra, D Vockley, CMW Zackai, EH Zadeh, TM Brueton, L Black, GCM Biesecker, LG AF Johnston, JJ Olivos-Glander, I Killoran, C Elson, E Turner, JT Peters, KF Abbott, MH Aughton, DJ Aylsworth, AS Bamshad, MJ Booth, C Curry, CJ David, A Dinulos, MB Flannery, DB Fox, MA Graham, JM Grange, DK Guttmacher, AE Hannibal, MC Henn, W Hennekam, RCM Holmes, LB Hoyme, HE Leppig, KA Lin, AE MacLeod, P Manchester, DK Marcelis, C Mazzanti, L McCann, E McDonald, MT Mendelsohn, NJ Moeschler, JB Moghaddam, B Neri, G Newbury-Ecob, R Pagon, RA Phillips, JA Sadler, LS Stoler, JM Tilstra, D Vockley, CMW Zackai, EH Zadeh, TM Brueton, L Black, GCM Biesecker, LG TI Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: Robust phenotype prediction from the type and position of GLI3 mutations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INTERSTITIAL DELETION; HYPOTHALAMIC HAMARTOMA; ACROCALLOSAL SYNDROME; POINT MUTATIONS; FAMILIES; DISEASE; MICRODELETION; DELINEATION; ANOMALIES; SPECTRUM AB Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations ( among 60 probands); when these were combined with previously published mutations, two genotype- phenotype correlations were evident. First, GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/ nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/ nonsense and splicing mutations. Second, among the frameshift/ nonsense mutations, there was a clear genotype- phenotype correlation. Mutations in the first third of the gene ( from open reading frame [ORF] nucleotides [nt] 1 - 1997) caused GCPS, and mutations in the second third of the gene ( from ORF nt 1998 - 3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3' third of the gene ( after ORF nt 3481), and no patients with PHS had mutations in this region. These results demonstrate a robust correlation of genotype and phenotype for GLI3 mutations and strongly support the hypothesis that these two allelic disorders have distinct modes of pathogenesis. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Cent Manchester Univ Hosp, Natl Hlth Serv Trust, St Marys Hosp, Dept Clin Genet, Manchester, Lancs, England. Manchester Childrens Univ Hosp, Natl Hlth Serv Trust, St Marys Hosp, Dept Clin Genet, Manchester, Lancs, England. Penn State Univ, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. Baltimore Huntington Dis Ctr, Dept Psychiat, Baltimore, MD USA. William Beaumont Hosp, Dept Pediat, Div Genet, Royal Oak, MI 48072 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Univ Utah, Hlth Sci Ctr, Eccles Inst Human Genet, Salt Lake City, UT USA. Lutheran Gen Hosp, Park Ridge, IL 60068 USA. Univ Calif, Fresno, CA USA. Ctr Hosp Univ, Serv Genet, Nantes, France. Dartmouth Coll, Childrens Hosp, Div Genet & Child Dev, Lebanon, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA USA. St Louis Childrens Hosp, Dept Pediat, Div Med Genet, St Louis, MO 63110 USA. Univ Washington, Childrens Hosp Reg Med Ctr, Div Genet & Dev Med, Seattle, WA 98195 USA. Univ Washington, Childrens Hosp Reg Med Ctr, Dept Pediat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Genet Serv, Seattle, WA 98121 USA. Univ Saarland, Inst Humangenet, Homburg, Germany. Univ Amsterdam, Childrens Acad Med Ctr, Div Emma Childrens Hosp, Amsterdam, Netherlands. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Pediat, Div Med Genet, Stanford, CA 94305 USA. Natl Birth Defects Ctr, Waltham, MA USA. Victoria Gen Hosp, Med Genet Sect, Victoria, BC, Canada. Childrens Hosp, Denver, CO 80218 USA. Univ Med Ctr Nijmegen, Dept Clin Genet, Nijmegen, Netherlands. SantOrsola Malpighi Hosp, Dept Pediat, Bologna, Italy. Royal Liverpool Childrens Hosp, Dept Clin Genet, Liverpool L7 7DG, Merseyside, England. Duke Univ, Med Ctr, Div Med Genet, Durham, NC USA. Childrens Hosp & Clin, Minneapolis, MN USA. Univ Oklahoma, Schusterman Ctr, HA Chapman Inst, Tulsa, OK USA. Univ Cattolica, Inst Med Genet, Rome, Italy. St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Childrens Hosp, Dept Pediat, Div Genet, Buffalo, NY 14222 USA. CentraCare Clin, Dept Pediat, St Cloud, MN USA. Mayo Fdn, Dept Med Genet, Rochester, MN USA. Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA. Genet Ctr, Orange, CA USA. Kennedy Galton Ctr, Dept Clin Genet, London, England. RP Johnston, JJ (reprint author), NHGRI, NIH, Bldg 49 Room 4B75,MSC4472,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jjohnsto@mail.nih.gov OI Black, Graeme/0000-0001-8727-6592 FU NICHD NIH HHS [HD22657-11, P01 HD022657]; NIGMS NIH HHS [GM08243, T32 GM008243] NR 49 TC 121 Z9 127 U1 2 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2005 VL 76 IS 4 BP 609 EP 622 DI 10.1086/429346 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 904RS UT WOS:000227516000007 PM 15739154 ER PT J AU Riaz, N Steinberg, S Ahmad, J Pluzhnikov, A Riazuddin, S Cox, NJ Drayna, D AF Riaz, N Steinberg, S Ahmad, J Pluzhnikov, A Riazuddin, S Cox, NJ Drayna, D TI Genomewide significant linkage to stuttering on chromosome 12 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MISSPECIFIED RELATIONSHIPS; TESTS; PROGRAM AB Stuttering is a common and sometimes severe communication disorder, of unknown primary etiology, that exists in populations worldwide. Many types of evidence suggest a genetic contribution to stuttering; however, the complex inheritance of this disorder has hindered identification of these factors. We have employed highly inbred families to increase the power of linkage analysis of this disorder. Forty-four Pakistani families with documented or probable consanguinity, from the city of Lahore and surrounding areas, were included. Each family contained multiple cases of stuttering, which were diagnosed using the Stuttering Severity Instrument. Using the Marshfield Weber 9 marker panel, we performed a genomewide linkage scan focused on affected individuals and their parents. The analysis included 199 genotyped individuals, 144 affected and 55 unaffected. The Pedigree Relationship Statistical Test (PREST) was used to identify pedigrees that required additional specification of inbreeding. Initial nonparametric analysis gave evidence of linkage on chromosomes 1, 5, 7, and 12. Additional genotyping was performed on chromosome 12 to a 5-cM level of resolution, and 16 additional individuals were then included, bringing the number of families to 46. Analysis of the enlarged data set provided consistent evidence of linkage on chromosome 12: the S-homoz scoring function gave a nonparametric LOD score of 4.61, and a LOD score of 3.51 was obtained using the S-all scoring function. These results suggest that a locus on chromosome 12q may contain a gene with a large effect in this sample. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan. RP Drayna, D (reprint author), 5 Res Court,Room 2B-46, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov RI Ahmad, Jamil/D-4130-2009; SHEIKH, RIAZUDDIN/L-2406-2015 FU NIDCD NIH HHS [DC-04415, R01 DC004415]; PHS HHS [Z01-000046-04] NR 18 TC 52 Z9 58 U1 1 U2 12 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2005 VL 76 IS 4 BP 647 EP 651 DI 10.1086/429226 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 904RS UT WOS:000227516000010 PM 15714404 ER PT J AU Nicol, CJ Adachi, M Akiyama, TE Gonzalez, FJ AF Nicol, CJ Adachi, M Akiyama, TE Gonzalez, FJ TI PPAR gamma in endothelial cells influences high fat diet-induced hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE PPAR gamma; conditional null mice; endothelial cells; blood pressure; type 2 diabetes ID ACTIVATED-RECEPTOR-GAMMA; VASCULAR SMOOTH-MUSCLE; LOWERS BLOOD-PRESSURE; CARDIAC-HYPERTROPHY; INSULIN SENSITIVITY; IN-VIVO; PRO12ALA SUBSTITUTION; TRANSGENIC MICE; NITRIC-OXIDE; GENE AB Background: Peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPAR gamma expression in many cell types, including endothelial cells (ECs). Methods: To evaluate the vascular role of PPAR gamma we used a conditional null mouse model. Specific disruption of PPAR gamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPAR gamma-floxed (fl/fl) mice to generate PPAR gamma (fl/fl)T2T+ (PPARy E-null) mice. Conscious 8- to 12-week-old congenic PPAR gamma (fl/fl)Cre-(wild type) and PPAR gamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). Results: Untreated PPAR gamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPAR gamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPAR gamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPAR gamma E-null mice. Conclusions: These results suggest that PPAR gamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPAR-gamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful. (c) 2005 American Journal of Hypertension, Ltd. C1 NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Canc Res Ctr, NIH, Bldg 37,Room 3106B1, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 43 TC 68 Z9 72 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 2005 VL 18 IS 4 BP 549 EP 556 DI 10.1016/j.amjhyper.2004.10.032 PN 1 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 918MO UT WOS:000228546100018 PM 15831367 ER PT J AU Gordon, EJ Prohaska, T Siminoff, LA Minich, PJ Sehgal, AR AF Gordon, EJ Prohaska, T Siminoff, LA Minich, PJ Sehgal, AR TI Needed: Tailored exercise regimens for kidney transplant recipients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID PHYSICAL-ACTIVITY; RENAL-TRANSPLANTATION; HEART; DISEASE; MANAGEMENT; RISK C1 Loyola Univ, Stritch Sch Med, Neiswenger Inst Bioeth & Hlth Policy, Maywood, IL 60153 USA. NIDDKD, Bethesda, MD 20892 USA. RP Gordon, EJ (reprint author), Loyola Univ, Stritch Sch Med, Neiswenger Inst Bioeth & Hlth Policy, 2160 S 1st Ave, Maywood, IL 60153 USA. EM egordo1@Lumc.edu RI Siminoff, Laura /H-6277-2012 FU NIDDK NIH HHS [DK51472, DK063953, K01 DK063953, R01 DK051472] NR 39 TC 21 Z9 22 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2005 VL 45 IS 4 BP 769 EP 774 DI 10.1063/j.ajkd.2005.01.002 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 920VJ UT WOS:000228718000019 PM 15806481 ER PT J AU Biesecker, L AF Biesecker, L TI Accuracy and precision in Bayesian analysis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material ID LOWE OCULOCEREBRORENAL SYNDROME; LINKED FLANKING MARKERS C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Biesecker, L (reprint author), NHGRI, NIH, Bldg 49,Room 4A80, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR 1 PY 2005 VL 134A IS 1 BP 111 EP 111 DI 10.1002/ajmg.a.30471 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 910XY UT WOS:000227966700021 PM 15704123 ER PT J AU Chalas, E Costantino, JP Wickerham, DL Wolmark, N Lewis, GC Bergman, C Runowicz, CD AF Chalas, E Costantino, JP Wickerham, DL Wolmark, N Lewis, GC Bergman, C Runowicz, CD TI Benign gynecologic conditions among participants in the Breast Cancer Prevention Trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 09-11, 2004 CL Bolton Landing, NY SP Amer Gynecol & Obstet Soc DE breast cancer; prevention trial; gynecologic conditions; tamoxifen ID ADJUVANT TAMOXIFEN THERAPY; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; RISK; MANAGEMENT; TUMORS AB Objective: This study was undertaken to report on the benign gynecologic conditions occurring among women with an intact uterus at enrollment in the Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project. Study design: The incidence rates of several benign gynecologic conditions were determined and risks were compared among women receiving tamoxifen and those receiving placebo, based on risk ratios (RRs) with 95% CIs. Comparisons included stratification by menopausal status, body mass index, and history of estrogen use. Results: Compared with women taking placebo, premenopausal women taking tamoxifen had a greater incidence of endometrial polyps (RR = 1.9, 95% CI = 1.55-2.41), leiomyomas(RR = 1.3, 95% CI = 1.14-1.55), endometriosis (RR = 1.9, 95% CI = 1.35-2.70), ovarian cysts (RR = 1.5, 95% CI = 1.20-1.78), and gynecologic surgical procedures, including hysterectomy (RR = 1.6, 95% CI = 1.29-1.88). Postmenopausal women taking tamoxifen also had an increased incidence of endometrial polyps (RR = 2.4, 95% CI = 1.76-3.24), leiomyomas (RR = 1.4, 95% Cl = 1.04-1.80), endometriosis (RR = 1.9, 95% CI = 1.29-5.58), and gynecologic surgical procedures, including hysterectomy (RR = 2.2, 95% CI = 1.60-3.13), compared with women taking placebo. All women taking tamoxifen also had an increased incidence of simple endometrial hyperplasia without atypia (overall RR = 2.06, 95% CI = 1.64-2.60) compared with those taking placebo. Conclusions: Our results strongly support the estrogen agonist role of tamoxifen as the causative factor for the increased risk of endometrial polyps, leiomyomas, endometriosis, and endometrial hyperplasia among women taking this agent. (c) 2005 Elsevier Inc. All rights reserved. C1 SUNY Stony Brook, Dept Obstet Gynecol & Reprod Med, Stony Brook, NY 11794 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, NSABP, Pittsburgh, PA 15261 USA. Allegheny Gen Hosp, NSABP, Pittsburgh, PA 15212 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. Univ Connecticut, Sch Med, Ctr Comprehens Canc, Dept Obstet & Gynecol, Farmington, CT USA. RP Chalas, E (reprint author), Long Isl Womens Canc Ctr, 944 Jericho Turnpike, Smithtown, NY 11787 USA. EM echalas78@hotmail.com FU NCI NIH HHS [U10-CA-37377, U10-CA-69974] NR 20 TC 43 Z9 44 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2005 VL 192 IS 4 BP 1230 EP 1237 DI 10.1016/j.ajog.2004.12.083 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 916YD UT WOS:000228421800039 PM 15846210 ER PT J AU Carey, JC Klebanoff, MA AF Carey, JC Klebanoff, MA TI Is a change in the vaginal flora associated with an increased risk of preterm birth? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 09-11, 2004 CL Bolton Landing, NY SP Amer Gynecol & Obstet Soc DE preterm birth; vaginal infections; antibiotic therapy ID PLACEBO-CONTROLLED TRIAL; BACTERIAL VAGINOSIS; PREGNANT-WOMEN; UREAPLASMA-UREALYTICUM; PREMATURE DELIVERY; CLINDAMYCIN; METRONIDAZOLE; INFECTIONS; ERYTHROMYCIN; WEIGHT AB Objective: The purpose of this study was to determine if a change in the vaginal flora was associated with an increased risk of preterm birth, and to determine if metronidazole therapy before 32 weeks increased the risk of preterm birth. Study design: We compared cultures taken at 23 to 26 weeks of gestation with cultures taken at delivery from women enrolled in the Vaginal Infections and Preterm Birth study to analyze the association of changes in the vaginal flora with preterm birth. Results: Metronidazole therapy before 32 weeks was associated with an increased risk of preterm birth (OR 1.5, 95%CI 1.05-2.1) in an unadjusted model. A change to heavy growth of Escherichia coli or Klebsiella pneumoniae at delivery was found to be associated with preterm birth (OR 2.4, 95%CI 1.6-3.8). After controlling for race, parity, prepregnancy weight < 100 pounds, smoking or drinking during pregnancy, Trichomonas vaginalis, bacterial vaginosis, chlamydia, mycoplasmas, group B streptococcus, metronidazole therapy before 32 weeks, vaginal pH > 5.0, and an increase in E coli or K pneumoniae, only prepregnancy weight < 100 pounds (adjusted odds ratio [AOR] 2.07, 95%CI 1.01-4.21) and increased E coli or K pneumoniae in the vagina Lit delivery (AOR 2.99, 95%CI 1.37-6.53) were found to be significantly associated with preterm birth. Conclusion: An increase in E coli or K pneumoniae in the vagina is an independent risk factor for preterm birth. Changes in the vaginal flora may explain the increased risk of preterm birth seen with vaginal clindamycin or oral metronidazole therapy. (c) 2005 Elsevier Inc. All rights reserved. C1 Maricopa Cty Gen Hosp, Phoenix Integrated Residency Program, Phoenix, AZ USA. St Josephs Hosp, Phoenix, AZ USA. NICHHD, Bethesda, MD 20892 USA. RP Carey, JC (reprint author), Maricopa Cty Gen Hosp, Phoenix Integrated Residency Program, Phoenix, AZ USA. NR 26 TC 39 Z9 47 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2005 VL 192 IS 4 BP 1341 EP 1346 DI 10.1016/j.ajog.2004.12.069 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 916YD UT WOS:000228421800070 PM 15846235 ER PT J AU Zcharia, E Philp, D Edovitsky, E Aingorn, H Metzger, S Kleinman, HK Vlodavsky, I Elkin, M AF Zcharia, E Philp, D Edovitsky, E Aingorn, H Metzger, S Kleinman, HK Vlodavsky, I Elkin, M TI Heparanase regulates murine hair growth SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FOLLICULAR STEM-CELLS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; MAMMALIAN HEPARANASE; MEDIATED DEGRADATION; COMPREHENSIVE GUIDE; RAT VIBRISSA; SKIN; EXPRESSION; BULGE AB Heparanase is an endoglycosidase that cleaves heparan sulfate, the main polysaccharide component of the extracellular matrix. Heparan sulfate moieties are responsible for the extracellular matrix barrier function, as well as for sequestration of heparin-binding growth factors in the extracellular matrix. Degradation of heparan sulfate by heparanase enables cell movement through extracellular barriers and releases growth factors from extracellular matrix depots, making them bioavailable. Here, we demonstrate a highly coordinated temporospatial pattern of heparanase expression and enzymatic activity during hair follicle cycling. This pattern paralleled the route and timing of follicular stem cell progeny migration and reconstitution of the lower part of the follicle, which is a prerequisite for hair shaft formation. By monitoring in vivo activation of luciferase reporter gene driven by heparanase promoter, we observed activation of heparanase gene transcription at a specific stage of the hair cycle. Heparanase was produced by rat vibrissa bulge keratinocytes, closely related to a follicular stem cell population. Heparanase contributed to the ability of the bulge-derived keratinocytes to migrate through the extracellular matrix barrier in vitro. In heparanase-overexpressing transgenic mice, increased levels of heparanase enhanced active hair growth and enabled faster hair recovery after chemotherapy-induced alopecia. Collectively, our results identify heparanase as an important regulator of hair growth and suggest that cellular mechanisms of its action involve facilitation of follicular stem cell progeny migration and release of extracellular matrix-resident, heparin-bound growth factors, thus regulating hair cycle. C1 Technion Israel Inst Technol, Bruce Rappaport Fac Med, Canc & Vasc Biol Res Ctr, IL-31096 Haifa, Israel. Hadassah Hebrew Univ, Med Ctr, Dept Oncol, Jerusalem, Israel. Hadassah Hebrew Univ, Med Ctr, Dept Internal Med, Jerusalem, Israel. Natl Inst Dent & Craniofacial Res, Cell Biol Sect, NIH, Bethesda, MD USA. RP Vlodavsky, I (reprint author), Technion Israel Inst Technol, Bruce Rappaport Fac Med, Canc & Vasc Biol Res Ctr, POB 9649, IL-31096 Haifa, Israel. EM vlodavsk@cc.huji.ac.il FU NCI NIH HHS [R01 CA106456, R01-CA106456-01] NR 54 TC 34 Z9 36 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2005 VL 166 IS 4 BP 999 EP 1008 DI 10.1016/S0002-9440(10)62321-8 PG 10 WC Pathology SC Pathology GA 910GS UT WOS:000227919500007 PM 15793281 ER PT J AU Heselmeyer-Haddad, K Sommerfeld, K White, NM Chaudhri, N Morrison, LE Palanisamy, N Wang, ZY Auer, G Steinberg, W Ried, T AF Heselmeyer-Haddad, K Sommerfeld, K White, NM Chaudhri, N Morrison, LE Palanisamy, N Wang, ZY Auer, G Steinberg, W Ried, T TI Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS; CHROMOSOMAL-ABERRATIONS; INVASIVE-CARCINOMA; RECURRENT PATTERN; UTERINE CERVIX; HYBRIDIZATION; GAIN; INSTABILITY; CYTOGENETICS; PROGRESSION AB Invasive cervical carcinomas almost invariably carry extra copies of chromosome arm 3q, resulting in a gain of the human telomerase gene (TERC). This provided the rationale for the development of a multicolor fluorescence in situ hybridization (FISH) probe set as a diagnostic tool for the direct detection of TERC gains in Pap smears. We previously used this probe set to show that cervical intraepithelial neoplasia (CIN) 2 and CIN3 lesions could be distinguished from normal samples, atypical squamous cell of undetermined significance (ASCUS) and CIN1, with a sensitivity and specificity exceeding 90%, independent of the cytomorphological assessment. In the current study, we explored whether gain of 3q and amplification of TERC could predict progression from CIN1/CIN2 to CIN3 and invasive carcinoma. We applied our probe set to a series of 59 previously stained Pap smears for which repeat Pap smears and clinical follow-up were available. The samples included CIN1/CIN2 lesions that progressed to CIN3 (progressors), CIN1/CIN2 lesions that regressed spontaneously (regressors), and normal Pap smears from women who subsequently developed CIN3 or cervical cancer. Here, we show that progressors displayed a gain of 3q whereas none of the regressors showed this genetic aberration. These data suggest that 3q gain is required for the transition from CIN1/CIN2 to CIN3 and that it predicts progression. Of note, 3q gain was found in 33% of cytologically normal Pap smears from women who were diagnosed with CIN3 or invasive cervical carcinoma after a short latency. The sensitivity of our test for predicting progression from CIN1/CIN2 to CIN3 was 100% and the specificity, ie, the prediction of regression, was 70%. We conclude that the detection of 3q gain and amplification of TERC in routinely collected Pap smears can assist in identifying low-grade lesions with a high progression risk and in decreasing false-negative cytological screenings. C1 NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Vysis Inc, Abbott Labs, Downers Grove, IL USA. Canc Genet Inc, Milford, MA USA. Karolinska Inst, Canc Ctr Karolinska, Stockholm, Sweden. Lab Cytopathol, Klin Kloster Paradiese, Soest, Germany. RP Ried, T (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM riedt@mail.nih.gov OI Palanisamy, Nallasivam/0000-0002-0633-9772 NR 32 TC 103 Z9 131 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2005 VL 166 IS 4 BP 1229 EP 1238 DI 10.1016/S0002-9440(10)62341-3 PG 10 WC Pathology SC Pathology GA 910GS UT WOS:000227919500027 PM 15793301 ER PT J AU Jutai, JW Fuhrer, MJ Demers, L Scherer, MJ DeRuyter, F AF Jutai, JW Fuhrer, MJ Demers, L Scherer, MJ DeRuyter, F TI Toward a taxonomy of assistive technology device outcomes SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE assistive device; assistive technology; outcome measure; taxonomy ID QUALITY-OF-LIFE; REHABILITATION; STROKE AB The advancement of assistive technology device (ATD) outcomes research requires a substantive taxonomy for ATD outcomes. This article describes the assumptions and principles that should underlie such a taxonomy. It advocates for an approach to classifying outcomes that would promote consistency in how ATDs are distinguished, based on their intended effect on the user. The approach is designed to accommodate the widest variety of ATD applications, reflecting combinations of user population, ATD type, service, and context for use. In essence the provisional taxonomy proposes that ATD outcomes can be effectively operationalized from three vantages- effectiveness, social significance, and subjective well-being. It emphasizes a distinction between the proximal effect of ATDs and the more distal outcomes associated with their use. Because it promotes consistency in the language used for categorizing outcomes, the taxonomic approach should facilitate the development of ATD-specific causal models. The utility of a taxonomy in ATD outcomes research is discussed. C1 Univ Western Ontario, Fac Med & Dent, Dept Phys Med & Rehabil, Parkwood Hosp, London, ON N6C 5J1, Canada. NICHHD, NIH, Damascus, MD USA. Univ Montreal, Ecole Readapt, Montreal, PQ, Canada. Inst Matching Person & Technol, Webster, NY USA. Duke Univ, Med Ctr, Div Speech Pathol & Audiol, Durham, NC USA. RP Jutai, JW (reprint author), Univ Western Ontario, Fac Med & Dent, Dept Phys Med & Rehabil, Parkwood Hosp, 801 Commiss Rd E, London, ON N6C 5J1, Canada. OI Scherer, Marcia/0000-0001-8374-6526; Jutai, Jeffrey/0000-0002-7294-1323 NR 43 TC 43 Z9 43 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD APR PY 2005 VL 84 IS 4 BP 294 EP 302 DI 10.1097/01.PHM.0000157313.88732.DC PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 909VW UT WOS:000227889800009 PM 15785265 ER PT J AU Roper, JM Gehen, SC Staversky, RJ Hollander, MC Fornace, AJ O'Reilly, MA AF Roper, JM Gehen, SC Staversky, RJ Hollander, MC Fornace, AJ O'Reilly, MA TI Loss of Gadd45a does not modify the pulmonary response to oxidative stress SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE DNA damage; lung; mice; in situ nick-end labeling; 8-hydroxy-2 '-deoxoguanosine ID HYPEROXIA-INDUCED APOPTOSIS; CELL-DEATH; LUNG INJURY; DNA-DAMAGE; CHROMOSOMAL INSTABILITY; EPITHELIAL-CELLS; OXYGEN-TOXICITY; GROWTH ARREST; MOUSE LUNG; RAT LUNG AB It is well established that exposure to high levels of oxygen (hyperoxia) injures and kills microvascular endothelial and alveolar type I epithelial cells. In contrast, significant death of airway and type II epithelial cells is not observed at mortality, suggesting that these cell types may express genes that protect against oxidative stress and damage. During a search for genes induced by hyperoxia, we previously reported that airway and alveolar type II epithelial cells uniquely express the growth arrest and DNA damage ( Gadd) 45a gene. Because Gadd45a has been implicated in protection against genotoxic stress, adult Gadd45a (+/+) and Gadd45a (-/-) mice were exposed to hyperoxia to investigate whether it protected epithelial cells against oxidative stress. During hyperoxia, Gadd45a deficiency did not affect loss of airway epithelial expression of Clara cell secretory protein or type II epithelial cell expression of pro-surfactant protein C. Likewise, Gadd45a deficiency did not alter recruitment of inflammatory cells, edema, or overall mortality. Consistent with Gadd45a not affecting the oxidative stress response, p21(Cip1/WAF1) and heme oxygenase-1 were comparably induced in Gadd45a ( +/+) and Gadd45a (-/-) mice. Additionally, Gadd45a deficiency did not affect oxidative DNA damage or apoptosis as assessed by oxidized guanine and terminal deoxyneucleotidyl transferase-mediated dUTP nick-end labeling staining. Overexpression of Gadd45a in human lung adenocarcinoma cells did not affect viability or survival during exposure, whereas it was protective against UV-radiation. We conclude that increased tolerance of airway and type II epithelial cells to hyperoxia is not attributed solely to expression of Gadd45a. C1 Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. NCI, Gene Response Sect, Ctr Canc Res, Bethesda, MD USA. RP O'Reilly, MA (reprint author), Univ Rochester, Sch Med & Dent, Dept Pediat, Box 850,601 Elmwood Ave, Rochester, NY 14642 USA. EM michael_oreilly@urmc.rochester.edu RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NHLBI NIH HHS [HL-67392, HL-66988]; NIEHS NIH HHS [ES-01247, ES-07026] NR 47 TC 7 Z9 7 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2005 VL 288 IS 4 BP L663 EP L671 DI 10.1152/ajplung.00355.2004 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 904KA UT WOS:000227495300012 PM 15653712 ER PT J AU Kwon, TH Nielsen, J Knepper, MA Frokiaer, J Nielsen, S AF Kwon, TH Nielsen, J Knepper, MA Frokiaer, J Nielsen, S TI Angiotensin II AT(1) receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporin; calcium; cAMP; type 1 bumetanide-sensitive Na-K-2Cl cotransporter; urine concentration ID THICK ASCENDING LIMB; MEDULLARY COLLECTING DUCT; LITHIUM-INDUCED NDI; ALTERED EXPRESSION; HENLES LOOP; ARGININE-VASOPRESSIN; NA+ TRANSPORTERS; DOWN-REGULATION; MICE LACKING; CYCLIC-AMP AB Angiotensin II AT(1) receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats. Am J Physiol Renal Physiol 288: F673-F684, 2005. First published December 7, 2004;doi:10.1152/ajprenal.00304. 2004.-Vasopressin and ANG II, which are known to play a major role in renal water and sodium reabsorption, are mainly coupled to the cAMP/PKA and phosphoinositide pathways, respectively. There is evidence for cross talk between these intracellular signaling pathways. We therefore hypothesized that vasopressin-induced water reabsorption could be attenuated by ANG II AT(1) receptor blockade in rats. To address this, three protocols were used: 1) DDAVP treatment (20 ng/h sc for 7 days, n = 8); 2) DDAVP ( 20 ng/h sc for 7 days) and candesartan (1 mg (.) kg(-1) (.) day(-1) sc for 7 days) cotreatment (n = 8); and 3) vehicle infusion as the control (n = 8). All rats were maintained on a NaCl-deficient diet (0.1 meq Na(+) (.) 200 g body wt(-1) (.) day(-1)) during the experiment. DDAVP treatment alone resulted in a significant decrease in urine output (3.1 +/- 0.2 ml/day) compared with controls (11.5 +/- 2.2 ml/ day, P < 0.05), whereas the urine output was significantly increased in response to DDAVP and candesartan cotreatment (9.8 +/- 1.0 ml/ day, P < 0.05). Consistent with this, rats cotreated with DDAVP and candesartan demonstrated decreased urine osmolality (1,319 +/- 172 mosmol/kgH(2)O) compared with rats treated with DDAVP alone (3,476 +/- 182 mosmol/kgH(2)O, P < 0.05). Semiquantitative immunoblotting revealed significantly decreased expression of medullary aquaporin-2 (AQP2) and AQP2 phosphorylated in the PKA phosphorylation consensus site Ser-256 (p-AQP2) in response to DDAVP and candesartan cotreatment compared with DDAVP treatment alone. In addition, cortical and medullary AQP1 was also downregulated. Fractional sodium excretion (FE(Na)) and plasma potassium levels were markedly increased, and the expressions of the cortical type 3 Na(+)/H(+) exchanger (NHE3), thiazidesensitive Na-Cl cotransporter (NCC), and Na-K-ATPase were significantly decreased in response to DDAVP and candesartan cotreatment. Moreover, medullary type 1 bumetanide-sensitive Na-K-2Cl cotransporter expression showed a marked gel mobility shift from 160 to similar to180 kDa corresponding to enhanced glycosylation, whereas expression was unchanged. In conclusion, ANG II AT1 receptor blockade in DDAVP-treated rats was associated with decreased urine concentration and decreased AQP2 and AQP1 expression. Moreover, FENa was increased in parallel with decreased expression of NHE3, NCC, and Na-K-ATPase. These results suggest that ANG II AT1 receptor activation plays a significant role in regulating aquaporin and sodium transporter expression and modulating urine concentration in vivo. C1 Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Aarhus Univ, Inst Anat, DK-8000 Aarhus C, Denmark. Aarhus Univ, Inst Clin Med, DK-8000 Aarhus C, Denmark. Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu 702701, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Bldg 233-234, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk OI Frokiaer, Jorgen/0000-0002-6206-8065 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 59 TC 55 Z9 56 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2005 VL 288 IS 4 BP F673 EP F684 DI 10.1152/ajprenal.00304.2004 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 904JY UT WOS:000227495000009 PM 15585668 ER PT J AU Hillsdon, MM Brunner, EJ Guralnik, JM Marmot, MG AF Hillsdon, MM Brunner, EJ Guralnik, JM Marmot, MG TI Prospective study of physical activity and physical function in early old age SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HEALTH SURVEY SF-36; PEOPLE; ADULTS; RISK; DISABILITY; DECLINE; CONSUMPTION; ELDERS; LIFE AB Background: In the elderly, higher levels of physical function have consistently been associated with higher levels of physical activity. In this study, we test the hypothesis that physical activity earlier in the life course preserves high physical function over an extended period of time, before the onset of major age-related declines in physical function. Methods: A cohort study with an average of 8.8 years of follow-up (1991-1993 to 2001). Logistic regression analyses were conducted adjusting for long-standing illness, baseline physical function, smoking, body mass index, and employment grade. Participants were 6398 London-based civil servants aged 39 to 63 years at baseline, 90% of whom were working. The main outcome measure was physical function measured by the Short Form (SF-36) General Health Survey. Results: Relatively fit and healthy, mainly working, middle-aged men and women who were physically active at recommended levels, were more likely to report high physical function at follow-up, compared to their sedentary counterparts (odds ratio 1.63, 95% confidence interval 1.32-2.00). The association between initial level of physical activity and high physical function at follow-up remained after adjustment for baseline level of physical function and the presence of long-standing illness. Conclusions: Participation in a physically active lifestyle during mid-life appears to be critical to the maintenance of high physical function in those who are fit and well enough to work and do or do not report any long-standing illness. (Am J Prev Med 2005;28(3):245-250) (c) 2005 American Journal of Preventive Medicine. C1 UCL, Dept Epidemiol & Publ Hlth, Int Ctr Hlth & Soc, London WC1E 6BT, England. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Hillsdon, MM (reprint author), UCL, Dept Epidemiol & Publ Hlth, Int Ctr Hlth & Soc, 1-19 Torrington Pl, London WC1E 6BT, England. EM m.hillsdon@ucl.ac.uk RI Brunner, Eric/H-2114-2011; OI Marmot, Michael/0000-0002-2431-6419 FU AHRQ HHS [5R01 HS 06516]; NHLBI NIH HHS [2R01 HL 36310] NR 31 TC 57 Z9 61 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2005 VL 28 IS 3 BP 245 EP 250 DI 10.1016/j.amepre.2004.12.008 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 908MA UT WOS:000227789900001 PM 15766611 ER PT J AU Neumeister, A Yuan, PX Young, TA Bonne, O Luckenbaugh, DA Charney, DS Manji, H AF Neumeister, A Yuan, PX Young, TA Bonne, O Luckenbaugh, DA Charney, DS Manji, H TI Effects of tryptophan depletion on serum levels of brain-derived neurotrophic factor in unmedicated patients with remitted depression and healthy subjects SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEVELOP AB Objective: Data suggest the involvement of serotonergic and neurotrophic systems in major depressive disorder. To investigate their potential interaction, the authors studied changes in serum levels of brain-derived neurotrophic factor ( BDNF) during tryptophan depletion and sham depletion in unmedicated patients with remitted major depressive disorder and in a group of healthy comparison subjects. Method: Twenty-seven patients with remitted major depressive disorder and 20 healthy subjects underwent tryptophan depletion and sham depletion in a randomized, placebo-controlled, double-blind crossover study. Serum BDNF concentrations and plasma tryptophan concentrations as well as behavioral assessments were obtained. Results: During tryptophan depletion, BDNF levels increased in healthy volunteers. By contrast, patients with remitted major depressive disorder were unable to mount this presumed compensatory response, and BDNF levels remained low in these patients. Conclusions: The results further substantiate the potential role of BDNF in major depressive disorder. C1 NIMH, Sect Expt Therapeut & Pathophysiol, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Neumeister, A (reprint author), Yale Univ, Sch Med, Clin Neurosci Div, Mol Imaging Program, 950 Campbell Ave, West Haven, CT 06516 USA. EM alexander.neumeister@yale.edu NR 6 TC 38 Z9 38 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2005 VL 162 IS 4 BP 805 EP U3 DI 10.1176/appi.ajp.162.4.805 PG 3 WC Psychiatry SC Psychiatry GA 911XR UT WOS:000228040600030 PM 15800160 ER PT J AU Royall, J AF Royall, J TI Faces of change SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIH, Natl Lib Med, Int Programs, Bethesda, MD 20894 USA. RP Royall, J (reprint author), NIH, Natl Lib Med, Int Programs, 8600 Rockville Pike,Bldg 38,Room 2S-22, Bethesda, MD 20894 USA. EM jroyall@nl.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2005 VL 95 IS 4 BP 559 EP 561 DI 10.2105/AJPH.2004.054478 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 911JP UT WOS:000227998700007 PM 15798108 ER PT J AU Fink, JN Ortega, HG Reynolds, HY Cormier, YF Fan, LL Franks, TJ Kreiss, K Kunkel, S Lynch, D Quirce, S Rose, C Schleimer, RP Schuyler, MR Selman, M Trout, D Yoshizawa, Y AF Fink, JN Ortega, HG Reynolds, HY Cormier, YF Fan, LL Franks, TJ Kreiss, K Kunkel, S Lynch, D Quirce, S Rose, C Schleimer, RP Schuyler, MR Selman, M Trout, D Yoshizawa, Y TI Needs and opportunities for research in hypersensitivity pneumonitis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HIGH-RESOLUTION CT; EXTRINSIC ALLERGIC ALVEOLITIS; BRONCHOALVEOLAR LAVAGE FLUID; BIRD FANCIERS LUNG; FARMERS LUNG; MODULATES EXPRESSION; COMPUTED-TOMOGRAPHY; CAUSATIVE AGENT; CELL DEPLETION; DISEASE AB Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known. Strategies to improve detection and diagnosis are needed, and treatment options, principally avoidance, are limited. A workshop recommended: a population-based study to more accurately document the incidence and prevalence of HP; better classification of disease stages, including natural history; evaluation of diagnostic tests and biomarkers used to detect disease; better correlation of computerized tomography lung imaging and pathologic changes; more study of inflammatory and immune mechanisms; and improvement of animal models that are more relevant for human disease. C1 NHLBI, DLD, NIH, Bethesda, MD 20892 USA. NHLBI, Off Rare Dis, NIH, Bethesda, MD 20892 USA. RP Reynolds, HY (reprint author), NHLBI, DLD, NIH, 2 Rockledge Ctr,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov NR 80 TC 81 Z9 90 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2005 VL 171 IS 7 BP 792 EP 798 DI 10.1164/rccm.200409-1205WS PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 912BV UT WOS:000228053000019 PM 15657460 ER PT J AU Quan, SF Katz, R Olson, J Bonekat, W Enright, PL Young, T Newman, A AF Quan, SF Katz, R Olson, J Bonekat, W Enright, PL Young, T Newman, A TI Factors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: The cardiovascular health study SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE sleep disturbances; elderly; epidemiology; depression ID LATE-LIFE INSOMNIA; GENERAL ADULT-POPULATION; RISK-FACTORS; COMPLAINTS; IMPACT; PREVALENCE; DISEASES; SCALE; MEN AB Background: There are limited data pertaining to the factors influencing the incidence and persistence of sleep symptoms in the elderly. The purpose of this study was to determine the incidence and nonremission rates of the following sleep symptoms: trouble falling asleep (TFA), frequent awakenings (FA), and excessive daytime sleepiness (EDS) in the Cardiovascular Health Study (CHS), a prospective multicenter study of cardiovascular disease in a large cohort of elderly adults. Factors influencing these rates were assessed as well. Methods: 4467 participants in CHS were surveyed for the presence of TFA, FA, and EDS as well as other health problems at their baseline examination and at a follow-up examination I to 4 years later. Results: Annualized incidence and nonremission rates were the following: TFA (2.8% and 15.4%), FA (12.3% and 22.7%), and EDS (4.4% and 13.4%). Women were more likely to have incident and persistent TFA. Depression was the primary factor predicting the incidence of all three sleep symptoms. However, other health conditions, including respiratory symptoms and cardiovascular disease, and limitation in activities of daily living were important as well. Depression also was the most important factor associated with persistence of these sleep symptoms. The role of other health conditions in determining non-remission was much more limited. Conclusions: Incidence of sleep disturbances in the elderly is related to depression, health conditions, and physical functioning. However, persistence of sleep disturbances is best predicted by the presence of depression. C1 Univ Arizona, Coll Med, Dept Med, Ctr Arizona Resp, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Dept Med, Div Sleep, Tucson, AZ 85724 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. Univ Wisconsin, Dept Prevent Med, Madison, WI USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Quan, SF (reprint author), Univ Arizona, Coll Med, Dept Med, Ctr Arizona Resp, Room 2305,1501 N Campbell, Tucson, AZ 85724 USA. EM squan@resp-sci.arizona.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-15103, N01-HC-35129, N01-HC-85086] NR 40 TC 49 Z9 51 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 2005 VL 329 IS 4 BP 163 EP 172 DI 10.1097/00000441-200504000-00001 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 916TT UT WOS:000228409800001 PM 15832098 ER PT J AU Bromberg, JS Silverstein, JH Kirk, AD AF Bromberg, JS Silverstein, JH Kirk, AD TI Proposal for the American Journal of Transplantation policy for review of ethical standards of clinical research involving live human subjects SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 CUNY Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Immunobiol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Gene & Cell Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Surg, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Anesthesiol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Human Subjects Protect Program, New York, NY 10029 USA. NIDDK, Transplantat Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Bromberg, JS (reprint author), CUNY Mt Sinai Sch Med, Recanati Miller Transplantat Inst, Dept Immunobiol, New York, NY 10029 USA. EM jon.bromberg@mountsinai.org RI Kirk, Allan/B-6905-2012 NR 2 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2005 VL 5 IS 4 BP 648 EP 650 DI 10.1111/j.1600-6143.2005.00872.x PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 904YO UT WOS:000227534700006 PM 15760387 ER PT J AU Wang, XH Mu, JB Li, GQ Chen, PQ Guo, XB Fu, LC Chen, L Su, XZ Wellems, TE AF Wang, XH Mu, JB Li, GQ Chen, PQ Guo, XB Fu, LC Chen, L Su, XZ Wellems, TE TI Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P-falciparum malaria in Hainan, People's Republic of China SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID DRUG SENSITIVITY; IN-VITRO; MUTATIONS; PFMDR1; PIPERAQUINE; PFCRT; AMPLIFICATION; MEFLOQUINE; THAILAND; INVITRO AB The use of chloroquine treatment for Plasmodium falciparuni malaria was abandoned in China in 1979 because of widespread drug resistance. Subsequent studies found decreases in the prevalence of chloroquine-resistant strains. To evaluate these decreases and assess the current status of chloroquine sensitivity in Hainan, China, we determined the prevalence of the P. falciparum chloroquine resistance transporter (PfCRT) 76T marker in the DNA of blood samples collected from 1978 to 2001. Results showed the presence of PfCRT 76T in 101 of 112 samples (90%) from 1978 to 1981, 30 of 43 samples (70%) from 1986, 22 of 34 samples (65%) from 1997 to 1998, and 37 of 68 samples (54%) from 2001. The prevalence of PfCRT 76T thus progressively decreased after chloroquine was discontinued as a treatment 2 for P. falciparurn malaria (X-2 = 5.2, P < 0.022 [1978-1981 versus 1986]; X-2 = 7.4, P < 0.006 [1978-1981 versus 1997-1998]; and X-2 = 28.8, P < 0.0001 [1978-1981 versus 2001]). Reduced prevalence of the PfCRT 76T marker is consistent with greater rates of chloroquine sensitivity from in vitro drug assays of blood samples in 1997 and 2001. Monitoring for continued decreases will provide valuable information for future drug-use policies in China. C1 Guangzhou Univ Tadit Chinese Med, Inst Trop Med, Guangzhou, Peoples R China. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Wang, XH (reprint author), Guangzhou Univ Tadit Chinese Med, Inst Trop Med, 12 Jichang Rd, Guangzhou, Peoples R China. EM xinhuaw@yahoo.com; xsu@niaid.nih.gov; tew@helix.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 NR 26 TC 71 Z9 73 U1 0 U2 4 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 APR PY 2005 VL 72 IS 4 BP 410 EP 414 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 915KP UT WOS:000228303400009 PM 15827277 ER PT J AU Zelazny, AM Fedorko, DP Li, L Neva, FA Fischer, SH AF Zelazny, AM Fedorko, DP Li, L Neva, FA Fischer, SH TI Evaluation of 7SL RNA gene sequences for the identification of Leishmania spp. SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID POLYMERASE-CHAIN-REACTION; NEW-WORLD LEISHMANIA; CUTANEOUS LEISHMANIASIS; PCR ASSAY; DIAGNOSIS; DNA; EVOLUTION; TRYPANOSOMATIDAE; AMPLIFICATION; DONOVANI AB We evaluated the use of 7SL RNA gene sequences for the identification of Leishmania spp. A fragment (similar to 1.37 basepairs) of the 7SL RNA gene from 13 reference strains and 18 clinical isolates of 11 different Leishniania species was amplified and sequenced using conserved primers. Reference strains from each Leishmania spp. complex showed unique sequences. The nucleotide sequences were compared pairwise and a range of 81.0-99.3% intercomplex similarity was observed. Clinical isolates of the same species had sequences identical to the corresponding reference strains; thus, the intraspecies similarity was 100%. A phylogenetic tree derived from the 7SL RNA gene partial sequences was constructed and is in agreement with accepted phylogenetic schemes. C1 NIH, Ctr Clin, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fischer, SH (reprint author), NIH, Ctr Clin, Dept Lab Med, Microbiol Serv, Bldg 10,Room 2C-381B,10 Ctr Dr, Bethesda, MD 20892 USA. EM azelazny@cc.nih.gov; dfedorko@cc.nih.gov; lli@cc.nih.gov; fneva@niaid.nih.gov; sfischer@cc.nih.gov NR 32 TC 26 Z9 27 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 APR PY 2005 VL 72 IS 4 BP 415 EP 420 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 915KP UT WOS:000228303400010 PM 15827278 ER PT J AU Murray, EA Kralik, JD Wise, SP AF Murray, EA Kralik, JD Wise, SP TI Learning to inhibit prepotent responses: successful performance by rhesus macaques, Macaca mulatta, on the reversed-contingency task SO ANIMAL BEHAVIOUR LA English DT Article ID CHIMPANZEES PAN-TROGLODYTES; ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; SYMBOLIC REPRESENTATIONS; MONKEYS; QUANTITY; INTERFERENCE; LESIONS; NUMBER; REWARD AB To reinvestigate whether macaque monkeys could learn the reversed-contingency task, we trained six rhesus monkeys on the problem. On each trial, the monkeys chose between one and four pieces of the same food item. If a monkey selected four pieces of food, it received one instead; choice of one piece of food led to the receipt Of four. All of the monkeys initially tended to select the larger quantity of food, but eventually learned to choose the smaller amount. The results confirmed a previous report that macaque monkeys quickly reached a performance level of roughly 50% 'correct', defined as choosing the smaller amount of food, and some individuals continued to perform at that level for a protracted period of testing. Contrary to that report, however, the present findings show that macaque monkeys can master the reversed-contingency task. (c) 2005 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. EM eam@ln.nimh.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 37 TC 34 Z9 34 U1 2 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0003-3472 J9 ANIM BEHAV JI Anim. Behav. PD APR PY 2005 VL 69 BP 991 EP 998 DI 10.1016/j.anbehav.2004.06.034 PN 4 PG 8 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 918AY UT WOS:000228511900027 ER PT J AU Conwit, RA Hart, RG Moy, CS Marler, JR AF Conwit, RA Hart, RG Moy, CS Marler, JR TI Data and safety monitoring in clinical research: A National Institute of Neurologic Disorders and Stroke perspective SO ANNALS OF EMERGENCY MEDICINE LA English DT Review ID CAROTID ENDARTERECTOMY; RANDOMIZED-TRIAL; TICLOPIDINE; PREVENTION; ASPIRIN; BOARDS AB The National Institute of Neurologic Disorders and Stroke supports a broad spectrum of research in the diagnosis and treatment of neurologic disease. Emergency medicine is increasingly involved in clinical research for patients with neurologic emergencies. Independent data and safety monitoring are critical components of clinical trials to ensure the protection of patients and the scientific integrity of the research. We review National Institute of Neurologic Disorders and Stroke principles of data and safety monitoring and provide examples to illustrate key concepts. C1 NINDS, Ctr Neurosci, NIH, Bethesda, MD 20850 USA. RP Conwit, RA (reprint author), NINDS, Ctr Neurosci, NIH, 6001 Execut Blvd,Room 2107, Bethesda, MD 20850 USA. EM conwitr@ninds.nih.gov NR 20 TC 3 Z9 3 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2005 VL 45 IS 4 BP 388 EP 392 DI 10.1016/j.annemergmed.2004.08.006 PG 5 WC Emergency Medicine SC Emergency Medicine GA 912NU UT WOS:000228086600007 PM 15795717 ER PT J AU Bernstein, E Bernstein, J AF Bernstein, E Bernstein, J TI Preventing alcohol misuse among adolescents SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID EMERGENCY-DEPARTMENT; ONSET; AGE; INVOLVEMENT; DRINKING C1 Boston Univ, Sch Med, Dept Emergency Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02118 USA. Boston Univ Publ Hlth, Youth Alcohol Prevent Ctr, NIAAA, Boston, MA USA. RP Bernstein, E (reprint author), Boston Univ, Sch Med, Dept Emergency Med, 815 Albany St, Boston, MA 02118 USA. EM ebernste@bu.edu OI Bernstein, Judith/0000-0003-1330-5340 NR 19 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2005 VL 45 IS 4 BP 430 EP 432 DI 10.1016/j.annemergmed.2004.12.003 PG 3 WC Emergency Medicine SC Emergency Medicine GA 912NU UT WOS:000228086600014 PM 15795724 ER PT J AU Blair, A Sandler, DP Tarone, R Lubin, J Thomas, K Hoppin, JA Samanic, C Coble, J Kamel, F Knott, C Dosemeci, M Zahm, SH Lynch, CF Rothman, N Alavanja, MCR AF Blair, A Sandler, DP Tarone, R Lubin, J Thomas, K Hoppin, JA Samanic, C Coble, J Kamel, F Knott, C Dosemeci, M Zahm, SH Lynch, CF Rothman, N Alavanja, MCR TI Mortality among participants in the agricultural health study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE farmers; mortality; pesticides; agriculture; cancer ID PESTICIDE APPLICATORS; INJURY MORTALITY; NORTH-CAROLINA; HEART-DISEASE; IOWA FARMERS; LIFE-STYLE; CANCER; METAANALYSIS; OCCUPATION; WORKERS AB PURPOSE: This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses. METHODS: This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa and North Carolina. At enrollment, each pesticide applicator completed a 2 1 page enrollment questionnaire. Mortality assessment from enrollment (1994-1997) through 2000 provided an average follow-up of about 5.3 years, 447,154 person-years, and 2055 deaths. RESULTS: Compared with the general population in the two states, the cohort experienced a very low mortality rate. Standardized mortality ratios (SMRs) for total mortality, cardiovascular disease, diabetes, COPD, total. cancer, and cancers of the esophagus, stomach, and lung were 0.6 or lower for both farmers and spouses. These deficits varied little by farm size, type of crops or livestock on the farm, years of handling pesticides, holding a non-farm job, or length of follow up. SMRs among ever smokers were not as low as among never smokers, but were still less than 1.0 for all smoking-related causes of death. No statistically significant excesses occurred, but slightly elevated SMRs, or those near 1.0, were noted for diseases that have been associated with farming in previous studies. CONCLUSIONS: Several factors may contribute to the low mortality observed in this population, including the healthy worker effect typically seen in cohorts of working populations (which may decline in future years), a short follow-up interval, and a healthier lifestyle manifested through lower cigarette use and an occupation that has traditionally required high levels of physical activity. (c) 2004 Elsevier Inc. All rights reserved. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA. US EPA, Res Triangle Pk, NC 27711 USA. Battelle Mem Inst, Durham, NC USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. RP Blair, A (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Execut Pl N,Room 8118, Rockville, MD 20852 USA. EM blaira@mail.nih.gov RI Zahm, Shelia/B-5025-2015; OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 NR 43 TC 63 Z9 65 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 2005 VL 15 IS 4 BP 279 EP 285 DI 10.1016/j.annepidem.2004.08.008 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 914RZ UT WOS:000228246600006 PM 15780775 ER PT J AU Oh, U Yamano, Y Mora, CA Ohayon, J Bagnato, F Butman, JA Dambrosia, J Leist, TP McFarland, H Jacobson, S AF Oh, U Yamano, Y Mora, CA Ohayon, J Bagnato, F Butman, JA Dambrosia, J Leist, TP McFarland, H Jacobson, S TI Interferon-beta 1a therapy in human T-lymphotropic virus type I-associated neurologic disease SO ANNALS OF NEUROLOGY LA English DT Article ID MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; KAPPA-B SITE; HTLV-I; PROVIRAL LOAD; CELL PHENOTYPE; LYMPHOCYTES-T; EXPRESSION; ALPHA; ACTIVATION; INFECTION AB Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immane-mediated inflammatory disorder of the central nervous system. Immune activation in the host, which results from high levels of persistent antigenic stimulation and from transactivation of host immunoregulatory genes by HTLV-I, appears important in the pathogenesis of HAM/TSP. In a single-center, open-label trial, 12 patients with HAM/TSP were treated with doses of interferon-beta 1a of up to 60 mu g twice weekly, based on its antiviral and immunomodulatory effects. Primary end points were immunological and virological measures that are potential biomarkers for HAM/TSP. Interferon-beta 1a therapy reduced the HTLV-1 tax messenger RNA load and the frequency of potentially pathogenic HTLV-I-specific CD8+ cells. The HTLV-I proviral DNA load remained unchanged. Spontaneous lymphoproliferation, a marker of T-cell activation in HAM/TSP, also was reduced. Some measures of motor function were improved, and no significant clinical progression occurred during therapy. These results indicate that interferon-beta 1a may beneficially affect the immune mechanisms central to the pathogenesis of HAM/TSP. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Kagoshima City Hosp, Dept Neurol, Kagoshima, Japan. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Thomas Jefferson Univ Hosp, Dept Neurol, Philadelphia, PA 19107 USA. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 6B16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov RI Butman, John/A-2694-2008 NR 34 TC 41 Z9 43 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2005 VL 57 IS 4 BP 526 EP 534 DI 10.1002/ana.20429 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 912CA UT WOS:000228053500009 PM 15786444 ER PT J AU Lonser, RR Walbridge, S Murray, GJ Aizenberg, MR Vortmeyer, AO Aerts, JMFG Brady, RO Oldfield, EH AF Lonser, RR Walbridge, S Murray, GJ Aizenberg, MR Vortmeyer, AO Aerts, JMFG Brady, RO Oldfield, EH TI Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease SO ANNALS OF NEUROLOGY LA English DT Article ID MANNOSE-TERMINAL GLUCOCEREBROSIDASE; INHERITED ENZYME DEFICIENCY; REPLACEMENT THERAPY; ENHANCED DELIVERY; PRIMATE BRAIN; INFUSION; MACROMOLECULES; STORAGE AB Systemic enzyme replacement for Gaucher's disease has not prevented premature death or severe morbidity in patients with a neuronopathic phenotype, because the enzyme does not cross the blood-brain barrier. We used convection-enhanced delivery for regional distribution of glucocerebrosidase in rat and primate brains and examined its safety and feasibility for neuronopathic Gaucher's disease. Rats underwent intrastriatal infusion and were observed and then sacrificed at 14 hours, 4 days, or 6 weeks. Primates underwent serial magnetic resonance imaging during enzyme perfusion of the right frontal lobe or brainstem, were observed and then sacrificed after infusion completion. Animals underwent histologic and enzymatic tissue analyses. Magnetic resonance imaging revealed perfusion of the primate right frontal lobe or Pons with infitsate. Enzyme activity was substantially and significantly (p < 0.05) increased in cortex and white matter of the infused frontal lobe and pons compared to control. Immunohistochemistry demonstrated intraneuronal glucocerebrosidase. There was no toxicity. Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Patients with neuronopathic Gaucher's disease and similar central nervous system disorders may benefit from this treatment. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Neurosurg, Washington, DC 20037 USA. Univ Amsterdam, Acad Med Ctr, Dept Biochem, NL-1105 AZ Amsterdam, Netherlands. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Aerts, Johannes/A-1028-2009 NR 24 TC 36 Z9 36 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2005 VL 57 IS 4 BP 542 EP 548 DI 10.1002/ana.20444 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 912CA UT WOS:000228053500011 PM 15786474 ER PT J AU Kearney, PR Poletto, CJ Mann, EA Ludlow, CL AF Kearney, PR Poletto, CJ Mann, EA Ludlow, CL TI Suppression of thyroarytenoid muscle responses during repeated air pressure stimulation of the laryngeal mucosa in awake humans SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY APR 30-MAY 01, 2004 CL Phoenix, AZ SP Amer Laryngol Assoc DE air pressure; conditioning; laryngeal adductor reflex; larynx; sensation; spasmodic dysphonia; thyroarytenoid muscle ID SPASMODIC DYSPHONIA; NERVE-STIMULATION; REFLEX; CAT AB Repeated stimulation of the laryngeal mucosa occurs during speech. Single stimuli, however, can elicit the laryngeal adductor response (LAR). Our hypothesis was that the LAR to repeated rapid air pressure stimuli is centrally suppressed in humans. Hooked-wire electrodes were inserted into the thyroarytenoid and cricothyroid muscles on both sides and into the posterior cricoarytenoid muscle on one side. Pairs of air puff stimuli were presented to the mucosa over the arytenoids at pressure levels three times threshold with interstimulus intervals from 250 to 5,000 ms. Bilateral thyroarytenoid responses occurred at around 150 ms to more than 70% of the initial stimuli. With repeated presentation at intervals of 2 seconds or less, the percent occurrence decreased to less than 40% and response amplitudes were reduced by 50%. Central suppression of adductor responses to repeated air puff stimuli may allow speakers to produce voice without eliciting reflexive spasms that could disrupt speech. C1 NINDS, LSS, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, LSS, NIH, Bldg 10,Room 5D38, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-08] NR 23 TC 14 Z9 14 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 2005 VL 114 IS 4 BP 264 EP 270 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 916UL UT WOS:000228411600003 PM 15895780 ER PT J AU Tudor, G Alley, M Nelson, CM Huang, RL Covell, DG Gutierrez, P Sausville, EA AF Tudor, G Alley, M Nelson, CM Huang, RL Covell, DG Gutierrez, P Sausville, EA TI Cytotoxicity of RH1: NAD(P)H : quinone acceptor oxidoreductase (NQO1)-independent oxidative stress and apoptosis induction SO ANTI-CANCER DRUGS LA English DT Article DE antitumor; aziridinylbenzoquinones; apoptosis; free radicals; NQO1; redox cycling ID ANTICANCER DRUG SCREEN; DT-DIAPHORASE ACTIVITY; COLON-CARCINOMA CELLS; INDUCED DNA DAMAGE; MITOMYCIN-C; ANTITUMOR QUINONES; BIOREDUCTIVE ACTIVATION; TUMOR-CELLS; NQO1 GENE; METABOLISM AB The elevated expression of the flavoprotein NAD(P)H: quinone acceptor oxidoreductase (NQO1) (EC 1.6.99.2) in many human solid tumors, along with its ability to activate quinone-based anticancer agents, makes it an excellent target for enzyme-directed drug development. Previous studies have shown a significant statistical correlation between NQO1 enzymatic activity and the cytotoxicity of certain antitumor quinones. RH1 [2,5-diaziridinyl-3(hydroxymethyl)-6-methyl-1,4-benzoquinone], presently in late preclinical and entering early clinical development, has been previously considered to be an excellent substrate for activation by NQO1. In this study we investigate the cytotoxicity of RH1 in cell lines selected from the NCI's 60 tumor cell line panel, expressing varying levels of NQO1 activity. Exposure time- and concentration-dependent cytotoxicity was seen, apparently independent from levels of NQO1 activity in these cells. Furthermore, the NQO1 inhibitor dicoumarol had no impact on the sensitivity profiles of RH1 response. The HL-60 myeloid leukemia cells, which do not have detectable NQO1 activity, were further investigated. RH1 treatment of HL-60 cells generated high levels of free radicals, which was accompanied by robust redox cycling, oxygen consumption and induction of apoptosis. These results are in agreement with previous data suggesting that, in addition to its activation by NQO1, RH1-induced cytotoxicity might involve alternative pathways for activation of this compound. Furthermore, the high cytotoxicity of RH1 in the leukemia/lymphoma subpanel of the NCl in vitro cell line screen would suggest an empirical rationale for the utilization of this compound in the treatment of these malignancies. (c) 2005 Lippincott Williams T Wilkins. C1 Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Natl Canc Inst, Sci Applicat Int Corp, Frederick, MD USA. Natl Canc Inst, DCTD, Biol Testing Branch, Dev Therapeut Program, Frederick, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Natl Canc Inst, Screening Technol Branch, Dev Therapeut Program, Frederick, MD USA. RP Sausville, EA (reprint author), Univ Maryland, Greenbaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM esausville@umm.edu FU PHS HHS [N01-C0-56000] NR 43 TC 16 Z9 17 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 APR PY 2005 VL 16 IS 4 BP 381 EP 391 DI 10.1097/00001813-200504000-00004 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 910GV UT WOS:000227919800004 PM 15746574 ER PT J AU Simitsopoulou, M Roilides, E Dotis, J Dalakiouridou, M Dudkova, F Andreadou, E Walsh, TJ AF Simitsopoulou, M Roilides, E Dotis, J Dalakiouridou, M Dudkova, F Andreadou, E Walsh, TJ TI Differential expression of cytokines and chemokines in human monocytes induced by lipid formulations of amphotericin B SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; COLLOIDAL DISPERSION; NEUTROPENIC PATIENTS; EMPIRICAL-TREATMENT; MONONUCLEAR-CELLS; DOUBLE-BLIND; IMBALANCE; INFUSION; FEVER; IL-1 AB The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA and protein profiles of five cytokines and chemokines expressed by human monocyte-enriched mononuclear leukocytes (MNCs) were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays; they were compared to those of deoxycholate amphotericin B (DAMB). mRNAs of interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1 beta (MIP-1 beta) were assessed after treatment of MNCs with each drug for 0.5, 2, 6, and 22 h. The cytokine protein profiles were obtained after incubation of MNCs with the drugs for 2 h (TNF-a) or 6 h (all the others). In the mRNA studies, DAMB resulted in an early increase of inflammatory cytokines or chemokines IL-1 beta, TNF-alpha, MCP-1, and MIP-1 beta (2 to 6 h) and in a late increase of antinflammatory IL-1ra (22 h). ABCD showed a general similar trend of inflammatory gene up-regulation. LAMB and ABLC decreased or did not affect IL-1 beta and TNF-ot, whereas ABLC additionally decreased MIP-1 beta. In protein measurement studies, DAMB and ABCD up-regulated production of IL-I beta ( < 0.05), decreased the IL-1ra/IL-1 beta ratio, and up-regulated the production of MCP-1 and MIP-1 beta. In comparison, LAMB and ABLC down-regulated or did not affect the production of these cytokines/chemokines compared to untreated MNCs; furthermore, ABLC tended to increase the IL-1ra/IL-1 beta ratio. These studies demonstrate that amphotericin B formulations differentially affect gene expression and release of an array of proinflammatory and anti-inflammatory cytokines that potentially may explain the differences in infusion-related reactions and dosedependent dependent nephrotoxicity as well as modulation of the host immune response to invasive fungal infections. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Aristole Univ, Sch Med, Dept Pediat 3, Infect Dis Lab, Thessaloniki, Greece. Inst Educ Technol, Lab Med Biotechnol, Dept Med Labs, Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 43 TC 35 Z9 38 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 APR PY 2005 VL 49 IS 4 BP 1397 EP 1403 DI 10.1128/AAC.49.4.1397-1403.2005 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 912MK UT WOS:000228082500022 PM 15793118 ER PT J AU Petraitis, V Petraitiene, R Lin, PX Calis, K Kelaher, AM Muray, HA Mya-San, C Mickiene, D Bacher, J Walsh, TJ AF Petraitis, V Petraitiene, R Lin, PX Calis, K Kelaher, AM Muray, HA Mya-San, C Mickiene, D Bacher, J Walsh, TJ TI Efficacy and safety of generic amphotericin B in experimental pulmonary aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID EPIDEMIOLOGY; FORMULATIONS; INFECTIONS; VANCOMYCIN; RABBITS AB The recent shortage of the brand name drug Fungizone has necessitated a change to generic formulations of amphotericin B deoxycholate. Clinical trials cannot be conducted in a timely manner to provide data on the safety and efficacy of these formulations. We therefore compared generic amphotericin B and Fungizone for activity and safety in the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Fungizone and generic amphotericin B are similar in efficacy, pharmacokinetics, and safety in the treatment of experimental IPA. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, CRC, Bethesda, MD 20892 USA. NIH, Surg Serv, Vet Resources Program, Off Res Serv, Bethesda, MD USA. Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD USA. SAIC Frederick Inc, Frederick, MD USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, CRC, Bldg 10,Rm 1W-5740,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 17 TC 8 Z9 8 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 APR PY 2005 VL 49 IS 4 BP 1642 EP 1645 DI 10.1128/AAC.49.4.1642-1645.2005 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 912MK UT WOS:000228082500065 PM 15793161 ER PT J AU Sugui, JA Chang, YC Kwon-Chung, KJ AF Sugui, JA Chang, YC Kwon-Chung, KJ TI Agrobacterium tumefaciens-mediated transformation of aspergillus fumigatus: an efficient tool for insertional mutagenesis and targeted gene disruption SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID T-DNA TRANSFER; VIRULENCE; BIOLOGY AB Agrobacterium tumefaciens was used to transform Aspergillus fumigatus by either random or site-directed integration of transforming DNA (T-DNA). Random mutagenesis via Agrobacterium tumefaciens-mediated transformation (ATMT) was accomplished with T-DNA containing a hygromycin resistance cassette. Cocultivation of A. fumigatus conidia and Agrobacterium (1:10 ratio) for 48 h at 24 degrees C resulted in high frequencies of transformation (> 100 transformants/10(7) conidia). The majority of transformants harbored a randomly integrated single copy of T-DNA and were mitotically stable. We chose alb1, a polyketide synthase gene, as the target gene for homologous integration because of the clear phenotype difference between the white colonies of Delta alb1 mutant strains and the bluish-green colonies of wild-type strains. ATMT with a T-DNA-containing alb1 disruption construct resulted in 66% albino transformants. Southern analysis revealed that 19 of the 20 randomly chosen albino transformants (95%) were disrupted by homologous recombination. These results suggest that ATMT is an efficient tool for transformation, random insertional mutagenesis, and gene disruption in A. fumigatus. C1 NIAID, LCID, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, LCID, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov NR 18 TC 78 Z9 102 U1 2 U2 8 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 APR PY 2005 VL 71 IS 4 BP 1798 EP 1802 DI 10.1128/AEM.71.4.1798-1802.2005 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 915UY UT WOS:000228338000015 PM 15812003 ER PT J AU Meyer-Lindenberg, AS Olsen, RK Kohn, PD Brown, T Egan, MF Weinberger, DR Berman, KF AF Meyer-Lindenberg, AS Olsen, RK Kohn, PD Brown, T Egan, MF Weinberger, DR Berman, KF TI Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSTERIOR PARIETAL CORTEX; CEREBRAL BLOOD-FLOW; WORKING-MEMORY; RHESUS-MONKEY; MONOZYGOTIC TWINS; FRONTAL-LOBE; DYSFUNCTION; BRAIN; RAT; PET AB Background: Two brain regions often implicated in schizophrenia are the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF). It has been hypothesized that the pathophysiology of the disorder might involve an alteration of functional interactions between medial temporal and prefrontal areas. Methods: We used neuroimaging data acquired during a working memory challenge and a sensorimotor control task in 22 medication-free schizophrenic patients and 22 performance-, age-, and sex-matched healthy subjects to investigate "functional connectivity" between HF and DLPFC in schizophrenia. The HF blood flow, measured with positron emission tomography, was assessed within a probabilistic template. Brain areas whose activity was positively or negatively coupled to HF were identified using voxelwise analysis of covariance throughout the entire brain and analyzed using a random effects model. Results: During working memory, patients showed reduced activation of the right DLPFC and left cerebellum. In both groups, inverse correlations were observed between the HF and the contralateral DLPFC and inferior parietal lobule. While these did not differ between diagnostic groups during the control task, the working memory challenge revealed a specific abnormality in DLPFC-HF functional connectivity-while the right DLPFC was significantly coupled to the left HF in both groups during the control task, this correlation was not seen in healthy subjects during working memory but persisted undiminished in patients, resulting in a significant task-by-group interaction. Conclusions: Our results suggest a regionally specific alteration of HF-DLPFC functional connectivity in schizophrenia that manifests as an unmodulated persistence of an HF-DLPFC linkage during working memory activation. Thus, a mechanism by which HF dysfunction may manifest in schizophrenia is by inappropriate reciprocal modulatory interaction with the DLPFC. C1 Natl Inst Mental Hlth, Unit Integrat Neuroimaging, Bethesda, MD USA. Natl Inst Mental Hlth, Genes Cognit & Psychosis Program, Bethesda, MD USA. RP Meyer-Lindenberg, AS (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov OI Olsen, Rosanna/0000-0002-2918-4152; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 52 TC 309 Z9 314 U1 2 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2005 VL 62 IS 4 BP 379 EP 386 DI 10.1001/archpsyc.62.4.379 PG 8 WC Psychiatry SC Psychiatry GA 913FO UT WOS:000228137200004 PM 15809405 ER PT J AU Lossos, A Dobson-Stone, C Monaco, AP Soffer, D Rahamim, E Newman, JP Mohiddin, S Fananapazir, L Lerer, I Linetsky, E Reches, A Argov, Z Abramsky, O Gadoth, N Sadeh, M Gomori, JM Boher, M Meiner, V AF Lossos, A Dobson-Stone, C Monaco, AP Soffer, D Rahamim, E Newman, JP Mohiddin, S Fananapazir, L Lerer, I Linetsky, E Reches, A Argov, Z Abramsky, O Gadoth, N Sadeh, M Gomori, JM Boher, M Meiner, V TI Early clinical heterogeneity in choreoacanthocytosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID CHOREA-ACANTHOCYTOSIS; AMYOTROPHIC CHOREA; CHAC GENE; NEUROACANTHOCYTOSIS; PROTEIN AB Background: Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. Objective: To describe the early clinical features and possible genotype-phenotype correlation in CHAC. Design and Setting: Case series in a tertiary care center. Patients and Main Outcome Methods: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A. Results: Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. Conclusions: These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling. C1 Hadassah Hebrew Univ Hosp, Dept Neurol, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Agnes Ginges Ctr Human Neurogenet, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Dept Pathol, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Dept Radiol, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, Dept Med Biophys, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Electron Microscopy Lab, Interdept Equipment Unit, Kefar Sava, Israel. Meir Hosp, Dept Neurol, Kefar Sava, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Wolfson Med Ctr, Dept Neurol, Holon, Israel. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. NHLBI, Inherited Cardiac Dis Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. RP Lossos, A (reprint author), Hadassah Hebrew Univ Hosp, Dept Neurol, POB 12000, IL-91120 Jerusalem, Israel. EM alos@hadassah.org.il RI Monaco, Anthony/A-4495-2010 OI Monaco, Anthony/0000-0001-7480-3197 NR 19 TC 16 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2005 VL 62 IS 4 BP 611 EP 614 DI 10.1001/archneur.62.4.611 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 914KZ UT WOS:000228227800013 PM 15824261 ER PT J AU Rapoport, SI Schapiro, MB May, C AF Rapoport, SI Schapiro, MB May, C TI Brain delivery of homovanillic acid to cerebrospinal fluid during human aging - In reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. EM sir@helix.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2005 VL 62 IS 4 BP 690 EP 691 DI 10.1001/archneur.62.4.690-b PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 914KZ UT WOS:000228227800033 ER PT J AU Smolen, JS Han, C Bala, M Maini, RN Kalden, JR van der Heijde, D Breedveld, FC Furst, DE Lipsky, PE AF Smolen, JS Han, C Bala, M Maini, RN Kalden, JR van der Heijde, D Breedveld, FC Furst, DE Lipsky, PE CA ATTRACT Study Grp TI Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement - A detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MEDIATED JOINT DESTRUCTION; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; DISEASE-ACTIVITY; RADIOLOGIC DAMAGE; BONE-RESORPTION; SYNOVIAL-FLUID; PROGRESSION; OSTEOCLASTS; CYTOKINES AB To assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment. Methods. Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial. Results. At week 54, patients who did not show 20% improvement by American College of Rheumatology criteria (ACR20 nonresponders) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables, including the 28-joint Disease Activity Score (DAS28) (P < 0.001), tender joint count (P = 0.014), swollen joint count (P < 0.001), and Greactive protein (CRP) level (P < 0.001). Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment, radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited (P < 0.001) compared with ACR20 nonresponders to MTX plus placebo. Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX, irrespective of ACR response status (mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group, versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group). Furthermore, among patients who were ACR20 nonresponders through week 54, patients who were DAS nonresponders at weeks 30 and 54, and patients without any improvement in individual clinical variables, those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo (P < 0.05 to P < 0.001). C1 Med Univ Vienna, Div Rheumatol, Dept Internal Med 3, A-1090 Vienna, Austria. Lainz Hosp, A-1090 Vienna, Austria. Centocor Inc, Malvern, PA USA. Kennedy Inst, London W6 7DW, England. Univ Erlangen Nurnberg, Erlangen, Germany. Univ Hosp Maastricht, Maastricht, Netherlands. Leiden Univ, Ctr Med, Leiden, Netherlands. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. RP Smolen, JS (reprint author), Med Univ Vienna, Div Rheumatol, Dept Internal Med 3, Waehriinger Guertal 18-20, A-1090 Vienna, Austria. EM josef.smolen@wienkav.at NR 39 TC 271 Z9 285 U1 0 U2 4 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 APR PY 2005 VL 52 IS 4 BP 1020 EP 1030 DI 10.1002/art.20982 PG 11 WC Rheumatology SC Rheumatology GA 920KQ UT WOS:000228688200005 PM 15818697 ER PT J AU Suter, LG Murabito, JM Felson, DT Fraenkel, L AF Suter, LG Murabito, JM Felson, DT Fraenkel, L TI The incidence and natural history of Raynaud's phenomenon in the community SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PREVALENCE; POPULATION; DIAGNOSIS; WOMEN AB Objective. Raynaud's phenomenon (RIP) is a common disorder, yet its incidence and natural history are unknown. Our objective was to determine the incidence and natural history of R-P not associated with a connective tissue disease in a large, community-based population. Methods. Using serial examinations of the Framingham Heart Study offspring cohort, we collected data regarding RP symptoms for 717 women and 641 men over a 7-year period. We used validated criteria for RP classification and categorized participants as having incident, persistent, or remitted RP. We performed sex-specific analyses of RP status by age, body mass index, vibratory tool use, season of examination, state of residence, use of antihypertensive medications, and smoking status. Results. The mean +/- SD age of participants was 53.5 +/- 10 years. The incidence of RP was 2.2% in women (n = 14) and 1.5% in men (n = 9). Of the 78 women and 50 men who had RP at baseline, 36% of women (n = 28) and 36% of men (n = 18) had persistent RP. RP remitted in 64% of women (n = 50) and 64% of men (n = 32), with 41 women and 25 men meeting no or only 1 RP criterion at followup. RP episodes were infrequent and rarely interfered with daily activities. Conclusion. This is the first prospective study to determine the incidence and natural history of R-P in a community-based cohort. Our data demonstrate that RP not associated with a connective tissue disease is frequently a transient phenomenon and rarely interferes with daily activities. C1 Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Suter, LG (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, 1E-61 SHM,POB 208088, New Haven, CT 06520 USA. EM lisa.suter@yale.edu OI Murabito, Joanne/0000-0002-0192-7516; Felson, David/0000-0002-2668-2447 FU NHLBI NIH HHS [N01-HC-25195]; NIAMS NIH HHS [AR-47785, AR-048826-01] NR 15 TC 48 Z9 50 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 APR PY 2005 VL 52 IS 4 BP 1259 EP 1263 DI 10.1002/art.20988 PG 5 WC Rheumatology SC Rheumatology GA 920KQ UT WOS:000228688200032 PM 15818710 ER PT J AU Siebert, S Amos, N Fielding, CA Wang, ECY Aksentijevich, I Williams, BD Brennan, P AF Siebert, S Amos, N Fielding, CA Wang, ECY Aksentijevich, I Williams, BD Brennan, P TI Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PERIODIC SYNDROME; AUTOINFLAMMATORY SYNDROMES; MUTATIONS; APOPTOSIS; GENERATION AB Objective. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autoinflammatory syndrome associated with mutations in the gene that encodes tumor necrosis factor receptor superfamily 1A (TNFRSF1A). The purpose of this study was to describe a novel TNFRSF1A mutation (C43S) in a patient with TRAPS and to examine the effects of this TNFRSF1A mutation on tumor necrosis factor alpha (TNF alpha)-induced signaling in a patient-derived primary dermal fibroblast line. Methods. TNFRSF1A shedding from neutrophils was measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Primary dermal fibroblast lines were established from the patient with the C43S TRAPS mutation and from healthy volunteers. Activation of NF-kappa B and activator protein 1 (AP-1) was evaluated by electrophoretic mobility shift assays. Cytokine production was measured by ELISA. Cell viability was measured by alamar blue assay. Apoptosis was measured by caspase 3 assay in the fibroblasts and by annexin V assay in peripheral blood mononuclear cells. Results. Activation-induced shedding of the TNFRSF1A from neutrophils was not altered by the C43S TRAPS mutation. TNF alpha-induced activation of NF-kappa B and AP-1 was decreased in the primary dermal fibroblasts with the C43S TNFRSF1A mutation. Nevertheless, the C43S TRAPS fibroblasts were capable of producing interleukin-6 (IL-6) and IL-8 in response to TNF alpha. However, TNF alpha-induced cell death and apoptosis were significantly decreased in the samples from the patient with the C43S TRAPS mutation. Conclusion. The C43S TNFRSF1A mutation results in decreased TNF alpha-induced nuclear signaling and apoptosis. Our data suggest a new hypothesis, in that the C43S TRAPS mutation may cause the inflammatory phenotype by increasing resistance to TNF alpha-induced apoptosis. C1 Cardiff Univ, Wales Coll Med, Sect Infect & Immun, Cardiff CF14 4XX, S Glam, Wales. NIAMSD, Bethesda, MD 20892 USA. RP Siebert, S (reprint author), Cardiff Univ, Wales Coll Med, Sect Infect & Immun, Henry Wellcome Bldg, Cardiff CF14 4XX, S Glam, Wales. EM sieberts@cardiff.ac.uk RI Brennan, Paul/B-9210-2009; Fielding, Ceri/F-5638-2014; OI Brennan, Paul/0000-0001-8792-0499; Fielding, Ceri/0000-0002-5817-3153; Siebert, Stefan/0000-0002-1802-7311 FU Medical Research Council [G0500617(74644), G0300180, G0300180(65735), G0500617, G9827961] NR 17 TC 35 Z9 37 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2005 VL 52 IS 4 BP 1287 EP 1292 DI 10.1002/art.20955 PG 6 WC Rheumatology SC Rheumatology GA 920KQ UT WOS:000228688200036 PM 15818692 ER PT J AU Illoh, KO Illoh, OC Feseha, HB Hallenbeck, JM AF Illoh, KO Illoh, OC Feseha, HB Hallenbeck, JM TI Antibiotics for vascular diseases: a meta-analysis of randomized controlled trials SO ATHEROSCLEROSIS LA English DT Article DE antibiotics; clinical trials; vascular diseases; arteriosclerosis; meta-analysis ID CORONARY-ARTERY-DISEASE; PLACEBO-CONTROLLED TRIAL; CHLAMYDIA-PNEUMONIAE; SECONDARY PREVENTION; DOUBLE-BLIND; MYOCARDIAL-INFARCTION; ISCHEMIC EVENTS; CLINICAL-TRIALS; HEART-DISEASE; AZITHROMYCIN AB Back.-round: Trials of antibiotic treatment of vascular diseases, in attempts to eradicate possible microbial initiators, have had mixed results. We sought to evaluate the efficacy of antibiotics in treating patients with atherosclerotic vascular diseases, using a meta-analysis. Methods: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials and also used cross-references. Randomized controlled trials of antibiotic treatment of vascular diseases were included. Two independent raters assessed the trials for quality. We performed summary estimates, Subgroup analyses and tests for homogeneity. Results: Twelve trials, with a total of 12,236 patients, were included. Antibiotic treatment resulted in a non-significant reduction in the risk of new vascular events or death (odds ratio (OR), 0.84; 95% confidence interval (Cl), 0.67-1.05). There was significant heterogeneity between the sub-groups in type of vascular disease (coronary heart disease, CHD versus non-CHD (p=0.01)). Among the 72 non-CHD patients, a trend appears for treatment benefit in reducing recurrent events or death (OR, 0.22; 95% CL 0.07-0.66). Conclusions: Overall, antibiotic treatment did not significantly reduce occurrence of new vascular events or death. However, further trials are needed to confirm the benefit demonstrated in non-CHD patients. (c) 2004 Published by Elsevier Ireland Ltd. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Howard Univ Hosp, Dept Cardiol, Washington, DC USA. RP Illoh, KO (reprint author), Univ Texas, Med Branch, Dept Neurol, Galveston, TX 77550 USA. EM koilloh@utmb.edu NR 42 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2005 VL 179 IS 2 BP 403 EP 412 DI 10.1016/j.atherosclerosis.2004.10.034 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 912VV UT WOS:000228108900026 PM 15777560 ER PT J AU Gudnason, V Asperlund, T Thorsson, B Thorgeirsson, G Erksdottir, G Sigurdsson, S Karlsdottir, G Launer, L Detrano, R Bots, M AF Gudnason, V Asperlund, T Thorsson, B Thorgeirsson, G Erksdottir, G Sigurdsson, S Karlsdottir, G Launer, L Detrano, R Bots, M TI How well do subclinical atherosclerosis imaging measurements correlate with prior coronary event in old age the ages. Reykjavik Study SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 75th Congress of the European-Atherosclerosis-Society CY APR 23-26, 2005 CL Prague, CZECH REPUBLIC SP European Atherosclerosis Soc C1 Iceland Heart Assoc, Heart Prevent Clin, Kopavogur, Iceland. Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. Natl Inst Aging, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Med, Div Cardiol, Torrance, CA 90509 USA. Univ Utrecht, Med Ctr, Vasc Imaging Ctr, Utrecht, Netherlands. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD APR PY 2005 VL 6 IS 1 BP 125 EP 125 DI 10.1016/S1567-5688(05)80490-8 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 921BK UT WOS:000228739000491 ER PT J AU Horwitz, B Husain, FT Guenther, FH AF Horwitz, B Husain, FT Guenther, FH TI Auditory object processing and primate biological evolution SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB This commentary focuses on the importance of auditory object processing for producing and comprehending human language, the relative lack of development of this capability in nonhuman primates, and the consequent need for hominid neurobiological evolution to enhance this capability in making the transition from protosign to protospeech to language. C1 Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. EM horwitz@helix.nih.gov; husainf@nidcd.nih.gov; guenther@cns.bu.edu NR 9 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR PY 2005 VL 28 IS 2 BP 134 EP + PG 10 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 956DX UT WOS:000231280500011 ER PT J AU Thayer, JF Lane, RD AF Thayer, JF Lane, RD TI The importance of inhibition in dynamical systems models of emotion and neurobiology SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Lewis makes a compelling case for a dynamical systems approach to emotion and neurobiology. These models involve both excitatory and inhibitory processes. It appears that a critical role for inhibitory processes is implied but not emphasized in Lewis's model. We suggest that a greater understanding of inhibitory processes both at the psychological and neurobiological levels might further enhance Lewis's model. C1 NIA, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. RP Thayer, JF (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. EM jt182f@nih.gov; lane@email.arizona.edu NR 2 TC 6 Z9 6 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR PY 2005 VL 28 IS 2 BP 218 EP + PG 14 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 956DX UT WOS:000231280500054 ER PT J AU Christian, KM Thompson, RF AF Christian, KM Thompson, RF TI Long-term storage of an associative memory trace in the cerebellum SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE cerebellum; eyeblink conditioning; long-term memory; memory storage; classical conditioning ID NICTITATING-MEMBRANE RESPONSE; BASOLATERAL AMYGDALA; INTERPOSITUS NUCLEUS; EYELID RESPONSES; ACQUISITION; RETENTION; LESIONS; CONSOLIDATION; RABBITS; RATS AB Distinct neural regions may be engaged during acquisition and maintenance of some memories. In delay classical conditioning of the eyeblink response, the cerebellum is necessary for acquisition and expression of the conditioned response (CR), but loci of long-term memory storage are not known. Rabbits (Oryctolagus cuniculus) were trained, overtrained, and given either 30 additional days of training or 30 days of rest. Half the subjects in the rest group were given a reminder training session. Subjects then received either reversible inactivation of the cerebellar interpositus nucleus (muscimol) or permanent electrolytic lesions. In all cases, inactivation and lesions of the interpositus completely abolished the CR. The site of memory formation in the interpositus nucleus also appears to be the site of long-term memory storage. C1 Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA. RP Christian, KM (reprint author), NIH, Unit Genet Cognit & Behav, 35 Convent Dr,MSC 3710,Bldg 35,Room 1C-1006, Bethesda, MD 20892 USA. EM christiank@mail.nih.gov NR 29 TC 41 Z9 41 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2005 VL 119 IS 2 BP 526 EP 537 DI 10.1037/0735-7044.119.2.526 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 917AR UT WOS:000228428700017 PM 15839799 ER PT J AU Shrimali, RK Lobanov, AV Xu, XM Rao, M Carlson, BA Mahadeo, DC Parent, CA Gladyshev, VN Hatfield, DL AF Shrimali, RK Lobanov, AV Xu, XM Rao, M Carlson, BA Mahadeo, DC Parent, CA Gladyshev, VN Hatfield, DL TI Selenocysteine tRNA identification in the model organisms Dictyostelium discoideum and Tetrahymena thermophila SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE computational analysis; Dictyostelium; protozoans; selenium; selenocysteine; selenocysteine tRNA; Tetrahymena ID CHLAMYDOMONAS-REINHARDTII; GENETIC-CODE; LIBRARIES; SELENIUM; PLANT AB Characterizing See tRNAs that decode UGA provides one of the most direct and easiest means of determining whether an organism possesses the ability to insert selenocysteine (See) into protein. Herein, we used a combination of two techniques, computational to identify Sec tRNA genes and RT-PCR to sequence the gene products, to unequivocally demonstrate that two widely studied, model protozoans, Dictyostelium discoideum and Tetrahymena thermophila, encode See tRNA in their genomes. The advantage of using both procedures is that computationally we could easily detect potential See tRNA genes and then confirm by sequencing that the See tRNA was present in the tRNA population, and thus the identified gene was not a pseudogene. See tRNAs from both organisms decode UGA. T thermophila See tRNA, like all other sequenced See tRNAs, is 90 nucleotides in length, while that from D. discoideum is 91 nucleotides long making it the longest eukaryotic sequenced to date. Evolutionary analyses of known See tRNAs reveal the two forms identified herein are the most divergent eukaryotic See tRNAs thus far sequenced. (C) 2005 Elsevier Inc. All rights reserved. C1 NCI, Canc Res Ctr, Lab Canc Prevent, Mol Biol Selenium Sect,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Ctr Canc Res, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hatfield, DL (reprint author), NCI, Canc Res Ctr, Lab Canc Prevent, Mol Biol Selenium Sect,NIH, Bethesda, MD 20892 USA. EM hatfield@dc37a.nci.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU NIGMS NIH HHS [GM061603] NR 17 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 1 PY 2005 VL 329 IS 1 BP 147 EP 151 DI 10.1016/j.bbrc.2005.01.120 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 903HE UT WOS:000227415700023 PM 15721286 ER PT J AU Huang, RL Wallqvist, A Covell, DG AF Huang, RL Wallqvist, A Covell, DG TI Anticancer metal compounds in NCI's tumor-screening database: putative mode of action SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE data mining; NCI tumor screen; metal compounds; mechanism of action; drug discovery; cancer ID RIBONUCLEOTIDE REDUCTASE INHIBITOR; REACTIVE-OXYGEN; SUPEROXIDE-DISMUTASE; THIOREDOXIN REDUCTASE; ANTITUMOR-ACTIVITY; IRON CHELATORS; CANCER-THERAPY; ELECTRON-TRANSFER; TITANIUM-DIOXIDE; CELL-DEATH AB Clustering analysis of tumor cell cytotoxicity profiles for the National Cancer Institute (NCI)'s open compound repository has been used to catalog over 1100 metal or metalloid containing compounds with potential anticancer activity. The molecular features and corresponding reactivity of these compounds have been analyzed in terms of properties of their metals, their associated organic components (ligands) and their capacity to inhibit tumor cell growth. Cytotoxic responses are influenced by both the identity of the metal and the properties of its coordination ligand, with clear associations between structural similarities and cytotoxicity. Assignments of mechanisms of action (MOAs) for these compounds could be segregated into four broad response classes according to preference for binding to biological sulfhydryl groups, chelation, generation of reactive oxygen species (ROS), and production of lipophilic ions. Correlations between specific cytotoxic responses and differential gene expression profiles within the NCI's tumor cell panel serve as a validation for candidate biological targets and putative MOA classes. In addition, specific sensitivity toward subsets of metal containing agents has been found for certain tumor cell panels. Taken together, our results expand the knowledge base available for evaluating, designing and developing new metal-based anticancer drugs that may provide the basis for target-specific therapeutics. Published by Elsevier Inc. C1 NCI, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. NCI, Sci Appl Int Corp, NIH, Frederick, MD 21702 USA. RP Covell, DG (reprint author), NCI, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. EM covell@mail.ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 156 TC 101 Z9 103 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 1 PY 2005 VL 69 IS 7 BP 1009 EP 1039 DI 10.1016/j.bcp.2005.01.001 PG 31 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 911IA UT WOS:000227994600002 PM 15763539 ER PT J AU Yu, YK Altschul, SF AF Yu, YK Altschul, SF TI The construction of amino acid substitution matrices for the comparison of proteins with non-standard compositions SO BIOINFORMATICS LA English DT Article ID PSI-BLAST; SEQUENCE AB Motivation: Amino acid substitution matrices play a central role in protein alignment methods. Standard log-odds matrices, such as those of the PAM and BLOSUM series, are constructed from large sets of protein alignments having implicit background amino acid frequencies. However, these matrices frequently are used to compare proteins with markedly different amino acid compositions, such as transmembrane proteins or proteins from organisms with strongly biased nucleotide compositions. It has been argued elsewhere that standard matrices are not ideal for such comparisons and, furthermore, a rationale has been presented for transforming a standard matrix for use in a non-standard compositional context. Results: This paper presents the mathematical details underlying the compositional adjustment of amino acid or DNA substitution matrices. C1 NIH, Natl Biotechnol Ctr, Natl Lib Med, Bethesda, MD 20894 USA. RP Altschul, SF (reprint author), NIH, Natl Biotechnol Ctr, Natl Lib Med, Bethesda, MD 20894 USA. EM altschul@ncbi.nlm.nih.gov NR 23 TC 57 Z9 59 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2005 VL 21 IS 7 BP 902 EP 911 DI 10.1093/bioinformatics/bti070 PG 10 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 911CB UT WOS:000227977800010 PM 15509610 ER PT J AU Bilke, S Chen, QR Whiteford, CC Khan, J AF Bilke, S Chen, QR Whiteford, CC Khan, J TI Detection of low level genomic alterations by comparative genomic hybridization based on cDNA micro-arrays SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; NEUROBLASTOMA; AMPLIFICATION; MICROARRAYS; TUMORS; DELETION; CANCER AB Motivation: The accumulation of genomic alterations is an important process in tumor formation and progression. Comparative genomic hybridization performed on cDNA arrays (cDNA aCGH) is a common method to investigate the genomic alterations on a genome-wide scale. However, when detecting low-level DNA copy number changes this technology requires the use of noise reduction strategies due to a low signal to noise ratio. Results: Currently a running average smoothing filter is the most frequently used noise reduction strategy. We analyzed this strategy theoretically and experimentally and found that it is not sensitive to very low level genomic alterations. The presence of systematic errors in the data is one of the main reasons for this failure. We developed a novel algorithm which efficiently reduces systematic noise and allows for the detection of low-level genomic alterations. The algorithm is based on comparison of the biological relevant data to data from so-called self-self hybridizations, additional experiments which contain no biological information but contain systematic errors. We find that with our algorithm the effective resolution for +/- 1 DNA copy number changes is about 2 Mb. For copy number changes larger than three the effective resolution is on the level of single genes. C1 NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP Bilke, S (reprint author), NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM bilkes@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 26 TC 22 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2005 VL 21 IS 7 BP 1138 EP 1145 DI 10.1093/bioinformatics/bti133 PG 8 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 911CB UT WOS:000227977800039 PM 15539449 ER PT J AU Denslow, S Lomarev, M George, MS Bohning, DE AF Denslow, S Lomarev, M George, MS Bohning, DE TI Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: An interleaved TMS/functional magnetic resonance imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE BOLD; fMRI; motor cortex; motor circuits; transcranial magnetic stimulation ID PRIMARY MOTOR CORTEX; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; SENSORIMOTOR CORTEX; BASAL GANGLIA; FMRI SIGNAL; BOLD-FMRI; ACTIVATION; TMS AB Background: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. Methods: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. Results: Both TMS (110016 motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected posttask "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant effects. Differences were detectable, however, in primary data time-intensity profiles differences between TMS- and volition-induced of diferrence. Conclusions: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Labs, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. NINDS, Bethesda, MD 20892 USA. Inst Human Brain, St Petersburg, Russia. RP Denslow, S (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. EM denslows@musc.edu FU NCRR NIH HHS [R01 RR14080-02] NR 45 TC 45 Z9 45 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 APR 1 PY 2005 VL 57 IS 7 BP 752 EP 760 DI 10.1016/j.biopsych.2004.12.017 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 913BK UT WOS:000228125000009 PM 15820232 ER PT J AU Snider, LA Lougee, L Slattery, M Grant, P Swedo, SE AF Snider, LA Lougee, L Slattery, M Grant, P Swedo, SE TI Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE streptococcal; autoimmune; obsessive-compulsive disorder; tic disorder ID OBSESSIVE-COMPULSIVE SCALE; GROUP-A STREPTOCOCCI; RHEUMATIC-FEVER; VALIDITY; ERYTHROMYCIN; RELIABILITY; PHARYNGITIS; RESISTANCE; CONSUMPTION; PREVENTION AB Background: The acronym PANDAS (pediatric autoimmune neuropyschiatric disorders associated with streptococcal infections) describes a subgroup of children with obsessive-compulsive disorder and/or tic disorder that experience symptom exacerbations following streptococcal infections. We hypothesized That the prevention of streptococcal infections among children in the PANDAS subgroup would decrease neuropsychiatric symptom exacerbations. Methods: Twenty-three subjects with PANDAS were enrolled in a double blind, randomized controlled trial. Antibiotic prophylaxis with penicillin or azithromycin was administered for 12 months. Rates of streptococcal infections and neuropsychiatric symptom exacerbations were compared between the study year and the baseline year prior to entry. Results: Significant decreases in streptococcal infections during the study year were found with a mean of .1 (.3 SD) per subject, compared to the baseline year with 1.9 (1.2 SD) in the penicillin group and 2.4 (1.1 SD) in the azithromycin group [p <.01]. Significant decreases in neuropsychiatric exacerbations during the study year were also found with a mean of .5 (.5 SD) per subject in the penicillin group and .8 (.6 SD) in the azithromycin group, compared to the baseline year with 2.0 (.9 SD) in the penicillin group and 1.8 (.6 SD) in the azithromycin group [p <.01] Conclusions: Penicillin and azithromycin were found to be effective in decreasing streptococcal infections and neuropsychiatric symptom exacerbations among children in the PANDAS subgroup. C1 NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med, Dept Psychiat, Madison, WI 53792 USA. RP Snider, LA (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 4N208,MSC 1255, Bethesda, MD 20892 USA. EM sniderl@intra.nimh.nih.gov NR 24 TC 96 Z9 99 U1 2 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 APR 1 PY 2005 VL 57 IS 7 BP 788 EP 792 DI 10.1016/j.biopsych.2004.12.035 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 913BK UT WOS:000228125000013 PM 15820236 ER PT J AU Koh, CY Welniak, LA Murphy, WJ AF Koh, CY Welniak, LA Murphy, WJ TI Lack of correlation between an assay used to determine early marrow allograft rejection and long-term chimerism after murine allogeneic bone marrow transplantation: Effects of marrow dose SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE acute rejection; bone marrow transplantation; long-term chimerism; CFU-GM ID NATURAL-KILLER-CELLS; VERSUS-HOST-DISEASE; HEMATOPOIETIC STEM-CELLS; GRAFT-REJECTION; PECULIAR IMMUNOBIOLOGY; NK CELLS; T-CELLS; MICE; ENGRAFTMENT; KINETICS AB The acute rejection of bone marrow (BM) allografts by host effectors can occur within a short period after BM transplantation (BMT) in lethally irradiated mice. Common assays used to ascertain engraftment/resistance involve measuring the growth of granulocyte/monocyte progenitors (colony-forming unit-granulocyte-macrophage) in vitro or splenocyte proliferation assessed by radioisotope incorporation in vivo 5 to 8 days after BMT. However, the correlation of the long-term outcome of BMT with the kinetics of recovery by using the dose of allogeneic BM cells (BMCs) that leads to early rejection as determined by the in vitro assessment has not been extensively studied. Thus, to investigate whether the early rejection of donor BMCs is an indication of a long-term engraftment failure, C57BL/6 (H2(b)) mice were lethally irradiated and transplanted with various doses of BALB/c (H2(d)) BMCs. The short-term engraftment of donor precursors (colony-forming unit-granulocyte-macrophage), the kinetics of hematopoietic cell recovery, the extent of donor chimerism, and the proportion of the recipients with long-term survival were determined. The results show that the kinetics and extent of hematopoietic cell recovery were significantly delayed in mice receiving limiting doses of BMCs that were rejected or severely resisted at day 8 after BMT. However, a proportion of these mice survived up to 98 days after BMT with mixed chimerism or donor chimerism. This study demonstrates that early rejection of BM precursors, as assessed by measurement of myeloid progenitors in the spleen after BMT, does not always correlate with the long-term outcome of the marrow allograft and that significant variability is inherent in the extent of chimerism when threshold amounts of BMCs are used. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA. Natl Inst Allergy & Infect Dis, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD USA. Univ Nevada, Dept Microbiol & Immunol, Reno, NV USA. Nevada Canc Inst, Las Vegas, NV USA. RP Murphy, WJ (reprint author), Univ Nevada, Dept Microbiol & Immunol, 1664 N Virginia St,Mail Stop 199, Reno, NV 89557 USA. EM wmurphv@unr.edu RI Koh, Crystal/D-9986-2013 FU NCI NIH HHS [R01 CA093527, N01-CO-12400] NR 29 TC 6 Z9 6 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2005 VL 11 IS 4 BP 252 EP 259 DI 10.1016/j.bbmt.2005.01.006 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 918AP UT WOS:000228510800003 PM 15812390 ER PT J AU Ryu, JK Song, SU Han, JY Chu, YC Lee, M Kim, JS Kim, SJ Suh, JK AF Ryu, JK Song, SU Han, JY Chu, YC Lee, M Kim, JS Kim, SJ Suh, JK TI Establishment of penile fibrosis model in a rat using mouse NIH 3T3 fibroblasts expressing transforming growth factor beta 1 SO BIOLOGY OF REPRODUCTION LA English DT Article DE male sexual function; penis ID GROWTH-FACTOR-BETA; PEYRONIES-LIKE CONDITION; SMOOTH-MUSCLE; LUNG FIBROSIS; TGF-BETA; ATHEROSCLEROSIS; FACTOR-BETA(1); DYSFUNCTION; INDUCTION; DISEASE AB Transforming growth factor (TGF) beta 1 has been suggested to have an important role in cavernous fibrosis and resultant erectile dysfunction. For further elucidation of TGF beta 1 signaling in association with cavernous fibrosis, we developed a rat model of cavernous fibrosis using TGF beta 1-producing NIH 3T3 fibroblasts (NIH 3T3-TGF beta 1). The NIH 3T3-TGF beta 1 cells were injected into male Sprague-Dawley rats intracavernously. Masson trichrome staining at 20 days postinjection showed multiple fibrous scars in the rats injected with the NIH 3T3-TGF beta 1 cells (group 3), whereas no histological evidence of cavernous fibrosis was found in the control rats (group 1) or the recombinant human TGF beta 1 protein-injected rats (group 2). Immunohistochemical staining revealed a higher expression of TGF beta 1 and its type II receptor in group 3 than in groups 1 and 2. Electrostimulation of the cavernous nerve revealed that the maximal intracavernous pressure was significantly lower in group 3 than in groups 1 and 2 (P < 0.01). The expression of transgenic TGF beta 1 mRNA continued to 10 days after injection of the cells. The NIH 3T3-TGF beta 1 cells sufficiently induced relatively long-lasting cavernous fibrosis. This novel animal model may contribute to future investigations of the pathogenesis of penile fibrosis associated with TGF beta 1 signaling and the development of new therapeutics targeting this pathway. C1 Inha Univ, Coll Med, Dept Urol, Inchon 400103, South Korea. Inha Univ, Coll Med, Clin Res Ctr, Inchon 400103, South Korea. Inha Univ, Coll Med, Dept Pathol, Inchon 400103, South Korea. Inha Univ, Coll Med, Dept Emergency Med, Inchon 400103, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Suh, JK (reprint author), Inha Univ Hosp, Dept Urol, 7-206 3rd St, Inchon 400103, South Korea. EM jksuh@inha.ac.kr NR 16 TC 4 Z9 6 U1 2 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 2005 VL 72 IS 4 BP 916 EP 921 DI 10.1095/biolreprod.104.035089 PG 6 WC Reproductive Biology SC Reproductive Biology GA 909US UT WOS:000227886800016 PM 15601922 ER PT J AU Berger, VW AF Berger, VW TI Quantifying the magnitude of baseline covariate imbalances resulting from selection bias in randomized clinical trials SO BIOMETRICAL JOURNAL LA English DT Article DE allocation concealment; confounding; predictable allocation; randomized blocks ID QUALITY AB Selection bias is most common in observational studies, when patients select their own treatments or treatments are assigned based on patient characteristics, such as disease severity. This first-order selection bias, as we call it, is eliminated by randomization, but there is residual selection bias that may occur even in randomized trials which occurs when, subconsciously or otherwise, an investigator uses advance knowledge of upcoming treatment allocations as the basis for deciding whom to enroll. For example, patients more likely to respond may be preferentially enrolled when the active treatment is due to be allocated, and patients less likely to respond may be enrolled when the control group is due to be allocated. If the upcoming allocations can be observed in their entirety, then we will call the resulting selection bias second-order selection bias. Allocation concealment minimizes the ability to observe upcoming allocations, yet upcoming allocations may still be predicted (imperfectly), or even determined with certainty, if at least some of the previous allocations are known, and if restrictions (such as randomized blocks) were placed on the randomization. This mechanism, based on prediction but not observation of upcoming allocations, is the third-order selection bias that is controlled by perfectly successful masking, but without perfect masking is not controlled even by the combination of advance randomization and allocation concealment. Our purpose is to quantify the magnitude of baseline imbalance that can result from third-order selection bias when the randomized block procedure is used. The smaller the block sizes, the more accurately one can predict future treatment assignments in the same block as known previous assignments, so this magnitude will depend on the block size, as well as on the level of certainty about upcoming allocations required to bias the patient selection. We find that a binary covariate can, on average, be up to 50% unbalanced by third-order selection bias. C1 Univ Maryland Baltimore Cty, NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 25 TC 22 Z9 22 U1 0 U2 6 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2005 VL 47 IS 2 BP 119 EP 127 DI 10.1002/bimj.200410106 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 921WO UT WOS:000228796400002 PM 16389910 ER PT J AU Liu, AY Schisterman, EF Mazumdar, M Hu, J AF Liu, AY Schisterman, EF Mazumdar, M Hu, J TI Power and sample size calculation of comparative diagnostic accuracy studies with multiple correlated test results SO BIOMETRICAL JOURNAL LA English DT Article DE receiver operating characteristic curves; area under a curve; correlated measurements; power and sample size ID ROC CURVE; HELICAL CT; SYSTEM AB We consider the power and sample size calculation of diagnostic studies with normally distributed multiple correlated test results. We derive test statistics and obtain power and sample size formulas. The methods are illustrated using an example of comparison of CT and PET scanner for detecting extra-hepatic disease for colorectal cancer. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Liu, AY (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 16 TC 8 Z9 8 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2005 VL 47 IS 2 BP 140 EP 150 DI 10.1002/bimj.200410094 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 921WO UT WOS:000228796400007 PM 16389911 ER PT J AU Berger, VW AF Berger, VW TI Nonparametric adjustment techniques for binary covariates SO BIOMETRICAL JOURNAL LA English DT Article DE confounding; nonparametric; randomization; stratified 2 x 2 tables ID INFERENCE; TRIALS; TESTS AB Though a variety of reasons are often articulated for adjusting analyses for covariates, these reasons often fall into one of two general objectives, specifically to increase precision or to decrease bias. In practice, one does not generally choose between these objectives, because the methods that address one tend to address the other, as well. Because of this, no distinction is made in the methods used to correct for a baseline imbalance with respect to a prognostic covariate versus to ensure a fair comparison across treatment groups by making the comparisons within the levels of a prognostic covariate. Yet the literal translation of these two uses of covariate adjustment will lead to two distinct adjustment methods. We illustrate this divergence in the simplest case of a single binary covariate, a binary outcome, and two treatments, and we note that it is possible to combine the two approaches to derive yet a third approach. Each of these approaches is nonparametric and exact, and so it is the precise reason for adjusting that should dictate which would be used in any given situation. C1 NCI, Bethesda, MD 20892 USA. Univ Maryland Baltimore Cty, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, EPN 3131,6130 Execut Blvd,MSC-7354, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 18 TC 0 Z9 0 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2005 VL 47 IS 2 BP 199 EP 205 DI 10.1002/bimj.200410100 PG 7 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 921WO UT WOS:000228796400013 PM 16389917 ER PT J AU Oishi, S Karki, RG Shi, ZD Worthy, KM Bindu, L Chertov, O Esposito, D Frank, P Gillette, WK Maderia, M Hartley, J Nicklaus, MC Barchi, JJ Fisher, RJ Burke, TR AF Oishi, S Karki, RG Shi, ZD Worthy, KM Bindu, L Chertov, O Esposito, D Frank, P Gillette, WK Maderia, M Hartley, J Nicklaus, MC Barchi, JJ Fisher, RJ Burke, TR TI Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE macrocycle; Grb2 SH2 domain; peptide mimetic; ring-closing metathesis ID HUMAN BREAST-CANCER; DESIGN; AFFINITY; SPECIFICITY; LIGANDS; PROTEIN; SRC; ANTAGONISTS; INHIBITOR; RECEPTOR AB Preferential binding of ligands to Grb2 SH2 domains in beta-bend conformations has made peptide cyclization a logical means of effecting affinity enhancement. This is based on the concept that constraint of open-chain sequences to bend geometries may reduce entropy penalties of binding. The current study extends this approach by undertaking ring-closing metathesis (RCM) macrocyclization between i and i + 3 residues through a process involving allylglycines and beta-vinyl-functionalized residues. Ring closure in this fashion results in minimal macrocyclic tetrapeptide mimetics. The predominant effects of such macrocyclization on Grb2 SH2 domain binding affinity were increases in rates of association (from 7- to 16-fold) relative to an open-chain congener, while decreases in dissociation rates were less pronounced (approximately 2-fold). The significant increases in association rates were consistent with pre-ordering of solution conformations to near those required for binding. Data from NMR experiments and molecular modeling simulations were used to interpret the binding results. An understanding of the conformational consequences of such i to i + 3 ring closure may facilitate its application to other systems where bend geometries are desired. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. SAIC, Prot Chem, Frederick, MD 21702 USA. SAIC, Prot Express Lab, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, POB B,Bldg 376 Boyles St, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Nicklaus, Marc/N-4183-2014; Barchi Jr., Joseph/N-3784-2014; Burke, Terrence/N-2601-2014; Oishi, Shinya/C-1350-2011; OI Oishi, Shinya/0000-0002-2833-2539; Nicklaus, Marc/0000-0002-4775-7030 NR 32 TC 25 Z9 25 U1 0 U2 0 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 APR 1 PY 2005 VL 13 IS 7 BP 2431 EP 2438 DI 10.1016/j.bmc.2005.01.052 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 909WI UT WOS:000227891000009 PM 15755645 ER PT J AU Runyon, SP Burgess, JP Abraham, P Keverline-Frantz, KI Flippen-Anderson, J Deschamps, J Lewin, AH Navarro, HA Boja, JW Kuhar, MJ Carroll, FI AF Runyon, SP Burgess, JP Abraham, P Keverline-Frantz, KI Flippen-Anderson, J Deschamps, J Lewin, AH Navarro, HA Boja, JW Kuhar, MJ Carroll, FI TI Synthesis, structural identification, and ligand binding of tropane ring analogs of paroxetine and an unexpected aza-bicyclo[3.2.2]nonane rearrangement product SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE paroxetine; monoamine transporters; tropanes; aza-bicyclo[3.2.2]nonanes ID NOREPINEPHRINE TRANSPORTERS; DOPAMINE TRANSPORTER; COCAINE; SEROTONIN; AMPHETAMINE; ADDICTION AB The structural requirements for high affinity at the serotonin transporter (5-HTT) have been investigated through the preparation of rigid paroxetine analogs. Tropane-derived analogs (4a-i) of paroxetine (2) were designed and synthesized as potential inhibitors of serotonin reuptake based on the structural and biological similarity between the two compound classes. Overall, the affinity of tropane-derived analogs at the 5-HTT was found to be at least an order of magnitude lower than that of paroxetine and ranged from 2-400 nM. The reduced affinity at the 5-HTT may be attributed to the inability of the rigid tropane-derived analogs to adopt conformations favored by the 5-HTT. Within the series of tropane analogs, the 2 beta,3 beta- and 2 beta,3 alpha-isomers, 4a and 4d, were the most potent at the DAT and NET and are also significantly more potent than paroxetine (2) suggesting that their reduced conformational flexibility maximizes residence time in conformations favored by these transporters. Examination of the previously published preparation and structural assignment of 4a by additional NMR and X-ray crystallographic data has established that nucleophilic addition to the intermediate 2 beta-methanesulfonyloxymethyl-3 beta-(4-fluorophenyl)tropane unexpectedly provided the aza-bicyclo[3.2.2]nonane derivative 10a. (c) 2005 Elsevier Ltd. All rights reserved. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. NIDA, Addict Res Ctr, Neurosci Branch, Baltimore, MD 21224 USA. RP Carroll, FI (reprint author), Res Triangle Inst, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM fic@rti.org OI Deschamps, Jeffrey/0000-0001-5845-0010 FU NIDA NIH HHS [DA05477] NR 13 TC 7 Z9 7 U1 0 U2 2 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 APR 1 PY 2005 VL 13 IS 7 BP 2439 EP 2449 DI 10.1016/j.bmc.2005.01.046 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 909WI UT WOS:000227891000010 PM 15755646 ER PT J AU Ye, S Yoshida, S Frohlich, R Haufe, G Kirk, KL AF Ye, S Yoshida, S Frohlich, R Haufe, G Kirk, KL TI Fluorinated phenylcyclopropylamines. Part 4: Effects of aryl substituents and stereochemistry on the inhibition of monoamine oxidases by 1-aryl-2-fluoro-cyclopropylamines SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE monoamine oxidase; tyramine oxidase; fluorinated phenylcyclopropylamine; irreversible inhibition; stereochemistry ID MICROBIAL TYRAMINE OXIDASE; IRREVERSIBLE INHIBITORS; MECHANISM; ADDUCT; RING AB A series of para-ring-substituted (E)- and (Z)-1-aryl-2-fluorocyclopropylamines were examined as inhibitors of recombinant human liver monoamine oxidase A (MAO A) and B (MAO B). Unlike the parent 1-phenylcyclopropylamine, which is a selective inhibitor of MAO B, both (E)- and (Z)-diastereomers of derivatives having fluorine at the 2-position of the cyclopropane ring were potent and selective irreversible inhibitors of MAO A. Both electron releasing groups (Me, OMe) and electron attracting groups (Cl, F) substituted in the para-position caused a modest increase in activity. Geminal difluoro-substitution caused a loss of potency of 100-fold compared to either (E)- or (Z)-monofluorinated analogue. Surprisingly, (1S,2R)-2-fluoro-l-phenylcyclopropylamine and the (1R,2S)-enantiomer were essential equally potent as inhibitors of MAO A and MAO B. None of the tested 1-aryl-2-fluorocyclopropylamines exhibited significant inhibition of tyramine oxidase. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Ind Res Inst Tottori Prefecture, Tottori 6891112, Japan. Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov NR 15 TC 16 Z9 16 U1 0 U2 5 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 APR 1 PY 2005 VL 13 IS 7 BP 2489 EP 2499 DI 10.1016/j.bmc.2005.01.043 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 909WI UT WOS:000227891000015 PM 15755651 ER PT J AU Monine, MI Berezhkovskii, AM Joslin, EJ Wiley, HS Lauffenburger, DA Shvartsman, SY AF Monine, MI Berezhkovskii, AM Joslin, EJ Wiley, HS Lauffenburger, DA Shvartsman, SY TI Ligand accumulation in autocrine cell cultures SO BIOPHYSICAL JOURNAL LA English DT Article ID GROWTH-FACTOR RECEPTOR; QUANTITATIVE-ANALYSIS; SPATIAL RANGE; HER2 LEVELS; BINDING; SYSTEM; MECHANISMS; RELEASE; DECOYS; MODEL AB Cell-culture assays are routinely used to analyze autocrine signaling systems, but quantitative experiments are rarely possible. To enable the quantitative design and analysis of experiments with autocrine cells, we develop a biophysical theory of ligand accumulation in cell-culture assays. Our theory predicts the ligand concentration as a function of time and measurable parameters of autocrine cells and cell-culture experiments. The key step of our analysis is the derivation of the survival probability of a single ligand released from the surface of an autocrine cell. An expression for this probability is derived using the boundary homogenization approach and tested by stochastic simulations. We use this expression in the integral balance equations, from which we find the Laplace transform of the ligand concentration. We demonstrate how the theory works by analyzing the autocrine epidermal growth factor receptor system and discuss the extension of our methods to other experiments with cultured autocrine cells. C1 Princeton Univ, Lewis Sigler Inst Integrat Genom, Carl Icahn Lab, Princeton, NJ 08544 USA. Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. NIH, Math & Stat Comp Lab, Div Computat Biol, Ctr Informat Technol, Bethesda, MD 20892 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Pacific NW Natl Lab, Div Biol Sci, Richland, WA USA. RP Monine, MI (reprint author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Carl Icahn Lab, Washington Rd, Princeton, NJ 08544 USA. EM stas@princeton.edu OI Wiley, Steven/0000-0003-0232-6867 NR 23 TC 32 Z9 32 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2005 VL 88 IS 4 BP 2384 EP 2390 DI 10.1529/biophysj.104.051425 PG 7 WC Biophysics SC Biophysics GA 911EV UT WOS:000227986300002 PM 15653719 ER PT J AU Kucerka, N Liu, YF Chu, NJ Petrache, HI Tristram-Nagle, ST Nagle, JF AF Kucerka, N Liu, YF Chu, NJ Petrache, HI Tristram-Nagle, ST Nagle, JF TI Structure of fully hydrated fluid phase DMPC and DLPC lipid bilayers using X-ray scattering from oriented multilamellar arrays and from unilamellar vesicles SO BIOPHYSICAL JOURNAL LA English DT Article ID ANGLE NEUTRON-SCATTERING; GEL PHASE; LECITHIN BILAYERS; COMPONENT VOLUMES; DIFFRACTION; LIPOSOMES; THICKNESS; DENSITY; LENGTH; AREA AB Quantitative structures of the fully hydrated fluid phases of dimyristoylphosphatidylcholine ( DMPC) and dilauroylphosphatidylcholine ( DLPC) were obtained at 30 degrees C. Data for the relative form factors F(q(z)) for DMPC were obtained using a combination of four methods. 1), Volumetric data provided F(0). 2), Diffuse x-ray scattering from oriented stacks of bilayers provided relative form factors vertical bar F(q(z))vertical bar for high q(z), 0.22 < q(z) < 0.8 angstrom(-1). 3), X-ray scattering from extruded unilamellar vesicles with diameter 600 angstrom provided vertical bar F(p(z))vertical bar for low q(z), 0.1 < q(z) < 0.3 angstrom(-1). 4), Previous measurements using a liquid crystallographic x-ray method provided vertical bar F(2 pi h/D)vertical bar for h = 1 and 2 for a range of nearly fully hydrated D-spacings. The data from method 4 overlap and validate the new unilamellar vesicles data for DMPC, so method 4 is not required for DLPC or future studies. We used hybrid electron density models to obtain structural results from these form factors. Comparison of the model electron density profiles with that of gel phase DMPC provides areas per lipid A, 60.6 +/- 0.5 angstrom(2) for DMPC and 63.2 +/- 0.5 angstrom(2) for DLPC. Constraints on the model provided by volume measurements and component volumes obtained from simulations put the electron density profiles rho(z) and the corresponding form factors F(q(z)) on absolute scales. Various thicknesses, such as the hydrophobic thickness and the steric thickness, are obtained and compared to literature values. C1 Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Sci Biol, Pittsburgh, PA 15213 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Nagle, JF (reprint author), Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. EM nagle@andrew.cmu.edu RI Tristram-Nagle, Prof. Stephanie/N-7811-2014; Nagle, John/B-1917-2015 OI Tristram-Nagle, Prof. Stephanie/0000-0003-2271-7056; Nagle, John/0000-0002-9844-5934 FU NIGMS NIH HHS [GM44976, R01 GM044976] NR 38 TC 310 Z9 315 U1 4 U2 98 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2005 VL 88 IS 4 BP 2626 EP 2637 DI 10.1529/biophysj.104.056606 PG 12 WC Biophysics SC Biophysics GA 911EV UT WOS:000227986300023 PM 15665131 ER PT J AU Gail, MH Pfeiffer, RM AF Gail, MH Pfeiffer, RM TI On criteria for evaluating models of absolute risks SO BIOSTATISTICS LA English DT Article DE absolute risk model; accuracy; loss functions for clinical decisions; negative predictive value; positive predictive value; ROC curve ID BREAST-CANCER; LOGISTIC-REGRESSION; RESIDUAL VARIATION; TAMOXIFEN; CHEMOPREVENTION; PREVENTION; STATISTICS; PREDICTION; VALIDATION; DISPERSION AB Absolute risk is the probability that an individual who is free of a given disease at an initial age, a, will develop that disease in the subsequent interval (a, t]. Absolute risk is reduced by mortality from competing risks. Models of absolute risk that depend on covariates have been used to design intervention studies, to counsel patients regarding their risks of disease and to inform clinical decisions, such as whether or not to take tamoxifen to prevent breast cancer. Several general criteria have been used to evaluate models of absolute risk, including how well the model predicts the observed numbers of events in subsets of the population ('calibration'), and 'discriminatory power,' measured by the concordance statistic. In this paper we review some general criteria and develop specific loss function-based criteria for two applications, namely whether or not to screen a population to select subjects for further evaluation or treatment and whether or not to use a preventive intervention that has both beneficial and adverse effects. We find that high discriminatory power is much more crucial in the screening application than in the preventive intervention application. These examples indicate that the usefulness of a general criterion such as concordance depends on the application, and that using specific loss functions can lead to more appropriate assessments. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Execut Plaza S,EPS 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 28 TC 128 Z9 130 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2005 VL 6 IS 2 BP 227 EP 239 DI 10.1093/biostatistics/kxi005 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 917AM UT WOS:000228428200005 PM 15772102 ER PT J AU Araujo, RP Petricoin, EF Liotta, LA AF Araujo, RP Petricoin, EF Liotta, LA TI A mathematical model of combination therapy using the EGFR signaling network SO BIOSYSTEMS LA English DT Article DE cancer treatment; combination therapy; EGFR network; signal transduction; kinase inhibitors ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; PROTEIN-KINASE-A; TYROSINE KINASE; INHIBITORS; CHEMOTHERAPY; RADIATION; ZD1839 AB An increasing awareness of the significance of abnormal signal transduction in tumors and the concomitant development of target-based drugs to selectively modulate aberrantly-activated signaling pathways has given rise to a variety of promising new strategies in cancer treatment. This paper uses mathematical modeling to investigate a novel type of combination therapy in which multiple nodes in a signaling cascade are targeted simultaneously with selective inhibitors, pursuing the hypothesis that such an approach may induce the desired signal attenuation with lower doses of the necessary agents than when one node is targeted in isolation. A mathematical model is presented which builds upon previous theoretical work on EGFR signaling, simulating the effect of administering multiple kinase inhibitors in various combinations. The model demonstrates that attenuation of biochemical signals is significantly enhanced when multiple upstream processes are inhibited, in comparison with the inhibition of a single upstream process. Moreover, this enhanced attenuation is most pronounced in signals downstream of serially-connected target points. In addition, the inhibition of serially-connected processes appears to have a supra-additive (synergistic) effect on the attenuation of downstream signals, owing to the highly non-linear relationships between network parameters and signals. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NCI, FDA, Clin Proteom Program, Lab Pathol,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. US FDA, NCI, Clin Proteom Program, Off Cell & Gene Therapies,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Araujo, RP (reprint author), NCI, FDA, Clin Proteom Program, Lab Pathol,Ctr Canc Res,NIH, 8800 Rockville Pike,Bldg 29A,HFM 710, Bethesda, MD 20892 USA. EM araujor@mail.nih.gov NR 17 TC 58 Z9 61 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0303-2647 J9 BIOSYSTEMS JI Biosystems PD APR PY 2005 VL 80 IS 1 BP 57 EP 69 DI 10.1016/j.biosystems.2004.10.002 PG 13 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 908TF UT WOS:000227812400006 PM 15740835 ER PT J AU Rich, BA Vinton, D Grillon, C Bhangoo, RK Leibenluft, E AF Rich, BA Vinton, D Grillon, C Bhangoo, RK Leibenluft, E TI An investigation of prepulse inhibition in pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; children; prepulse inhibition; psychosis; sensorimotor gating; startle ID STARTLE REFLEX; SCHIZOPHRENIC-PATIENTS; ACOUSTIC STARTLE; ATYPICAL ANTIPSYCHOTICS; GATING DEFICITS; ANIMAL-MODEL; MODULATION; MANIA; PATHOPHYSIOLOGY; RELIABILITY AB Objectives: Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, have been noted in psychopathologies including schizophrenia and adult bipolar disorder (BPD). Sensorimotor gating deficits may contribute to the emotional and behavioral dysregulation characteristic of pediatric BPD. The current study investigated possible PPI deficits in children with BPD. Methods: Sixteen children with BPD (medicated, euthymic and non-psychotic) were compared with 13 control subjects on the magnitude of startle habituation, startle-alone response, and inhibition of startle following a 60 or 120-ms prepulse. Results: Both groups displayed startle inhibition by a prepulse, with no significant between-group differences on the magnitude of inhibition after the 60- or 120-ms prepulse. In addition, there were no between-group differences on habituation or baseline startle response. PPI level was not significantly correlated with mood symptoms and did not differ based on comorbid attention deficit hyperactivity disorder. Conclusions: A lack of PPI deficits in our pediatric bipolar sample contrasts with previous results in adult bipolar and schizophrenic samples. These negative results may reflect the fact that our sample was medicated and was neither acutely manic nor psychotic. Deficits in sensorimotor gating may not be implicated in the emotional and behavioral dysregulation in pediatric BPD. C1 NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Dept Hlth & Human Serv, Unit Affect Psychophysiol, Mood & Anxiety Program,NIH, Bethesda, MD 20892 USA. RP Rich, BA (reprint author), 10 Ctr Dr MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM brendanrich@mail.nih.gov NR 41 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2005 VL 7 IS 2 BP 198 EP 203 DI 10.1111/j.1399-5618.2005.00183.x PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 905SG UT WOS:000227589400013 PM 15762862 ER PT J AU Warren, KR Li, TK AF Warren, KR Li, TK TI Genetic polymorphisms: Impact on the risk of fetal alcohol spectrum disorders SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Teratology-Society CY JUN, 2004 CL Vancouver, CANADA SP Teratol Soc DE alcohol; teratogenesis; fetal alcohol syndrome; fetal alcohol spectrum disorders; alcohol dehydrogenase; ADH; polymorphisms ID INFANT-DEATH-SYNDROME; SEROTONIN TRANSPORTER GENE; WESTERN-CAPE PROVINCE; BIRTH-DEFECTS; PRENATAL ALCOHOL; DIZYGOTIC TWINS; SENSITIVE RATS; SOUTH-AFRICA; EXPOSURE; POPULATION AB Clinical reports on monozygotic and dizygotic twins provided the initial evidence for the involvement of genetic factors in risk vulnerability for fetal alcohol spectrum disorders (FASD) including fetal alcohol syndrome (FAS). Research with selectively bred and inbred rodents, genetic crosses of these lines and strains, and embryo culture studies have further clarified the role of both maternal and fetal genetics in the development of FASD. Research to identify specific polymorphisms contributing to FASD is still at an early stage. To date, polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to FASD vulnerability. In comparison with ADH1B*1, both maternal and fetal ADH1B*2 have been shown to reduce risk for FAS in a mixed ancestry South African population. ADH1B*3 appears to afford protection for FASD outcomes in African-American populations. Other candidate genes should be examined with respect to FASD risk, including those for the enzymes of serotonin metabolism, in particular the serotonin transporter. By its very nature, alcohol teratogenesis is the expression of the interaction of genes with environment. The study of genetic factors in FASD falls within the new field of ecogenetics. Understanding of the array of genetic factors in FASD will be enhanced by future genetic investigations, including case-control, family association, and linkage studies. Birth Defects Research (Part A) 73:195-203, 2005. Published 2005 Wiley-Liss, Inc(dagger). C1 NIAAA, Off Sci Affairs, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIAAA, Off Director, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Warren, KR (reprint author), NIAAA, Off Sci Affairs, NIH, US Dept HHS, 5635 Fishers Lane MSC 9304,Suite 2005, Bethesda, MD 20892 USA. EM kw46m@nih.gov NR 52 TC 80 Z9 81 U1 2 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD APR PY 2005 VL 73 IS 4 BP 195 EP 203 DI 10.1002/bdra.20125 PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 920OC UT WOS:000228699000001 PM 15786496 ER PT J AU Swanson, DA Pangilinan, F Mills, JL Kirke, PN Conley, M Weiler, A Frey, T Parle-McDermott, A O'Leary, VB Seltzer, RR Moynihan, KA Molloy, AM Burke, H Scott, JM Brody, LC AF Swanson, DA Pangilinan, F Mills, JL Kirke, PN Conley, M Weiler, A Frey, T Parle-McDermott, A O'Leary, VB Seltzer, RR Moynihan, KA Molloy, AM Burke, H Scott, JM Brody, LC TI Evaluation of transcobalamin II polymorphisms as neural tube defect risk factors in an Irish population SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE folate; neural tube defects; spina bifida; transcobalamin II gene; vitamin B-12 ID 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; AMNIOTIC-FLUID; SPINA-BIFIDA; METHYLENETETRAHYDROFOLATE REDUCTASE; VITAMIN SUPPLEMENTATION; LINKAGE DISEQUILIBRIUM; FOLATE LEVELS; GENE; PREVENTION; HOMOCYSTEINE AB BACKGROUND: Decreased maternal folate levels are associated with having a child with a neural tube defect (NTD), and periconceptual folic acid supplementation reduces this risk by >50%. Vitamin B-12 (as methylcobalamin) is a cofactor for methionine synthase, an enzyme that plays a key role in folate metabolism. Alterations in vitamin B12 metabolism may influence the development of NTDs. Low levels of maternal plasma vitamin B12 and reduced binding of vitamin B12 by transcobalamin II (TCII) are independent risk factors for NTDs. TCII levels are altered in the amniotic fluid of pregnancies affected by NTDs. Given this evidence, inherited variants in genes involved in vitamin B12 trafficking such as TCII are candidate NTD risk factors. METHODS: We used case/control and family-based association methods to investigate whether six common polymorphisms in the TCII gene influence NTD risk. TCII genotypes were determined for more than 300 Irish NTD families and a comparable number of Irish controls. RESULTS: Allele and genotype frequencies for each polymorphism did not differ between family members and controls. CONCLUSIONS: These six TCII polymorphisms do not strongly influence NTD risk in the Irish population. The Supplementary Material for this article can be found on the Birth Defects Research (Part A) website http://www.lnrw.interscience.wiley.com/suppmat/15420752/suppmat/2005/73/v73.4.html Birth Defects Research (Part A) 73:239-244, 2005. Published 2005 Wiley-Liss, Inc(dagger). C1 NHGRI, Genome Technol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. RP Brody, LC (reprint author), NHGRI, Genome Technol Branch, Dept Hlth & Human Serv, NIH, Bldg 50,Room 5306,50 S Dr,MSC 8004, Bethesda, MD 20892 USA. EM lbrody@helix.nih.gov OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830 NR 40 TC 24 Z9 25 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD APR PY 2005 VL 73 IS 4 BP 239 EP 244 DI 10.1002/bdra.20122 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 920OC UT WOS:000228699000005 PM 15782407 ER PT J AU Grajewski, B Coble, JB Frazier, LM McDiarmid, MA AF Grajewski, B Coble, JB Frazier, LM McDiarmid, MA TI Occupational exposures and reproductive health: 2003 Teratology Society Meeting Symposium Summary SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE National Institute for Occupational Safety and Health (US); reproductive medicine; occupational exposure; occupational medicine; interdisciplinary communication; health education; exposure assessment ID ETHYLENE-GLYCOL ETHERS; SAFETY DATA SHEETS; LEAD; EPIDEMIOLOGY; INFORMATION; POPULATION; TERATOGENS; CHILDREN; BLOOD; BONE AB Assuring reproductive health in the workplace challenges researchers, occupational safety and health practitioners, and clinicians. Most chemicals in the workplace have not been evaluated for reproductive toxicity. Although occupational exposure limits are established to protect 'nearly all' workers, there is little research that characterizes reproductive hazards. For researchers, improvements in epidemiologic design and exposure assessment methods are needed to conduct adequate reproductive studies. Occupational safety and health programs' qualitative and quantitative evaluations of the workplace for reproductive hazards may differ from standardized approaches used for other occupational hazards in that estimates of exposure intensity must be considered in the context of the time-dependent windows of reproductive susceptibility. Clinicians and counselors should place the risk estimate into context by emphasizing the limitations of the available knowledge and the qualitative nature of the exposure estimates, as well as what is known about other non-occupational risk factors for adverse outcomes. This will allow informed decision-making about the need for added protections or alternative duty assignment when a hazard cannot be eliminated. These policies should preserve a worker's income, benefits, and seniority. Applying hazard control technologies and hazard communication training can minimize a worker's risk. Chemical reproductive hazard training is required for workers by the Occupational Safety and Health Administration's Hazard Communication Standard. The National Institute for Occupational Safety and Health (NIOSH) has formed a National Occupational Research Agenda Team to promote communication and partnering among reproductive toxicologists, clinicians and epidemiologists, to improve reproductive hazard exposure assessment and management, and to encourage needed research. Published 2005 Wiley-Liss, Inc. C1 NIOSH, Cincinnati, OH 45226 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Univ Kansas, Sch Med, Dept Prevent Med & Publ Hlth, Wichita, KS 67214 USA. Univ Maryland, Occupat Hlth Project, Baltimore, MD 21201 USA. RP Grajewski, B (reprint author), NIOSH, 4676 Columbia Pkwy,R-15, Cincinnati, OH 45226 USA. EM BAG2@CDC.GOV NR 40 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD APR PY 2005 VL 74 IS 2 BP 157 EP 163 DI 10.1002/bdrb.20039 PG 7 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 921XN UT WOS:000228799200003 PM 15834899 ER PT J AU Wang, T Ward, Y Tian, LH Lake, R Guedez, L Stetler-Stevenson, WG Kelly, K AF Wang, T Ward, Y Tian, LH Lake, R Guedez, L Stetler-Stevenson, WG Kelly, K TI CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells SO BLOOD LA English DT Article ID LIGAND CD55; EGF-TM7 RECEPTOR; CELLULAR LIGAND; MOUSE CD97; GPS MOTIF; IN-VIVO; FIBRONECTIN; GROWTH; EXPRESSION; ALPHA(5)BETA(1) AB CD97, a membrane protein expressed at high levels on inflammatory cells and some carcinomas, is a member of the adhesion G protein-coupled receptor family, whose members have bipartite structures consisting of an extracellular peptide containing adhesion motifs noncovalently coupled to a class B 7-transmembrane domain. CD97 alpha, the extracellular domain of CD97, contains 3 to 5 fibrillin class 1 epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) tripeptide, and a mucin stalk. We show here that CD97a promotes angiogenesis in vivo as demonstrated with purified protein in a directed in vivo angiogenesis assay (DIVAA) and by enhanced vascularization of developing tumors expressing CD97. These data suggest that CD97 can contribute to angiogenesis associated with inflammation and tumor progression. Strong integrin alpha 5 beta 1 interactions with CD97 have been identified, but alpha v beta 3 also contributes to cell attachment. Furthermore, soluble CD97 acts as a potent chemoattractant for migration and invasion of human umbilical vein endothelial cells (HUVECs), and this function is integrin dependent. CD97 EGF-like repeat 4 is known to bind chondroitin sulfate. It was found that coengagement of alpha 6 beta 1 and chondroitotin sulfate proteoglycan by CD97 synergistically initiates endothelial cell invasion. Integrin alpha 5 beta 1 is the first high-affinity cellular counterreceptor that has been identified for a member within this family of adhesion receptors. C1 Ctr Canc Res, Cell & Canc Biol Brach, NIH, Bethesda, MD 20892 USA. RP Kelly, K (reprint author), Ctr Canc Res, Cell & Canc Biol Brach, NIH, Bldg 10,Rm 3B-43, Bethesda, MD 20892 USA. EM kkelly@helix.nih.gov RI Stetler-Stevenson, William/H-6956-2012; Guedez, Liliana/H-4951-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808; NR 43 TC 75 Z9 79 U1 0 U2 13 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2836 EP 2844 DI 10.1182/blood-2004-07-2878 PG 9 WC Hematology SC Hematology GA 911YM UT WOS:000228042900040 PM 15576472 ER PT J AU Lutsiak, MEC Semnani, RT De Pascalis, R Kashmiri, SVS Schlom, J Sabzevari, H AF Lutsiak, MEC Semnani, RT De Pascalis, R Kashmiri, SVS Schlom, J Sabzevari, H TI Inhibition of CD4(+)25(+) T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide SO BLOOD LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; AUTOIMMUNE-DISEASES; TUMOR-IMMUNITY; RECEPTOR; MOUSE; MICE; TRANSPLANTATION; IDENTIFICATION; IMMUNOTHERAPY; HOMEOSTASIS AB Regulatory T cells (T-REGs) control the key aspects of tolerance and play a role in the lack of antitumor immune responses. Cyclophosphamide (CY) is a chemotherapeutic agent with a dose-dependent, bimodal effect on the immune system. Although a previous study demonstrated that CY reduces the number of T-REGs, the mechanism involved in this process has yet to be defined. In this report, it is established that low-dose CY not only decreases cell number but leads to decreased functionality of TREGS-CY treatment enhances apoptosis and decreases homeostatic proliferation of these cells. Expression of GITR and FoxP3, which are involved in the suppressive activity of T-REGs, is down-regulated after CY administration, though the level of expression varies depending on the time studied. This is the first report demonstrating that CY, in addition to decreasing cell number, inhibits the suppressive capability of T-REGS. The relevance of the loss of suppressor functionality and the changes in gene expression are further discussed. C1 Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bldg 10,Rm 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 36 TC 481 Z9 517 U1 1 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2862 EP 2868 DI 10.1182/blood-2004-06-2410 PG 7 WC Hematology SC Hematology GA 911YM UT WOS:000228042900043 PM 15591121 ER PT J AU Ho, L Davis, RE Conne, B Chappuis, R Berczy, M Mhawech, P Staudt, LM Schwaller, J AF Ho, L Davis, RE Conne, B Chappuis, R Berczy, M Mhawech, P Staudt, LM Schwaller, J TI MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells SO BLOOD LA English DT Article; Proceedings Paper CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol ID TISSUE-TYPE LYMPHOMAS; CHROMOSOMAL TRANSLOCATION; LYMPHOCYTE DEVELOPMENT; SIGNALING PATHWAY; GERMINAL-CENTERS; LIPID RAFTS; T-CELL; ACTIVATION; BCL10; PROTEIN AB The most frequently recurring translocations in mucosa-associated lymphold tissue (MALT) B-cell non-Hodgkin lymphoma, t(11;18)(q21;q21) and t(14;18)(q32; q21), lead to formation of an API2-MALT1 fusion or IgH-mediated MALT1 overexpression. Various approaches have implicated these proteins in nuclear factor kappa B (NF-kappa B) signaling, but this has not been shown experimentally in human B cells. Immunohistochemistry showed that MALT1 is predominantly expressed in normal and malignant germinal center B cells, corresponding to the differentiation stage of MALT lymphoma. We expressed MALT1 and apoptosis inhibitor-2 API2/MALT1 in human B-cell lymphoma BJAB cells and found both transgenes in membrane lipid rafts along with endogenous MALT1 and 2 binding partners involved in NF-kappa B signaling, B-cell lymphoma 10 (BCL10) and CARMA1 (caspase recruitment domain [CARD]-containing membrane-associated guanylate kinase [MAGUK] 1). API2-MALT1 and exogenous MALT1 increased constitutive NF-kappa B activity and enhanced I kappa B kinase (IKK) activation induced by CD40 stimulation. Both transgenes protected BJAB cells from FAS (CD95)-induced death, consistent with increasesin NF-kappa B cytoprotective target gene expression, and increased their proliferation rate. Expression of a dominant-negative I kappa B alpha mutant showed that these survival and proliferative advantages are dependent on elevated constitutive NF-kappa B activity. Our findings support a model in which NF-kappa B signaling, once activated in a CD40-dependent immune response, is maintained and enhanced through deregulation of MALT1 or formation of an API2-MALT1 fusion. C1 Univ Hosp Geneva, Dept Clin Pathol, CMU, Geneva, Switzerland. Ctr Canc Res, Metab Branch, NCI, Bethesda, MD USA. RP Schwaller, J (reprint author), Univ Basel Hosp, Dept Res, Hebelstr 20, CH-4031 Basel, Switzerland. EM J.Schwaller@unibas.ch RI schwaller, juerg/A-3044-2016 NR 63 TC 48 Z9 53 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2891 EP 2899 DI 10.1182/blood-2004-06-2297 PG 9 WC Hematology SC Hematology GA 911YM UT WOS:000228042900047 PM 15598810 ER PT J AU Hopwood, B Gronthos, S Kuliwaba, JS Robey, PG Findlay, DM Fazzalari, NL AF Hopwood, B Gronthos, S Kuliwaba, JS Robey, PG Findlay, DM Fazzalari, NL TI Identification of differentially expressed genes between osteoarthritic and normal trabecular bone from the intertrochanteric region of the proximal femur using cDNA microarray analysis SO BONE LA English DT Article DE osteoarthritis; cDNA microarray; proximal femur; trabecular bone ID ENDOTHELIAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA; OSTEOCLAST DIFFERENTIATION; SIGNALING PATHWAYS; RECEPTOR ACTIVATOR; DNA MICROARRAYS; CANCELLOUS BONE; ILIAC CREST AB Osteoarthritis (OA) is a common age-related joint disease resulting in progressive degenerative damage to articular cartilage. The etiology of primary OA has not yet been determined. However, there is evidence supporting the hypothesis that primary OA is a disease affecting bone remodeling in addition to articular cartilage. In this study, we have used cDNA microarray analysis to compare gene expression in bone between normal (CTL) and OA individuals. Trabecular bone was sampled from the intertrochanteric region of the proximal femur, a site distal to the diseased hip joint. Total RNA was extracted from three pairs of age- and sex-matched CTL and OA bone samples, reverse-transcribed and radioactively labeled to generate cDNA probes, before hybridization with the Research Genetics GF211 human gene microarray filter. The CTL and OA samples were found to have similar levels of gene expression for more than 4000 known human genes. However, forty-one genes were identified that were differentially expressed, twofold or more, between all three CTL-OA sample pairs. Using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, three genes, fins-like tyrosine kinase 1(FLT1), plexin B1 (PLXNB1), and small inducible cytokine A2 (SCYA2), were confirmed to be consistently expressed at lower levels in OA, in a majority of twenty age- and sex-matched CTL-OA bone sample pairs tested. FLT1, PLXNB1, and SCYA2 have known or potential roles in angiogenesis and bone remodeling. Down-regulation of these genes is consistent with a role for bone in the pathogenesis of OA. © 2005 Elsevier Inc. All rights reserved. C1 Inst Med & Vet Sci, Div Tissue Pathol, Bone & Joint Res Lab, Adelaide, SA 5000, Australia. Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Lab, Adelaide, SA 5000, Australia. Univ Adelaide, Dept Pathol, Adelaide, SA 5005, Australia. Univ Adelaide, Dept Orthopaed & Trauma, Adelaide, SA 5005, Australia. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Hanson Inst, Adelaide, SA, Australia. RP Fazzalari, NL (reprint author), Inst Med & Vet Sci, Div Tissue Pathol, Bone & Joint Res Lab, Frome Rd, Adelaide, SA 5000, Australia. EM nick.fazzalari@imvs.sa.gov.au RI hopwood, Blair/B-7485-2012; Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 60 TC 14 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2005 VL 36 IS 4 BP 635 EP 644 DI 10.1016/j.bone.2005.02.003 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 924NX UT WOS:000228986600006 PM 15781004 ER PT J AU Zhou, QY Sparreboom, A Tan, EH Cheung, YB Lee, A Poon, D Lee, EJD Chowbay, B AF Zhou, QY Sparreboom, A Tan, EH Cheung, YB Lee, A Poon, D Lee, EJD Chowbay, B TI Pharmacogenetic profiling across the irinotecan pathway in Asian patients with cancer SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE ABC transporters; drug metabolizing enzymes; single nucleotide polymorphisms ID CAMPTOTHECIN DERIVATIVE IRINOTECAN; SINGLE NUCLEOTIDE POLYMORPHISMS; ACTIVE METABOLITE SN-38; UDP-GLUCURONOSYLTRANSFERASE; CLINICAL PHARMACOKINETICS; FUNCTIONAL POLYMORPHISMS; GENETIC POLYMORPHISMS; LUNG-CANCER; PHASE-I; CPT-11 AB Aims The aim of this exploratory study was to investigate associations between irinotecan pharmacokinetic parameters and allelic variants in genes encoding for drug transporters and drug metabolizing enzymes that are involved in irinotecan disposition in Asian patients with cancer. Methods Irinotecan was administered at 100 mg m(-2) over 90 min on a weekly schedule to 29 nasopharyngeal carcinoma patients and pharmacokinetic analysis was performed during the first cycle. All patients were genotyped for allelic variants in genes encoding drug metabolizing enzymes (CYP3A4, CYP3A5, UGT1A1) and drug transporters (ABCB1, ABCC2 and ABCG2) that are involved in irinotecan disposition. Results Of the six candidate genes that were analyzed, 11 genetic variants were found. Significant genotypic-phenotypic associations were apparent only for transporter genes. The C-max of irinotecan was significantly lower in patients carrying the CC genotype at exon 26 of the ABCB1 gene compared with those harbouring at least one variant allele (P = 0.047). Patients harbouring the wild type ABCG2 CTCA genotype were associated with significantly higher values for relative extent of conversion (REC) of irinotecan to SN-38 compared with patients carrying at least one deletion CTCA allele (P = 0.019). Conclusions The present exploratory study shows that genetic polymorphisms in drug transporter genes, particularly in ABCB1 and ABCG2 genes, may be important in influencing the pharmacokinetics of irinotecan and its metabolites. The predictive value of the identified allelic variants in the ABCG2 and ABCB1 genes on irinotecan disposition should be further investigated in a larger patient population as well as in other ethnic populations. C1 Natl Canc Ctr, Div Clin Trials & Epidemiol Sci, Lab Clin Pharmacol, Singapore 169610, Singapore. NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Natl Canc Ctr, Dept Med Oncol, Singapore 169610, Singapore. Natl Canc Ctr, Div Med Sci, Mol Oncol Lab, Singapore 169610, Singapore. Natl Univ Singapore, Fac Med, Dept Pharmacol, Singapore 117548, Singapore. RP Chowbay, B (reprint author), Natl Canc Ctr, Div Clin Trials & Epidemiol Sci, Lab Clin Pharmacol, 11 Hosp Dr, Singapore 169610, Singapore. EM ctebal@nccs.com.sg RI Sparreboom, Alex/B-3247-2008 NR 35 TC 62 Z9 66 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD APR PY 2005 VL 59 IS 4 BP 415 EP 424 DI 10.1111/j.1365-2125.2005.02330.x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 910YV UT WOS:000227969000007 PM 15801936 ER PT J AU Talar-Williams, C Sneller, MC Langford, CA Smith, JA Cox, TA Robinson, MR AF Talar-Williams, C Sneller, MC Langford, CA Smith, JA Cox, TA Robinson, MR TI Orbital socket contracture: a complication of inflammatory orbital disease in patients with Wegener's granulomatosis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTIC NEUROPATHY; MANIFESTATIONS; OBSTRUCTION; MANAGEMENT; HEAD AB Aim: To describe the clinical characteristics of orbital socket contracture in patients with Wegener's granulomatosis (WG). Methods: A retrospective cohort study The medical records of 256 patients with WG examined at the National Institutes of Health from 1967 to 2004 were reviewed to identify patients with orbital socket contracture. Details of the orbital disease including Hertel exophthalmometry readings, radiological findings, and results of eye examinations were recorded. Orbital socket contracture was defined as orbital inflammation with proptosis followed by the development of enophthalmos and radiographic evidence of residual fibrotic changes in the orbit. To examine for risk factors in the development of a contracted orbit, patients with orbital socket contracture were compared to patients without contracture with respect to multiple variables including history of orbital surgery, orbital disease severity, and major organ system involvement. The main outcome measures were the clinical characteristics of orbital socket contracture associated with inflammatory orbital disease in patients with WG. Results: Inflammatory orbital disease occurred in 34 of 256 (13%) patients and detailed clinical data on 18 patients were available and examined. Orbital socket contracture occurred during the clinical course in six patients; the features included restrictive ophthalmopathy (five), chronic orbital pain (three), and ischaemic optic nerve disease ( two) resulting in blindness (no light perception) in one patient. The orbital socket contracture occurred within 3 months of treatment with immunosuppressive medications for inflammatory orbital disease in five patients and was not responsive to immunosuppressive medications. The median degree of enophthalmos in the contracted orbit compared with the fellow eye was 2.8 mm (range 1.5-3.5 mm) by Hertel exophthalmometry. There were no risk factors that predicted development of orbital socket contracture. Conclusions: In six patients with WG and active inflammatory orbital disease, orbital socket contracture occurred during the treatment course with systemic immunosuppressive medications. The orbital socket contracture, presumably caused by orbital fibrosis, led to enophthalmos, restrictive ophthalmopathy, chronic orbital pain, and optic nerve disease and was not responsive to immunosuppressive therapy. Orbital socket contracture has not been previously reported as a complication of inflammatory orbital disease associated with WG and was an important cause of visual morbidity in our cohort of patients. C1 NIAID, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Talar-Williams, C (reprint author), NIAID, NIH, Room 11B13,10 Ctr Dr MSC 1863, Bethesda, MD 20892 USA. EM ctwilliams@niaid.nih.gov NR 21 TC 29 Z9 30 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD APR PY 2005 VL 89 IS 4 BP 493 EP 497 DI 10.1136/bjo.2004.050039 PG 5 WC Ophthalmology SC Ophthalmology GA 907JU UT WOS:000227713800023 PM 15774931 ER PT J AU Smith, FM Stephens, RB Petricoin, EF Liotta, LA Kennedy, MJ Reynolds, JV AF Smith, FM Stephens, RB Petricoin, EF Liotta, LA Kennedy, MJ Reynolds, JV TI Exploring the proteome as a response predictor for rectal cancer undergoing neoadjuvant radiochemotherapy SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT Annual Meeting of the Association-of-Surgeons-of-Great-Britian-and-Ireland CY APR 13-15, 2005 CL Glasgow, SCOTLAND SP Assoc Surg Great Britian & Ireland C1 St James Hosp, Dept Surg, Dublin, Ireland. St James Hosp, Acad Unit Clin & Mol Oncol, Dublin, Ireland. Trinity Coll Dublin, Dublin, Ireland. NCI, FDA NCI Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD APR PY 2005 VL 92 SU 1 BP 152 EP 152 PG 1 WC Surgery SC Surgery GA 922MY UT WOS:000228843200314 ER PT J AU Wood, CM Walsh, PJ Chew, SF Ip, YK AF Wood, CM Walsh, PJ Chew, SF Ip, YK TI Ammonia tolerance in the slender lungfish (Protopterus dolloi): the importance of environmental acidification SO CANADIAN JOURNAL OF ZOOLOGY-REVUE CANADIENNE DE ZOOLOGIE LA English DT Article ID LAKE MAGADI TILAPIA; MUDSKIPPER PERIOPHTHALMODON-SCHLOSSERI; PULSATILE UREA EXCRETION; TOADFISH OPSANUS-BETA; AFRICAN LUNGFISH; RAINBOW-TROUT; GULF TOADFISH; MOLECULAR CHARACTERIZATION; ALKALINE ENVIRONMENT; BOUNDARY-LAYER AB Protopterus dolloi Boulenger, 1900 is an obligate air-breather and exhibits ammoniotely (88% ammonia-N excretion, 12% urea-N excretion) under normal aquatic conditions, but tolerates 7 days of exposure to 30 mmol.L-1 NH4Cl, a treatment fatal to most other fish. Internal N accumulation is minimal and the subsequent washout of ammonia-N and urea-N after return to control conditions is negligible, indicating that N excretion continues and (or) that N metabolism is markedly depressed. Exposure to 30 mmol.L-1 NH4Cl in a closed system without aeration results in depressed urea-N excretion. The lungfish greatly acid/fies the external water, a volume 25-fold greater than its own volume. The extent of this acidification increases with time. After several days, the external pH falls from about 7.0 to below 5.0 over a 24-h period, thereby markedly reducing the concentration of NH3 (the form that diffuses across biological membranes). CO2 excretion is partially responsible for this acidification, because vigorous water aeration reduces but does not eliminate the acidification, and urea-N excretion increases moderately. However, a substantial excretion of titratable acid (non-CO2 acidity) also occurs. One exceptional lungfish was able to maintain its aerated environment at a stable pH of 3.7. Environmental acidification may be a less costly strategy for avoiding toxicity than detoxifying ammonia by increasing urea production. C1 McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Nanyang Technol Univ, Natl Inst Educ, Singapore 637616, Singapore. Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. RP Wood, CM (reprint author), McMaster Univ, Dept Biol, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM woodcm@mcmaster.ca RI Ip, Yuen Kwong/H-8041-2012; Chew, Shit Fun/I-2248-2012 NR 45 TC 6 Z9 7 U1 1 U2 4 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4301 J9 CAN J ZOOL JI Can. J. Zool.-Rev. Can. Zool. PD APR PY 2005 VL 83 IS 4 BP 507 EP 517 DI 10.1139/Z05-036 PG 11 WC Zoology SC Zoology GA 949TW UT WOS:000230812000001 ER PT J AU Unger, JM Thompson, IM LeBlanc, M Crowley, JJ Goodman, PJ Ford, LG Coltman, CA AF Unger, JM Thompson, IM LeBlanc, M Crowley, JJ Goodman, PJ Ford, LG Coltman, CA TI Estimated impact of the prostate cancer prevention trial on population mortality SO CANCER LA English DT Article DE prostate cancer; prevention; finasteride; statistical models; public health ID DIAGNOSIS AB BACKGROUND. The potential public health impact of the recently completed Prostate Cancer Prevention Trial (PCPT) is debated. The results indicated that the period prevalence of prostate cancer was reduced by 24.8% due to finasteride, whereas an increase in the rate of high-grade tumors (Gleason score 8-10) among men who were diagnosed with cancer also was found (5.0% in the PCPT placebo arm vs. 11.9% in the PCPT finasteride arm). Whether the increased Gleason score was valid or was a histologic artifact is under investigation. METHODS. The authors estimated the number of person-years saved assuming a 24.8% reduction in the incidence of prostate cancer for 5 years among United States males age >= 55 years. Scenarios for different proportions of patients with high-grade Gleason scores also were considered. RESULTS. With a 24.8% reduction in the number of men with newly diagnosed prostate cancer, the authors estimated that 316,760 person-years would be saved due to finasteride in the United States. An absolute increase of 6.9% in the proportion of men with high-grade tumors in the United States cancer population (corresponding to the difference between the rates on the placebo and finasteride arms of the PCPT) would reduce the number of person-years saved to 262,567. For each absolute increase of 5% in the proportion of patients with high-grade tumors, the number of person-years saved would be reduced by approximately 39,000. CONCLUSIONS. The results of the PCPT may have a major impact on population mortality from prostate cancer if they are applied clinically. The potential detrimental effects of an increased rate of patients who have prostate cancer with high-grade Gleason scores would be outweighed by a reduction in incidence. (c) 2005 American Cancer Society. C1 SW Oncol Grp, Operat Off, San Antonio, TX 78245 USA. Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX 78285 USA. NCI, Bethesda, MD 20892 USA. RP Unger, JM (reprint author), SW Oncol Grp, Operat Off, 14980 Omicron Dr, San Antonio, TX 78245 USA. EM pubs@swog.org FU NCI NIH HHS [CA38926, CA37429, CA32102] NR 13 TC 28 Z9 28 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2005 VL 103 IS 7 BP 1375 EP 1380 DI 10.1002/cncr.20919 PG 6 WC Oncology SC Oncology GA 908EO UT WOS:000227770400008 PM 15739207 ER PT J AU Muscat, JE Djordjevic, MV Colosimo, S Stellman, SD Richie, JP AF Muscat, JE Djordjevic, MV Colosimo, S Stellman, SD Richie, JP TI Racial differences in exposure and glucuronidation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) SO CANCER LA English DT Article ID SERUM COTININE LEVELS; LUNG CARCINOGEN; UDP-GLUCURONOSYLTRANSFERASES; URINARY METABOLITES; ETHNIC-DIFFERENCES; CIGARETTE-SMOKING; BLACK-AMERICANS; WHITE SMOKERS; UNITED-STATES; CANCER AB BACKGROUND: In the United States, Blacks who smoke cigarettes have a higher mean blood concentration of the nicotine metabolite cotinine than White smokers. It has not been determined whether there are racial differences in the exposure to the cigarette smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-l-butanone (NNK) and in the detoxification of NNK metabolites. METHODS: A community-based cross-sectional survey of 69 Black and 93 White smokers was conducted in lower Westchester County, New York. Information on smoking and lifestyle habits was collected and urinary concentrations of several tobacco smoke biomarkers were compared, including the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-l-butanol (NNAL) and its glucuronide (NNAL-Gluc). A frequency histogram and probit plot of NNAL-Gluc:NNAL ratios were constructed to determine slow and rapid gluctironidation phenotypes. RESULTS: The mean concentrations of total NNAL, urinary cotinine, plasma cotinine, and thiocyanate were significantly higher in Black men than in White men for each cigarette smoked. In women, the only biomarker that was significantly elevated in Blacks was plasma cotinine. A higher proportion of White versus Black women was categorized as "rapid" glucuronidators (two-tailed exact test, P = 0.03). In men, there were no significant differences in NNAL-Gluc:NNAL phenotypes. CONCLUSIONS: The higher rates of lung carcinoma in black men may be due in part to a higher level of exposure to tobacco smoke carcinogens. (c) 2005 American Cancer Society. C1 Penn State Univ, Coll Med, Penn State Canc Inst, Dept Hlth Evaluat Sci,Div Populat Sci, Hershey, PA 17033 USA. NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA. Inst Canc Prevent, Valhalla, NY USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Muscat, JE (reprint author), Penn State Univ, Coll Med, Penn State Canc Inst, Dept Hlth Evaluat Sci,Div Populat Sci, Rm C3739C,MC-H078,500 Univ Dr, Hershey, PA 17033 USA. EM jmuscat@hmc.psu.edu FU NCI NIH HHS [P01-CA-68384, CA-17613] NR 42 TC 44 Z9 46 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2005 VL 103 IS 7 BP 1420 EP 1426 DI 10.1002/cncr.20953 PG 7 WC Oncology SC Oncology GA 908EO UT WOS:000227770400015 PM 15726545 ER PT J AU Maki, RG Kraft, AS Scheu, K Yamada, J Wadler, S Antonescu, CR Wright, JJ Schwartz, GK AF Maki, RG Kraft, AS Scheu, K Yamada, J Wadler, S Antonescu, CR Wright, JJ Schwartz, GK TI A Multicenter phase II study of bortezomib in recurrent or metastatic sarcomas SO CANCER LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 03, 2003 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) DE bortezomib; proteasome; phase II; sarcoma; pharmacokinetics ID PROTEASOME INHIBITOR BORTEZOMIB; SOFT-TISSUE SARCOMA; MULTIPLE-MYELOMA; SOLID TUMORS; TRIAL; CHEMOTHERAPY; IMATINIB; PS-341; MALIGNANCIES; SENSITIVITY AB BACKGROUND. Based on evidence of activity in preclinical and Phase I studies, the authors undertook a study of bortezomib, a reversible proteasome inhibitor, for patients with metastatic sarcomas. METHODS. Two arms were opened, each using a Simon two-stage design. Arm A included patients with osteogenic sarcoma, Ewing sarcoma, and rhabdomyosarcoma. Arm B accrued patients with other types of soft tissue sarcomas. Patients were not allowed to have received previous chemotherapy for metastatic disease. The initial dose of bortezomib was a 1.5 mg/m(2) intravenous push twice weekly followed by a rest week. The dose was escalated to 1.7 mg/m(2) if patients tolerated Cycle I well. The dose escalation was eliminated due to toxicity observed in the first six patients. RESULTS. Painful neuropathy, myalgias, and asthenia were the most significant observed toxicities. The most frequent toxicities included fatigue, diarrhea, constipation, and nausea. Pharrnacodynamic data from 18 patients with complete data collection did not show consistent differences between patients with or without Grade 2 or Grade 3 neuropathy (toxicity graded according the National Cancer Institute Common Toxicity Criteria). Arm A had low accrual and was closed. One confirmed partial response among 21 evaluable patients was observed on Arm B in a patient with leiomyosarcoma. Due to the inactivity of this agent, the study was closed after the first stage of accrual. CONCLUSIONS. Bortezomib has minimal activity in soft tissue sarcoma as a single agent. If studied further in sarcomas, bortezomib should be investigated in combination with agents with demonstrated preclinical synergy. (c) 2005 American Cancer Society. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Univ Colorado, Ctr Canc, Div Med Oncol, Denver, CO 80262 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Ctr, Dept Med,Med Oncol Solid Tumor Program, New York, NY USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NCI, Clin Therapeut Evaluat Program, Bethesda, MD 20892 USA. RP Maki, RG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave,POB 223, New York, NY 10021 USA. EM makir@mskcc.org FU NCI NIH HHS [P01-CA47179, N01-CM17105] NR 21 TC 47 Z9 52 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2005 VL 103 IS 7 BP 1431 EP 1438 DI 10.1002/cncr.20968 PG 8 WC Oncology SC Oncology GA 908EO UT WOS:000227770400017 PM 15739208 ER PT J AU Leach, FS Koh, MS Chan, YW Bark, S Ray, R Morton, RA Remaley, AT AF Leach, FS Koh, MS Chan, YW Bark, S Ray, R Morton, RA Remaley, AT TI Prostate specific antigen as a clinical biomarker for prostate cancer - What's the take home message? SO CANCER BIOLOGY & THERAPY LA English DT Article DE PSA; home testing; biomarker; prostate cancer; screening ID TISSUE-SPECIFIC EXPRESSION; DIGITAL RECTAL EXAMINATION; INTRAEPITHELIAL NEOPLASIA; RADICAL PROSTATECTOMY; SERUM; MEN; CARCINOMA; KALLIKREIN; TRENDS; MORTALITY AB Prostate specific antigen (PSA) continues to be challenged as a legitimate clinical biomarker in early detection of prostate cancer due to lack of specificity for malignant transformation. Skepticism surrounding the utility of serum PSA as a clinical marker is not new and many questioned its initial use in widespread prostate cancer screening due to non-specific expression and low predictive value for cancer detection. Despite these initial concerns, serum PSA measurement along with digital rectal examination (DRE) is currently the accepted practice for prostate cancer screening in the United States with hundreds of thousands of men undergoing serum PSA measurement annually. In contrast to its role for early detection, serum PSA measurement as a surrogate for prostate cancer recurrence (biochemical failure) following curative intent therapy has consummate clinical utility in post-treatment surveillance. As thousands of men each year are aggressively treated for potentially curable prostate cancer, development of simple and effective diagnostic tools for detecting treatment failures should be an important area of biomedical and clinical investigation. We have constructed and tested a home-based prostate cancer surveillance device for use by patients to detect PSA from blood obtained by finger stick. Our initial results suggest that home based PSA testing is feasible and may have clinical utility in management of men treated for prostate cancer. C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. FlexSite Diagnost, Palm City, FL USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA. RP Remaley, AT (reprint author), NIH, Dept Lab Med, Bldg 10,Rm 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@nih.gov NR 53 TC 3 Z9 4 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 APR PY 2005 VL 4 IS 4 BP 371 EP 375 PG 5 WC Oncology SC Oncology GA 015IA UT WOS:000235543900012 PM 15846084 ER PT J AU Platz, EA Pollak, MN Leitzmann, MF Stampfer, MJ Willett, WC Giovannucci, E AF Platz, EA Pollak, MN Leitzmann, MF Stampfer, MJ Willett, WC Giovannucci, E TI Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era SO CANCER CAUSES & CONTROL LA English DT Article DE cohort study; insulin-like growth factor; prostate cancer; risk ID IGF-I; PREDICTORS; HYPERPLASIA; APOPTOSIS; COHORT; INDEX; DEATH AB Objective The insulin-like growth factor (IGF) axis is thought to contribute to the growth and progression of prostate cancer. Some prospective studies support a direct association between IGF-1 and prostate cancer, in particular advanced disease, whereas both inverse and direct associations with prostate cancer have been reported for insulin-like growth factor binding protein-3 (IGFBP-3), the major IGF-1 binding protein in circulation. We prospectively investigated the associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer detected in the PSA era. Methods: We identified 462 prostate cancer cases diagnosed after providing a blood specimen in 1993, but before January 1998 among men in the Health Professionals Follow-up Study. Controls were 462 age-matched men without prostate cancer who had had a PSA test after providing a blood specimen. We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer. Results: Men with higher concentrations of IGF-1 (comparing extreme quartiles OR=1.37, 95% CI 0.92-2.03, p-trend=0.05) and IGFBP-3 (OR=1.62, 95% CI 1.07-2.46, p-trend=0.08) had a higher risk of prostate cancer. After mutual statistical adjustment, these associations were attenuated for both IGF-1 (OR=1.17, 95% CI 0.69-1.99, p-trend=0.29) and IGFBP-3 (OR=1.40, 95% CI 0.80-2.44, p-trend=0.56). We found no significant association of IGF-1 with regionally invasive or metastatic (>= T3b, N1, or M1) prostate cancer, although the number of these cases was small (n=42). Conclusions: Our findings for IGF-1 and prostate cancer diagnosed in the PSA era are similar to most previous studies, albeit weaker in magnitude. Our suggestive positive findings for IGFBP-3 are similar to some studies, but in direct contrast to others. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. McGill Univ, Jewish Gen Hosp, Dept Med, Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Montreal, PQ, Canada. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 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 Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E6138,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU NCI NIH HHS [CA55075, CA72036]; NHLBI NIH HHS [HL35464] NR 18 TC 53 Z9 61 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2005 VL 16 IS 3 BP 255 EP 262 DI 10.1007/s10552-004-3484-8 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 934VK UT WOS:000229736900007 PM 15947877 ER PT J AU Baker, JA Buck, GM Vena, JE Moysich, KB AF Baker, JA Buck, GM Vena, JE Moysich, KB TI Fertility patterns prior to testicular cancer diagnosis SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; epidemiology; infertility; reproduction; spermatozoa; testicular neoplasms ID TESTIS CANCER; UNITED-STATES; SEX-RATIO; RISK; EPIDEMIOLOGY; MEN; EXPOSURE AB Although prenatal factors are associated with testicular cancer etiology, few studies have examined the reproductive profiles of men prior to diagnosis. This case-control study investigated fertility patterns prior to testicular cancer diagnosis by comparing pregnancies fathered by 201 men with testicular cancer and those fathered by 204 age- and neighborhood-matched controls. Regardless of histology, men with testicular cancer were less likely to have ever fathered a live-born infant (OR 0.67, 95% CI 0.42-1.06) and had fewer offspring than control men (means 1.8 and 2.1, respectively). Cases were more likely than controls to report having an infertility diagnosis (OR 9.47, 95% CI 1.19-75.2) or a low sperm count (OR 5.85, 95% CI 1.28-26.7) prior to cancer diagnosis. No differences were observed for pregnancy loss. These results indicate that men with testicular cancer may have impaired fecundity and fertility as evidenced by an infertility diagnosis or low sperm count and fewer live births. Further research is needed to determine the extent to which reproductive factors are involved in the etiology of testicular cancer. C1 Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. NICHHD, Div Epidemiol Stat & Prevent, NIH, Bethesda, MD USA. Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. RP Baker, JA (reprint author), Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, A-117 Carlton House,Elm & Carlton St, Buffalo, NY 14263 USA. EM jabaker@buffalo.edu OI Buck Louis, Germaine/0000-0002-1774-4490 NR 24 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2005 VL 16 IS 3 BP 295 EP 299 DI 10.1007/s10552-004-4024-2 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 934VK UT WOS:000229736900011 PM 15947881 ER PT J AU Fishel, ML Ganicsik, MP Delaney, SM Zuhowski, EG Maher, VM Karrison, T Moschel, RC Egorin, MJ Dolan, ME AF Fishel, ML Ganicsik, MP Delaney, SM Zuhowski, EG Maher, VM Karrison, T Moschel, RC Egorin, MJ Dolan, ME TI Role of glutathione and nucleotide excision repair in modulation of cisplatin activity with O-6-benzylguanine SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE cisplatin; modulation; chemotherapy ID SQUAMOUS-CELL CARCINOMA; HAMSTER OVARY CELLS; PHASE-I TRIAL; DNA-REPAIR; BUTHIONINE SULFOXIMINE; PLATINUM COMPOUNDS; MALIGNANT GLIOMA; INDUCED TOXICITY; DHFR GENE; RESISTANCE AB Purpose: Modulation of platinating agent cytotoxicity has important clinical implications as a result of their widespread use in the treatment of many different cancers. O-6-Benzylguanine (BG) enhances the cytotoxicity of cisplatin against several human tumor lines. The purpose of our work was to elucidate whether BG affects pathways prior to DNA damage (i.e., glutathione, GSH) or following DNA damage (i.e., nucleotide excision repair, NER). Methods: In efforts to determine the mechanism of enhancement we: (1) evaluated whether different sequences of BG plus cisplatin treatment differed in their ability to enhance cisplatin-induced cytotoxicity and DNA platination; (2) determined the effect of BG on GSH and glutathione S-transferase (GST) activity and; (3) determined whether BG enhanced cisplatin-induced cytotoxicity in cells lacking specific enzymes in the NER pathway. Colony-forming assay, atomic absorption spectroscopy and HPLC were employed to measure tumor cell growth inhibition, quantitate the amount of platinum on DNA, and determine intracellular GSH concentrations, respectively. Results: Increased cytotoxicity and platination of DNA was observed when cells were exposed to BG prior to and/or during cisplatin treatment and not when BG followed cisplatin treatment. BG did not significantly alter GST activity with minimal depletion of GSH. In contrast, buthionine sulfoximine (BSO) caused a much more dramatic decrease in GSH than BG that was not accompanied by a dramatic increase in sensitivity to cisplatin. Furthermore, BG enhanced the cytotoxicity of cisplatin in a series of cell lines deficient in NER. Conclusions: Overall, our results suggest that the mechanism of enhancement involves neither the GSH nor the NER pathways, but triggers an event prior to DNA platination damage that ultimately results in increased cytotoxicity, apoptosis and increased platination levels. C1 Univ Chicago, Dept Med, Comm Canc Biol, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Durham, NC 27701 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Michigan State Univ, Carcinogenesis Lab, E Lansing, MI 48824 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Dolan, ME (reprint author), Univ Chicago, Dept Med, Comm Canc Biol, 5841 S Maryland Ave,POB MC2115, Chicago, IL 60637 USA. EM edolan@medicine.bsd.uchicago.edu FU NCI NIH HHS [2 P30 CA47904, 5T32 CA09594, CA81485] NR 50 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2005 VL 55 IS 4 BP 333 EP 342 DI 10.1007/s00280-004-0901-3 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 906VB UT WOS:000227671100004 PM 15723259 ER PT J AU Kelley, MJ Glaser, EM Hemdon, JE Becker, F Bhagat, R Zhang, YJ Santella, RM Carmella, SG Hecht, SS Gallot, L Schilder, L Crowell, JA Perloff, M Folz, RJ Bergan, RC AF Kelley, MJ Glaser, EM Hemdon, JE Becker, F Bhagat, R Zhang, YJ Santella, RM Carmella, SG Hecht, SS Gallot, L Schilder, L Crowell, JA Perloff, M Folz, RJ Bergan, RC TI Safety and efficacy of weekly oral oltipraz in chronic smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HYDROCARBON-DNA ADDUCTS; LUNG-CANCER RISK; REPUBLIC-OF-CHINA; BREAST-CANCER; SMOKING; GLUTATHIONE; CELLS; TISSUES; BLOOD; CHEMOPREVENTION AB Cigarette smoking is thought to contribute to carcinogenesis by formation of DNA adducts of tobacco smoke constituents leading to genotoxic damage. The dithiolethione, oltipraz, is a putative cancer chemopreventive agent that induces phase II detoxifying enzymes in preclinical models and reduces aflatoxin adducts in humans living in areas with high dietary levels. To determine if oltipraz could reduce adduct levels of tobacco smoke constituents in the lungs and other target organs, chronic smokers were enrolled to one of three arms: 400 or 200 mg/wk oral oltipraz or placebo. Endobronchial tissue and bronchoalveolar lavage were done before and after 12 weeks of drug treatment; peripheral blood, urine, and oral saline rinse were also collected. Toxicity was assessed every 4 weeks. Fifty-nine of the 77 enrolled subjects completed the study. Of those receiving oltipraz, 15% experienced grade 2/3 toxicity, which was predominantly gastrointestinal. All subject withdrawals occurred in the oltipraz groups. There was no significant difference between pre- and postpolycyclic aromatic hydrocarbon-DNA adduct levels in lung epithelial cells measured by immunoperoxidase staining between treatment and placebo groups. Likewise, no significant differences were found in polycyclic aromatic hydrocarbon or benzo(a)pyrene-7,8-diol-9,10-epoxide adducts measured in blood, oral lining cells, or bladder lining cells. There was also no increase in mRNA or enzymatic activity of phase 11 enzymes and no change in glutathione levels. Thus, despite moderate drug-related toxicity, there was no significant effect on pharmacodynamic or surrogate risk biomarkers. Other agents with lower toxicity and greater activity to induce phase 11 enzymes are needed to definitively test the detoxification-induction paradigm in smokers. C1 Duke Univ, Vet Affairs Hosp, Dept Med, Durham, NC 27705 USA. NCI, Div Canc Prevent, Rockville, MD USA. Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA. Univ Minnesota, Minneapolis, MN USA. Northwestern Univ, Sch Med, Div Hematol Oncol, Chicago, IL USA. Northwestern Univ, Robert H Lurie Canc Ctr, Chicago, IL USA. RP Kelley, MJ (reprint author), Duke Univ, Vet Affairs Hosp, Dept Med, 508 Fulton St, Durham, NC 27705 USA. EM kelleym@duke.edu OI Kelley, Michael/0000-0001-9523-6080; Hecht, Stephen/0000-0001-7228-1356 FU NCI NIH HHS [N01CN95135]; NCRR NIH HHS [M01 RR00030, M01 RR00048]; NIEHS NIH HHS [P30 ES009089, P30 ES09089] NR 41 TC 21 Z9 21 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 892 EP 899 DI 10.1158/1055-9965.EPI-04-0585 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300022 PM 15824161 ER PT J AU Yang, XH Diehl, S Pfeiffer, R Chen, CJ Hsu, WL Dosemeci, M Cheng, YJ Sun, B Goldstein, AM Hildesheim, A AF Yang, XH Diehl, S Pfeiffer, R Chen, CJ Hsu, WL Dosemeci, M Cheng, YJ Sun, B Goldstein, AM Hildesheim, A CA Chinese Amer Gene Epidem NPC Team TI Evaluation of risk factors for nasopharyngeal carcinoma in high-risk nasopharyngeal carcinoma families in Taiwan SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EPSTEIN-BARR-VIRUS; CIGARETTE-SMOKING; GENETIC POLYMORPHISMS; OCCUPATIONAL-EXPOSURE; SUSCEPTIBILITY; FORMALDEHYDE; INFECTION; INFERENCE; THAILAND; ALCOHOL AB A study of nasopharyngeal carcinoma (NPC) families with two or more affected members was conducted in Taiwan (265 families with 2,444 individuals, 502 affected and 1,942 unaffected) to determine the association between NPC and potential etiologic factors in NPC high-risk families. Similar to results from a previous case-control study in Taiwan, Guangdong salted fish consumption during childhood, exposure to wood, and betel nut consumption were all associated with elevated NPC risk using conditional logistic regression, although these associations were not as strong as in the case-control study possibly due to shared environment among family members. Risk associated with cumulative wood exposure and salted fish consumption before age 10 was stronger in families with early NPC age-onset [odds ratio (ORwood), 5.10; 95% confidence interval (95% CI), 1.50-17.34; ORfish, 3.94; 95% CI, 1.47-10.55] or three or more affected members (ORwood, 4.41; 95% CI, 1.58-12.30; ORfish, 4.27; 95% CI, 1.10-16.47). In contrast, a tendency for elevated risk was noted for betel nut use in late age-onset families (OR, 2.44; 95% CI, 1.16-5.13) and the CYP2E1 c2 allele in families with less than three affected members (OR, 2.06; 95% CI, 1.04-3.35). Risk estimates associated with these exposures were similar when the analyses were restricted to EBV-seropositive subjects. To better adjust for degree of relationship among family members and residual genetic correlations, we also calculated ORs using a variance components model. The results from the two methods were similar indicating that the risk estimates from conditional logistic regression were unbiased. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. Univ Med & Dent New Jersey, New Jersey Dent Sch, Ctr Pharmacogenom & Complex Dis Res, Newark, NJ 07103 USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. Westat Corp, Rockville, MD USA. RP Yang, XH (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Room 7014, Rockville, MD 20852 USA. EM royang@mail.nih.gov RI Chen, Chien-Jen/C-6976-2008; Pfeiffer, Ruth /F-4748-2011 NR 32 TC 38 Z9 40 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 900 EP 905 DI 10.1158/1055-9965.EPI-04-0680 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300023 PM 15826929 ER PT J AU Morton, LM Hartge, P Holford, TR Holly, EA Chiu, BCH Vineis, P Stagnaro, E Willett, EV Franceschi, S La Vecchia, C Hughes, AM Cozen, W Davis, S Severson, RK Bernstein, L Mayne, ST Dee, FR Cerhan, JR Zheng, TZ AF Morton, LM Hartge, P Holford, TR Holly, EA Chiu, BCH Vineis, P Stagnaro, E Willett, EV Franceschi, S La Vecchia, C Hughes, AM Cozen, W Davis, S Severson, RK Bernstein, L Mayne, ST Dee, FR Cerhan, JR Zheng, TZ TI Cigarette smoking and risk of non-Hodgkin lymphoma: A pooled analysis from the international lymphoma epidemiology consortium (InterLymph) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MIDDLE-AGED MEN; ALCOHOL-CONSUMPTION; MULTIPLE-MYELOMA; UNITED-STATES; HEMATOLYMPHOPOIETIC MALIGNANCIES; OLDER WOMEN; TOBACCO; SUBTYPES; CANCER; CLASSIFICATION AB Background: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. Methods: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. Results: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1432). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking ( 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. Conclusions: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept HHS,NIH, Rockville, MD 20852 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Dept Hlth & Human Serv, Bethesda, MD USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Turin, Turin, Italy. Natl Inst Canc Res, Environm Epidemiol & Biostat Unit, Genoa, Italy. Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. IARC, Lyon, France. Ctr Riferimento Oncol, Serv Epidemiol & Biostat, I-33081 Aviano, Italy. Univ Milan, Ist Stat Med, Ist Ric Farmacol Mario Negri, Milan, Italy. Univ Sydney, Sch Publ Hlth, Sydney, NSW, Australia. Univ S Carolina, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98195 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. RP Morton, LM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept HHS,NIH, 6120 Execut Blvd,EPS-7055, Rockville, MD 20852 USA. EM mortonli@mail.nih.gov RI Kane, Eleanor/B-4349-2009; Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; La Vecchia, Carlo/0000-0003-1441-897X FU NCI NIH HHS [CA062006, CA045614, CA089745, CA10349, CA50850, CA51086, PC65064, PC67008, PC67009, PC67010, PC71105] NR 56 TC 102 Z9 113 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 925 EP 933 DI 10.1158/1055-9965.EPI-04-0693 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300027 PM 15824165 ER PT J AU Hartge, P Colt, JS Severson, RK Cerhan, JR Cozen, W Camann, D Zahm, SH Davis, S AF Hartge, P Colt, JS Severson, RK Cerhan, JR Cozen, W Camann, D Zahm, SH Davis, S TI Residential herbicide use and risk of non-Hodgkin lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SOFT-TISSUE SARCOMA; WESTERN WASHINGTON; PHENOXY HERBICIDES; UNITED-STATES; MORTALITY; CANCER; WORKERS; EXPOSURE AB Context: Environmental exposure to herbicides has been hypothesized to contribute to the long-term increase in non-Hodgkin lymphoma (NHL). Objective: To estimate the effects of residential herbicide exposure on NHL risk. Design: Population-based case-control study. Setting: Iowa and metropolitan Detroit, Los Angeles, and Seattle, 1998 to 2000. Participants: NHL patients ages 20 to 74 years and unaffected residents identified by random digit dialing and Medicare eligibility files. Main Outcome Measures: Computer-assisted personal interviews (1,321 cases, 1,057 controls) elicited data on herbicide use at each home occupied since 1970. Levels of 2,4-dichlorophenoxy-acetic acid and dicamba were measured in dust taken from used vacuum cleaner bags in the current home (679 cases, 510 controls who had owned at least half of their carpets for >= 5 years). Results: Herbicide use on the lawn or garden was similar among cases and controls (adjusted relative risk, 1.02; 95% confidence interval, 0.84-1.23). Estimated risk did not increase with greater duration, frequency, or total number of applications of herbicides to the lawn, the garden, or to both combined. Risk was not elevated for respondents who applied the herbicides themselves and not for those exposed during the 1970s, 1980s, or 1990s. We detected 2,4-dichlorophenoxy-acetic acid equally often in homes of cases and controls (78%). We found dicamba in homes of 15% of cases and 20% of controls. We also found no elevation in risk among the respondents who had the highest dust levels and highest self-reported exposures. We found no consistent patterns for specific histologies. Conclusions: We found no detectable excess associated with residential exposures. Residential herbicide exposures are unlikely to explain the long-term increase in NHL. C1 NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ So Calif, Los Angeles, CA USA. SW Res Inst, San Antonio, TX USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Hartge, P (reprint author), NCI, Epidemiol & Biostat Program, 6120 Execut Blvd,Room 8090, Rockville, MD 20852 USA. EM hartgep@mail.nih.gov RI Zahm, Shelia/B-5025-2015 FU NCI NIH HHS [N01-PC-67009, N01-PC-65064, N01-PC-67008, N01-PC-67010, N01-PC-71105] NR 22 TC 26 Z9 26 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 934 EP 937 DI 10.1158/1055-9965.EPI-04-0730 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300028 PM 15824166 ER PT J AU Bergen, AW Qi, Y Haque, KA Welch, RA Garcia-Closas, M Chanock, SJ Vaught, J Castle, PE AF Bergen, AW Qi, Y Haque, KA Welch, RA Garcia-Closas, M Chanock, SJ Vaught, J Castle, PE TI Effects of electron-beam irradiation on whole genome amplification SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DNA AB Electron-beam (E-beam) irradiation, currently being used to sterilize mail addressed to selected ZIP codes in the United States, has significant negative effects on the genomic integrity of DNA extracted from buccal-cell washes. We investigated the yield, composition, and genotyping performance of whole genome amplified DNA (wgaDNA) derived from 24 matched samples of E-beam-irradiated and nonirradiated genomic DNA (gDNA) as a model for the effects of degraded gDNA on the performance of whole genome amplification. gDNA was amplified using the Multiple Displacement Amplification method. Three methods of DNA quantification analysis were used to estimate the yield and composition of wgaDNA, and 65 short tandem repeat and single nucleotide polymorphism genotyping assays were used to evaluate the genotyping performance of irradiated and nonirradiated gDNA and wgaDNA. Compared with wgaDNA derived from nonirradiated gDNA, wgaDNA derived from irradiated gDNA exhibited a significantly reduced yield of wgaDNA and significantly reduced short tandem repeat and single nucleotide polymorphism genotyping completion and concordance rates (P < 0.0001). Increasing the amount of irradiated gDNA input into whole genome amplification improved genotyping performance of wgaDNA but not to the level of wgaDNA derived from nonirradiated gDNA. Multiple Displacement Amplification wgaDNA derived from E-beam-irradiated gDNA is not suitable for genotyping analysis. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD USA. NCI, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD USA. RP Bergen, AW (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM bergena@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Bergen, Andrew/0000-0002-1237-7644 NR 12 TC 13 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 1016 EP 1019 DI 10.1158/1055-9965.EPI-04-0686 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300044 PM 15824182 ER PT J AU Marrogi, AJ Mechanic, LE Welsh, JA Bowman, ED Khan, MA Enewold, L Shields, PG Harris, CC AF Marrogi, AJ Mechanic, LE Welsh, JA Bowman, ED Khan, MA Enewold, L Shields, PG Harris, CC TI TP53 mutation spectrum in lung cancer is not different in women and men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID DNA ADDUCT LEVELS; P53 MUTATIONS; SMOKING; EXPRESSION; GENDER; GENE AB Whether women are more susceptible to lung cancer than men has been controversial. Several case-control studies suggested that women have greater risk of lung cancer compared with men at similar levels of cigarette smoking, whereas some large cohort studies failed to observe this association. Other studies indicated that lung cancer may have biological characteristics and mechanisms of carcinogenesis that are gender specific. Therefore, we hypothesized that women are more susceptible to the carcinogenic effects of tobacco smoke exposure, as evidenced by a higher frequency of G:C-to-T:A somatic mutations in tumors from women in comparison with men at similar levels of tobacco smoke exposure. To investigate our hypothesis, we examined the TP53 mutational spectrum in a case-only (102 women and 201 men) series study where complete smoking information was available. A similar frequency and type of somatic TP53 mutations were observed in women and men. In conclusion, our study indicates that the TP53 mutation spectrum is similar in women and men. Our results are consistent with a recent large cohort study and summary of previous cohort studies, suggesting that women likely have equivalent susceptibility to lung cancer as men. C1 NCI, Human Carcinogenesis Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Lab Carcinogenesis & Biomarkers, Clin Breast Care Project Immunol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Res Ctr, Bethesda, MD 20814 USA. Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Canc Res Ctr, Room 3068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 16 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 1031 EP 1033 DI 10.1158/1055-9965.EPI-04-0640 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300050 PM 15824188 ER PT J AU Zhang, R Sengupta, S Yang, Q Linke, SP Yanaihara, N Bradsher, J Blais, V McGowan, CH Harris, CC AF Zhang, R Sengupta, S Yang, Q Linke, SP Yanaihara, N Bradsher, J Blais, V McGowan, CH Harris, CC TI BLM helicase facilitates Mus81 endonuclease activity in human cells SO CANCER RESEARCH LA English DT Article ID BLOOMS-SYNDROME HELICASE; SYNDROME GENE-PRODUCT; HOLLIDAY JUNCTIONS; DNA-DAMAGE; REPLICATION FORKS; RECOMBINATION; RESOLUTION; PROTEIN; P53; INVOLVEMENT AB Bloom syndrome is a rare, autosomal recessive inherited disorder in humans. The product of the Bloom syndrome mutated gene, designated BLM, is a member of the RecQ helicase family. BLM has been proposed to function at the interface of replication and recombination, and to facilitate the repair of DNA damage. Here, we report in vivo physical interaction and colocalization of BLM and a DNA structure-specific endonuclease, Mus81, at sites of stalled replication forks outside the promyelocytic leukemia nuclear bodies during the S-phase arrest of the cell cycle. Amino acids 125 to 244 of Mus81 interact with the C-terminal region (amino acids 1,007-1,417) of BLM. Whereas Mus81 does not have any effect on the helicase activity of BLM, BLM can stimulate Mus81 endonuclease activity on the nicked Holliday junctions and 3' flap. This stimulation is due to enhanced binding of Mus81 to the DNA substrates. These data suggest a new function of BLM in cooperating with Mus81 during processing and restoration of stalled replication forks. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Room 3068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov OI Sengupta, Sagar/0000-0002-6365-1770 NR 28 TC 35 Z9 37 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2526 EP 2531 DI 10.1158/0008-5472.CAN-04-2421 PG 6 WC Oncology SC Oncology GA 911AB UT WOS:000227972300005 PM 15805243 ER PT J AU Hu, N Wang, CY Hu, Y Yang, HH Giffen, C Tang, ZZ Han, XY Goldstein, AM Emmert-Buck, MR Buetow, KH Taylor, PR Lee, MP AF Hu, N Wang, CY Hu, Y Yang, HH Giffen, C Tang, ZZ Han, XY Goldstein, AM Emmert-Buck, MR Buetow, KH Taylor, PR Lee, MP TI Genome-wide association study in esophageal cancer using GeneChip mapping 10K array SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ALLELE SNP ARRAY; CHINESE POPULATION; GENETIC-VARIANTS; IDENTIFICATION; POLYMORPHISM; RISK; DNA; HETEROZYGOSITY; SUSCEPTIBILITY AB Whole genome association studies of complex human diseases represent a new paradigm in the postgenomic era. In this study, we report application of the Affymetrix, Inc. (Santa Clara, CA) high-density single nucleotide polymorphism (SNP) array containing 11,555 SNPs in a pilot case-control study of esophageal squamous cell carcinoma (ESCC) that included the analysis of germ line samples from 50 ESCC patients and 50 matched controls. The average genotyping call rate for the 100 samples analyzed was 96%. Using the generalized linear model (GLM) with adjustment for potential confounders and multiple comparisons, we identified 37 SNPs associated with disease, assuming a recessive mode of transmission; similarly, 48 SNPs were identified assuming a dominant mode and 53 SNPs in a continuous mode. When the 37 SNPs identified from the GLM recessive mode were used in a principal components analysis, the first principal component correctly predicted 46 of 50 cases and 47 of 50 controls. Among all the SNPs selected from GLMs for the three modes of transmission, 39 could be mapped to I of 33 genes. Many of these genes are involved in various cancers, including GASC1, shown previously to he amplified in ESCCs, and EPHB1 and PIK3C3. In conclusion, we have shown the feasibility of the Affymetrix 10K SNP array in genome-wide association studies of common cancers and identified new candidate loci to study in ESCC. C1 NCI, Lab Populat Genet, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. RP Lee, MP (reprint author), NCI, Lab Populat Genet, Canc Res Ctr, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM ptaylor@mail.nih.gov; leemax@mail.nih.gov NR 27 TC 65 Z9 74 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 APR 1 PY 2005 VL 65 IS 7 BP 2542 EP 2546 DI 10.1158/0008-5472.CAN-04-3247 PG 5 WC Oncology SC Oncology GA 911AB UT WOS:000227972300008 PM 15805246 ER PT J AU Ahmed-Choudhury, J Agathanggelou, A Fenton, SL Ricketts, C Clark, GJ Maher, ER Latif, F AF Ahmed-Choudhury, J Agathanggelou, A Fenton, SL Ricketts, C Clark, GJ Maher, ER Latif, F TI Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120(E4F) to the cyclin A2 promoter SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL-CYCLE; EPIGENETIC INACTIVATION; IDENTIFICATION; ASSOCIATION; EXPRESSION; PROTEIN; 3P21.3; LUNG; E4F AB Recent advances in the study of RASSFIA, the candidate tumor suppressor gene, indicate a possible role of RASSFIA in cell cycle regulation; however, very little is known regarding molecular mechanisms underlying this control. Using small interfering RNA to knockdown endogenous RASSFIA in the breast tumor cell line 11132 and in the cervical cancer cell line HeLa, we identify that a key player in cell cycle progression, cyclin A2, is concomitantly increased at both protein and mRNA levels. In A549 clones stably expressing RASSFIA, cyclin A2 levels were diminished compared with vector control. A known transcriptional regulator of cyclin A2, p120(E4F) (a repressor of cyclin A2), has been shown previously by our group to interact with RASSFIA. We show that levels of p120(E4F) are not affected by RASSFIA small interfering RNA in HB2 and HeLa cells. However, electrophoretic mobility shift assays indicate that knockdown of endogenous RASSFIA in HB2 and HeLa cells leads to a reduction in the binding capacity of p120(E4F) to the cyclin A2 promoter, whereas in the A549 clone stably expressing RASSFIA the binding capacity is increased. These data are further corroborated in vitro by the luciferase assay and in vivo by chromatin immunoprecipitation experiments. Together, these data identify the cyclin A2 gene as a cellular target for RASSFIA through p120(E4F) and for the first time suggest a transcriptional mechanism for RASSFIA-dependent cell cycle regulation. C1 Univ Birmingham, Biomed Res Inst, Div Reprod & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. NCI, Dept Cell & Canc Biol, Rockville, MD USA. RP Latif, F (reprint author), Univ Birmingham, Biomed Res Inst, Div Reprod & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. EM flatif@hgmp.mrc.ac.uk RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 30 TC 25 Z9 32 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2690 EP 2697 DI 10.1158/0008-5472.CAN-04-3593 PG 8 WC Oncology SC Oncology GA 911AB UT WOS:000227972300029 PM 15805267 ER PT J AU Kumakura, S Tsutsui, TW Yagisawa, J Barrett, JC Tsutsui, T AF Kumakura, S Tsutsui, TW Yagisawa, J Barrett, JC Tsutsui, T TI Reversible conversion of immortal human cells from telomerase-positive to telomerase-negative cells SO CANCER RESEARCH LA English DT Article ID PAPILLOMAVIRUS TYPE-16 E6; CO-60 GAMMA-RAYS; HUMAN FIBROBLASTS; HTERT GENE; ALTERNATIVE MECHANISM; CANCER-CELLS; LIFE-SPAN; METHYLATION; RECOMBINATION; MAINTENANCE AB Immortal cell lines and tumors maintain their telomeres via the telomerase pathway or via a telomerase-independent pathway, referred to as alternative lengthening of telomeres (ALT). Here, we show the reversible conversion of the human papillomavirus type 16 E6-induced immortal human fibroblasts E6 CI 6 from telomerase-positive (Tel(+)) to telomerasenegative (Tel(-)) cells. Tel(+) cells converted spontaneously to Tel(-)cells that reverted to Tel(+) cells following treatment with trichostatin A (TSA) and/or 5-aza-2'-deoxycytidine (5-AZC), which induced the reversion from complete to partial methylation of the CpG islands of the human telomerase reverse transcriptase (hTERT) promoter in Tel- E6 Cl 6 cells. Tel- E6 Cl 6 cells lacked the phenotypes characteristic of ALT cell lines such as very long and heterogenous telomeres and ALT-associated promyelocytic leukemia nuclear bodies (APB) but grew for > 240 population doublings (PD) after they became telomerase negative. The ratios of histone H3 (113) lysine (K) 9 methylation to each of H3-K4 methylnation, H3-K9 acetylation, and H3-KI4 acetylation of the chromatin containing the hTERT promoter in Tel- E6 Cl 6 cells and ALT cell lines were greater than those in Tel(+) cells and decreased following treatment with TSA and/or 5-AZC, inversely corresponding to telomerase activity. Our findings suggest the possibility that human tumors may be able to reversibly interconvert their telomere maintenance phenotypes by chromatin structure-mediated regulation of hTERT expression. C1 NCI, Ctr Canc Res, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. Nippon Dent Univ Tokyo, Dept Pharmacol, Sch Dent, Tokyo, Japan. RP Barrett, JC (reprint author), NCI, Ctr Canc Res, Lab Biosyst & Canc, NIH, Bldg 31,Room 3A11,31 Ctr Dr,MSC-2440, Bethesda, MD 20892 USA. EM barrett@mail.nih.gov NR 32 TC 28 Z9 29 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2778 EP 2786 DI 10.1158/0008-5472.CAN-04-1819 PG 9 WC Oncology SC Oncology GA 911AB UT WOS:000227972300040 PM 15805278 ER PT J AU Mukhopadhyay, UK Senderowicz, AM Ferbeyre, G AF Mukhopadhyay, UK Senderowicz, AM Ferbeyre, G TI RNA silencing of checkpoint regulators sensitizes p53-defective prostate cancer cells to chemotherapy while sparing normal cells SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; DNA-DAMAGE CHECKPOINT; IMMUNOHISTOCHEMICAL DETECTION; P53-DEFICIENT CELLS; E2F TRANSCRIPTION; P53 MUTATIONS; ONCOGENIC RAS; MUTANT P53; KINASE; ATM AB p53 is frequently mutated in patients with prostate cancer, especially in those with advanced disease. Therefore, the selective elimination of p53 mutant cells will likely have an impact in the treatment of prostate cancer. Because p53 has important roles in cell cycle checkpoints, it has been anticipated that modulation of checkpoint pathways should sensitize p53-defective cells to chemotherapy while sparing normal cells. To test this idea, we knocked down ataxia telangiectasia mutated (ATM) gene by RNA interference in prostate cancer cell lines and in normal human diploid fibroblasts IMR90. ATM knockdown in p53-defective PC3 prostate cancer cells accelerated their cell cycle transition, increased both E2F activity and proliferating cell nuclear antigen expression, and compromised cell cycle checkpoints, which are normally induced by DNA damage. Consequently, PC3 cells were sensitized to the killing effects of the DNA-damaging drug doxorubicin. Combining ATM knockdown with the Chk1 inhibitor UCN-01 further increased doxorubicin sensitivity in these cells. In contrast, the same strategy did not sensitize either IMR90 or LNCaP prostate cancer cells, both of which have normal p53. However, IMR90 and LNCaP cells became more sensitive to doxorubicin or doxorubicin plus UCN-01 when both p53 and ATM functions were suppressed. In addition, knockdown of the G(2) checkpoint regulators ATR and Chk1 also sensitized PC3 cells to doxorubicin and increased the expression of the E2F target gene PCNA. Together, our data support the concept of selective elimination of p53 mutant cells by combining DNA damage with checkpoint inhibitors and suggest a novel mechanistic insight into how such treatment may selectively kill tumor cells. C1 Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Ferbeyre, G (reprint author), Univ Montreal, Dept Biochim, E-515,CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM g.ferbeyre@umontreal.ca RI Ferbeyre, Gerardo/A-1569-2010 NR 56 TC 39 Z9 43 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2872 EP 2881 DI 10.1158/0008-5472.CAN-04-2502 PG 10 WC Oncology SC Oncology GA 911AB UT WOS:000227972300051 PM 15805289 ER PT J AU Qiu, CP Shan, L Yu, MS Snyderwine, EG AF Qiu, CP Shan, L Yu, MS Snyderwine, EG TI Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine SO CARCINOGENESIS LA English DT Article ID HUMAN BREAST-CANCER; FOOD-DERIVED CARCINOGEN; SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTOR; CELL-PROLIFERATION; COOKED FOOD; CYCLIN D1; ER-ALPHA; BETA AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet. Herein, the expression of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta) and progesterone receptor (PR) was examined in mammary gland carcinomas induced by PhIP in female Sprague-Dawley rats. Quantitative real-time polymerase chain reaction demonstrated that ER alpha, ER beta and PR were statistically elevated by 3-, 4- and 8-fold in carcinomas compared with normal mammary glands. By immunohistochemistry, carcinomas showed statistically higher nuclear expression of all three steroid receptors with the majority of carcinomas showing at least 10% of epithelial cells stained for ER alpha (49/55, 89%), ER beta (41/55, 75%) and PR (48/55, 87%). Furthermore, the level of expression of the three steroid hormone receptors was positively correlated with each other across the bank of carcinomas (Spearman analysis, P < 0.05). The expression of ER alpha in carcinomas was associated with tumor grade, extent of nuclear pleomorphism and cellular proliferation as measured by proliferating cell nuclear antigen (PCNA) and phospho-Rb immunostaining (Spearman analysis, P < 0.05). Confocal microscopy was used to measure the percentage of epithelial cells showing nuclear colocalization of receptors, PCNA, and cyclin D1. Colocalization of the receptors, and the colocalization of the receptors with PCNA and cyclin D1 was strikingly higher in carcinomas than in the normal mammary gland. In carcinoma cells, 37% of ER alpha positive epithelial cells were colocalized with PCNA in contrast to just 0.25% of cells in the normal mammary gland. The findings from this study indicate that ER alpha, ER beta and PR were co-upregulated and nuclear localized in epithelial cells from rat mammary carcinomas compared with normal mammary glands, and that the co-upregulation was positively correlated with proliferation and cell cycle progression in carcinomas. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), Bldg 37,Room 4146,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov NR 47 TC 23 Z9 24 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2005 VL 26 IS 4 BP 763 EP 769 DI 10.1093/carcin/bgi013 PG 7 WC Oncology SC Oncology GA 911BR UT WOS:000227976700007 PM 15637090 ER PT J AU Gao, B AF Gao, Bin TI Cytokines, STATs and Liver Disease SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE cytokine; STAT; liver AB The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. C1 [Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, NIH, 5625 Fishers Lane,Rm 2S-24, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 118 TC 153 Z9 157 U1 0 U2 6 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD APR PY 2005 VL 2 IS 2 BP 92 EP 100 PG 9 WC Immunology SC Immunology GA V32AU UT WOS:000208924900002 PM 16191414 ER PT J AU Xie, XZ Chang, SW Tatsumoto, T Chan, AML Miki, T AF Xie, XZ Chang, SW Tatsumoto, T Chan, AML Miki, T TI TIM, a Dbl-related protein, regulates cell shape and cytoskeletal organization in a Rho-dependent manner SO CELLULAR SIGNALLING LA English DT Article ID NUCLEOTIDE EXCHANGE FACTORS; JUN NH2-TERMINAL KINASE; RAC SIGNALING PATHWAYS; HUMAN BREAST-CANCER; C-JUN; GUANOSINE TRIPHOSPHATASES; FAMILY PROTEINS; FOCAL ADHESIONS; STRESS FIBERS; ACTIVATION AB The Dbl-like guanine nucleotide exchange factors (GEFs) have been implicated in direct activation of the Rho family of small GTPases. We previously isolated transforming immortalized mammary (TIM) as a Dbl-like protein. Here, we show that, when expressed in cells, TIM was a potent activator of RhoA. Like activated Rho proteins, expression of TIM potentiated the serum response factor (SRF)- and AP-1 regualted transcriptional activities and activated the SAPK/JNK signaling pathway. In NIH 3T3 cells, TIM induced transforming foci, which was inhibited by the ROCK inhibitor Y-27632 or the dominant negative mutants of Rho proteins. Expression of TIM led to pronounced changes in cell shape and organization of the actin cytoskeleton, including the formation of thick stress fibers at the cell periphery and cell rounding. TIM also promoted redistribution of vinculin-enriched focal adhesions at the cell periphery and increased the phosphorylation of myosin light chain (MLC). These results, taken together, suggest that TIM acts as an upstream regulator for the RhoA/ROCK-mediated cellular functions. Published by Elsevier Inc. C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Fukuoka Teishin Hosp, Chuo Ku, Fukuoka 8108798, Japan. Derald H Ruttenberg Canc Ctr, Mt Sinai Sch Med, New York, NY 10029 USA. RP Miki, T (reprint author), NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM toru@helix.nih.gov NR 36 TC 16 Z9 17 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD APR PY 2005 VL 17 IS 4 BP 461 EP 471 DI 10.1016/j.cellsig.2004.09.012 PG 11 WC Cell Biology SC Cell Biology GA 887AO UT WOS:000226274900006 PM 15601624 ER PT J AU Oishi, S Shi, ZD Worthy, KM Bindu, LK Fisher, RJ Burke, TR AF Oishi, S Shi, ZD Worthy, KM Bindu, LK Fisher, RJ Burke, TR TI Ring-closing metathesis of C-terminal allylglycine residues with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic as an approach to novel Grb2 SH2 domain-binding macrocycles SO CHEMBIOCHEM LA English DT Article DE ligand design; macrocycles; medicinal chemistry; peptidomimmetics; ring-closing metathesis ID RAS SIGNALING PATHWAY; STRUCTURE-BASED DESIGN; HUMAN BREAST-CANCER; OLEFIN METATHESIS; AFFINITY; LIGANDS; SPECIFICITY; PROTEIN; SRC; INHIBITOR AB Ring-closing metathesis (RCM) of peptides often requires insertion of allylglycines at the intended sites of ring juncture, which can result in the displacement of residues that are needed for biological activity, This type of side-chain deletion can be avoided by appending beta-vinyl substituents onto the parent residues at the intended sites of ring juncture, thereby effectively converting them into functionalized allylglycine equivalents. Such an approach has been previously applied in modified form to growth-factor receptor bound 2 (Grb2) SH2 domain-binding peptides by using an N-terminal beta-vinyl-functionalized phosphotyrosyl mimetic and C-terminal 2-allyl-3-aryl-1-propanamides that locked the a-carboxyl portion of allylglycine residues. These C-terminal moieties involved lengthy synthesis and once prepared, required an individual total synthesis of each final macrocycle. Work reported herein significantly enhances the versatility of the original approach through the use of C-terminal allylglycine amides that can be prepared from commercially available L- and D-allylglycines and suitable amines. This methodology could be generally useful where macrocylization is desired with maintenance of functionality at a site of ring juncture. C1 NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014; Oishi, Shinya/C-1350-2011 OI Oishi, Shinya/0000-0002-2833-2539 NR 30 TC 21 Z9 21 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD APR PY 2005 VL 6 IS 4 BP 668 EP 674 DI 10.1002/cbic.200400298 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 916VD UT WOS:000228413500014 PM 15719347 ER PT J AU Chambers, DA Ringeisen, H Hickman, EE AF Chambers, DA Ringeisen, H Hickman, EE TI Federal, state, and foundation initiatives around evidence-based practices for child and adolescent mental health SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article AB This article is a survey of many of the initiatives developed by federal and state agencies and foundations focusing on evidence-based mental health practices for children and adolescents. The article intends to show the tremendous interest in the development, dissemination, and implementation of evidence-based practice in child and adolescent mental health that is held by a wide variety of agencies and organizations. Several "next steps" for the field are suggested that might be developed in a subsequent series of initiatives. These steps include a better understanding of dissemination and implementation processes, increased clarity around definitions and terms, increased efforts to build infrastructure and support policy change, and the potential for an aggregation of data already gathered on the implementation of evidence-based practices. C1 NIMH, NIH, Bethesda, MD 20892 USA. Ctr Medicare & Medicaid Serv, Dept Hlth & Human Serv, Baltimore, MD 21244 USA. RP Chambers, DA (reprint author), NIMH, NIH, MSC 9631,6001 Execut Blvd, Bethesda, MD 20892 USA. EM dachambers@mail.nih.gov NR 11 TC 41 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2005 VL 14 IS 2 BP 307 EP + DI 10.1016/j.chc.2004.04.006 PG 22 WC Psychiatry SC Psychiatry GA 900HJ UT WOS:000227205700009 PM 15694788 ER PT J AU Wasserman, DH Ayala, JE AF Wasserman, DH Ayala, JE TI Interaction of physiological mechanisms in control of muscle glucose uptake SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC DE glucose analogue; hexokinase; isotope; metabolism; skeletal muscle; transgenic ID RAT SKELETAL-MUSCLE; HIGH-FAT DIET; II MESSENGER-RNA; POSITRON-EMISSION-TOMOGRAPHY; DEPENDENT DIABETES-MELLITUS; INDUCED INSULIN-RESISTANCE; UPTAKE IN-VIVO; HEXOKINASE-II; BLOOD-FLOW; TRANSGENIC MICE AB 1. Control of glucose uptake is distributed between three steps. These are the rate that glucose is delivered to cells, the rate of transport into cells, and the rate that glucose is phosphorylated within these same cells. The functional limitations to each one of these individual steps has been difficult to assess because they are so closely coupled to each other. Studies have been performed in recent years using complex isotopic techniques or transgenic mouse models to shed new light on the role that each step plays in overall control of muscle glucose uptake. 2. Membrane glucose transport is a major barrier and glucose delivery and glucose phosphorylation are minor barriers to muscle glucose uptake in the fasted, sedentary state. GLUT-4 is translocated to the muscle membrane during exercise and insulin-stimulation. The result of this is that it can become so permeable to glucose that it is only a minor barrier to glucose uptake. 3. In addition to increasing glucose transport, exercise and insulin-stimulation also increase muscle blood flow and capillary recruitment. This effectively increases muscle glucose delivery and by doing so, works to enhance muscle glucose uptake. 4. There is a growing body of data that suggests that insulin resistance to muscle glucose uptake can be because of impairments in any one or more of the three steps that comprise the process. C1 Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. RP Wasserman, DH (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, 221 Kirkland Hall, Nashville, TN 37232 USA. EM david.wasserman@vanderbilt.edu FU NIDDK NIH HHS [U24 DK59637, R01 DK54902] NR 86 TC 28 Z9 29 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD APR PY 2005 VL 32 IS 4 BP 319 EP 323 DI 10.1111/j.1440-1681.2005.04191.x PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 912AH UT WOS:000228049000015 PM 15810999 ER PT J AU Shimizu, M Deguchi, A Lim, JTE Moriwaki, H Kopelovich, L Weinstein, IB AF Shimizu, M Deguchi, A Lim, JTE Moriwaki, H Kopelovich, L Weinstein, IB TI (-)-epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; HUMAN HEPATOMA-CELLS; GREEN TEA; CARCINOMA-CELLS; EGF RECEPTOR; GENE-EXPRESSION; CYCLIN D1; EPIGALLOCATECHIN GALLATE; ZD1839 IRESSA; HUMAN HEAD AB Purpose: (-)-Epigallocatechin gallate (EGCG) inhibits activation of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) and multiple downstream signaling pathways in cancer cell lines. In this study we compared the cellular and molecular effects of EGCG with a well-standardized decaffeinated green tea catechin mixture Polyphenon E (Poly E) on human colon cancer cell lines. Experimental Design and Results: Both EGCG and Poly E preferentially inhibited growth of the Caco2, HCT116, HT29, SW480, and SW837 colon cancer cells when compared with the FHC normal human fetal colon cell line. The EGFR and HER2 proteins were overexpressed and constitutively activated in all of the colon cancer cell lines when compared with the FHC cell line. Treatment of HT29 cells with EGCG or Poly E caused an increase of cells in G(1) and induced apoptosis. Both EGCG and Poly E caused a decrease in the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of the extracellular signal-regulated kinase and Akt proteins. Similar effects of these compounds were seen when the cells were stimulated with transforming growth factor alpha. Reporter assays indicated that both EGCG and Poly E inhibited the transcriptional activity of the activator protein 1 (AP-1), c-fos, nuclear factor kappa B, and cyclin D1 promoters. The combination of only 1 mu g/mL of epicatechin plus 10 mu g/mL of EGCG displayed synergistic effects on growth inhibition and induction of apoptosis. Furthermore, when treatment was prolonged for 96 hours, 1 mu g/mL of EGCG or Poly E was sufficient to inhibit growth, reduce activation of EGFR and HER2, and induce apoptosis. Conclusion: Our findings suggest that EGCG or Poly E may be useful in the chemoprevention and/or treatment of colon cancer. Poly E contains about 60% EGCG, yet pure EGCG and Poly E had similar potencies (expressed as mu g/mL). Poly E may be preferable because it is easier to prepare and this mixture of catechins may exert synergistic effects. C1 Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. Gifu Univ, Sch Med, Dept Med, Gifu 500, Japan. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Shimizu, M (reprint author), Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, HHSC-1509,701 W 168 St, New York, NY 10032 USA. NR 49 TC 190 Z9 203 U1 4 U2 11 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 APR 1 PY 2005 VL 11 IS 7 BP 2735 EP 2746 DI 10.1158/1078-0432.CCR-04-2014 PG 12 WC Oncology SC Oncology GA 915QX UT WOS:000228320100038 PM 15814656 ER PT J AU Eisenhofer, G Lenders, JWM Goldstein, DS Mannelli, M Csako, G Walther, MM Brouwers, F Pacak, K AF Eisenhofer, G Lenders, JWM Goldstein, DS Mannelli, M Csako, G Walther, MM Brouwers, F Pacak, K TI Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines SO CLINICAL CHEMISTRY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HIPPEL-LINDAU-SYNDROME; BIOCHEMICAL-DIAGNOSIS; ELECTROCHEMICAL DETECTION; NOREPINEPHRINE; EPINEPHRINE; ADRENALINE; MARKERS; TYPE-2 AB Background: Measurements of plasma free metanephrines (normetanephrine and metanephrine) provide a useful test for diagnosis of pheochromocytoma and may provide other information about the nature of these tumors. Methods: We examined relationships of tumor size, location, and catecholamine content with plasma and urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We then prospectively examined whether measurements of plasma free metanephrines could predict tumor size and location in an additional 16 patients. Results: Relative proportions of epinephrine and norepinephrine in tumor tissue were closely matched by relative increases of plasma or urinary metanephrine and normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed strong positive relationships with summed plasma concentrations or urinary outputs of metanephrine and normetanephrine (r = 0.81 and 0.77; P < 0.001), whereas relationships with plasma or urinary catecholamines were weaker (r = 0.41 and 0.44). All tumors in which increases in plasma metanephrine were > 15% of the combined increases of normetanephrine and metanephrine either had adrenal locations or appeared to be recurrences of previously resected adrenal tumors. Measurements of plasma free metanephrines predicted tumor diameter to within a mean of 30% of actual diameter, and high plasma concentrations of free metanephrine relative to normetanephrine accurately predicted adrenal locations. Conclusions: Measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures. (c) 2005 American Association for Clinical Chemistry. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Univ Nijmegen St Radboud Hosp, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Univ Florence, Dept Clin Pathophysiol, Florence, Italy. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Center Dr, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov RI Lenders, J.W.M./L-4487-2015; OI Mannelli, Massimo/0000-0002-8001-9857 NR 27 TC 70 Z9 73 U1 0 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 APR PY 2005 VL 51 IS 4 BP 735 EP 744 DI 10.1373/clinchem.2004.045484 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 910MW UT WOS:000227936600008 PM 15718487 ER PT J AU Bowen, RAR George, DT Hortin, GL AF Bowen, RAR George, DT Hortin, GL TI False-negative result for cocaine metabolites on a lateral-flow drug test slide corrected by dilution SO CLINICAL CHEMISTRY LA English DT Letter C1 NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Clin Chem Serv, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Clin Chem Serv, Bldg 10,Rm 2C-407,10 Center Dr, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2005 VL 51 IS 4 BP 790 EP 791 DI 10.1373/clinchem.2004.046607 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 910MW UT WOS:000227936600018 PM 15788788 ER PT J AU Koslow, SH AF Koslow, Stephen H. TI Discovery and integrative neuroscience SO CLINICAL EEG AND NEUROSCIENCE LA English DT Article DE analytical tools; biological models; computational biology; data integration; data sharing; databases; discovery neuroscience; electronic collaboration; neuroinformatics; simulations AB Hypothesis driven research has been shown to be an excellent model for pursuing investigations in neuroscience. The Human Genome Project demonstrated the added value of discovery research, especially in areas where large amounts of data are produced. Neuroscience has become a data rich field, and one that would be enhanced by incorporating the discovery approach. Databases, as well as analytical, modeling and simulation tools, will have to be developed, and they will need to be interoperable and federated. This paper presents an overview of the development of the field of neuroscience databases and associate tools: Neuroinformatics. The primary focus is on the impact of NIH funding of this process. The important issues of data sharing, as viewed from the perspective of,the scientist and private and public funding organizations, are discussed. Neuroinformatics will provide more than just a sophisticated array of information technologies to help scientists understand and integrate nervous system data. It will make available powerful models of neural functions and facilitate discovery, hypothesis formulation and electronic collaboration. C1 NIMH, NIH, Bethesda, MD 20892 USA. Off Neuroinformat, Bethesda, MD USA. RP Koslow, SH (reprint author), Allen Inst Brain Sci, 551 N 34th St, Seattle, WA 98103 USA. EM steveko@alleninstitute.org NR 66 TC 8 Z9 8 U1 2 U2 4 PU EEG & CLINICAL NEUROSCIENCE SOC (E C N S) PI WHEATON PA 805 W LIBERTY DR, PO BOX 725, WHEATON, IL 60187 USA SN 1550-0594 J9 CLIN EEG NEUROSCI JI Clin. EEG Neurosci. PD APR PY 2005 VL 36 IS 2 BP 55 EP 63 PG 9 WC Clinical Neurology; Neurosciences; Neuroimaging; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA V44CJ UT WOS:000202980500002 PM 15999900 ER PT J AU Kim, UK Drayna, D AF Kim, UK Drayna, D TI Genetics of individual differences in bitter taste perception: lessons from the PTC gene SO CLINICAL GENETICS LA English DT Review DE bitter; gene; haplotypes; PTC; taste ID NORTHEASTERN BRAZIL; NATURAL-SELECTION; LINKAGE RELATIONS; PHENYLTHIOCARBAMIDE; SENSITIVITY; LOCUS; FOOD; MARKERS; FAMILY; TRAIT AB The ability or inability to taste the compound phenylthiocarbamide (PTC) is a classic inherited trait in humans and has been the subject of genetic and anthropological studies for over 70 years. This trait has also been shown to correlate with a number of dietary preferences and thus may have important implications for human health. The recent identification of the gene that underlies this phenotype has produced several surprising findings. This gene is a member of the T2R family of bitter taste receptor genes. It exists in seven different allelic forms, although only two of these, designated the major taster and major non-taster forms, exist at high frequency outside sub-Saharan Africa. The non-taster allele resides on a small chromosomal region identical by descent, indicating that non-tasters are descended from an ancient founder individual, and consistent with an origin of the non-taster allele preceding the emergence of modern humans out of Africa. The two major forms differ from each other at three amino acid positions, and both alleles have been maintained at high frequency by balancing natural selection, suggesting that the non-taster allele serves some function. We hypothesize that this function is to serve as a receptor for another, as yet unidentified toxic bitter substance. At least some of the remaining five haplotypes appear to confer intermediate sensitivity to PTC, suggesting future detailed studies of the relationships between receptor structure and taste function. C1 NIDCD, NIH, Rockville, MD 20850 USA. RP Drayna, D (reprint author), NIDCD, NIH, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU PHS HHS [Z01-000046-06] NR 27 TC 66 Z9 68 U1 19 U2 260 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2005 VL 67 IS 4 BP 275 EP 280 DI 10.1111/j.1399-0004.2004.00361.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 901WW UT WOS:000227313900001 PM 15733260 ER PT J AU Zangen, A Roth, Y Voller, B Hallett, M AF Zangen, A Roth, Y Voller, B Hallett, M TI Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; deep brain stimulation; magnetic coil; motor threshold; electric field ID ELECTRIC-FIELD; ELECTROMAGNETIC INDUCTION; MOTOR CORTEX; ACTIVATION; HUMANS; DESIGN; VOLUME; PULSE; AREA AB Objective: Standard coils used in research and the clinic for noninvasive magnetic stimulation of the human brain are not capable of stimulating deep brain regions directly. As the fields induced by these coils decrease rapidly as a function of depth, only very high intensities would allow functional stimulation of deep brain regions and such intensities would lead to undesirable side effects. We have designed a coil based on numerical simulations and phantom brain measurements that allows stimulation of deeper brain regions, termed the Hesed coil (H-coil). In the present study we tested the efficacy and some safety aspects of the H-coil on healthy volunteers. Methods: The H-coil was compared to a regular figure-8 coil in 6 healthy volunteers by measuring thresholds for activation of the abductor pollicis brevis (APB) representation in the motor cortex as a function of distance from each of the coils. Results: The rate of decrease in the coil intensity as a function of distance is markedly slower for the H-coil. The motor cortex could be activated by the H-coil at a distance of 5.5 cm compared to 2 cm with the figure-8 coil. Conclusions: The present study indicate that the H-coil is likely to have the ability of deep brain stimulation and without the need of increasing the intensity to extreme levels that would cause a much greater stimulation in cortical regions. Significance: The ability of non-invasive deep brain stimulation potentially opens a wide range of both research and therapeutic applications. (c) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. Natl Inst Drug Abuse, NIH, Baltimore, MD USA. Chaim Sheba Med Ctr, New Adv Technol Ctr, IL-52621 Tel Hashomer, Israel. NINDS, NIH, Bethesda, MD 20892 USA. RP Zangen, A (reprint author), Weizmann Inst Sci, Dept Neurobiol, POB 26, IL-76100 Rehovot, Israel. EM a.zangen@weizmann.ac.il OI Voller, Bernhard/0000-0001-5809-874X NR 20 TC 151 Z9 155 U1 6 U2 16 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2005 VL 116 IS 4 BP 775 EP 779 DI 10.1016/j.clinph.2004.11.008 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 919GU UT WOS:000228607200004 PM 15792886 ER PT J AU Fishbein, DH Eldreth, DL Hyde, C Matochik, JA London, ED Contoreggi, C Kurian, V Kimes, AS Breeden, A Grant, S AF Fishbein, DH Eldreth, DL Hyde, C Matochik, JA London, ED Contoreggi, C Kurian, V Kimes, AS Breeden, A Grant, S TI Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers SO COGNITIVE BRAIN RESEARCH LA English DT Review DE neural basis of behavior; cognition, drugs of abuse; decision making; drug abuse; anterior cingulate cortex; neuroimaging; PET imaging ID SUBSTANCE USE DISORDER; DEFICIT HYPERACTIVITY DISORDER; MEDIAL-FRONTAL-CORTEX; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; AGGRESSIVE-BEHAVIOR; FUTURE CONSEQUENCES; COCAINE ABUSERS; NEUROCOGNITIVE IMPAIRMENT; PERSONALITY-DISORDERS AB Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (>= 3 months) and healthy controls who underwent positron emission tomography scans with (H2O)-O-15. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes. (c) 2005 Elsevier B.V. All rights reserved. C1 RTI Int, Transdisciplinary Behav Sci Program, Baltimore, MD 21224 USA. BioAssessments Inc, Elkton, MD 21921 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Calif Los Angeles, Brain Res Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. NIDA, Div Clin Neurobiol Dev & Behav Treatment, Bethesda, MD 20892 USA. RP Fishbein, DH (reprint author), RTI Int, Transdisciplinary Behav Sci Program, 6801 Eastern Ave,Suite 203, Baltimore, MD 21224 USA. EM dfishbein@rti.org NR 103 TC 85 Z9 88 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD APR PY 2005 VL 23 IS 1 BP 119 EP 136 DI 10.1016/j.cogbrainres.2004.12.0 PG 18 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 919ZF UT WOS:000228655800012 ER PT J AU Rejeski, WJ Fielding, RA Blair, SN Guralnik, JM Gill, TM Hadley, EC King, AC Kritchevsky, SB Miller, ME Newman, AB Pahor, M AF Rejeski, WJ Fielding, RA Blair, SN Guralnik, JM Gill, TM Hadley, EC King, AC Kritchevsky, SB Miller, ME Newman, AB Pahor, M TI The lifestyle interventions and independence for elders (LIFE) pilot study: Design and methods SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE physical activity; disability; mobility; pre-frail older adults; mortality; group mediated interventions; functional limitations; randomized clinical trials; aging ID COUNSELING TRIAL ACT; PHYSICAL-ACTIVITY; OLDER-ADULTS; KNEE OSTEOARTHRITIS; RANDOMIZED-TRIAL; AEROBIC EXERCISE; HEALTH; MAINTENANCE; DISABILITY; DISEASE AB The LIFE study is a multicenter pilot for a proposed full scale, two-arm randomized controlled trial that will contrast the effect of a physical activity intervention with a successful aging education program on the occurrence of incident major mobility disability (the inability to complete a 400 m walk) or death in at-risk sedentary older adults. Four hundred older adults from 4 clinical sites will be recruited for this purpose. All participants will be followed for at least 1-year; however, we will continue to follow all participants until the final randomized individual has reached the 1-year mark. This will enable us to acquire additional information about maintenance. Additional outcomes will include lower extremity physical performance as well as gait speed over 4 m and 400 m. These latter measures will provide data on the efficacy of the intervention on intermediate endpoints linked to the primary outcome of interest. The goals of the pilot study are to (a) estimate the sample size needed for a full scale trial, (b) examine the consistency of the effects of the physical activity intervention on several continuous measures of physical function, (c) assess the feasibility of recruitment, (d) evaluate study adherence and retention, (d) evaluate the efficacy of a stepped care approach for managing intercurrent illness in this at-risk population, and (e) develop a comprehensive system for monitoring and ensuring participant safety. Other goals of this pilot phase include assessments of health-related quality of life and cost-effectiveness. © 2004 Elsevier Inc. All rights reserved. C1 Wake Forest Univ, Dept HES, Winston Salem, NC 27109 USA. Boston Univ, Boston, MA 02215 USA. Cooper Inst, Dallas, TX USA. NIA, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT 06520 USA. Stanford Univ, Stanford, CA 94305 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Rejeski, WJ (reprint author), Wake Forest Univ, Dept HES, Box 7868, Winston Salem, NC 27109 USA. EM rejeski@wfu.edu RI Newman, Anne B./C-6408-2013; OI Newman, Anne B./0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NCRR NIH HHS [UL1 RR029890]; NIA NIH HHS [P30 AG028740, R21 AG19353-01, U01 AG022376] NR 39 TC 81 Z9 81 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD APR PY 2005 VL 26 IS 2 BP 141 EP 154 DI 10.1016/j.cct.2004.12.005 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 926TB UT WOS:000229144700004 PM 15837437 ER PT J AU Toy, P Popovsky, MA Abraham, E Daniel, R Ambruso, DR Holness, LG Kopko, PM McFarland, JG Nathens, AB Silliman, CC Stroncek, D AF Toy, P Popovsky, MA Abraham, E Daniel, R Ambruso, DR Holness, LG Kopko, PM McFarland, JG Nathens, AB Silliman, CC Stroncek, D CA Natl Heart Lung Blood Inst TI Transfusion-related acute lung injury: Definition and review SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT TRALI Consensus Conference CY APR 01-02, 2004 CL Toronto, CANADA DE blood transfusion; red blood cell transfusion; platelet transfusion; acute lung injury; acute respiratory distress syndrome; shock lung; critical care ID RESPIRATORY-DISTRESS SYNDROME; EUROPEAN CONSENSUS CONFERENCE; CLINICAL-TRIAL COORDINATION; PLATELET-ACTIVATING-FACTOR; NEUTROPHIL NADPH OXIDASE; STORED-BLOOD COMPONENTS; PULMONARY-EDEMA; LEUKOCYTE ANTIBODIES; MASSIVE TRANSFUSION; RELEVANT OUTCOMES AB Background., Transfusion-related acute lung injury (TRALI) is now the leading cause of transfusion-associated mortality, even though it is probably still underdiagnosed and underreported. National Heart, Lung, and Blood Institute Action. The National Heart, Lung, and Blood Institute convened a working group to identify areas of research needed in TRALI. The working group identified the immediate need for a common definition and thus developed the clinical definition in this report. Major Concepts in the Definition. The major concept is that TRALI is defined as new acute lung injury occurring during or within 6 hrs after a transfusion, with a clear temporal relationship to the transfusion. Also, another important concept is that acute lung injury temporally associated with multiple transfusions can be TRALI, because each unit of blood or blood component can carry one or more of the possible causative agents: antileukocyte antibody, biologically active substances, and other yet unidentified agents. Recommendation. Using the definition in this report, clinicians can diagnose and report TRALI cases to the blood bank; importantly, researchers can use this definition to determine incidence, pathophysiology, and strategies to prevent this leading cause of transfusion-associated mortality. C1 UCSF, Sch Med, Lab Med, San Francisco, CA 94143 USA. Haemonet Corp, Braintree, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Colorado, Sch Med, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Bonfils Blood Ctr, Denver, CO USA. US FDA, Ctr Biol Evaluat & Res, Div Blood Applicat, Off Blood Res & Review, Rockville, MD 20857 USA. Blood Source, Sacramento, CA USA. Blood Ctr SE Wisconsin Inc, Platelet & Neutrophil Immunol Lab, Milwaukee, WI 53233 USA. Univ Washington, Seattle, WA 98195 USA. Harborview Med Ctr, Harborview Injury Prevent Ctr, Acute Care Sect, Seattle, WA 98104 USA. Harborview Med Ctr, Harborview Injury Prevent Ctr, Surg Crit Care Serv, Seattle, WA 98104 USA. NIH, Warren G Magnuson Clin Ctr, Lab Serv Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Toy, P (reprint author), UCSF, Sch Med, Lab Med, Box 0100, San Francisco, CA 94143 USA. NR 49 TC 329 Z9 353 U1 0 U2 8 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 APR PY 2005 VL 33 IS 4 BP 721 EP 726 DI 10.1097/01.CCM.0000159849.94750.51 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 915FF UT WOS:000228282700004 PM 15818095 ER PT J AU Silverman, HJ Luce, JM Lanken, PN Morris, AH Harabin, AL Oldmixon, CF Thompson, BT Bernard, GR AF Silverman, HJ Luce, JM Lanken, PN Morris, AH Harabin, AL Oldmixon, CF Thompson, BT Bernard, GR CA NHLBI ARDSNet TI Recommendations for informed consent forms for critical care clinical trials SO CRITICAL CARE MEDICINE LA English DT Review DE informed consent; research ethics; critical care; proxy consent; clinical trials ID ACUTE MYOCARDIAL-INFARCTION; THERAPEUTIC MISCONCEPTION; READABILITY; EMERGENCY; OUTCOMES; RISKS; DRUG AB Background., Many subjects enrolled in research studies have a limited understanding of the research to which they consented. Objective: To develop recommendations to enhance comprehensiveness and understanding of informed consent forms used in critical care clinical trials. Design: Consensus process. Recommendations. We provide recommendations regarding the U.S. federally required basic and additional elements of informed consent as applied to critical care clinical trials. We also identify issues that investigators need to address, if relevant, in the informed consent forms of critical care clinical trials. These include the description, in understandable language, of complex and detailed experimental protocols that are the focus of the clinical trial, disclosure of death as a risk factor if mortality is an outcome variable, and the identification of who can legally serve as the prospective subject's surrogate. We also offer suggestions to enhance subjects' understanding of informed consent forms. Conclusions. The literature on informed consent forms suggest that shorter informed consent forms written at a lower reading level, when read carefully, might provide better subject understanding. Prospective evaluation is needed to determine whether our recommendations enhance the informed consent process. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Penn, Sch Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. Univ Utah, Salt Lake City, UT 84112 USA. LDS Hosp, Div Pulm, Salt Lake City, UT USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. RP Silverman, HJ (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. FU NHLBI NIH HHS [N01 HR 46054-64] NR 49 TC 36 Z9 38 U1 2 U2 4 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 APR PY 2005 VL 33 IS 4 BP 867 EP 882 DI 10.1097/01.CCM.0000159201.08203.10 PG 16 WC Critical Care Medicine SC General & Internal Medicine GA 915FF UT WOS:000228282700026 PM 15818118 ER PT J AU Rhee, SG Kang, SW Jeong, W Chang, TS Yang, KS Woo, HA AF Rhee, SG Kang, SW Jeong, W Chang, TS Yang, KS Woo, HA TI Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID TYROSINE-PHOSPHATASE 1B; CYSTEINE-SULFINIC ACID; THIOL-SPECIFIC ANTIOXIDANT; EPIDERMAL-GROWTH-FACTOR; ACTIVE-SITE CYSTEINE; REACTIVE OXYGEN; REVERSIBLE INACTIVATION; MAMMALIAN PEROXIREDOXIN; SIGNAL-TRANSDUCTION; TUMOR-SUPPRESSOR AB Hydrogen peroxide (H2O2) accumulates transiently in various cell types stimulated with peptide growth factors and participates in receptor signaling by oxidizing the essential cysteine residues of protein tyrosine phosphatases and the lipid phosphatase PTEN. The reversible inactivation of these phosphatases by H2O2 is likely required to prevent futile cycles of phosphorylation-dephosphorylation of proteins and phosphoinositides. The accumulation of H2O2 is possible even in the presence of large amounts of the antioxidant enzymes peroxiredoxin I and II in the cytosol, probably because of a built-in mechanism of peroxiredoxin inactivation that is mediated by H2O2 and reversed by an ATIP-dependent reduction reaction catalyzed by sulfiredoxin. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 47 TC 433 Z9 456 U1 3 U2 29 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2005 VL 17 IS 2 BP 183 EP 189 DI 10.1016/j.ceb.2005.02.004 PG 7 WC Cell Biology SC Cell Biology GA 914GI UT WOS:000228215400013 PM 15780595 ER PT J AU Laky, K Fowkes, BJ AF Laky, K Fowkes, BJ TI Receptor signals and nuclear events in CD4 and CD8 T cell lineage commitment SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID POSITIVE SELECTION; THYMOCYTE DEVELOPMENT; LYMPHOCYTE DEVELOPMENT; GENE-EXPRESSION; IN-VIVO; DIFFERENTIATION; NOTCH; MICE; DECISION; THYMUS AB MHC specificity in positive selection is a major determinant in the CD4/CD8 T cell lineage decision. Previous studies support the view that quantitative differences in T cell receptor (TCR) signaling in immature CD4(+)CD8(+) double positive thymocytes leads to an instructive bias in CD4/CD8 T cell lineage commitment that must be re-inforced in subsequent selection steps to ensure that MHC-restricted antigen recognition is linked to appropriate effector functions in mature T cells. Recent work has further defined the TCR signaling pathways involved in this process, but a major effort has been made to identify transcription factors and other regulators of CID4 and CD8 T cell lineage commitment. Methods and screens for detecting changes in gene expression, associated with TCR signaling in positive selection and lineage determination, are starting to provide a better understanding of these complex developmental processes. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Laky, K (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM klaky@niaid.nih.gov; bfowlkes@nih.gov NR 51 TC 22 Z9 22 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2005 VL 17 IS 2 BP 116 EP 121 DI 10.1016/j.coi.2005.02.004 PG 6 WC Immunology SC Immunology GA 910BL UT WOS:000227904300004 PM 15766669 ER PT J AU Wrzesinski, C Restifo, NP AF Wrzesinski, C Restifo, NP TI Less is more: lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor immunotherapy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID BASAL HOMEOSTATIC PROLIFERATION; CUTTING EDGE; IN-VIVO; CANCER REGRESSION; TUMOR-IMMUNITY; LUNG-CANCER; NAIVE; MEMORY; CD4(+); EXPANSION AB Adoptive T-cell immunotherapy combined with nonmyeloablative lymphodepletion has emerged as the most effective immunotherapy treatment for patients with metastatic melanoma (objective response rates of 50%). The mechanisms underlying this major advance in the field of immunotherapy include the elimination of regulatory elements and increased access to activating cytokines. This results in the activation of low-affinity T cells, enabling them to destroy tumors. We propose that a more complete depletion of the patient's immune system followed by transplantation with hematopoietic stem cells, which can be genetically modified, would be more effective in the treatment of metastatic cancer. C1 NCI, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Wrzesinski, C (reprint author), NCI, NIH, Clin Res Ctr, Room 3-5816,10 Ctr Dr, Bethesda, MD 20892 USA. EM wrzesinc@mail.nih.gov RI Wrzesinski, Claudia/A-3077-2008; Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 60 TC 68 Z9 70 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2005 VL 17 IS 2 BP 195 EP 201 DI 10.1016/j.coi.2005.02.002 PG 7 WC Immunology SC Immunology GA 910BL UT WOS:000227904300016 PM 15766681 ER PT J AU Zhang, MY Choudhry, V Xiao, XD Dimitrov, DS AF Zhang, MY Choudhry, V Xiao, XD Dimitrov, DS TI Human monoclonal antibodies to the S glycoprotein and related proteins as potential therapeutics for SARS SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE antibodies; prophylaxis; SARS; S glycoprotein; S protein; therapy; treatment ID ACUTE RESPIRATORY SYNDROME; CORONAVIRUS SPIKE PROTEIN; ANGIOTENSIN-CONVERTING ENZYME-2; NEUTRALIZING ANTIBODIES; PROTECTIVE IMMUNITY; INFECTIOUS-DISEASES; AFRICAN-GREEN; BALB/C MICE; VIRUS; VACCINE AB Polyclonal antibodies have a century-old history of being effective against some viruses and, recently, monoclonal antibodies (mAbs) have also shown some clinical success. Human mAbs to the severe acute respiratory syndrome (SARS) coronavirus spike glycoprotein have been developed by several research groups at an amazing pace. These antibodies potently neutralize infectious virus in tissue cultures and animal models, and, alone or in combination with vaccines and other drugs, may have potential for the prevention and treatment of SARS. C1 NCI, NIH, Frederick Ctr Canc Res, Lab Expt & Computat Biol,Prot Interact Grp, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, NIH, Frederick Ctr Canc Res, Lab Expt & Computat Biol,Prot Interact Grp, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov NR 54 TC 12 Z9 14 U1 0 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD APR PY 2005 VL 7 IS 2 BP 151 EP 156 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 916XT UT WOS:000228420800009 PM 15844623 ER PT J AU Friederici, AD Ungerleider, LG AF Friederici, AD Ungerleider, LG TI Cognitive neuroscience SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Editorial Material C1 Max Planck Inst Human Cognit & Brain Sci, Dept Neurpsychol, D-04103 Leipzig, Germany. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Friederici, AD (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Neurpsychol, Stephanstr 1A, D-04103 Leipzig, Germany. EM angelafr@cbs.mpg.de; ungerlel@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2005 VL 15 IS 2 BP 131 EP 134 DI 10.1016/j.conb.2005.03.019 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 925OT UT WOS:000229063100001 PM 15831393 ER PT J AU Beauchamp, MS AF Beauchamp, MS TI See me, hear me, touch me: multisensory integration in lateral occipital-temporal cortex SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID HUMAN VISUAL-CORTEX; CEREBRAL-CORTEX; RHESUS-MONKEY; HUMAN BRAIN; OBJECT RECOGNITION; AUDIOVISUAL SPEECH; MACAQUE MONKEY; MOTION; SULCUS; REPRESENTATION AB Our understanding of multisensory integration has advanced because of recent functional neuroimaging studies of three areas in human lateral occipito-temporal cortex: superior temporal sulcus, area LO and area MT (V5). Superior temporal sulcus is activated strongly in response to meaningful auditory and visual stimuli, but responses to tactile stimuli have not been well studied. Area LO shows strong activation in response to both visual and tactile shape information, but not to auditory representations of objects. Area MT, an important region for processing visual motion, also shows weak activation in response to tactile motion, and a signal that drops below resting baseline in response to auditory motion. Within superior temporal sulcus, a patchy organization of regions is activated in response to auditory, visual and multisensory stimuli. This organization appears similar to that observed in polysensory areas in macaque superior temporal sulcus, suggesting that it is an anatomical substrate for multisensory integration. A patchy organization might also be a neural mechanism for integrating disparate representations within individual sensory modalities, such as representations of visual form and visual motion. C1 NIMH, Lab Brain & Cognit, Intramural Res Program, Dept Hlth & Human Serv,NIH, Bethesda, MD USA. RP Beauchamp, MS (reprint author), NIMH, Lab Brain & Cognit, Intramural Res Program, Dept Hlth & Human Serv,NIH, Bethesda, MD USA. OI Beauchamp, Michael/0000-0002-7599-9934 NR 55 TC 174 Z9 175 U1 5 U2 17 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2005 VL 15 IS 2 BP 145 EP 153 DI 10.1016/j.conb.2005.03.011 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 925OT UT WOS:000229063100003 PM 15831395 ER PT J AU Steven, AC Heymann, JB Cheng, NQ Trus, BL Conway, JF AF Steven, AC Heymann, JB Cheng, NQ Trus, BL Conway, JF TI Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID HERPES-SIMPLEX-VIRUS; QUATERNARY STRUCTURE CHANGES; CRYOELECTRON MICROSCOPY; SCAFFOLDING PROTEIN; ANGSTROM RESOLUTION; CAPSID MATURATION; RNA VIRUS; DNA; BACTERIOPHAGE-P22; ARCHITECTURE AB For many viruses, the final stage of assembly involves structural transitions that convert an innocuous precursor particle into an infectious agent. This process - maturation - is controlled by proteases that trigger large-scale conformational changes. In this context, protease inhibitor antiviral drugs act by blocking maturation. Recent work has succeeded in determining the folds of representative examples of the five major proteins major capsid protein, scaffolding protein, portal, protease and accessory protein - that are typically involved in capsid assembly. These data provide a framework for detailed mechanistic investigations and elucidation of mutations that affect assembly in various ways. The nature of the conformational change has been elucidated: it entails rigid-body rotations and translations of the arrayed subunits that transfer the interactions between them to different molecular surfaces, accompanied by refolding and redeployment of local motifs. Moreover, it has been possible to visualize maturation at the submolecular level in movies based on time-resolved cryo-electron microscopy. C1 NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Inst Biol Struct JP Ebel, F-38027 Grenoble, France. RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. EM alasdair_Steven@nih.gov RI Heymann, Bernard/F-6825-2011; OI Conway, James/0000-0002-6581-4748; Heymann, Bernard/0000-0002-8872-5326 FU CIT NIH HHS [Z01 CT000090-25] NR 62 TC 119 Z9 120 U1 0 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2005 VL 15 IS 2 BP 227 EP 236 DI 10.1016/j.sbi.2005.03.008 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 925PU UT WOS:000229065800015 PM 15837183 ER PT J AU Wolfson, HJ Shatsky, M Schneidman-Duhovny, D Dror, O Shulman-Peleg, A Ma, BY Nussinov, R AF Wolfson, HJ Shatsky, M Schneidman-Duhovny, D Dror, O Shulman-Peleg, A Ma, BY Nussinov, R TI From structure to function: Methods and applications SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE structural pattern discovery; structural genomics; structure comparison; structural alignment; docking; drug design; conservation; flexible structural alignment; flexible docking; multiple structural alignment; folding; hinge-bending ID PROTEIN-PROTEIN DOCKING; 3D COORDINATE TEMPLATES; STRUCTURE ALIGNMENT; MOLECULAR DOCKING; GENETIC ALGORITHM; BINDING-SITE; STRUCTURE CLASSIFICATIONS; CONFORMATIONAL-CHANGES; SHAPE COMPLEMENTARITY; STRUCTURE PREDICTION AB The rapid increase in experimental data along with recent progress in computational methods has brought modem biology a step closer toward solving one of the most challenging problems: prediction of protein function. Comprehension of protein function at its most basic level requires understanding of molecular interactions. Currently, it is becoming universally accepted that the scale of the accumulated data for analysis and for prediction necessitate highly efficient computational tools with appropriate application capabilities. The review presents the up-to-date advances in computational methods for structural pattern discovery and for prediction of molecular associations. We focus on their applications toward a range of biological problems and highlight the advantages of the combination of these methods and their integration with biological experiments. We provide examples, synergistically merging structural modeling, rigid and flexible structural alignment and detection of conserved structural patterns and docking (rigid and flexible with hinge-bending movements). We hope the review will lead to a broader utilization of computational methods, and their cross-fertilization with experiment. C1 SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI, Bldg 469,Rm 151, Ft Detrick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011; Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 115 TC 23 Z9 24 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PD APR PY 2005 VL 6 IS 2 BP 171 EP 183 DI 10.2174/1389203053545435 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 918TL UT WOS:000228570400005 PM 15853653 ER PT J AU Fukushige, T Krause, M AF Fukushige, T Krause, M TI The myogenic potency of HLH-1 reveals wide-spread developmental plasticity in early C-elegans embryos SO DEVELOPMENT LA English DT Article DE C. elegans; MyoD; muscle; myogenesis ID STRIATED-MUSCLE DEVELOPMENT; MYOD HOMOLOG HLH-1; CAENORHABDITIS-ELEGANS; SKELETAL-MUSCLE; BLASTOMERE IDENTITY; CELL FATE; HOMEODOMAIN PROTEIN; ECTOPIC EXPRESSION; SINGLE BLASTOMERE; POLARITY SIGNALS AB In vertebrates, striated muscle development depends on both the expression of members of the myogenic regulatory factor family (MRFs) and on extrinsic cellular cues, including Wnt signaling. The 81 embryonically born body wall muscle cells in C elegans are comparable to the striated muscle of vertebrates. These muscle cells all express the gene hlh-1, encoding HLH-1 (CeMyoD) which is the only MRF-related factor in the nematode. However, genetic studies have shown that body wall muscle development occurs in the absence of HLH-1 activity, making the role of this factor in nematode myogenesis unclear. By ectopically expressing hlh-1 in early blastomeres of the C. elegans embryo, we show that CeMyoD is a bona fide MRF that can convert almost all cells to a muscle-like fate, regardless of their lineage of origin. The window during which ectopic HLH-1 can function is surprisingly broad, spanning the first 3 hours of development when cell lineages are normally established and non-muscle cell fate markers begin to be expressed. We have begun to explore the maternal factors controlling zygotic hlh-1 expression. We find that the Caudal-related homeobox factor PAL-1 can activate hlh-1 in blastomeres that either lack POP-1/TCF or that have down-regulated POP-1/TCF in response to Wnt/MAP kinase signaling. The potent myogenic activity of HLH-1 highlights the remarkable developmental plasticity of early C. elegans blastomeres and reveals the evolutionary conservation of MyoD function. C1 NIDDKD, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. RP Krause, M (reprint author), NIDDKD, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. EM mwkrause@helix.nih.gov OI Krause, Michael/0000-0001-6127-3940 NR 82 TC 67 Z9 80 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 APR PY 2005 VL 132 IS 8 BP 1795 EP 1805 DI 10.1242/dev.01774 PG 11 WC Developmental Biology SC Developmental Biology GA 926DO UT WOS:000229103300005 PM 15772130 ER PT J AU Thomas, BJ AF Thomas, BJ TI Cell-cycle control during development: Taking it up a notch SO DEVELOPMENTAL CELL LA English DT Editorial Material ID DROSOPHILA EYE DEVELOPMENT; PATTERN-FORMATION; PROGRESSION; G(1) C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thomas, BJ (reprint author), NCI, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 14 Z9 16 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR PY 2005 VL 8 IS 4 BP 451 EP 452 DI 10.1016/j.devcel.2005.03.013 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 917DG UT WOS:000228435600001 PM 15809024 ER PT J AU Atkinson, JJ Holmbeck, K Yamada, S Birkedal-Hansen, H Parks, WC Senior, RM AF Atkinson, JJ Holmbeck, K Yamada, S Birkedal-Hansen, H Parks, WC Senior, RM TI Membrane-type 1 matrix metalloproteinase is required for normal alveolar development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE matrix metalloproteinase; lung; alveolar; ernphysema; development; Clara; pore ID DEVELOPING MOUSE LUNG; GROWTH-FACTOR; EXTRACELLULAR-MATRIX; BRANCHING MORPHOGENESIS; MT1-MMP-DEFICIENT MICE; INTERALVEOLAR PORES; ELECTRON-MICROSCOPY; CONNECTIVE-TISSUE; EGF RECEPTOR; EMPHYSEMA AB Matrix metalloproteinases (MMPs) are expressed during lung development, but their role may be limited, as mice deficient in MMP-3, 7, 9, or 12 develop a normal adult lung. Because membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in the developing lung epithelium, we examined the lung structure of MT1-MMP- deficient (-/-) mice. Branching morphogenesis was normal, but alveolar development was abnormal in the MT1-MMP-/- lungs with 40% less alveolar surface area at 1 month (P < 0.01). MT1-/IMP-/- airways and alveoli had an abnormal ultrastructural appearance, but epithelial cell differentiation markers were distributed similarly in both strains. There was no evidence of excess extracellular matrix deposition or inflammation at the time points examined. In contrast, by adulthood MMP-2-/- mice had normal alveolar size and structure, indicating normal alveolar development was not dependent on the ability of MT1-MMP to activate pro-MMP-2. These data indicate that MT1-MMP is required for normal lung development. (c) 2005 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Internal Med, Div Pulm & Crit Care, St Louis, MO USA. NIDCR, Skeletal Dis Branch, Matrix Metalloproteinase Unit, NIH, Bethesda, MD USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Senior, RM (reprint author), Barnes Jewish Hosp, 216 S Kingshighway,Campus Box 8052, St Louis, MO 63110 USA. EM rsenior@im.wustl.edu FU NHLBI NIH HHS [HL29594, HL47328, HL56419, T32 HL07317] NR 65 TC 54 Z9 56 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 2005 VL 232 IS 4 BP 1079 EP 1090 DI 10.1002/dvdy.20267 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 912ZO UT WOS:000228119400022 PM 15739229 ER PT J AU Tataranni, PA Ortega, E AF Tataranni, PA Ortega, E TI A burning question - Does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? SO DIABETES LA English DT Review ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE ATHEROSCLEROSIS; SCOTLAND CORONARY PREVENTION; MULTIPLE SERINE KINASES; ACUTE-PHASE PROTEINS; HUMAN ADIPOSE-TISSUE; BLOOD-CELL COUNT; MIDDLE-AGED MEN; METABOLIC SYNDROME AB There is growing support for the hypothesis that obesity is an inflammatory condition leading to chronic activation of the innate immune system, which ultimately causes progressive impairment of glucose tolerance. Experimental studies in animals and evidence from prospective and longitudinal studies in humans are consistent with an etiologic role of subclinical inflammation in the pathogenesis of type 2 diabetes, primarily as a mediator of obesity-induced insulin resistance. However, the exact chain of molecular events linking overnutrition, activation of the innate immune system, and impairment of insulin signaling in peripheral tissues remains incompletely understood. Notwithstanding this limitation, treating the underlying subclinical inflammation may constitute a novel approach to prevention and/or treatment of type 2 diabetes. C1 NIDDKD, Obes & Diabe Clin Res Sect, Dept Hlth & Human Serv, NIH, Phoenix, AZ USA. RP Tataranni, PA (reprint author), Sanofi Aventis, 42-50 Quai Rapee, F-75601 Paris, France. EM antonio.tataranni@sanofi-aventis.com NR 113 TC 134 Z9 144 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2005 VL 54 IS 4 BP 917 EP 927 DI 10.2337/diabetes.54.4.917 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 912QM UT WOS:000228094300001 PM 15793228 ER PT J AU Scuteri, A Najjar, SS Morrell, CH Lakatta, EG AF Scuteri, A Najjar, SS Morrell, CH Lakatta, EG TI The metabolic syndrome in older individuals: Prevalence and prediction of cardiovascular events - The Cardiovascular Health Study SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE SYNDROME; SAN-ANTONIO HEART; CAROTID ATHEROSCLEROSIS; DIABETES-MELLITUS; MORTALITY; DISEASE; DEFINITIONS; WOMEN; MEN AB OBJECTIVE - The prevalence of the metabolic syndrome, a potent risk factor for cardiovascular diseases (CVDs), has not been adequately explored in older individuals. Moreover, two sets of criteria have been proposed for the definition of metabolic syndrome, one by the World Health Organization (WHO) and one by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). We therefore investigated the prevalence of this syndrome in a subgroup of older participants from the Cardiovascular Health Study (CHS) who were free of CVD at baseline. We also compared the prognostic significance of the two definitions of the metabolic syndrome. RESEARCH DESIGN AND METHODS - A total of 2,175 subjects from the CHS who were free of CVD at baseline and not taking antihypertensive or lipid-lowering medications were studied. Prevalence of the metabolic syndrome was assessed with both the WHO and ATPIII criteria. The incidence of coronary or cerebrovascular disease was ascertained during a median follow-up nine of 4.1 years. RESULTS - Prevalence of the metabolic syndrome was 28.1% by ATPIII criteria and 21.0% by WHO criteria. The two Sets of criteria provided concordant classification for 80.6% of participants. Multivariate Cox propotional hazard models showed that the metabolic syndrome defined with the ATPIII criteria, but not with the WHO criteria, was an independent predictor of coronary or cerebrovascular events and was associated With a 38% increased risk (hazard ratio 1.38 [95% CI 1.06-1.79], P < 0.01). CONCLUSIONS - Prevalence of the metabolic syndrome in older individuals is similar to 21-28% (depending on the definition used). The two sets of criteria have 80% concordance in classifying subjects. As defined by the ATPIII criteria, the metabolic syndrome yields independent prognostic in formation, even after adjusting for traditional cardiovascular risk factors and the individual domains of the metabolic syndrome. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Ist Nazl Ricovero E Cura Anziari, Unita Operat Geriatria, Rome, Italy. RP Scuteri, A (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Scuteria@mail.nih.gov FU NHLBI NIH HHS [N01 HC 85079, N01 HC 15103, N01 HC 35129, N01 HC 85080, N01 HC 85081, N01 HC 85082, N01 HC 85083, N01 HC 85084, N01 HC 85085, N01 HC 85086] NR 22 TC 160 Z9 172 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 APR PY 2005 VL 28 IS 4 BP 882 EP 887 DI 10.2337/diacare.28.4.882 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001PE UT WOS:000234548000020 PM 15793190 ER PT J AU Kiratisin, P Li, L Murray, PR Fischer, SH AF Kiratisin, P Li, L Murray, PR Fischer, SH TI Use of housekeeping gene sequencing for species identification of viridans streptococci SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Streptococcus; housekeeping genes; zwf; gki ID NEUTROPENIC PATIENTS; LENGTH POLYMORPHISM; BACTEREMIA; CANCER; MITIS; PCR; GORDONII; SANGUIS; LEVEL AB Based on the genetic analysis of 20 reference strains, we describe an approach using the sequencing of 2 housekeeping genes, zwf and gki, to identify members of the mitis-sanguinis group of viridans streptococci to the species level, with a better discrimination compared with 16S rDNA sequencing. This approach also suggested that some reference strains may not be correctly classified. (c) 2005 Elsevier Inc. All rights reserved. C1 NIH, Ctr Clin, US Dept HHS, Dept Lab Med, Bethesda, MD 20892 USA. Mahidol Univ, Siriraj Hosp, Fac Med, Dept Microbiol, Bangkok 10700, Thailand. RP Fischer, SH (reprint author), NIH, Ctr Clin, US Dept HHS, Dept Lab Med, Bethesda, MD 20892 USA. EM sfischer@cc.nih.gov NR 22 TC 19 Z9 19 U1 0 U2 5 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 APR PY 2005 VL 51 IS 4 BP 297 EP 301 DI 10.1016/j.diagmicrobio.2004.12.001 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 919WN UT WOS:000228648400011 PM 15808322 ER PT J AU Ma, XC Idle, JR Krausz, KW Gonzalez, FJ AF Ma, XC Idle, JR Krausz, KW Gonzalez, FJ TI Metabolism of melatonin by human cytochromes P450 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID SERUM MELATONIN; OXIDATIVE STRESS; HEALTHY-SUBJECTS; CEREBRAL-CORTEX; CYP1A2; TISSUES; 6-HYDROXYMELATONIN; XENOBIOTICS; FLUVOXAMINE; EXPRESSION AB In humans, the pineal hormone melatonin (MEL) is principally metabolized to 6-hydroxymelatonin (6-HMEL), which is further conjugated with sulfate and excreted in urine. MEL O-demethylation represents a minor reaction. The exact role of individual human cytochromes P450 (P450s) in these pathways has not been established. We used a panel of 11 recombinant human P450 isozymes to investigate for the first time the 6-hydroxylation and O-demethylation of MEL. CYP1A1, CYP1A2, and CYP1B1 all 6-hydroxylated MEL, with CYP2C19 playing a minor role. These reactions were NADPH-dependent. CYP2C19 and, to some extent CYP1A2, O-demethylated MEL. The K-m (mu M) and V-max (k(cat), pmol min(-1) pmol(-1) P450) for 6-hydroxylation were estimated as 19.2 +/- 2.01 and 6.46 +/- 0.22 (CYP1A1), 25.9 +/- 2.47 and 10.6 +/- 0.32 (CYP1A2), and 30.9 +/- 3.76 and 5.31 +/- 0.21 (CYP1B1). These findings confirm the suggestion of others that CYP1A2 is probably the foremost hepatic P450 in the 6-hydroxylation of MEL and a single report that CYP1A1 is also able to mediate this reaction. However, this is the first time that CYP1B1 has been shown to 6-hydroxylate MEL. The IC50 for the CYP1B1-selective inhibitor (E)-2,4,3',5'-tetramethoxystilbene was estimated to be 30 nM for MEL 6-hydroxylation by recombinant human CYP1B1. Comparison of brain homogenates from wild-type and cyp1b1-null mice revealed that MEL 6-hydroxylation was clearly mediated to a significant degree by CYP1B1. CYP1B1 is not expressed in the liver but has a ubiquitous extrahepatic distribution, and is found at high levels in tissues that also accumulate either MEL or 6-HMEL, such as intestine and cerebral cortex, where it may assist in regulating levels of MEL and 6-HMEL. C1 NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. Charles Univ, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 NR 36 TC 128 Z9 135 U1 0 U2 14 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 APR PY 2005 VL 33 IS 4 BP 489 EP 494 DI 10.1124/dmd.104.002410 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 908QU UT WOS:000227804900003 PM 15616152 ER PT J AU Sullivan, DC Kelloff, G AF Sullivan, DC Kelloff, G TI Seeing into cells - The promise of in vivo molecular imaging in oncology SO EMBO REPORTS LA English DT Editorial Material ID GENE-EXPRESSION; CANCER C1 NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Sullivan, DC (reprint author), NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM ds274k@nih.gov NR 12 TC 10 Z9 12 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 APR PY 2005 VL 6 IS 4 BP 292 EP 296 DI 10.1038/sj.embor.7400382 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 915SR UT WOS:000228327200002 PM 15809653 ER PT J AU Fauci, AS Touchette, NA Folkers, GK AF Fauci, AS Touchette, NA Folkers, GK TI Emerging infectious diseases: a 10-year perspective from the National Institute of Allergy and Infectious Diseases SO EMERGING INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY SYNDROME CORONAVIRUS; INFLUENZA-A VIRUSES; PLASMODIUM-FALCIPARUM; SARS CORONAVIRUS; SMALLPOX VACCINE; GENOME SEQUENCE; SPIKE PROTEIN; TUBERCULOSIS; EFFICACY; MICE AB Although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [SARS]), reemerging (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. Over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world's most dangerous pathogens has resulted in considerable progress. Intramural and extramural investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have contributed substantially to this effort. This overview highlights selected NIAID-sponsored research advances over the past decade, with a focus on progress in combating HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, and potential bioterror agents. Many basic research discoveries have been translated into novel diagnostics, antiviral and antimicrobial compounds, and vaccines, often with extraordinary speed. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Touchette, NA (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 31,Room 7A05, Bethesda, MD 20892 USA. EM ntouchette@niaid.nih.gov NR 49 TC 80 Z9 87 U1 2 U2 7 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR PY 2005 VL 11 IS 4 BP 519 EP 525 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 910OH UT WOS:000227940700001 PM 15829188 ER PT J AU Ribe, D Yang, J Patel, S Koumanov, FO Cushman, SW Holman, GD AF Ribe, D Yang, J Patel, S Koumanov, FO Cushman, SW Holman, GD TI Endofacial competitive inhibition of glucose transporter-4 intrinsic activity by the mitogen-activated protein kinase inhibitor SB203580 SO ENDOCRINOLOGY LA English DT Article ID STIMULATED GLUCOSE-TRANSPORT; GLUT4 TRANSLOCATION; 3T3-L1 ADIPOCYTES; P38 MAPK; KINETIC-PARAMETERS; POTENTIAL ROLE; ADIPOSE-CELLS; INSULIN; BINDING; MUSCLE AB The translocation of glucose transporter-4 (GLUT4) to the cell surface is a complex multistep process that involves movement of GLUT4 vesicles from a reservoir compartment, and docking and fusion of the vesicles with the plasma membrane. It has recently been proposed that a p38 mitogen-activated protein kinase ( MAPK)-dependent step may lead to intrinsic activation of the transporters exposed at the cell surface. In contrast to data obtained in muscle and adipocyte cell lines, we found that no insulin activation of p38 MAPK occurred in rat adipose cells. However, the p38 MAPK inhibitor SB203580 consistently inhibited transport activity after preincubation with the adipose cells. These apparently contradictory findings led us to hypothesize that the inhibitor may have a direct effect on the transport catalytic activity of GLUT4 that was independent of inhibition of the kinase. Kinetic analysis of 3-O-methyl-D-glucose transport activity revealed that SB203580 was a noncompetitive inhibitor of zero-trans ( substrate outside but not inside) transport, but was a competitive inhibitor of equilibrium-exchange ( substrate inside and outside) transport. This pattern of inhibition of GLUT4 was also observed with cytochalasin B. The pattern of inhibition is consistent with interaction at the endofacial surface, but not the exofacial surface of the transporter. Occupation of the endofacial substrate site reduces maximum velocity under zero-trans conditions, because return of the substrate site to the outside is blocked, and no substrate is present inside to displace the inhibitor. Under equilibrium-exchange conditions, internal substrate competitively displaces the inhibitor, and the transport K-m is increased. C1 Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. NIDDKD, EDMNS DB, NIH, Bethesda, MD 20892 USA. RP Holman, GD (reprint author), Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. EM g.d.holman@bath.ac.uk OI Holman, Geoffrey/0000-0001-7045-1358 FU British Heart Foundation [PG/03/096/15794]; Medical Research Council [G0300415, G9225018, MR/J003417/1, G9225018(63350)] NR 31 TC 25 Z9 28 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 APR PY 2005 VL 146 IS 4 BP 1713 EP 1717 DI 10.1210/en.2004-1294 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400010 PM 15661859 ER PT J AU Kim, H Barton, E Muja, N Yakar, S Pennisi, P LeRoith, D AF Kim, H Barton, E Muja, N Yakar, S Pennisi, P LeRoith, D TI Intact insulin and insulin-like growth factor-I receptor signaling is required for growth hormone effects on skeletal muscle growth and function in vivo SO ENDOCRINOLOGY LA English DT Article ID SATELLITE CELL-PROLIFERATION; TRANSGENIC MICE; IGF-I; PROTEIN-METABOLISM; DEFICIENT ADULTS; EXPRESSION; DIFFERENTIATION; GENE; RATS; GH AB GH and IGF-I are potent regulators of muscle growth and function. Although IGF-I is known to mediate many of the effects of GH, it is not yet clear whether all effects of GH are completely dependent on the IGF-I system. To evaluate the biological effects of the GH/IGF-I axis on muscle growth, we administrated recombinant human GH to mice, which lack IGF-I function specifically in skeletal muscle, due to the overexpression of a dominant-negative IGF-I receptor in this tissue (MKR mice). GH treatment significantly increased the levels of hepatic IGF-I mRNA and serum IGF-I levels in both wild-type (WT) and MKR mice. These GH-induced effects were paralleled by increases in body weight and in the weights of most GH-responsive organs in both groups of mice. Interestingly, unlike WT mice, GH treatment had no effect on skeletal muscle weight in MKR mice. GH treatment failed to reverse the impaired muscle function in MKR mice. Furthermore, MKR mice exhibited no effects of GH on the cross-sectional area of myofibers and the proliferation of satellite cells. Taken together, these data suggest that the in vivo effects of GH on muscle mass and strength are primarily mediated by activation of the IGF-I receptor. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. RP LeRoith, D (reprint author), NIDDKD, Diabet Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 8D12, Bethesda, MD 20892 USA. EM Derek@helix.nih.gov NR 47 TC 55 Z9 61 U1 2 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2005 VL 146 IS 4 BP 1772 EP 1779 DI 10.1210/en.2004-0906 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400017 PM 15618350 ER PT J AU Burkart, AD Mukherjee, A Sterneck, E Johnson, PF Mayo, KE AF Burkart, AD Mukherjee, A Sterneck, E Johnson, PF Mayo, KE TI Repression of the inhibin alpha-subunit gene by the transcription factor CCAAT/enhancer-binding protein-beta SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; RECEPTOR MESSENGER-RNA; RAT OVARIAN-FOLLICLES; NF-KAPPA-B; GRANULOSA-CELL LINES; C/EBP-BETA; DNA-BINDING; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; LEUCINE ZIPPER; CHORIONIC-GONADOTROPIN AB Inhibin is a dimeric peptide hormone produced in ovarian granulosa cells that suppresses FSH synthesis and secretion in the pituitary. Expression of inhibin alpha- and beta- subunit genes in the rodent ovary is positively regulated by FSH and negatively regulated after the preovulatory LH surge. We have investigated the role of the transcription factor CCAAT/ enhancer- binding protein- beta ( C/ EBP beta) in repressing the inhibin alpha- subunit gene. C/ EBP beta knockout mice fail to appropriately down- regulate inhibin alpha- subunit mRNA levels after treatment with human chorionic gonadotropin, indicating that C/ EBP beta may function to repress inhibin gene expression. The expression and regulation of C/ EBP beta were examined in rodent ovary, and these studies show that C/ EBP beta is expressed in ovary and granulosa cells and is induced in response to human chorionic gonadotropin. Transient cotransfections with an inhibin promoter- luciferase reporter in a mouse granulosa cell line, GRMO2 cells, show that C/ EBP beta is capable of repressing both basal and forskolin- stimulated inhibin gene promoter activities. An upstream binding site for C/ EBP beta in the inhibin alpha- subunit promoter was identified by electrophoretic mobility shift assays, which, when mutated, results in elevated inhibin promoter activity. However, C/ EBP beta also represses shorter promoter constructs lacking this site, and this component of repression is dependent on the more proximal promoter cAMP response element ( CRE). Electrophoretic mobility shift assays show that C/ EBP beta effectively competes with CRE- binding protein for binding to this atypical CRE. Thus, there are two distinct mechanisms by which C/ EBP beta represses inhibin alpha- subunit gene expression in ovarian granulosa cells. C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Northwestern Univ, Ctr Reprod Sci, Evanston, IL 60208 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Mol Mech Dev Grp, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Eukaryot Transcript Regulat Sect, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA. EM k-mayo@northwestern.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NICHD NIH HHS [P01-HD-21921, U54-HD-41857]; NIGMS NIH HHS [T32 GM008061, T32-GM-08061] NR 84 TC 32 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2005 VL 146 IS 4 BP 1909 EP 1921 DI 10.1210/en.2004-0842 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400031 PM 15650079 ER PT J AU Schwartz, DA AF Schwartz, DA TI A vision for the future SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM schwartz@niehs.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2005 VL 113 IS 4 BP A220 EP A220 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 913NO UT WOS:000228158900002 ER PT J AU Galperin, MY AF Galperin, MY TI On the bottom of the deep blue sea SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID COMPLETE GENOME SEQUENCE; THERMOCOCCUS-KODAKARAENSIS KOD1; SHEWANELLA-ONEIDENSIS; REVEALS; PATHOGEN; AGENT C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 23 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD APR PY 2005 VL 7 IS 4 BP 453 EP 458 DI 10.1111/j.1462-2920.2005.00812.x PG 6 WC Microbiology SC Microbiology GA 905TI UT WOS:000227592500001 PM 15816911 ER PT J AU Angst, J Gamma, A Neuenschwander, M Ajdacic-Gross, V Eich, D Rossler, W Merikangas, KR AF Angst, J Gamma, A Neuenschwander, M Ajdacic-Gross, V Eich, D Rossler, W Merikangas, KR TI Prevalence of mental disorders in the Zurich Cohort Study: a twenty year prospective study SO EPIDEMIOLOGIA E PSICHIATRIA SOCIALE LA English DT Article DE prevalence; community; cohort study; mental disorders; sub-diagnostic syndromes ID PSYCHOSOMATIC SYNDROMES; GENERAL-POPULATION; YOUNG-ADULTS; CO-MORBIDITY; BIPOLAR-II; DEPRESSION; ANXIETY; EPIDEMIOLOGY; INTERVIEW; COMORBIDITY AB Background - In order to minimise retrospective recall in developing estimates of the prevalence of mental disorders in the general population, we conducted a prospective study of a cohort of youth from Zurich, Switzerland. Method - A 20 year prospective study of a community-based cohort aged 19-20 from Zurich Switzerland. The sample was enriched by subjects scoring high on the Symptom Checklist 90 R (Derogatis, 1977). A semi-structured diagnostic interview was administered by clinically experienced psychologists and psychiatrists. The six interviews from 1979 to 1999 assessed diagnoses and sub-threshold manifestations of major diagnostic categories (with the exception of schizophrenia) for the past twelve months, depending on the current DSM versions (DSM-III, DSM-III R, DSM-IV). Additional information on symptoms and treatment were collected for the years between the interviews. The reported prevalence rates are weighted for stratified sampling and cumulate the one-year rates of the six interviews. Results-The cumulative weighted prevalence rates for any psychiatric disorder were 48.6% excluding, and 57.7% including tobacco dependence. In addition 29.2% and 21.8%, respectively manifested sub-diagnostic syndromes. Overall there were no significant gender differences. The corresponding treatment prevalence rates were 22.4% and 31.1%, respectively for the diagnostic subjects and 6.9% and 6.1%, respectively for the sub-diagnostic groups. The total treatment prevalence rate was 37.2% of the population (males 30.0%, females 44.1%). Conclusions - Our findings reveal that psychiatric disorders are quite common in the general population. When the spectra of mental disorders are considered, nearly three quarters of the general population will have manifested at least one of the mental disorders across their lifetime. Limitations - The data are based on a relatively small sample; a single age cohort, and the study was conducted in Zurich, Switzerland. These study features may diminish the generalisability of the findings. C1 Univ Zurich, Hosp Psychiat, CH-8029 Zurich, Switzerland. NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Angst, J (reprint author), Univ Zurich, Hosp Psychiat, Lenggstr 31,Mail Box 68, CH-8029 Zurich, Switzerland. EM jangst@bli.unizh.ch OI Ajdacic-Gross, Vladeta/0000-0002-7032-9237 FU NIDA NIH HHS [DA00293]; NIMH NIH HHS [MH 46376] NR 32 TC 81 Z9 84 U1 1 U2 5 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 1121-189X J9 EPIDEMIOL PSICHIAT S JI Epidemiol. Psichiatr. Soc. PD APR-JUN PY 2005 VL 14 IS 2 BP 68 EP 76 PG 9 WC Psychiatry SC Psychiatry GA 971EN UT WOS:000232364400005 PM 16001703 ER PT J AU Sabroe, I Jorritsma, A Stubbs, VEL Xanthou, G Jopling, LA Panath, PD Williams, TJ Murphy, PM Pease, JE AF Sabroe, I Jorritsma, A Stubbs, VEL Xanthou, G Jopling, LA Panath, PD Williams, TJ Murphy, PM Pease, JE TI The carboxyl terminus of the chemokine receptor CCR3 contains distinct domains which regulate chemotactic signaling and receptor down-regulation in a ligand-dependent manner SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE chemokines; chemokine receptors; eosinophils; chemotaxis ID EOSINOPHIL CHEMOATTRACTANT; PHOSPHORYLATION SITES; EOTAXIN RECEPTOR; INTERNALIZATION; ACTIVATION; EXPRESSION; DESENSITIZATION; BINDING; IDENTIFICATION; RECRUITMENT AB The chemokine receptor CCR3 regulates the chemotaxis of leukocytes implicated in allergic disease, such as eosinophils. Incubation of eosinophils with CCL11, CCL13 or CCL5 resulted in a rapid decrease of cell-surface CCR3 which was replicated using CCR3 transfectants. Progressive truncation of the CCR3 C terminus by 15 amino acids produced three constructs, Delta 340, Delta 325 and Delta 310. Delta 340 and Delta 325 were able to bind CCL11 with affinities similar to wild-type CCR3. Delta 340 transfectants exhibited enhanced migration and reduced receptor down-regulation in response to CCL11 and CCL13. Delta 325 transfectants displayed chemotactic responses to CCL11 and CCL13 similar to wild-type CCR3, and had impaired down-regulation when stimulated with CCL13 but not CCL11. In contrast, neither the Delta 325 nor Delta 340 truncation affected chemotaxis or receptor down-regulation induced by CCL5. Delta 310 transfectants bound CCL11 poorly and were biologically inactive. Inhibitors of p38 mitogen-activated protein kinase and PI3-kinase antagonized eosinophil shape change responses and chemotaxis of transfectants to CCL11 and CCL13. In contrast, shape change but not chemotaxis was sensitive to inhibition of the extracellular signal-regulated kinase kinase pathway suggesting differential regulation of the two responses. Thus, the CCR3 C terminus contains distinct domains responsible for the regulation of receptor desensitization and for coupling to chemotactic responses. C1 Univ London Imperial Coll Sci Technol & Med, Leukocyte Biol Sect, Div Biomed Sci, Fac Med, London SW7 2AZ, England. LeukoSite Inc, Cambridge, MA USA. NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bethesda, MD USA. RP Pease, JE (reprint author), Univ London Imperial Coll Sci Technol & Med, Leukocyte Biol Sect, Div Biomed Sci, Fac Med, Sir Alexander Fleming Bldg, London SW7 2AZ, England. EM j.pease@imperial.ac.uk RI Sabroe, Ian/I-5981-2013 OI Sabroe, Ian/0000-0001-9750-8975 NR 28 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2005 VL 35 IS 4 BP 1301 EP 1310 DI 10.1002/eji.200425171 PG 10 WC Immunology SC Immunology GA 916VE UT WOS:000228413700032 PM 15739168 ER PT J AU Selkirk, JV Stiefel, TH Stone, IM Naeve, GS Foster, AC Poulsen, DJ AF Selkirk, JV Stiefel, TH Stone, IM Naeve, GS Foster, AC Poulsen, DJ TI Over-expression of the human EAAT2 glutamate transporter within neurons of mouse organotypic hippocampal slice cultures leads to increased vulnerability of CA1 pyramidal cells SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE adeno-associated virus; glutamate transport; hippocampus; neuronal degeneration; organotypic slice culture ID MICE LACKING; RAT-BRAIN; GLT-1; ISCHEMIA; ASTROCYTES; FLUX AB Excitatory amino acid transporters (EAATs) maintain the balance between pathological and physiological conditions by limiting the extracellular concentration of glutamate within the CNS and thus preventing excitotoxic injury. The loss of EAAT2 has been associated with the development of neurological diseases such as amyotrophic lateral sclerosis. It has therefore been suggested that the over-expression of specific EAATs may provide some degree of neuroprotection. However, the inability to isolate and study the function of the different EAAT isoforms in a cell type-specific manner has made it difficult to determine the exact contribution of individual EAATs toward neuroprotection or neurodegeneration in the context of excitotoxic injury. To address this question, we transduced hippocampal slice cultures from 1-week-old C57B/6 mice with recombinant adeno-associated virus carrying an EAAT2 gene expression cassette. EAAT2 gene expression was driven in neurons with the neuron-specific enolase promoter. Using this model system, we were able to induce a significant increase in the expression of functional EAAT2. Consequently, a significant increase in CA1 neuronal damage was observed in slices over-expressing EAAT2 in neurons following an acute exposure to exogenous glutamate. These data suggest that the increased expression of EAAT2 within neurons may contribute to neurodegeneration. C1 Neurocrine Biosci Inc, Dept Neurosci, San Diego, CA 92130 USA. Univ Montana, Dept Biomed & Pharmaceut Sci, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. RP Selkirk, JV (reprint author), Neurocrine Biosci Inc, Dept Neurosci, 12790 EL Camino Real, San Diego, CA 92130 USA. EM jselkirk@neurocrine.com FU NCRR NIH HHS [P20 RR15583] NR 25 TC 17 Z9 20 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 APR PY 2005 VL 21 IS 8 BP 2291 EP 2296 DI 10.1111/j.1460-9568.2005.04059.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA 921GJ UT WOS:000228751900027 PM 15869527 ER PT J AU Toyama, H Ye, D Ichise, M Liow, JS Cai, LS Jacobowitz, D Musachio, JL Hong, J Crescenzo, M Tipre, D Lu, JQ Zoghbi, S Vines, DC Seidel, J Katada, K Green, MV Pike, VW Cohen, RM Innis, RB AF Toyama, H Ye, D Ichise, M Liow, JS Cai, LS Jacobowitz, D Musachio, JL Hong, J Crescenzo, M Tipre, D Lu, JQ Zoghbi, S Vines, DC Seidel, J Katada, K Green, MV Pike, VW Cohen, RM Innis, RB TI PET imaging of brain with the beta-amyloid probe, [C-11]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE small animal PET; transgenic mice; [C-11]6-OH-BTA-1; beta-amyloid plaques; Alzheimer's disease ID SMALL ANIMAL PET; IN-VIVO; GLUCOSE-UTILIZATION; PRECURSOR PROTEIN; A-BETA; MICE; PLAQUES; DERIVATIVES; SCANNERS; DEPOSITS AB Purpose: The purpose of this study was to evaluate the capacity of [C-11] 6-OH-BTA-1 and positron emission tomography (PET) to quantify β-amyloid (Aβ) plaques in the Tg2576 mouse model of Alzheimer's disease ( AD). Methods: PETimaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0 +/- 1.8 months; 23.6 +/- 2.6 g) overexpressing a mutated form of human β-amyloid precursor protein (APP) known to result in the production of Aβ plaques, and in six elderly wild-type litter mates ( age 21.8 +/- 1.6 months; 29.5 +/- 4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13 - 46 MBq of [C-11] 6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons ( PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time - activity curves (TACs) ( expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. Results: TACs for [C-11] 6-OH-BTA-1 in all ROIs peaked early ( at 30 - 55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase ( 12 - 30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice ( 1.06 +/- 0.04 vs 0.98 +/- 0.07, p= 0.04; 1.06 +/- 0.09 vs 0.93 +/- 0.08 p= 0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread Aβ plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type mice. Conclusion: Marked reductions in brain uptake of this radioligand in transgenic mice may be due to reduced cerebral blood flow relative to that in wild-type mice. Specific [C-11] 6-OH-BTA-1 binding to Aβ plaques, if any, is probably very low, as reflected in the small FR/CE and PA/CE ratio differences. FR/CE and PA/CE ratios are considerably higher in AD patients while Aβ plaque densities in 22-month-old transgenic mice may be expected to show essentially the same density as is observed in the AD brain. This implies that the absence of tracer retention in 22-month-old transgenic mice may be due to the smaller number of Aβ plaque binding sites and/or to lower affinity of the binding sites for [C-11] 6-OH-BTA-1 as compared with AD patients. [C-11] 6-OH-BTA-1 shows excellent brain uptake in mice. C1 Fujita Hlth Univ, Dept Radiol, Aichi 4701192, Japan. NIMH, Mol Imaging Branch, NIH, Bethesda, MD USA. NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD USA. USUHS, Dept Anat Physiol & Genet, Bethesda, MD USA. NIH, Dept Nucl Energy, Warren Grant Magnuson Clin Ctr, Bethesda, MD USA. RP Toyama, H (reprint author), Fujita Hlth Univ, Dept Radiol, 1-98 Dengakugakubo, Aichi 4701192, Japan. EM htoyama@fujita-hu.ac.jp NR 29 TC 91 Z9 97 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD APR PY 2005 VL 32 IS 5 BP 593 EP 600 DI 10.1007/s00259-005-1780-5 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 924IC UT WOS:000228971400012 PM 15791432 ER PT J AU Due, P Holstein, BE Lynch, J Diderichsen, F Gabhain, SN Scheidt, P Currie, C AF Due, P Holstein, BE Lynch, J Diderichsen, F Gabhain, SN Scheidt, P Currie, C CA Hlth Behaviour School-Aged Childre TI Bullying and symptoms among school-aged children: international comparative cross sectional study in 28 countries SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE bullying; children; international survey; symptoms ID PSYCHIATRIC-SYMPTOMS; HEALTH; INTERVENTION; ASSOCIATION; DEPRESSION; REDUCE AB Baskground There have been no large-scale international comparisons on bullying and health among adolescents. This study examined the association between bullying and physical and psychological symptoms among adolescents in 28 countries. Methods: This international cross-sectional survey included 123,227 students 11, 13 and 15 years of age from a nationally representative sample of schools in 28 countries in Europe and North America in 1997-98.The main outcome measures were physical and psychological symptoms. Results: The proportion of students being bullied varied enormously across countries. The lowest prevalence was observed among girls in Sweden (6.3%, 95% Cl: 5.2-7.4), the highest among boys in Lithuania (41.4%, 95% Cl 39.4-43.5). The risk of high symptom load increased with increasing exposure to bullying in all countries. In pooled analyses, with sex stratified multilevel logistic models adjusted for age, family affluence and country the odds ratios for symptoms among students who were bullied weekly ranged from 1.83 (95% Cl 1.70-1.97) to 2.11 (95% Cl 1.95-2.29) for physical symptoms (headache, stomach ache, backache, dizziness) and from 1.67 (95% Cl 1.55-1.78) to 7.47 (95% Cl 6.87-8.13) for psychological symptoms (bad temper, feeling nervous, feeling low, difficulties in getting to sleep, morning tiredness, feeling left out, loneliness, helplessness). Conclusion: There was a consistent, strong and graded association between bullying and each of 12 physical and psychological symptoms among adolescents in all 28 countries. C1 Univ Copenhagen, Dept Social Med, Inst Publ Hlth, DK-2200 Copenhagen, Denmark. Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Inst Social Res, Ann Arbor, MI 48109 USA. Natl Univ Ireland Univ Coll Galway, Dept Hlth Promot, Galway, Ireland. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Edinburgh, Unit Child & Adolescent Hlth Res, Dept Phys Educ Sport & Leisure Studies, Edinburgh, Midlothian, Scotland. RP Due, P (reprint author), Univ Copenhagen, Dept Social Med, Inst Publ Hlth, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM P.Due@socmed.ku.dk RI Lynch, John/A-4797-2008; Gaspar de Matos, Margarida/H-3824-2012; OI Lynch, John/0000-0003-2781-7902; Gaspar de Matos, Margarida/0000-0003-2114-2350; Diderichsen, Finn/0000-0002-9998-4972 NR 26 TC 214 Z9 223 U1 1 U2 35 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2005 VL 15 IS 2 BP 128 EP 132 DI 10.1093/eurpub/cki105 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 937OC UT WOS:000229934400007 PM 15755782 ER PT J AU Savchenko, NM Witkin, JM AF Savchenko, NM Witkin, JM TI Experimental pharmacological evaluation of Sydnocarb effects: comparisons with methamphetamine SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 8th Regional Meeting of the European Congress of Neuropathology CY APR 14-16, 2005 CL Moscow, RUSSIA C1 Russian Acad Med Sci, State Zakusov Inst Pharmacol, Dept Alcoholism & Narcomania Pharmacol, Moscow 125315, Russia. Natl Inst Drug Abuse, Addict Res Ctr, Drug Dev Grp, Natl Inst Hlth, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Addict Res Ctr, Integrat Neurosci Unit, Natl Inst Hlth, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD APR PY 2005 VL 15 SU 2 BP S267 EP S268 DI 10.1016/S0924-977X(05)80519-X PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 920QM UT WOS:000228705200314 ER PT J AU Nguyen, DH Giri, B Collins, G Taub, DD AF Nguyen, DH Giri, B Collins, G Taub, DD TI Dynamic reorganization of chemokine receptors, cholesterol, lipid rafts, and adhesion molecules to sites of CD4 engagement SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE chemokine receptor; lipid rafts; cholesterol; CD4; HIV ID IMMUNODEFICIENCY-VIRUS TYPE-1; TO-CELL TRANSMISSION; IMMUNOLOGICAL SYNAPSE; MEMBRANE MICRODOMAINS; ACTIN CYTOSKELETON; HIV-1 INFECTION; HOST-CELLS; ACTIVATION; POLARIZATION; ASSOCIATION AB T cell polarization and redistribution of cellular components are critical to processes such as activation, migration, and potentially HIV infection. Here, we investigate the effects of CD4 engagement on the redistribution and localization of chemokine receptors, CXCR4 and CCR5, adhesion molecules, and lipid raft components including cholesterol, GM1, and glycosyl-phosphatidylinositol (GPI)-anchored proteins. We demonstrate that anti-CD4-coated beads (alpha CD4-B) rapidly induce co-capping of chemokine receptors as well as GPI-anchored proteins and adhesion molecules with membrane cholesterol and lipid rafts on human T cell lines and primary T cells to the area of bead-cell contact. This process was dependent on the presence of cellular cholesterol, cytoskeletal reorganization, and lck signaling. Lck-deficient JCaM 1.6 cells failed to cap CXCR4 or lipid rafts to alpha CD4-B. Biochemical analysis reveals that CXCR4 and LFA-1 are recruited to lipid rafts upon CD4 but not CD45 engagement. Furthermore, we also demonstrate T cell capping of both lipid rafts and chemokine receptors at sites of contact with HIV-infected cells, despite the binding of an HIV inhibitory mAb to CXCR4. We conclude that cell surface rearrangements in response to CD4 engagement may serve as a means to enhance cell-to-cell signaling at the immunological synapse and modulate chemokine responsiveness, as well as facilitate HIV entry and expansion by synaptic transmission. Published by Elsevier Inc. C1 NIA, Immunol Lab, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Immunol Lab, Intramural Res Program, NIH,DHHS, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Taubd@grc.nia.nih.gov NR 46 TC 65 Z9 66 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 1 PY 2005 VL 304 IS 2 BP 559 EP 569 DI 10.1016/j.yexcr.2004.11.022 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 908DU UT WOS:000227768400019 PM 15748900 ER PT J AU Solfrizzi, V D'Introno, A Colacicco, AM Capurso, C Del Parigi, A Capurso, S Gadaleta, A Capurso, A Panza, F AF Solfrizzi, V D'Introno, A Colacicco, AM Capurso, C Del Parigi, A Capurso, S Gadaleta, A Capurso, A Panza, F TI Dietary fatty acids intake: possible role in cognitive decline and dementia SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE MUFA; PUFA; fatty acids; dementia; Alzheimer's disease; vascular dementia; mild cognitive impairment; cognitive decline ID AMYLOID PRECURSOR PROTEIN; INCIDENT ALZHEIMER-DISEASE; APOLIPOPROTEIN-E GENOTYPE; VASCULAR DEMENTIA; FISH CONSUMPTION; ELDERLY PEOPLE; DOCOSAHEXAENOIC ACID; SIGNAL-TRANSDUCTION; MEDITERRANEAN DIET; TOTAL CHOLESTEROL AB There is a recent increase in the level of interest in the possible role of dietary fatty acids in age-related cognitive decline, and cognitive impairment of both degenerative (Alzheimer's disease, AD) or vascular origin. At present, several Studies suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions. Furthermore, a clear reduction of risk of cognitive decline has been found in a population sample with a high intake of polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). These findings were confirmed by Studies in which high intakes of n-6 PUFA, n-3 PUFA, MUFA, and weekly fish consumption, providing large amount of n-3 PUFA, appear to be protective against the risk of AD. In our elderly population from Southern Italy, elevated unsaturated fatty acids intake (MUFA and PUFA), high levels of antioxidant compounds, and very low SFA intake could act synergistically in improving cognitive performance. Epidemiological studies on the association between diet and cognitive decline suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia, both of degenerative or vascular origin. Appropriate dietary measures or supplementation with specific micro- and macronutrients might open new ways for the prevention and management of cognitive decline and dementia. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Bari, Dept Geriatr, Ctr Aging Brain, Policlin,Memory Unit, I-70124 Bari, Italy. Univ Foggia, Dept Geriatr, Foggia, Italy. NIDDKD, NIH, Phoenix, AZ USA. RP Solfrizzi, V (reprint author), Univ Bari, Dept Geriatr, Ctr Aging Brain, Policlin,Memory Unit, Piazza Giulio Cesare 11, I-70124 Bari, Italy. EM v.solfrizzi@geriatria.uniba.it OI Capurso, Cristiano/0000-0002-1152-3371; Panza, Francesco/0000-0002-7220-0656 NR 97 TC 77 Z9 81 U1 2 U2 24 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 APR PY 2005 VL 40 IS 4 BP 257 EP 270 DI 10.1016/j.exger.2005.01.001 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 920IN UT WOS:000228682700001 PM 15820606 ER PT J AU Walston, J Arking, DE Fallin, D Li, T Beamer, B Xue, Q Ferrucci, L Fried, LP Chakravarti, A AF Walston, J Arking, DE Fallin, D Li, T Beamer, B Xue, Q Ferrucci, L Fried, LP Chakravarti, A TI IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE IL-6; IL-6 haplotypes; frailty; muscle strength; aging; disability; IL-6 gene variation ID PROMOTER POLYMORPHISMS; ELEVATED INTERLEUKIN-6; STRENGTH; HEALTH; DISABILITY; HAPLOTYPES; REGION; PREDICTORS; DISEASE; PLASMA AB Elevated levels of the inflammatory cytokine IL-6 are associated with the development of disability, frailty, and mortality in older adults. These outcomes are likely mediated through inflammatory activity that alters hormones, skeletal muscle, and the immune system. Polymorphic variants in the IL-6 gene influence IL-6 expression. We hypothesized that IL-6 alleles associate with increased serum of IL-6 decreased Muscle strength, and frailty, and tested this in the Women's Health and Aging cohorts. We genotyped 463 participants age 70-79, and identified three common IL-6 haplotype blocks for the Caucasian (n = 363) and African American (n = 100) subsets. Using linear and logistic regression, and adjusting for age, BMI, race, and osteoarthritis, we identified no significant or clinically meaningful relationship between any single IL-6 single nucleotide polymorphism (SNP) or any IL-6 haplotype and serum IL-6 level, grip, knee, or hip strength, or frailty. Given that the promoter SNP (rs1800795) has been reported to influence IL-6 levels and health outcomes, we performed a similar association study in the In Chianti population (n = 266) and confirmed lack of association. These results suggest that IL-6 gene variation may not be an important factor in the determination of elevated IL-6 levels and related phenotypes found in older women. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Baltimore, MD 21224 USA. RP Walston, J (reprint author), Johns R Burton Pavil,5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM jwalston@jhmi.edu FU NCRR NIH HHS [M01-RR-02719, M01-RR000052]; NIA NIH HHS [P30 AG021334, R01 AG11703, R37 AG19905] NR 27 TC 36 Z9 38 U1 0 U2 3 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 APR PY 2005 VL 40 IS 4 BP 344 EP 352 DI 10.1016/j.exger.2005.01.012 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 920IN UT WOS:000228682700011 PM 15820616 ER PT J AU Kirshenbaum, AS Akin, C Goff, JP Metcalfe, DD AF Kirshenbaum, AS Akin, C Goff, JP Metcalfe, DD TI Thrombopoietin alone or in the presence of stem cell factor supports the growth of KIT(CD117)(low)/MPL(CD110)(+) human mast cells from hematopoietic progenitor cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID FC-EPSILON-RI; PERIPHERAL-BLOOD; ALPHA-GRANULES; IN-VITRO; EXPRESSION; CYTOKINE; DIFFERENTIATION; MEGAKARYOCYTES; PROTOONCOGENE; BASOPHILS AB Objectives. Thrombopoietin (TPO) is known to promote platelet number, have growth-promoting potential for human megakaryocytes (HuMKs), and increase erythrocyte, monocyte, mast cell, and granulocyte numbers in the presence of additional growth factors. We explored the ability of TPO alone or in the presence of stem cell factor (SCF) to support human mast cells (HuMCs). Methods. CD34(+) pluripotent and CD34(+)/CD117(+)/CD13(+) HuMC progenitor cells were cultured in rhTPO and examined for HuMCs. Similarly, we added rhTPO to CD34(+) cells cultured in stem cell factor (SCF), which promotes HuMC development. Results. When CD34(+) cells were cultured in 10 ng/mL rhTPO and 10 ng/mL rhSCF, TPO enhanced HuMC numbers compared to rhSCF alone. Higher concentrations of rhTPO (50 ng/mL) in the presence of 100 ng/mL rhSCF inhibited the rhSCF-dependent subpopulation of CD117(high) HuMCs, while promoting CD117(low) HuMCs. Human CD34(+)/CD117(+)/CD13(+) cells cultured in rhTPO alone for 1 to 2 weeks differentiated into CD41(+)/CD110(+) HuMKs (85-90%) and Fc epsilon RI+/CD117(low)/CD13(+) HuMCs (5-10%). RhTPO-induced HuMCs expressed the TPO (CD110) receptor, tryptase, and chymase and survived when recultured in rhSCF. Conclusion. The effect of TPO on HuMCs in the presence of rhSCF varies, depending on the relative concentration of each growth factor, while TPO alone or in combination with rhSCF supports a unique population of CD117(low)/CD110(+) HuMCs. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA USA. RP Kirshenbaum, AS (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C208,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM Akirshenba@niaid.nih.gov OI Akin, Cem/0000-0001-6301-4520 NR 22 TC 12 Z9 14 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 APR PY 2005 VL 33 IS 4 BP 413 EP 421 DI 10.1016/j.exphem.2004.12.005 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 916IB UT WOS:000228377500004 PM 15781331 ER PT J AU Kawai, T Choi, U Whiting-Theobald, NL Linton, GF Brenner, S Sechler, JMG Murphy, PM Malech, HL AF Kawai, T Choi, U Whiting-Theobald, NL Linton, GF Brenner, S Sechler, JMG Murphy, PM Malech, HL TI Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; IMMUNODEFICIENCY-VIRUS CORECEPTOR; AMINO-ACID TRANSPORTER; PERIPHERAL-BLOOD; CHEMOKINE RECEPTOR; CD34(+) CELLS; SEVERE NEUTROPENIA; BONE-MARROW; MYELOKATHEXIS; MOBILIZATION AB Objective. WHIM (warts, hypogammaglobulinemia, recurrent bacterial infection, myelokathexis) syndrome is an autosomal dominant immune deficiency with severe chronic neutropenia and marrow neutrophil apoptosis. Carboxy-termini truncating mutations in the chemokine receptor CXCR4 have been identified in WHIM patients. We created a retrovirus encoding mutated CXCR4 (truncating point mutation 1000C -> T [R334X] inherited heterozygously in several WHIM patients) in order to transducer healthy human CD34 stem cells and K562 to overexpress mutated CXCR4 and determined its effect on receptor responses to stromal-derived factor-1 (SDF1). Methods. Retrovirus vector was engineered to coexpress WHIM-associated R334X mutated CXCR4 together with green fluorescent protein (GFP). Control vectors included similar constructs with wild-type CXCR4 (WT-CXCR4) or only GFP. CD34(+) cells and K562 were transduced with these vectors. Populations of 100% transduced K562 were established by sorting GFP(+) cells by flow cytometry. We performed migration and calcium flux assays of transduced CD34(+) cells and transduced/sorted K562. We also examined receptor recycling in response to SDF1. Results. Healthy human CD34(+) cells and/or human erythroleukemia K562 cells transduced to express mutated CXCR4, WT-CXCR4, or GFP alone demonstrated that mutated CXCR4 was associated with enhanced calcium flux and enhanced migration. There was also decreased receptor internalization and enhanced recovery of surface mutated CXCR4 in response to SDF1 compared with WT-CXCR4. Conclusion. We propose that decreased internalization of WHIM-associated mutated CXCR4 leads to prolongation/enhancement of signaling in response to SDF1 and that this may provide the biochemical basis for the autosomal dominant abnormalities of cell trafficking and function associated with WHIM syndrome. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan. Univ Dresden, Clin Carl Gustav Carus, Dept Pediat, Dresden, Germany. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10-CRC 5 W Labs,Room 5-3750,10 Ctr Dr MSC 14, Bethesda, MD 20892 USA. EM hmalech@nih.gov RI Brenner, Sebastian/D-7456-2013; OI Malech, Harry/0000-0001-5874-5775 NR 34 TC 43 Z9 48 U1 0 U2 4 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 APR PY 2005 VL 33 IS 4 BP 460 EP 468 DI 10.1016/j.exphem.2005.01.001 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 916IB UT WOS:000228377500010 PM 15781337 ER PT J AU Groll, AH Stergiopoulou, T Roilides, E Walsh, TJ AF Groll, AH Stergiopoulou, T Roilides, E Walsh, TJ TI Micafungin: pharmacology, experimental therapeutics and clinical applications SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE 1,3-beta-D-glucan synthesis; antifungal therapy; Aspergillus spp.; Candida spp.; echinocandin; FK-463; micafungin; pharmacokinetics; pharmacology ID LIPOPEPTIDE ANTIFUNGAL AGENT; IN-VITRO ACTIVITY; INVASIVE PULMONARY ASPERGILLOSIS; ECHINOCANDIN-LIKE LIPOPEPTIDE; CANDIDA-ALBICANS; AMPHOTERICIN-B; MURINE ASPERGILLOSIS; MOUSE MODELS; FK463; FUMIGATUS AB Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. Echinocandins are a new class of antifungal drugs, which inhibit the synthesis of 1,3-beta-D-glucan. This homopolysaccharide is an important component of the cell wall of many pathogenic fungi, providing osmotic stability and functioning in cell growth and cell division. Micafungin, which is a member of the echinocandin class, exhibits in vitro fungicidal or fungistatic activity against a variety of fungal pathogens which include Candida and Aspergillus species but not Cryptococcus, Fusarium or Zygomyce.tes. Micafungin demonstrates linear pharmacokinetics, which are not altered by drugs metabolised through the P450 enzyme system. The preclinical and clinical data strongly support the development of micafungin for treatment of proven or suspected mucosal and invasive Candida infections in immunocompetent and immuno-compromised patients. This paper reviews the preclinical and clinical pharmacology of micafungin and its potential role for treatment of fungal invasive infections in patients. C1 Univ Munster, Med Ctr, Ctr Bone Marrow Transplantat, Univ Childrens Hosp, D-4400 Munster, Germany. Univ Munster, Med Ctr, Infect Dis Res Program, Dept Pediat Hematol Oncol, D-4400 Munster, Germany. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Hippokration Hosp, Paediat Dept 3, GR-54642 Thessaloniki, Greece. RP Groll, AH (reprint author), Univ Munster, Med Ctr, Ctr Bone Marrow Transplantat, Univ Childrens Hosp, D-4400 Munster, Germany. EM walsht@mail.nih.gov NR 69 TC 23 Z9 24 U1 2 U2 3 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 APR PY 2005 VL 14 IS 4 BP 489 EP 509 DI 10.1517/13543784.14.4.489 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 930JC UT WOS:000229410900011 PM 15882123 ER PT J AU Post, RM AF Post, RM TI Adjunctive strategies in the treatment of refractory bipolar depression: clinician options in the absence of a systematic database SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review ID TREATMENT-RESISTANT-DEPRESSION; POSTTRAUMATIC-STRESS-DISORDER; PLACEBO-CONTROLLED TRIAL; TRANSCRANIAL MAGNETIC STIMULATION; UNILATERAL ELECTROCONVULSIVE-THERAPY; RANDOMIZED CONTROLLED-TRIAL; BRIGHT LIGHT THERAPY; HIGH-DOSE THYROXINE; N-ACETYL-ASPARTATE; DOUBLE-BLIND AB Multiple approaches to enhancing antidepressant treatment response in bipolar depression are available and should, in many instances, be explored despite a lack of definitive controlled trial literature supporting their efficacy. Given that the morbidity of depression is three times greater than mania in bipolar illness, a range of treatment approaches to this phase of illness should be pursued. This paper highlights the preliminary evidence of efficacy versus side effects, tolerability, and safety in order to suggest an overall provisional utility grade for each well-studied to highly-experimental option. Given the general paucity of evidence to support efficacy or to sequence different approaches for augmenting treatment of bipolar depression, it is critical that patient and physician adopt a systematic and, preferably, daily rating approach to the assessment of benefit for a given patient of each strategy contemplated. The goal is to achieve and maintain remission of depressive symptoms and associated comorbidities, which is often not accomplished using primary mood stabiliser treatments alone, or in combination; thus, an active clinical approach to augmentation strategies is indicated even when the literature provides only highly preliminary guidance. C1 NIMH, Biol Psychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Dept Hlth & Human Serv, 10 Ctr Dr MSC 1272,Bldg 10,Room 3S239, Bethesda, MD 20892 USA. EM Robert.Post@nih.gov NR 140 TC 7 Z9 7 U1 3 U2 4 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD APR PY 2005 VL 6 IS 4 BP 531 EP 546 DI 10.1517/14656566.6.4.531 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 919VX UT WOS:000228646800001 PM 15934880 ER PT J AU Fay, JR Crowell, JA Kopelovich, L AF Fay, JR Crowell, JA Kopelovich, L TI Targeting epigenetic regulatory mechanisms in cancer chemoprevention SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE cancer; chemoprevention; DNA methylation; epigenetics; histone modification ID CPG-ISLAND HYPERMETHYLATION; HISTONE-DEACETYLASE INHIBITORS; ABERRANT PROMOTER METHYLATION; PROSTATIC INTRAEPITHELIAL NEOPLASIA; HYDROXAMIC ACID SAHA; PROTEIN-KINASE GENE; DNA METHYLATION; BREAST-CANCER; COLORECTAL-CANCER; BARRETTS-ESOPHAGUS AB Dysregulation of the epigenome plays a fundamental role in tumour development. Epigenetic events are a major mechanism for inactivating tumour suppressor and DNA repair genes and occur ubiquitously during the early stages of tumour development. Unlike genes inactivated by mutation, genes silenced epigenetically are intact and potentially responsive to reactivation by small molecules. This review discusses the potential for restoring epigenetic balance as a means to prevent cancer. C1 Natl Canc Inst, Div Canc Prevent, Bethesda, MD 20892 USA. RP Kopelovich, L (reprint author), Natl Canc Inst, Div Canc Prevent, Execut Plaza N,Room 2144,MSC 7322, Bethesda, MD 20892 USA. EM jfay@ccsainc.com; jcrowell@mail.nih.gov; lk94c@nih.gov NR 131 TC 5 Z9 5 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD APR PY 2005 VL 9 IS 2 BP 315 EP 328 DI 10.1517/14728222.9.2.315 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 919VU UT WOS:000228646500009 PM 15934918 ER PT J AU Gulley, J Dahut, WL AF Gulley, J Dahut, WL TI Clodronate in the prevention and treatment of skeletal metastasis SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE bisphosphonate; bone metastasis; bone mineral density; bone pain; breast cancer; prostate cancer; skeletal complications ID BREAST-CANCER PATIENTS; BONE-MINERAL DENSITY; ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ORAL CLODRONATE; PROSTATE-CANCER; DOUBLE-BLIND; PAGETS-DISEASE; ZOLEDRONIC ACID AB Many solid tumors, including breast and prostate cancer, metastasize to bone, thereby puffing patients at high risk for developing skeletal complications including pathologic fracture, spinal cord compression and debilitating bone pain. Patients often live for many years after developing bone metastasis, a fact that highlights the importance of therapies to reduce morbidity from skeletal complications. Bisphosphonates, including clodronate, have been shown to be useful in reducing skeletal complications in patients with cancer. This review will highlight the role of clodronate for skeletal metastasis. C1 NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Gulley, J (reprint author), NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Canc Res Ctr, 10 Ctr Dr,8B07 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov; dahutw@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 53 TC 6 Z9 8 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD APR PY 2005 VL 5 IS 2 BP 221 EP 230 DI 10.1586/14737104.5.2.221 PG 10 WC Oncology SC Oncology GA 993UE UT WOS:000233979800004 PM 15877520 ER PT J AU Engels, EA AF Engels, EA TI Cancer risk associated with receipt of vaccines contaminated with simian virus 40: epidemiologic research SO EXPERT REVIEW OF VACCINES LA English DT Review DE adenovirus vaccine; brain neoplasms; cancer; mesothelioma; non-Hodgkin's lymphoma; osteosarcoma; poliovirus vaccine; simian virus 40 ID NON-HODGKIN-LYMPHOMA; SIMIAN VIRUS 40; ACUTE RESPIRATORY DISEASE; KIDNEY CELL CULTURES; LARGE T-ANTIGEN; ADENOVIRUS VACCINE; VACUOLATING VIRUS; PLEURAL MESOTHELIOMA; POLIOVIRUS VACCINES; SEROLOGIC EVIDENCE AB Simian virus (SV)40 was an accidental contaminant of poliovirus vaccines used widely in the USA and other countries in 1955-1962. Exposure to SV40 via contaminated vaccines has led to concern as SV40 causes cancer in laboratory animals. In addition, some laboratories, although not all, have detected SV40 DNA in human tumors including mesothelioma, certain brain tumors, osteosarcoma and non-Hodgkin's lymphoma. This article reviews the data regarding contamination of poliovirus vaccines with SV40 and summarizes the results from epidemiologic studies of vaccine recipients. Long-term follow-up studies have not revealed recipients of SV40-contaminated poliovirus vaccines to be at an increased risk for cancer. Thus, these studies are somewhat reassuring and indicate that either SV40 does not readily infect humans or, following infection, does not cause cancer. Recognizing that the history of SV40 contamination of vaccines highlights an inherent risk of contamination of vaccines with adventitious agents, the Institute of Medicine recently called for the development of a comprehensive US plan to prevent vaccine contamination and respond to potential contamination events when they arise. C1 NCI, Viral Epidemiol Res, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Res, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Bldg,EPS 8010, Bethesda, MD 20892 USA. EM engelse@exchange.nih.gov NR 55 TC 16 Z9 18 U1 0 U2 2 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2005 VL 4 IS 2 BP 197 EP 206 DI 10.1586/14760584.4.2.197 PG 10 WC Immunology SC Immunology GA 982YZ UT WOS:000233199600020 PM 15889993 ER PT J AU Li, GR Cui, G Tzeng, NS Wei, SJ Wang, TG Block, ML Hong, JS AF Li, GR Cui, G Tzeng, NS Wei, SJ Wang, TG Block, ML Hong, JS TI Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage SO FASEB JOURNAL LA English DT Article DE DM; femtomolar; inflammation; microglia; neuroprotection; Parkinson's disease ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; INJURY FOLLOWING TRANSIENT; NEURODEGENERATIVE DISEASES; MICROGLIAL ACTIVATION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; OPIOID PEPTIDE; FOCAL ISCHEMIA; NADPH OXIDASE; RAT AB Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neuro degenerative disorders, including Parkinson's disease (PD). Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. We previously showed that micromolar concentrations of dextromethorphan (DM), a major ingredient of widely used antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through the inhibition of microglial activation. In this study, we report that femto- and micromolar concentrations of DM (both pre- and post-treatment) showed equal efficacy in protecting lipopolysaccharide (LPS)-induced dopaminergic neuron death in midbrain neuron-glia cultures. Both concentrations of DM decreased LPS-induced release of nitric oxide, tumor necrosis factor-alpha, prostaglandin E-2 and superoxide from microglia in comparable degrees. The important role of superoxide was demonstrated by DM's failure to show a neuroprotective effect in neuron-glia cultures from NADPH oxidase-deficient mice. These results suggest that the neuroprotective effect elicited by femtomolar concentrations of DM is mediated through the inhibition of LPS-induced proinflammatory factors, especially superoxide. These findings suggest a novel therapeutic concept of using "ultra-low" drug concentrations for the intervention of inflammation-related neurodegenerative diseases. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. RP Li, GR (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233,MD-F1-01 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM guorongl@med.unc.edu; hong3@niehs.nih.gov NR 37 TC 53 Z9 59 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2005 VL 19 IS 6 BP 489 EP 496 DI 10.1096/fj.04-2555com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 922UP UT WOS:000228865300032 PM 15790998 ER PT J AU Zhang, W Wang, TG Pei, Z Miller, DS Wu, XF Block, ML Wilson, B Zhang, WQ Zhou, Y Hong, JS Zhang, J AF Zhang, W Wang, TG Pei, Z Miller, DS Wu, XF Block, ML Wilson, B Zhang, WQ Zhou, Y Hong, JS Zhang, J TI Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease SO FASEB JOURNAL LA English DT Article DE microglia; phagocytosis; innate immunity; aging; oxidative stress; protein aggregation; inflammation ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; ROTENONE-INDUCED DEGENERATION; NIGRAL DOPAMINERGIC-NEURONS; NADPH OXIDASE; NEURODEGENERATIVE DISEASES; MESENCEPHALIC NEURONS; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; MOUSE MODEL; MUTATION AB A growing body of evidence indicates that an inflammatory process in the substantia nigra, characterized by activation of resident microglia, likely either initiates or aggravates nigral neurodegeneration in Parkinson's disease (PD). To study the mechanisms by which nigral microglia are activated in PD, the potential role of alpha-synuclein (a major component of Lewy bodies that can cause neurodegeneration when aggregated) in microglial activation was investigated. The results demonstrated that in a primary mesencephalic neuron-glia culture system, extracellular aggregated human alpha-synuclein indeed activated microglia; microglial activation enhanced dopaminergic neurodegeneration induced by aggregated alpha-synuclein. Furthermore, microglial enhancement of alpha-synuclein-mediated neurotoxicity depended on phagocytosis of alpha-synuclein and activation of NADPH oxidase with production of reactive oxygen species. These results suggest that nigral neuronal damage, regardless of etiology, may release aggregated alpha-synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators, thereby leading to persistent and progressive nigral neuro degeneration in PD. Finally, NADPH oxidase could be an ideal target for potential pharmaceutical intervention, given that it plays a critical role in alpha-synuclein-mediated microglial activation and associated neurotoxicity. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. Dalian Med Univ, Clin Hosp 1, Dept Neurol, Dalian, Peoples R China. RP Zhang, J (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, Div Neuropathol, 703C Res & Training Bldg,Campus Box 359635,325 9t, Seattle, WA 98104 USA. EM zhangj@u.washington.edu NR 50 TC 479 Z9 500 U1 4 U2 37 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2005 VL 19 IS 6 BP 533 EP 542 DI 10.1096/fj.04-2751com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 922UP UT WOS:000228865300037 PM 15791003 ER PT J AU Qin, IY Block, ML Liu, YX Bienstock, RJ Pei, Z Zhang, W Wu, XF Wilson, B Burka, T Hong, JS AF Qin, IY Block, ML Liu, YX Bienstock, RJ Pei, Z Zhang, W Wu, XF Wilson, B Burka, T Hong, JS TI Microglial NADPH oxidase is a novel target for femtomolar neuroprotection against oxidative stress SO FASEB JOURNAL LA English DT Article DE dynorphin; pepide; ROS; GGF; Parkinson's disease ID PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; TETRAZOLIUM SALT; PEPTIDE; HORMESIS; INFLAMMATION; INHIBITION; NALOXONE; LIPOPOLYSACCHARIDE; NEUROTOXICITY AB Inflammation has been increasingly recognized to contribute to the pathogenesis of Parkinson's disease. Several compounds are neuroprotective at femtomolar concentrations through the inhibition of inflammation. However, the mechanisms mediating femtomolar-acting compounds are poorly understood. Here we show that both gly-gly-phe (GGF), a tri-peptide contained in the dynorphin opioid peptide, and naloxone are neuroprotective at femtomolar concentrations against LPS-induced dopaminergic neurotoxicity through the reduction of microglial activation. Mechanistic studies demonstrated the critical role of NADPH oxidase in the GGF and naloxone inhibition of microglial activation and associated DA neurotoxicity. Pharmacophore analysis of the neuroprotective dynorphin peptides and naloxone revealed common chemical properties (hydrogen bond acceptor, hydrogen bond donor, positive ionizable, hydrophobic) of these femtomolar-acting compounds. These results support a common high-affinity site of action for several femtomolar-acting compounds, where NADPH oxidase is the critical mechanism governing neuroprotection, suggesting a novel avenue of anti-inflammatory and neuroprotective therapy. C1 NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Chem Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Dalian Univ Technol, Dept Biosci & Bioengn, Dalian, Peoples R China. Dalian Med Univ, Clin Hosp 1, Dept Neurol, Dalian, Peoples R China. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM Hong3@niehs.nih.gov OI Bienstock, Rachelle/0000-0001-5228-3610 NR 40 TC 14 Z9 14 U1 1 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 APR PY 2005 VL 19 IS 6 BP 550 EP 557 DI 10.1096/fj.04-2857com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 922UP UT WOS:000228865300039 ER PT J AU Komarova, EA Krivokrysenko, V Wang, KH Neznanov, N Chernov, MV Komarov, PG Brennan, ML Golovkina, TV Rokhlin, O Kuprash, DV Nedospasov, SA Hazen, SR Feinstein, E Gudkov, AV AF Komarova, EA Krivokrysenko, V Wang, KH Neznanov, N Chernov, MV Komarov, PG Brennan, ML Golovkina, TV Rokhlin, O Kuprash, DV Nedospasov, SA Hazen, SR Feinstein, E Gudkov, AV TI p53 is a suppressor of inflammatory response in mice SO FASEB JOURNAL LA English DT Article DE inflammation; nuclear factor kappa B; cytokines ID NF-KAPPA-B; RHEUMATOID-ARTHRITIS SYNOVIUM; AGE-ASSOCIATED DIFFERENCES; OXIDE SYNTHASE EXPRESSION; NITRIC-OXIDE; INDUCED APOPTOSIS; HELICOBACTER-PYLORI; GENE-EXPRESSION; BLADDER-CANCER; TNF-ALPHA AB Chronic inflammation is known to promote cancer, suggesting that negative regulation of inflammation is likely to be tumor suppressive. We found that p53 is a general inhibitor of inflammation that acts as an antagonist of nuclear factor kappa B (NF kappa B). We first observed striking similarities in global gene expression profiles in human prostate cancer cells LNCaP transduced with p53 inhibitory genetic element or treated with TNF, suggesting that p53 inhibits transcription of TNF-inducible genes that are largely regulated by NF kappa B. Consistently, ectopically expressed p53 acts as an inhibitor of transcription of NF kappa B-dependent promoters. Furthermore, suppression of inflammatory response by p53 was observed in vivo in mice by comparing wild-type and p53 null animals at molecular (inhibition of transcription of genes encoding cytokines and chemokines, reducing accumulation of reactive oxygen species and protein oxidation products), cellular (activation of macrophages and neutrophil clearance) and organismal (high levels of metabolic markers of inflammation in tissues of p53-deficient mice and their hypersensitivity to LPS) levels. These observations indicate that p53, acting through suppression of NF kappa B, plays the role of a general "buffer" of innate immune response in vivo that is well consistent with its tumor suppressor function and frequent constitutive activation of NF kappa B in tumors. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. Quark Biotech Inc, Fremont, CA USA. Cleveland BioLabs Inc, Cleveland, OH USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow, Russia. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21701 USA. SAIC Frederick Inc, Frederick, MD 21701 USA. RP Gudkov, AV (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM gudkov@ccf.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; FU NCI NIH HHS [CA75179, CA88071, N01-CO-12400] NR 62 TC 120 Z9 128 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2005 VL 19 IS 6 BP 1030 EP + DI 10.1096/fj.04-3213fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 922UP UT WOS:000228865300027 PM 15811878 ER PT J AU Wang, TG Pei, Z Zhang, W Liu, B Langenbach, R Lee, C Wilson, B Reece, JM Miller, DS Hong, JS AF Wang, TG Pei, Z Zhang, W Liu, B Langenbach, R Lee, C Wilson, B Reece, JM Miller, DS Hong, JS TI MPP+-induced COX-2 activation and subsequent dopaminergic neurodegeneration SO FASEB JOURNAL LA English DT Article DE cyclooxygenase-2; prostaglandin E-2; microglia; neuron; Parkinson's disease ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; PARKINSONS-DISEASE; NITRIC-OXIDE; SUBSTANTIA-NIGRA; MICROGLIAL ACTIVATION; ALZHEIMERS-DISEASE; PROSTAGLANDIN E-2; MOUSE MODEL; MPTP MODEL; CYCLOOXYGENASE AB The importance of cyclooxygenase-2 (COX-2) in mediating Parkinson's disease (PD) was suggested in reports, indicating that COX-2 selective inhibitors or genetic knockout reduce 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic (DA) neurotoxicity in a mouse model of PD. However, cell types and mechanisms underlying the activation of COX-2 have not been clearly elucidated in these animal studies. Using primary neuron-glia cultures, we aimed to determine 1) whether microglia participate in 1-methyl-4-phenylpryridinium (MPP)-induced COX-2 activation and 2) whether the activation of COX-2 contributes to subsequent neurotoxicity. MPP+, in a concentration-dependent manner, increased prostaglandin E-2 (PGE(2)) production in mixed neuron-microglia cultures but not in enriched neuron, microglia, or astroglia cultures nor in mixed neuron-astroglia cultures. MPP+-induced PGE2 increase was completely abolished by treatment with DuP697, a COX-2 selective inhibitor. DuP697 also significantly reduced MPP+-induced DA neurotoxicity as determined by DA uptake assay. Immunocytochemistry and confocal microscopy studies showed enhanced COX-2 expression in both microglia and neurons after MPP+ treatment. However, neuronal increase in COX-2 expression was not totally dependent on the production of PGE(2) from microglia, since microglia deficient in COX-2 only attenuated, but did not completely block, MPP+-increased PGE(2) production in mixed neuron-microglia cultures, suggesting that part of PGE(2) production was originated from neurons. Together, these results indicate that MPP+-induced COX-2 expression and subsequent PGE(2) production depend on interactions between neurons and microglia. Microgliosis may also be responsible for the COX-2 activation in neurons, leading to the enhanced DA neurotoxicity, which, in turn, reinforces microgliosis. Thus inhibition of microgliosis and COX-2 activity may stop this vicious circle and be valuable strategies in PD therapy. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Confocal Microscopy Ctr, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov RI liu, Bin/A-7695-2009 NR 31 TC 65 Z9 89 U1 2 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2005 VL 19 IS 6 BP 1134 EP + DI 10.1096/fj.04-2457fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 922UP UT WOS:000228865300010 PM 15845609 ER PT J AU Galperin, MY Penn, CW Pallen, MJ AF Galperin, MY Penn, CW Pallen, MJ TI Thematic Issue - Bacterial genomics SO FEMS MICROBIOLOGY REVIEWS LA English DT Editorial Material C1 NCBL, NLM, NIH, Bethesda, MD 20892 USA. Univ Birmingham, Birmingham, W Midlands, England. RP Galperin, MY (reprint author), NCBL, NLM, NIH, Bethesda, MD 20892 USA. RI Pallen, Mark/E-7619-2011; Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD APR PY 2005 VL 29 IS 2 BP 145 EP 145 DI 10.1016/j.femsre.2005.01.002 PG 1 WC Microbiology SC Microbiology GA 917YT UT WOS:000228506000001 ER PT J AU Aravind, L Anantharaman, V Balaji, S Babu, MM Iyer, LM AF Aravind, L Anantharaman, V Balaji, S Babu, MM Iyer, LM TI The many faces of the helix-turn-helix domain: Transcription regulation and beyond SO FEMS MICROBIOLOGY REVIEWS LA English DT Review DE helix-tum-helix; DNA-binding; transcription regulation; evolution; two-component systems; structure ID DNA-BINDING DOMAIN; PHOSPHORYL TRANSFER PROTEINS; NUCLEAR-MAGNETIC-RESONANCE; BACTERIAL RNA-POLYMERASE; HORIZONTAL GENE-TRANSFER; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; STRUCTURAL BASIS; COMPARATIVE GENOMICS AB The helix-turn-helix (HTH) domain is a common denominator in basal and specific transcription factors from the three super-kingdoms of life. At its core, the domain comprises of an open tri-helical bundle, which typically binds DNA with the 3rd helix. Drawing on the wealth of data that has accumulated over two decades since the discovery of the domain, we present an overview of the natural history of the HTH domain from the viewpoint of structural analysis and comparative genomics. In structural terms, the HTH domains have developed several elaborations on the basic 3-helical core, such as the tetra-helical bundle, the winged-helix and the ribbon-helix helix type configurations. In functional terms, the HTH domains are present in the most prevalent transcription factors of all prokaryotic genomes and some eukaryotic genomes. They have been recruited to a wide range of functions beyond transcription regulation, which include DNA repair and replication, RNA metabolism and protein-protein interactions in diverse signaling contexts. Beyond their basic role in mediating macromolecular interactions, the HTH domains have also been incorporated into the catalytic domains of diverse enzymes. We discuss the general domain architectural themes that have arisen amongst the HTH domains as a result of their recruitment to these diverse functions. We present a natural classification, higher-order relationships and phyletic pattern analysis of all the major families of HTH domains. This reconstruction suggests that there were at least 6-11 different HTH domains in the last universal common ancestor of all life forms, which covered much of the structural diversity and part of the functional versatility of the extant representatives of this domain. In prokaryotes the total number of HTH domains per genome shows a strong power-equation type scaling with the gene number per genome. However, the HTH domains in two-component signaling pathways show a linear scaling with gene number, in contrast to the non-linear scaling of HTH domains in single-component systems and sigma factors. These observations point to distinct evolutionary forces in the emergence of different signaling systems with HTH transcription factors. The archaea and bacteria share a number of ancient families of specific HTH transcription factors. However, they do not share any orthologous HTH proteins in the basal transcription apparatus. This differential relationship of their basal and specific transcriptional machinery poses an apparent conundrum regarding the origins of their transcription apparatus. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Room 5N50, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 NR 181 TC 123 Z9 127 U1 3 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD APR PY 2005 VL 29 IS 2 BP 231 EP 262 DI 10.1016/j.femsre.2004.12.008 PG 32 WC Microbiology SC Microbiology GA 917YT UT WOS:000228506000006 PM 15808743 ER PT J AU Ghosal, D Omelchenko, MV Gaidamakova, EK Matrosova, VY Vasilenko, A Venkateswaran, A Zhai, M Kostandarithes, HM Brim, H Makarova, KS Wackett, LP Fredrickson, JK Daly, MJ AF Ghosal, D Omelchenko, MV Gaidamakova, EK Matrosova, VY Vasilenko, A Venkateswaran, A Zhai, M Kostandarithes, HM Brim, H Makarova, KS Wackett, LP Fredrickson, JK Daly, MJ TI How radiation kills cells: Survival of Deinococcus radiodurans and Shewanella oneidensis under oxidative stress SO FEMS MICROBIOLOGY REVIEWS LA English DT Review DE oxidative stress; UV; desiccation; ionizing radiation; cytochromes; flavins; nucleoid; manganese; iron; Shewanella; Deinococcus; Kineococcus ID MICROCOCCUS-RADIODURANS; SUPEROXIDE-DISMUTASE; IONIZING-RADIATION; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI; GAMMA-RADIATION; DESERT VARNISH; RESISTANCE; MANGANESE; BACTERIUM AB We have recently shown that Demococcus radiodurans and other radiation resistant bacteria accumulate exceptionally high intracellular manganese and low iron levels. In comparison, the dissimilatory metal-reducing bacterium Shewanella oneidensis accumulates Fe but not Mn and is extremely sensitive to radiation. We have proposed that for Fe-rich, Mn-poor cells killed at radiation doses which cause very little DNA damage, cell death might be induced by the release of Fe(II) from proteins during irradiation, leading to additional cellular damage by Fe(II)-dependent oxidative stress. in contrast, Mn(II) ions concentrated in D. radiodurans might serve as antioxidants that reinforce enzymic systems which defend against oxidative stress during recovery. We extend our hypothesis here to include consideration of respiration, tricarboxylic acid cycle activity, peptide transport and metal reduction, which together with Mn(II) transport represent potential new targets to control recovery from radiation injury. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Bethesda, MD 20894 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. Howard Univ, Washington, DC 20059 USA. Univ Minnesota, St Paul, MN 55108 USA. RP Daly, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. EM mdaly@usuhs.mil NR 68 TC 129 Z9 137 U1 11 U2 38 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD APR PY 2005 VL 29 IS 2 BP 361 EP 375 DI 10.1016/j.femsre.2004.12.007 PG 15 WC Microbiology SC Microbiology GA 917YT UT WOS:000228506000011 PM 15808748 ER PT J AU Mechsner, SV Bartley, J Loddenkemper, C Salomon, DS Starzinski-Powitz, A Ebert, AD AF Mechsner, SV Bartley, J Loddenkemper, C Salomon, DS Starzinski-Powitz, A Ebert, AD TI Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts SO FERTILITY AND STERILITY LA English DT Article DE oxytocin receptor; endometriosis; smooth muscle metaplasia; smooth muscle actin; prostaglandin synthesis ID MYOMETRIAL ZONAL DIFFERENTIATION; NONPREGNANT HUMAN-UTERUS; UTERINE JUNCTIONAL ZONE; RAPID SPERM TRANSPORT; MENSTRUAL-CYCLE; EARLY-PREGNANCY; PROSTAGLANDIN-F2-ALPHA; LOCALIZATION; CONTRACTIONS; LABOR AB Objective: To investigate the expression of oxytocin receptor (OTR) in peritoneal and ovarian endometriotic lesions. Design: Retrospective nonrandomized study. Setting: University hospital endometriosis research center. Patient(s): Premenopausal women with histologically confirmed endometriosis were selected. Peritoneal endometriotic lesions (n = 120); ovarian endometriotic cysts (n = 40); peritoneal biopsies, distant from the endometriotic lesion (n = 55); and unaffected peritoneal biopsies from patients without endometriosis (n = 11) were obtained. Hysterectomy specimens from patients without endometriosis and/or adenomyosis were used for controls (n = 10). Intervention (S): Histopathological examination of peritoneal and ovarian specimens for OTR expression and identification of smooth muscle cells by immunobistochemistry staining with antibodies against OTR and smooth muscle actin. In addition, Western blot analysis, double-immunofluorescence, and in vitro studies with primary cell cultures have been performed. Main Outcome Measure(s): Comparison of the immunoreactive score of the OTR and smooth muscle actin expression with the smooth muscle content in peritoneum with and without endometriosis. Result(s): In the epithelial cells of endometriotic lesions, we could demonstrate a high OTR expression. The stromal cells were OTR negative with the exception of some single cells. By using a monoclonal anti-smooth muscle actin antibody, these cells could be identified as intrastromal OTR-positive smooth muscle cells. The peritoneum of women with endometriosis shows a significantly higher smooth muscle content than the peritoneum of women without endometriosis. There were no significant differences between the smooth muscle content of active or inactive lesions and the stage of disease. Conclusion(s): Oxytocin receptor is expressed in smooth muscle cells and epithelial cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. The inhibition of OTR by specific inhibitors might be a useful approach for the treatment of endometriosis-associated pain. (Fertil Steril((R)) 2005;83(Suppl 1): 1220-31. (c) 2005 by American Society for Reproductive Medicine.) C1 Charite, Endometriosis Res Ctr Berlin, Dept Gynecol, D-12200 Berlin, Germany. Charite, Inst Pathol, Consultat & reference Ctr Lymph Node Pathol & Hae, D-12200 Berlin, Germany. NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. Univ Frankfurt, Inst Human Genet, D-6000 Frankfurt, Germany. RP Ebert, AD (reprint author), Charite, Endometriosis Res Ctr Berlin, Dept Gynecol, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany. EM andreas.ebert@charite.de NR 56 TC 31 Z9 32 U1 0 U2 3 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 APR PY 2005 VL 83 SU 1 BP 1220 EP 1231 DI 10.1016/j.fertnstert.2004.11.038 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 918FB UT WOS:000228526600019 PM 15831296 ER PT J AU Detweiler, CD Lardinois, OM Deterding, LJ de Montellano, PRO Tomer, KB Mason, RP AF Detweiler, CD Lardinois, OM Deterding, LJ de Montellano, PRO Tomer, KB Mason, RP TI Identification of the myoglobin tyrosyl radical by immuno-spin trapping and its dimerization SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE antibodies; DMPO; myoglobin tyrosyl radical; western blot; dityrosine; free radicals ID SPERM-WHALE MYOGLOBIN; HYDROGEN-PEROXIDE; MASS-SPECTROMETRY; PROTEIN RADICALS; CROSS-LINKING; METMYOGLOBIN; TRYPTOPHAN; TYR-151; HEME; SITE AB 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) spin trapping in conjunction with antibodies specific for the DNIPO nitrone epitope was used on hydrogen peroxide-treated sperm whale and horse heart myoglobins to determine the site of protein nitrone adduct formation. The present study demonstrates that the sperm whale myoglobin tyrosyl radical, formed by hydrogen peroxide-dependent self-peroxidation, can either react with another tyrosyl radical, resulting in a dityrosine cross-linkage, or react with the spin trap DMPO to form a diamagnetic mitotic adduct. The reaction of sperm whale myoglobin with equimolar hydrogen peroxide resulted in the formation of a myoglobin dinner detectable by electrophoresis/protein staining. Addition of DMPO resulted in the trapping of the globin radical, which was detected by Western blot. The location of this adduct was demonstrated to be at tyrosine-103 by MS/MS and site-specific mutagenicity. Interestingly, formation of the myoglobin dimer, which is known to be formed primarily by cross-linkage of tyrosine-151, was inhibited by the addition of DMPO. Published by Elsevier Inc. C1 NIEHS, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. RP Mason, RP (reprint author), NIEHS, NIH, Lab Pharmacol & Chem, POB 12233,MD F0-01, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 21 TC 47 Z9 47 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 1 PY 2005 VL 38 IS 7 BP 969 EP 976 DI 10.1016/j.freeradbiomed.2004.12.031 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 907ZG UT WOS:000227756200016 PM 15749393 ER PT J AU Gourraud, PA Feolo, M Cambon-Thomsen, A AF Gourraud, PA Feolo, M Cambon-Thomsen, A CA Msat-14 IHWG Grp TI Microsatellites: InHLA region development of interface at NCBI's dbMHC SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 19th European Immunogenetics and Histocompatibility Conference CY APR 23-26, 2005 CL Istanbul, TURKEY SP European Federat Immunogenet C1 Fac Med Toulouse, INSERM, U558, F-31073 Toulouse, France. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RI Gourraud, Pierre-Antoine/O-3024-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD APR PY 2005 VL 6 SU 1 BP S7 EP S7 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 922WF UT WOS:000228869900026 ER PT J AU Helmberg, W Nelson, L Pugliese, A Feolo, M Hoffman, D AF Helmberg, W Nelson, L Pugliese, A Feolo, M Hoffman, D TI Two new clincal resources at DBMHC: The Rheumatoid Arthritis project and the Diabetes project of the 13. IHWC. SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 19th European Immunogenetics and Histocompatibility Conference CY APR 23-26, 2005 CL Istanbul, TURKEY SP European Federat Immunogenet C1 UBT, Univ Clin, Graz, Austria. NCBI, NIH, Bethesda, MD USA. Univ Miami, DRI, Miami, FL USA. FHCRC, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD APR PY 2005 VL 6 SU 1 BP S31 EP S31 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 922WF UT WOS:000228869900125 ER PT J AU Helmberg, W Feolo, M Dunivin, R AF Helmberg, W Feolo, M Dunivin, R TI DBLRC-KIR, a new specialised database for genes of the leucocyte recptor complex. SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 19th European Immunogenetics and Histocompatibility Conference CY APR 23-26, 2005 CL Istanbul, TURKEY SP European Federat Immunogenet C1 Univ Clin Graz, UBT, Graz, Austria. NIH, NCBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD APR PY 2005 VL 6 SU 1 BP S3 EP S3 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 922WF UT WOS:000228869900011 ER PT J AU Yeager, M Shen, M Li, GL He, XZ Welch, R Zheng, TZ Chanock, S Lan, Q AF Yeager, M Shen, M Li, GL He, XZ Welch, R Zheng, TZ Chanock, S Lan, Q TI Differences in allele frequencies in cytokine genes by populations: Implications for molecular evolution and selection of candidate genes for association studies SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 19th European Immunogenetics and Histocompatibility Conference CY APR 23-26, 2005 CL Istanbul, TURKEY SP European Federat Immunogenet C1 NCI, CGF, DCEG, HHS, Gaithersburg, MD 20877 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD APR PY 2005 VL 6 SU 1 BP S33 EP S33 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 922WF UT WOS:000228869900130 ER PT J AU Silva, S Wiener, F Klein, G Janz, S AF Silva, S Wiener, F Klein, G Janz, S TI Location of Myc, Igh, and Igk on Robertsonian fusion chromosomes is inconsequential for Myc translocations and plasmacytoma development in mice, but Rb(6.15)-carrying tumors prefer Igk-Myc inversions over Translocations SO GENES CHROMOSOMES & CANCER LA English DT Article ID C-MYC; NEOPLASTIC DEVELOPMENT; MURINE PLASMACYTOMA; BURKITT-LYMPHOMA; CELLS; GENE; MOUSE; INDUCTION; PRISTANE; LEUKEMIA AB The location of the Myc and immunoglobulin (lg) loci on metacentric Robertsonian (Rb) fusion chromosomes may affect the development of mouse plasmacytornas (Pcts) by changing the probability with which chromosomal Myc-lg translocations occur. To test this hypothesis, we induced Pcts in BALB/c (C) mice that carried Rb(4.12) and/or Rb(6.15) chromosomes. The Rb mice developed Pcts (n = 198) with similar onset and incidence to that in the inbred C mice. Karyotyping of 70 Rb-carrying Pcts demonstrated that in these tumors, just as in their counterparts in inbred C mice, the lgh heavy-chain locus was translocated with Myc more often than was the lgk light-chain locus. Pcts harboring lgh or lgk on normal and Rb chromosomes showed no bias toward either in generating Myc translocations. These findings indicated that the location of Myc, lgh, and lgk on normal or Rb chromosomes is inconsequential for Myc translocation and Pct development. In contrast, in Rb(6.15) mice, in which chromosomal inversions competed with chromosomal translocations for lgk-Myc juxtapositions, the former occurred more frequently than the latter in the resulting Pcts. This suggested that spatial proximity of lgk and Myc on the same chromosome facilitates the rearrangement of these loci. Myc translocation-depenclent mouse Pct may provide a good model system for furthering our understanding of the relationship of higher-order genome organization in the interphase nucleus, origin of chromosomal translocations, and development of cancer. Published 2005 Wiley-Liss, Inc. C1 NCI, Genet Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Microbiol & Tumor Biol Ctr, Stockholm, Sweden. RP Janz, S (reprint author), NCI, Genet Lab, Ctr Canc Res, NIH, Bldg 37,Room 2B10, Bethesda, MD 20892 USA. EM sj4s@nih.gov NR 30 TC 6 Z9 6 U1 0 U2 0 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 APR PY 2005 VL 42 IS 4 BP 416 EP 426 DI 10.1002/gcc.20149 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 899UF UT WOS:000227170100008 PM 15645495 ER PT J AU Voronina, VA Kozlov, S Mathers, PH Lewandoski, M AF Voronina, VA Kozlov, S Mathers, PH Lewandoski, M TI Conditional alleles for activation and inactivation of the mouse Rx homeobox gene SO GENESIS LA English DT Article DE Rx; Rax; eye; retina; optic vesicle; Cre recombinase; FLIP recombinase; conditional knockout; anophthalmia; craniofacial defects ID XRX1 CONTROLS PROLIFERATION; VERTEBRATE EYE DEVELOPMENT; EXPRESSION; MICE; CRE; MUTATION; EYELESS; REGION; RX/RAX; CELLS AB The Rx homeobox gene is a transcriptional regulator indispensable for development of the eye and ventral forebrain. Rx-null homozygotes lack optic pits, which are the earliest ocular structures. To study the roles Rx may play at various stages of eye and brain development, we generated an allelic series at the Rx locus. The targeted allele, Rx(neo), is a severely hypomorphic or null allele. This Rx(neo) allele is converted via FLP-mediated recombination to the Rx(flox) allele, which is phenotypically identical to the wildtype allele. Cre-mediated conversion of Rx(flox) generates the Rx(Delta 2) allele, which, when homozygous, results in an Rx-null phenotype that includes perinatal lethality, anophthalmia, and anterior neural and craniofacial defects. Mice carrying these alleles allow both Cre-mediated inactivation and FLP-mediated activation of Rx gene activity on a conditional basis and will be useful in examining Rx function at different developmental stages and in distinct tissue environments. (c) 2005Wiley-Liss, Inc. C1 NCI, NIH, Lab Canc & Dev Biol, Frederick, MD 21701 USA. W Virginia Univ, Sensory Neurosci Res Ctr, Morgantown, WV 26506 USA. W Virginia Univ, Dept Mol Pharmacol & Biochem, Morgantown, WV 26506 USA. W Virginia Univ, Dept Otolaryngol, Morgantown, WV 26506 USA. RP Lewandoski, M (reprint author), NCI, NIH, Lab Canc & Dev Biol, 539 Boyles St, Frederick, MD 21701 USA. EM mlewandoski@mail.ncfcrf.gov NR 26 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD APR PY 2005 VL 41 IS 4 BP 160 EP 164 DI 10.1002/gene.20109 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 922LI UT WOS:000228839000003 PM 15789424 ER PT J AU Bebenek, A Carver, GT Kadyrov, FA Kissling, GE Drake, JW AF Bebenek, A Carver, GT Kadyrov, FA Kissling, GE Drake, JW TI Processivity clamp gp45 and ssDNA-binding-protein gp32 modulate the fidelity of bacteriophage RB69 DNA polymerase in a sequence-specific manner, sometimes enhancing and sometimes compromising accuracy SO GENETICS LA English DT Article ID ESCHERICHIA-COLI; REPLICATION FIDELITY; ACCESSORY PROTEINS; BASE SUBSTITUTION; MUTATIONAL SPECIFICITY; DELETION MUTATIONS; CATALYTIC SUBUNIT; DELTA HOLOENZYME; III HOLOENZYME; IN-VITRO AB Numerous studies of the impact of accessory proteins upon the fidelity of DNA synthesis have provided a complex and sometimes discordant picture. We previously described such an analysis conducted in vitro using various bacteriophage RB69 gp43 mutator DNA polymerases with or without the accessory proteins gp32 (which binds single-stranded DNA) plus gp45/44/62 (processivity clamp and its loaders). Mutations were scored at many sites in the lacZ alpha mutation reporter sequence. Unexpectedly, the accessory proteins sometimes decreased and sometimes increased fidelity at a handful of specific sites. Here, we enlarge our analysis with one particular mutator polymerase compromised in both insertion accuracy and proofreading and also extend the analysis to reactions supplemented only with gp32 or only with gp45/44/62. An overall 1.56-fold increase in mutation frequencies was produced by adding single or multiple accessory proteins and was driven mainly by increased T(template)center dot G(primer) mispairs. Evidence was found for many additional sites where the accessory proteins influence fidelity, indicating the generality of the effect. Thus, accessory proteins contribute to the site-specific variability in mutation rates characteristically seen in mutational spectra. C1 Natl Inst Environm Hlth Sci, Lab Mol Genet E3 01, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Drake, JW (reprint author), Natl Inst Environm Hlth Sci, Lab Mol Genet E3 01, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov NR 36 TC 13 Z9 13 U1 1 U2 3 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 2005 VL 169 IS 4 BP 1815 EP 1824 DI 10.1534/genetics.104.037630 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 928IA UT WOS:000229263700004 PM 15695359 ER PT J AU Garfinkel, DJ Nyswaner, KM Stefanisko, KM Chang, C Moore, SP AF Garfinkel, DJ Nyswaner, KM Stefanisko, KM Chang, C Moore, SP TI Ty1 copy number dynamics in Saccharomyces SO GENETICS LA English DT Article ID TRANSFER-RNA GENES; YEAST RETROTRANSPOSON; TRANSPOSABLE ELEMENT; HOMOLOGOUS RECOMBINATION; POLYMERASE-III; CEREVISIAE; TRANSPOSITION; GENOME; EVOLUTION; CDNA AB To understand long terminal repeat (LTR)-retrotransposon copy number dynamics, Ty1 elements were reintroduced into a "Ty-less" Saccharomyces strain where elements had been lost by LTR-LTR recombination. Repopulated strains exhibited alterations in chromosome size that were associated with Ty1 insertions, but did not become genetically isolated. The rates of element gain and loss under genetic and environmental conditions known to affect Ty1 retrotransposition were determined using genetically tagged reference elements. The results show that Ty1 retrotransposition varies with copy number, temperature, and cell type. In contrast to retrotransposition, TO loss by LTR-LTR recombination was more constant and not markedly influenced by copy number. Endogenous Ty1 cDNA was poorly utilized for recombination when compared with LTR-LTR recombination or ectopic gene conversion. Ty1 elements also appear to be more susceptible to copy number fluctuation in haploid cells. Ty1 gain/loss ratios obtained under different conditions suggest that copy number oscillates over time by altering the rate of retrotransposition, resulting in the diverse copy numbers observed in Saccharomyces. C1 NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Garfinkel, DJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, POB B, Frederick, MD 21701 USA. EM garfinke@ncifcrf.gov NR 73 TC 11 Z9 11 U1 1 U2 6 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 2005 VL 169 IS 4 BP 1845 EP 1857 DI 10.1534/genetics.104.037317 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 928IA UT WOS:000229263700007 PM 15687270 ER PT J AU Hwang, JY Smith, S Myung, K AF Hwang, JY Smith, S Myung, K TI The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; GENOME INSTABILITY; S-PHASE; MITOTIC RECOMBINATION; NUCLEAR ABNORMALITIES; REPLICATION; YEAST; CANCER; SUPPRESSION AB Gross chromosomal rearrangements (GCRs) have been observed in many cancers. Previously, we have demonstrated many mechanisms for suppression of GCR formation in yeast. However, pathways that promote the formation of GCRs are not as well understood. Here, we present evidence that the Rad1-Rad10 endonuclease, which plays an important role in nucleotide excision and recombination repairs, has a novel role to produce GCRs. A mutation of either the RAD1 or the RAD10 gene reduced GCR rates in many GCR mutator strains. The inactivation of Rad1 or Rad10 in GCR mutator strains also slightly enhanced methyl methanesulfonate sensitivity. Although the GCRs induced by treatment with DNA-damaging agents were not reduced by rad1 or rad10 mutations, the translocation- and deletion-type GCRs created by a single double-strand break are mostly replaced by de novo telomere-addition-type GCR. Results presented here suggest that Rad1-Rad10 functions at different stages of GCR formation and that there is an alternative pathway for the GCR formation that is independent of Rad1-Rad10. C1 NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A22, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov OI Hwang, Ji-Young/0000-0001-8044-1989 NR 55 TC 14 Z9 14 U1 0 U2 0 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 2005 VL 169 IS 4 BP 1927 EP 1937 DI 10.1534/genetics.104.039768 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 928IA UT WOS:000229263700014 PM 15687264 ER PT J AU Green, MJ Peterson, SK Baker, MW Friedman, LC Harper, GR Rubinstein, WS Peters, JA Mauger, DT AF Green, MJ Peterson, SK Baker, MW Friedman, LC Harper, GR Rubinstein, WS Peters, JA Mauger, DT TI Use of an educational computer program before genetic counseling for breast cancer susceptibility: Effects on duration and content of counseling sessions SO GENETICS IN MEDICINE LA English DT Article DE genetic counseling; breast cancer; decision aids; computer based education; genes BRCA1/2 ID PRIMARY-CARE; PHYSICIANS ATTITUDES; OVARIAN-CANCER; BRCA1; BRCA1/BRCA2; KNOWLEDGE; MUTATION; SOCIETY; RISK AB Purpose: Patients seeking genetic testing for inherited breast cancer risk are typically educated by genetic counselors; however, the growing demand for cancer genetic testing will likely exceed the availability of counselors trained in this area. We compared the effectiveness of counseling alone versus counseling preceded by use of a computer-based decision aid among women referred to genetic counseling for a family or personal history of breast cancer. Methods: We developed and evaluated an interactive computer program that educates women about breast cancer, heredity, and genetic testing. Between May 2000 and September 2002, women at six study sites were randomized into either: Counselor Group (n = 105), who received standard genetic counseling, or Computer Group (n = 106), who used the interactive computer program before counseling. Clients and counselors both evaluated the effectiveness of counseling sessions, and counselors completed additional measures for the Computer Group. Counselors also recorded the duration of each session. Results: Baseline characteristics did not differ significantly between groups. Participants and counselors both rated the counseling sessions as highly effective, whether or not the sessions were preceded by computer use. Computer use resulted in significantly shorter counseling sessions among women at low risk for carrying BRCA1/2 mutations. In approximately half of the sessions preceded by clients' computer use, counselors indicated that clients' use of the computer program affected the way they used the time, shifting the focus away from basic education toward personal risk and decision-making. Conclusion: This study shows that the interactive computer program "Breast Cancer Risk and Genetic Testing" is a valuable adjunct to genetic counseling. Its use before counseling can shorten counseling sessions and allow counselors to focus more on the clients' individual risks and specific psychological concerns. As the demand for counseling services increases, a program such as this can play a valuable role in enhancing counseling efficiency. C1 Penn State Coll Med, Dept Humanities, Hershey, PA 17033 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Penn State Canc Inst, Milton S Hershey Med Ctr, Hershey, PA USA. Baylor Coll Med, Houston, TX 77030 USA. Lehigh Valley Hosp Ctr, Penn State Canc Inst, Allentown, PA USA. Evanston NW Healthcare, Evanston, IL USA. NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Green, MJ (reprint author), Penn State Coll Med, Dept Humanities, Hershey, PA 17033 USA. FU NCI NIH HHS [R01CA84770, R03CA70638]; NINR NIH HHS [R21 NR008539] NR 45 TC 51 Z9 51 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2005 VL 7 IS 4 BP 221 EP 229 DI 10.1097/01.GIM.0000159905.13125.86 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 917AQ UT WOS:000228428600001 PM 15834239 ER PT J AU De la Vega, FM Isaac, H Collins, A Scafe, CR Halldorsson, BV Su, XP Lippert, RA Wang, Y Laig-Webster, M Koehler, RT Ziegle, JS Wogan, LT Stevens, JF Leinen, KM Olson, SJ Guegler, KJ You, XQ Xu, LH Hemken, HG Kalush, F Itakura, M Zheng, Y de The, G O'Brien, SJ Clark, AG Istrail, S Hunkapiller, MW Spier, EG Gilbert, DA AF De la Vega, FM Isaac, H Collins, A Scafe, CR Halldorsson, BV Su, XP Lippert, RA Wang, Y Laig-Webster, M Koehler, RT Ziegle, JS Wogan, LT Stevens, JF Leinen, KM Olson, SJ Guegler, KJ You, XQ Xu, LH Hemken, HG Kalush, F Itakura, M Zheng, Y de The, G O'Brien, SJ Clark, AG Istrail, S Hunkapiller, MW Spier, EG Gilbert, DA TI The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern SO GENOME RESEARCH LA English DT Article ID PSORIASIS-SUSCEPTIBILITY LOCUS; CLASS-II REGION; HUMAN GENOME; HAPLOTYPE DIVERSITY; GENETIC-VARIATION; WIDE DISTRIBUTION; LD MAPS; ASSOCIATION; SEQUENCE; BLOCKS AB The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping. LD reaches almost twice as far in chromosome 6 as in chromosomes 21 or 22, in agreement with their differences in recombination rates. By all measures used, out-of-Africa populations showed over a third more LD than African-Americans, highlighting the role of the population's demography in shaping the patterns of LD. Despite those differences, the long-range contour of the LD maps is remarkably similar across the four populations, presumably reflecting common localization of recombination hot spots. Our results have practical implications for the rational design and selection of SNPs for disease association studies. C1 Appl Biosyst Inc, Foster City, CA 94404 USA. Univ Southampton, Div Human Genet, Southampton SO16 6YD, Hants, England. Celera Genom, Rockville, MD 20850 USA. Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan. Chinese Acad Prevent Med, Inst Virol, Beijing 100052, Peoples R China. Inst Pasteur, CNRS, Dept Viral Oncol Epidemiol, F-75015 Paris, France. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Cornell Univ, Ithaca, NY 14853 USA. RP De la Vega, FM (reprint author), Appl Biosyst Inc, 850 Lincoln Ctr Dr, Foster City, CA 94404 USA. EM delavefm@appliedbiosystems.com RI Collins, Andrew/A-6595-2010; OI Collins, Andrew/0000-0001-7108-0771; Halldorsson, Bjarni/0000-0003-0756-0767 NR 52 TC 52 Z9 56 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD APR PY 2005 VL 15 IS 4 BP 454 EP 462 DI 10.1101/gr.3241705 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 914CT UT WOS:000228203000002 PM 15781572 ER PT J AU Svartman, M Stone, G Stanyon, R AF Svartman, M Stone, G Stanyon, R TI Molecular cytogenetics discards polyploidy in mammals SO GENOMICS LA English DT Article DE polyploidy; mammals; chromosome painting; FISH ID OCTODONTID RODENTS; CHROMOSOMES; DNA AB Polyploidy, the presence of more than two chromosome sets, is common in plants, but extremely rare in animals. The absence of polyploid organisms with well-differentiated sex chromosomes suggests that the disruption of the dosage between autosomes and sex chromosomes is incompatible with normal development. Thus, the announcement in 1999 of tetraploidy in a mammal, the South American red vizcacha rat Tympanoctomys barrerae, provoked great interest, even though the definitive proof of tetraploidy, the presence of four copies of each chromosome, was never provided. Here we used classical and molecular cytogenetics to test the ploidy level of T barrerae and demonstrate that only two copies of each chromosome are present in this karyotype. The red vizcacha rat is clearly diploid and the amplification and dispersion of repetitive sequences best explain the large genome size of this mammal. Thus, polyploidy in mammals remains as unlikely as it has always been. Published by Elsevier Inc. C1 Natl Canc Inst, Comparat Mol Cytogenet Core, Frederick, MD 21702 USA. RP Svartman, M (reprint author), Natl Canc Inst, Comparat Mol Cytogenet Core, Frederick, MD 21702 USA. EM svartmanm@ncifcrf.gov RI Svartman, Marta/B-4528-2008; OI Svartman, Marta/0000-0003-3239-1862; Stanyon, Roscoe/0000-0002-7229-1092 NR 20 TC 32 Z9 32 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 0888-7543 J9 GENOMICS JI Genomics PD APR PY 2005 VL 85 IS 4 BP 425 EP 430 DI 10.1016/j.ygeno.2004.12.004 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 913BV UT WOS:000228126100002 PM 15780745 ER PT J AU LopezJimenez, ND Sainz, E Cavenagh, MM Cruz-Ithier, MA Blackwood, CA Battey, JF Sullivan, SL AF LopezJimenez, ND Sainz, E Cavenagh, MM Cruz-Ithier, MA Blackwood, CA Battey, JF Sullivan, SL TI Two novel genes, Gpr113, which encodes a family 2 G-protein-coupled receptor, and Trcg1, are selectively expressed in taste receptor cells SO GENOMICS LA English DT Article ID SWEET TASTE; PROTEOLYTIC CLEAVAGE; MAMMALIAN SWEET; CELLULAR LIGAND; BITTER TASTE; UMAMI TASTE; RAT; 7-TRANSMEMBRANE; IDENTIFICATION; TRANSDUCTION AB To identify genes important for taste receptor cell function, we analyzed the sequences and expression patterns of clones isolated from a mouse taste receptor cell-enriched cDNA library. Here, we report the analyses of two novel genes, Gpr113 and Trcg1. Gpr113 encodes a G-protein-coupled receptor belonging to family 2B, members of which are characterized by having long N-terminal, extracellular domains. The predicted N-terminal extracellular domain of GPR113 contains 696 amino acids with two functional domains, a peptide hormone-binding domain and a G-protein-coupled receptor proteolytic site. Expression analyses indicate that Gpr113 expression is highly restricted to a subset of taste receptor cells. TRCG1 is also selectively expressed in a subset of taste receptor cells. Trcg1 is alternatively spliced and encodes Trcg1 isoforms of 209 and 825 amino acids. BLAST searches of genomic sequences indicate that a putative homolog of Trcg1 resides on human chromosome 15q22. Published by Elsevier Inc. C1 Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Sullivan, SL (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. EM sullivas@nidcd.nih.gov NR 55 TC 14 Z9 16 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR PY 2005 VL 85 IS 4 BP 472 EP 482 DI 10.1016/j.ygeno.2004.12.005 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 913BV UT WOS:000228126100007 PM 15780750 ER PT J AU Han, B Phillips, C Ferrucci, L Bandeen-Roche, K Jylha, M Kapser, J Guralnik, JM AF Han, B Phillips, C Ferrucci, L Bandeen-Roche, K Jylha, M Kapser, J Guralnik, JM TI Change in self-rated health and mortality among community-dwelling disabled older women SO GERONTOLOGIST LA English DT Article DE change in self-rated health; mortality; disabled older women; time-dependent covariates ID GENDER-DIFFERENCES; ASSOCIATION; SURVIVAL; ADULTS AB Purpose: Our study assessed whether change in self-rated health is a stronger predictor of mortality than baseline self-rated health and the most recent self-rated health (prior to death or loss to follow-up) among disabled older women. Design and Methods: The Women's Health and Aging Study examined disabled older women at baseline and every 6 months for 3 years. During the follow-up period, 253 out of the 905 examined participants died. Cox regression models with time-dependent covariates were used. Results: After baseline characteristics were adjusted for, baseline self-rated health was not related to mortality. After covariates at the most recent observation and covariates measured only at baseline were controlled for, the most recent self-rated health was not associated with mortality either. After time-dependent covariates and covariates measured only at baseline were adjusted for, decline in self-rated health was significantly associated with increased mortality. Implications: Change in self-rated health is a stronger predictor of mortality than self-rated health at baseline and at the most recent observation. Older women with "fair" health are worse off if they are on a declining health trajectory than if their "fair" health is stable. Family caregivers and clinicians need to closely monitor change in self-rated health among disabled older women. C1 Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. Univ Tampere, Sch Publ Hlth, FIN-33101 Tampere, Finland. RP Han, B (reprint author), 3311 Toledo Rd,Room 3409, Hyattsville, MD 20782 USA. EM hih9@cdc.gov NR 27 TC 46 Z9 47 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD APR PY 2005 VL 45 IS 2 BP 216 EP 221 PG 6 WC Gerontology SC Geriatrics & Gerontology GA 911BX UT WOS:000227977400008 PM 15799986 ER PT J AU Davila, JA Morgan, RO Shaib, Y McGlynn, KA El-Serag, HB AF Davila, JA Morgan, RO Shaib, Y McGlynn, KA El-Serag, HB TI Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study SO GUT LA English DT Article ID PRIMARY LIVER-CANCER; NONALCOHOLIC STEATOHEPATITIS; CRYPTOGENIC CIRRHOSIS; NATURAL-HISTORY; MELLITUS; PATHOGENESIS; PREDICTORS; HEPATITIS; FIBROSIS; DISEASE AB Background: Diabetes has been associated with an increased risk of hepatocellular carcinoma (HCC) in studies of referred patients. This is the first population based case control study in the USA to examine this association while adjusting for other major risk factors related to HCC. Methods: We used the Surveillance Epidemiology and End-Results Program (SEER)-Medicare linked database to identify patients aged 65 years and older diagnosed with HCC and randomly selected noncancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index date were examined. Inpatient and outpatient claims files were searched for diagnostic codes indicative of diabetes, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease, and haemochromatosis. HCC patients without these conditions were categorised as idiopathic. Unadjusted and adjusted odds ratios were calculated in logistic regression analyses. Results: We identified 2061 HCC patients and 6183 non-cancer controls. Compared with non-cancer controls, patients with HCC were male ( 66% v 36%) and non-White (34% v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demographics features and other HCC risk factors ( HCV, HBV, alcoholic liver disease, and haemochromatosis), diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjusted odds ratio for diabetes declined but remained significant ( adjusted odds ratio 2.87 (95% confidence interval 2.49-3.30)). A significant positive interaction between HCV and diabetes was detected (p<0.0001). Similar findings persisted in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. Conclusions: Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors. Findings from this population based study suggest that diabetes is an independent risk factor for HCC. C1 Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. RP El-Serag, HB (reprint author), Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu RI Morgan, Robert/A-8577-2009 NR 25 TC 329 Z9 352 U1 2 U2 15 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 APR PY 2005 VL 54 IS 4 BP 533 EP 539 DI 10.1136/gut.2004.052167 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 904BS UT WOS:000227471000021 PM 15753540 ER PT J AU Smith, MG Hold, GL Rabkin, C Chow, WH Fraumeni, JF Mowat, NAG Ando, T Goto, H El-Omar, EM AF Smith, MG Hold, GL Rabkin, C Chow, WH Fraumeni, JF Mowat, NAG Ando, T Goto, H El-Omar, EM TI IL-8-251 promoter polymorphism and risk of gastric cancer in white and Japanese populations SO GUT LA English DT Meeting Abstract CT Annual Meeting of the British-Society-of-Gastroenterology CY MAR 14-17, 2005 CL Birmingham, ENGLAND SP British Soc Gastroenterol C1 Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. NCI, NIH, Rockville, MD USA. Nagoya Univ, Grad Sch Med, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2005 VL 54 SU 2 MA 033 BP A9 EP A9 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 907JJ UT WOS:000227712600034 ER PT J AU Lin, FE Gladwin, MT Machado, RF AF Lin, FE Gladwin, MT Machado, RF TI Pulmonary hypertension in patients with hemoglobinopathies: could a mechanism for dysfunction provide an avenue for novel therapeutics? SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID SICKLE-CELL-DISEASE; MICROANGIOPATHIC HEMOLYTIC-ANEMIA; NITRIC-OXIDE BIOAVAILABILITY; BETA-THALASSEMIA MAJOR; HEREDITARY STOMATOCYTOSIS; THROMBOEMBOLIC DISEASE; SPLENECTOMY; SPHEROCYTOSIS; INTERMEDIA; THROMBOCYTOPENIA C1 NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Lin, FE (reprint author), NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bldg 10, Bethesda, MD 20892 USA. EM robertom@nhlbi.nih.gov NR 42 TC 2 Z9 2 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD APR PY 2005 VL 90 IS 4 BP 441 EP 444 PG 4 WC Hematology SC Hematology GA 943YC UT WOS:000230390800001 ER PT J AU Simons-Morton, B Haynie, D Saylor, K Crump, AD Chen, RA AF Simons-Morton, B Haynie, D Saylor, K Crump, AD Chen, RA TI Impact analysis and mediation of outcomes: The going places program SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE adolescents; randomized trial; problem behavior ID ADOLESCENT SUBSTANCE USE; INNER-CITY ADOLESCENTS; PREVENTION PROGRAMS; ALCOHOL-USE; SCHOOL ADJUSTMENT; PARENT INFLUENCES; DRUG-ABUSE; SMOKING; PEER; EXPECTANCIES AB The purpose of the study was to evaluate the impact of the Going Places Program and mediation of treatment effects. Seven middle schools were randomized to intervention or comparison conditions and students (n = 1,320) in two successive cohorts provided five waves of data from sixth through eighth grade. The Going Places Program included classroom curriculum, parent education, and school environment components. Latent growth curve analyses demonstrated significant treatment group effects on outcome expectancies, friends who smoke, and smoking. Friends who smoke mediated the program effect on adolescents' smoking progression. The protective effect of the Going Places Program on smoking progression was due in part to the prevention of increases in friends who smoke. C1 NICHD, Prevent Res Branch, DESPR, NIH, Rockville, MD 20852 USA. NeuroSci Inc, Bethesda, MD USA. NIDA, Prevent Res Branch, NIH, Rockville, MD USA. Georgetown Univ, Washington, DC USA. RP Simons-Morton, B (reprint author), NICHD, Prevent Res Branch, DESPR, NIH, 6100 Execut Blvd 7B13M, Rockville, MD 20852 USA. EM mortonb@exchange.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 FU NICHD NIH HHS [N01-HD-4-3207] NR 53 TC 20 Z9 20 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2005 VL 32 IS 2 BP 227 EP 241 DI 10.1177/1090198104272002 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 907DH UT WOS:000227695000006 PM 15749968 ER PT J AU Michielutte, R Sharp, PC Foley, KL Cunningham, LE Spangler, JG Paskett, ED Case, LD AF Michielutte, R Sharp, PC Foley, KL Cunningham, LE Spangler, JG Paskett, ED Case, LD TI Intervention to increase screening mammography among women 65 and older SO HEALTH EDUCATION RESEARCH LA English DT Article ID BREAST-CANCER; PROMOTING MAMMOGRAPHY; ELDERLY-WOMEN; HMO WOMEN; TELEPHONE; AGE; TRIALS; MODEL AB This paper reports the results of a practice-based intervention program to increase mammography screening among women 65 and older who receive their health care in the private sector. Forty-three primary-care practices and 2147 women in central and western North Carolina were enrolled in the study, and 1911 women completed all phases of the study. The intervention was a three-stage educational and counseling program designed to become progressively more intensive at each stage. The interventions included provider education in the form of current information on issues in mammography for older women, simply written educational materials on breast cancer and screening mailed to women, and a brief telephone counseling session for the women. While the analysis revealed no overall effect across all three stages of the intervention program, tests for interaction indicated a significant program effect for women who were 80 or older, had less than 9 years of education, were black, or had no private insurance to supplement Medicare. The results suggested that providing primary-care physicians with information on screening older women and providing the women with useful educational materials can increase participation in screening mammography among subgroups of women currently least likely to receive mammography screening. C1 Wake Forest Univ, Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. NCI, Off Educ & Special Initiat, Bethesda, MD 20892 USA. Ohio State Univ, Ctr Comprehens Canc, Sch Publ Hlth, Columbus, OH 43210 USA. RP Michielutte, R (reprint author), Wake Forest Univ, Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. EM bmichiel@wfubmc.edu FU NCI NIH HHS [CA79746] NR 42 TC 17 Z9 17 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD APR PY 2005 VL 20 IS 2 BP 149 EP 162 DI 10.1093/her/cyg108 PG 14 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 903DJ UT WOS:000227405400004 PM 15254001 ER PT J AU Murano, A Morinaga, N Iwamaru, Y Yahiro, K Tagashira, M Moss, J Tanzawa, H Noda, M AF Murano, A Morinaga, N Iwamaru, Y Yahiro, K Tagashira, M Moss, J Tanzawa, H Noda, M TI Acidic conditions enhance bactericidal effects of sodium bisulfite on Helicobacter pylori SO HELICOBACTER LA English DT Article DE Helicobacter pylori; sodium bisulfite; acidic condition; urease ID IN-VITRO; SULFUR-DIOXIDE; LIQUID-MEDIA; GROWTH; SULFITE; CELLS; CULTURE; ATPASE AB Background. The Brucella broth medium, which is often used for the cultivation of microaerobic bacteria including Helicobacter pylori. It contains sodium bisulfite to decrease oxygen content in the medium. The growth of H. pylori, however, is inhibited by sodium bisulfite. In this study, the effect of sodium bisulfite was compared with several antioxidants and quantified under acidic conditions, mimicking the gastric environment. Methods. Growth of H. pylori in the presence of several antioxidants was evaluated at OD655 nm. Effect of sodium bisulfite on H. pylori under acidic conditions was evaluated by measuring colony forming units (cfu). Results. Under neutral conditions, sodium bisulfite was a more potent suppressor of H. pylori. Resveratrol, a polyphenol found in wine, exhibited the most potent inhibitory activity. To quantify the effect of sodium bisulfite on H. pylori under acidic conditions, the bacteria were grown at 37 degrees C for 30 minutes in 0.15 mol/l HCl/KCl (pH 2.0) with or without urea and sodium bisulfite. Sodium bisulfite (0.5 mmol/l) did not affect the viability at neutral pH 7.0, however, it killed H. pylori under acidic conditions, even if urea, the key substance enabling H. pylori to survive under acidic conditions, was present. The bacteria, which had been incubated under acidic conditions in the presence of urea, could survive a subsequent 30 minute-incubation at pH 2.0 without urea. Presence of sodium bisulfite, however, in the subsequent 30 minute-incubation, killed the bacteria. Conclusions. The bactericidal effect of sodium bisulfite on H. pylori was greater under acidic conditions and independent of urease activity. C1 Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Clin Mol Biol, Chuo Ku, Chiba 2608670, Japan. Asahi Brewery Co Ltd, Fundamental Res Lab, Ibaraki 3020106, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Noda, M (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM noda@faculty.chiba-u.jp NR 22 TC 6 Z9 6 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD APR PY 2005 VL 10 IS 2 BP 132 EP 135 DI 10.1111/j.1523-5378.2005.00299.x PG 4 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 905TN UT WOS:000227593200005 PM 15810943 ER PT J AU Javor, ED Ghany, MG Cochran, EK Oral, EA DePaoli, AM Premkumar, A Kleiner, DE Gorden, P AF Javor, ED Ghany, MG Cochran, EK Oral, EA DePaoli, AM Premkumar, A Kleiner, DE Gorden, P TI Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; INSULIN-RESISTANCE; HEPATIC STEATOSIS; REPLACEMENT THERAPY; CLINICAL-COURSE; WHITE ADIPOSE; RECEPTOR; TROGLITAZONE; TISSUE; ADIPOCYTES AB Severe lipodystrophy is characterized by diminished adipose tissue and hypoleptinemia, leading to ectopic triglyceride accumulation. In the liver, this is associated with steatosis, potentially leading to nonalcoholic steatohepatitis (NASH). We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipodystrophy (8 patients) or Dunnigan's partial lipodystrophy (2 patients) were included in this analysis. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 months. The extents of portal and parenchymal inflammation, steatosis, ballooning, presence of Mallory bodies, and fibrosis in liver biopsy specimens were scored using a previously validated system developed to assess NASH activity. Histological disease activity was defined as the sum of ballooning, steatosis, and parenchymal inflammation scores. We concurrently tested serum triglycerides and aminotransferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. After treatment with r-metHuLeptin, repeat histological examinations showed significant improvements in steatosis (P = .006) and ballooning injury (P = .005), with a reduction of mean NASH activity by 60% (P = .002). Fibrosis was unchanged. Significant reductions were seen in mean serum triglycerides (1206 -> 226 mg/dL, P = .002), glucose (220 -> 144 mg/dL, P = .02), insulin (46.4 -> 24.8 mu IU/mL, P = .004), ALT (54 -> 24 U/L, P = .02), AST (47 -> 22 U/L, P = .046), liver volume (3209 -> 2391 cm(3), p = .007), and liver fat content (31 -> 11%, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced triglycerides, transaminases, hepatomegaly, and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Javor, ED (reprint author), 10 Ctr Dr,MSC 1612,CRC Room 6-5940, Bethesda, MD 20892 USA. EM edwardj@intra.niddk.nih.gov OI Oral, Elif/0000-0002-9171-1144; Kleiner, David/0000-0003-3442-4453 NR 40 TC 115 Z9 122 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2005 VL 41 IS 4 BP 753 EP 760 DI 10.1002/hep.20672 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911MD UT WOS:000228006000011 PM 15791619 ER PT J AU Mohammed, FF Pennington, CJ Kassiri, Z Rubin, JS Soloway, PD Ruther, U Edwards, DR Khokha, R AF Mohammed, FF Pennington, CJ Kassiri, Z Rubin, JS Soloway, PD Ruther, U Edwards, DR Khokha, R TI Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration SO HEPATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; FACTOR SCATTER FACTOR; ADULT-RAT LIVER; GROWTH-FACTOR; PARTIAL-HEPATECTOMY; EXTRACELLULAR-MATRIX; RAPID ACTIVATION; TRANSGENIC MICE; TUMOR; PROLIFERATION AB Liver regeneration depends on timely restoration of cellular mass while orchestrating structural matrix remodeling. Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are known to regulate the extracellular matrix (ECM) turnover and, more recently, the processing of growth factors and cytokines. We have previously demonstrated that TIMP-I inhibits preneoplastic hepatocyte proliferation by attenuating growth factor bioavailability. In the present study, we examined the role of TIMP-1 in de novo hepatocyte cell division during liver regeneration. Comprehensive real-time reverse-transcriptase polymerase chain reaction analyses of regenerating livers revealed significant inductions in the messenger RNA of TIMP-1, TIMP-3, TIMP-4, MMP-2, MMP-9, MMP-13, MMP-14, and MMP-24, while MMP-15 expression was significantly reduced. Induction of TIMP-1 occurred during the peak of hepatocyte DNA synthesis. Studies using genetically altered mice revealed that TIMP-1 loss of function accelerated hepatocyte cell cycle progression. This finding was demonstrated by earlier expression of cyclin D1, proliferating cell nuclear antigen, and phosphorylated histone H3, which mark the G(1)-S, S, and M phase, respectively. Conversely, TIMP-I gain of function delayed cell cycle progression. MMP activity was increased in the absence of Timp-1. Examination of hepatocyte growth factor (HGF), and its receptor Met, both of which provide a mitogenic signal for hepatocyte division, showed increased HGF activity in Timp-1(-/-)-regenerating livers. HGF is released from the ECM and is proteolytically processed to its active form. Active HGF was elevated in Timp-1(-/-) mice, leading to increased immunostaining of phosphorylated Met as well as activation of a downstream effector, p38. In conclusion, TIMP-1 is a novel negative regulator of HGF activity during liver regeneration. C1 Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. NIH, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Univ Dusseldorf, Inst Anim Dev & Mol Biol, D-4000 Dusseldorf, Germany. RP Khokha, R (reprint author), Ontario Canc Inst, Dept Med Biophys, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM rkhokha@uhnres.utoronto.ca RI Edwards, Dylan/B-4734-2009 OI Edwards, Dylan/0000-0002-3292-2064 NR 54 TC 88 Z9 95 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 APR PY 2005 VL 41 IS 4 BP 857 EP 867 DI 10.1002/hep.20618 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911MD UT WOS:000228006000023 PM 15726641 ER PT J AU Sharabi, Y Zimlichman, R Alesci, S Huynh, T Mansouri, R Chun, J Perera, S Pacak, K Goldstein, DS AF Sharabi, Y Zimlichman, R Alesci, S Huynh, T Mansouri, R Chun, J Perera, S Pacak, K Goldstein, DS TI Glucagon does not affect catecholamine release in primary cultures of bovine adrenal chrornaffin cells SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE adrenal medulla; glucagon; catecholamines; chromaffin cell; pheochromocytoma ID IN-VITRO; PHEOCHROMOCYTOMA; SECRETION; RATS; DIAGNOSIS; PEPTIDES; PANCREAS; RECEPTOR; INSULIN AB objective: Human pheochromocytoma tumor cells express glucagon receptors, and bolus i.% glucagon injection rapidly increases plasma epinephrine levels, suggesting that glucagon can directly stimulate adrenomedullary secretion. In this study, we tested whether the catecholamine secretory response to glucagon was present in bovine chromaffin cells or exclusive to the tumor cells. Design and Methods: Adrenomedullary cells were cultured in 24-well plates (10(6)cells per well). After 48 - 72 hours, wells were incubated for 1 - 20 minutes with (1) incubation medium (control), (2) catecholamine secretagogues (nicotine or potassium ion), or (3) glucagc.n (10(-8) to 10(-5) M). After incubation, catecholamine contents in medium and cells were assayed by high-pressure liquid chromatography with electrochemical detection. Fractional release rates of epinephrine, norepinephrine, and dopamine were calculated and compared to controls. Reverse-transcriptase PCR was performed to compare expression of mRNA of the glucagon receptor in chromaffin cells and pheochromocytoma cells. Results: Nicotine and potassium evoked time-dependent release of epinephrine, norepinephrine, and dopamine. Glucagon did not affect catecholamine secretion at any concentration. Reverse-transcriptase PCR failed to detect mRNA for glucagon receptor in bovine adrenomedullary cells, but did detect it in human pheochromocytoma cells. Conclusions: In contrast to pheochromocytoma tumor cells, bovine adrenomedullary chromaffin cells do not express the glucagon receptor, and therefore do not secrete catecholamines in response to glucagon. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Wolfson Med Ctr, Tel Aviv, Israel. Tel Aviv Univ, Brunner Inst Cardiovasc Res, Tel Aviv, Israel. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NINDS, Clin Neuroendocrinol Branch, NIH, Bethesda, MD USA. RP Sharabi, Y (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10 Room 6N252,10 Ctr Dr,MSC 1620, Bethesda, MD 20892 USA. EM sharabiy@ninds.nih.gov NR 19 TC 4 Z9 4 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD APR PY 2005 VL 37 IS 4 BP 205 EP 208 DI 10.1055/s-2005-861415 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931WD UT WOS:000229515300003 PM 15952078 ER PT J AU Chang, E Chalikonda, S Friedl, J Xu, H Phan, GQ Marincola, FM Alexander, HR Bartlett, DL AF Chang, E Chalikonda, S Friedl, J Xu, H Phan, GQ Marincola, FM Alexander, HR Bartlett, DL TI Targeting vaccinia to solid tumors with local hyperthermia SO HUMAN GENE THERAPY LA English DT Article ID ISOLATED LIMB PERFUSION; THYMIDINE KINASE; NECROSIS-FACTOR; PERITONEAL PERFUSION; GENE-THERAPY; CANCER; VIRUS; DELIVERY; PERMEABILITY; EXPRESSION AB We have previously demonstrated that mutant vaccinia viruses target tumors in vivo after systemic delivery, and they have potential as vectors for tumor-directed gene therapy. We hypothesized that hyperthermia may augment vaccinia delivery to tumors after systemic injection, as hyperthermia increases the permeability of the endothelial vasculature to nanoparticles. In our in vitro experiments, we have shown that hyperthermia does not alter tumor cells' susceptibility to the intrinsic cytopathogenicity of the vaccinia virus compared with normothermic controls. Hyperthermia also does not change the viral infectivity or the level of viral marker gene expression when compared with normothermia. In an in vitro model of endothelial cell monolayer permeability, we have demonstrated that hyperthermia increases the permeability of the monolayer to vaccinia virus and that this phenomenon is completely reversible. In vivo we have demonstrated that the tumors that were treated with systemic vaccinia under conditions of hyperthermia (41.5&DEG; C for 30 min) had significantly higher levels of vaccinia marker gene activity (>100-fold) than those treated under normothermic conditions (p<0.05) and that this effect was specific to tumor. We also demonstrated that mice with 1 cm subcutaneous tumors treated with a systemically delivered, conditionally replicating vaccinia under conditions of hyperthermia had complete tumor regression in 50% and significantly improved antitumor response, compared with normothermic viral-treated controls ( mean tumor volume of 110 mm(3) vs 3169 mm(3), 13 days after treatment) and compared with hyperthermic, nonvirally treated control animals (p<0.0001). Regional hyperthermia improves vaccinia targeting to tumors, and thereby enhances the antitumor response. C1 Univ Pittsburgh, Med Ctr, Div Surg Oncol, Pittsburgh, PA 15232 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), Univ Pittsburgh, Med Ctr, Div Surg Oncol, 5150 Ctr Ave,Suite 459, Pittsburgh, PA 15232 USA. EM bartlettdl@upmc.edu NR 34 TC 29 Z9 31 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2005 VL 16 IS 4 BP 435 EP 444 DI 10.1089/hum.2005.16.435 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 924SB UT WOS:000228999500005 PM 15871675 ER PT J AU Hughes, MS Yu, YYL Dudley, ME Zheng, ZL Robbins, PF Li, Y Wunderlich, J Hawley, RG Moayeri, M Rosenberg, SA Morgan, RA AF Hughes, MS Yu, YYL Dudley, ME Zheng, ZL Robbins, PF Li, Y Wunderlich, J Hawley, RG Moayeri, M Rosenberg, SA Morgan, RA TI Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions SO HUMAN GENE THERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; BONE-MARROW-TRANSPLANTATION; METASTATIC MELANOMA; RETROVIRAL VECTORS; ADOPTIVE TRANSFER; IN-VIVO; AUTOLOGOUS MELANOMA; CANCER REGRESSION; DONOR LEUKOCYTES; TRANSFER THERAPY AB The genes for the α and β chains of a highly reactive anti-MART-1 T-cell receptor were isolated from T-lymphocytes that mediated in vivo regression of tumor in a patient with metastatic melanoma. These genes were cloned and inserted into MSCV-based retroviral vectors. After transduction, greater than 50% gene transfer efficiency was demonstrated in primary T-lymphocytes stimulated by an anti-CD3 antibody. The specificity and biologic activity of TCR gene-transduced T-cells was determined by cytokine production after coculture of T-cells with stimulator cells pulsed with MART-1 peptide. The production of interferon-γ and granulocyte macrophage-colony stimulating factor (GM-CSF) was comparable to highly active MART-1 specific peripheral blood lymphocytes (PBL) in the amount of cytokine produced and transduced cells recognized peptide pulsed cells at dilutions similar to cytotoxic T lymphocyte (CTL) clones. Human leukocyte antigen (HLA) class I restricted recognition was demonstrated by mobilization of degranulation marker CD107a, by cell lysis, by cytokine production, and by proliferation in the presence of HLA-A2-positive but not HLA-A2-negative melanoma cell lines. Similar data was obtained when tumor-infiltrating lymphocytes (TIL) were transduced with the TCR genes, converting previously nonreactive cells to tumor reactive cells. TCR-transduced T-cells are thus attractive candidates for evaluation in cell transfer therapies of patients with cancer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD 20855 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, Bldg 10,CRC Rm 3-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 49 TC 117 Z9 122 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2005 VL 16 IS 4 BP 457 EP 472 DI 10.1089/hum.2005.16.457 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 924SB UT WOS:000228999500007 PM 15871677 ER PT J AU Kung, SKP Bonifacino, A Metzger, ME Ringpis, GE Donahue, RE Chen, ISY AF Kung, SKP Bonifacino, A Metzger, ME Ringpis, GE Donahue, RE Chen, ISY TI Lentiviral vector-transduced dendritic cells induce specific T cell response in a nonhuman primate model SO HUMAN GENE THERAPY LA English DT Article ID RHESUS-MACAQUES; ENHANCED GREEN; GENE-TRANSFER; IMMUNODEFICIENCY; LYMPHOCYTES; IMMUNITY; TOLERANCE AB Dendritic cells (DCs) are effective in stimulating and controlling the outcome of T cell responses. Human immunodeficiency virus type 1-based lentiviral vectors can achieve sustained transduction of genes/antigens in dividing and nondividing cells, thus representing a candidate vector for stable expression of antigens in DCs. We previously established conditions for transduction of purified cytokine mobilized rhesus CD34(+) cells in vitro, and transplantation of the autologous transduced cells in a nonhuman primate model in vivo. In the present study, we transplanted DCs derived from EGFP-transduced CD34(+) cells into nonmyeloablated rhesus macaques. Transplantation of DCs stably expressing EGFP into autologous animals induces persistent, long-lived (up to 100 weeks) EGFP-specific T cell responses. Of note, no humoral responses against EGFP are detected in the transplanted animals. These studies provide, to our knowledge, the first demonstration that lentiviral transduction of CD34(+) progenitor cells subsequently differentiated to DCs is capable of priming a specific T cell response in a nonhuman primate in vivo. Taken together, our data provide formal in vivo evidence that lentivirus-transduced dendritic cells represent a potential approach in eliciting cellular immune responses in primates. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol & Immunol & Med, Los Angeles, CA 90095 USA. NHLBI, Hematol Branch, Rockville, MD 20850 USA. RP Chen, ISY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol & Immunol & Med, 10833 Le Conte Ave,11-934 Factor Bldg, Los Angeles, CA 90095 USA. EM syuchen@mednet.ucla.edu FU NIAID NIH HHS [P30 AI28697] NR 21 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2005 VL 16 IS 4 BP 527 EP 532 DI 10.1089/hum.2005.16.527 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 924SB UT WOS:000228999500014 PM 15871684 ER PT J AU Ahmad, J Khan, SN Khan, SY Ramzan, K Riazuddin, S Ahmed, ZM Wilcox, ER Friedman, TB Riazuddin, S AF Ahmad, J Khan, SN Khan, SY Ramzan, K Riazuddin, S Ahmed, ZM Wilcox, ER Friedman, TB Riazuddin, S TI DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1 SO HUMAN GENETICS LA English DT Article ID SENSORINEURAL HEARING-LOSS; NON-SYNDROMIC DEAFNESS; MYOSIN VIIA GENE; UNCONVENTIONAL MYOSIN; NUCLEAR RECEPTOR; SYNDROME BBS4; MUTATIONS; DOMINANT; IDENTIFICATION; MICE AB Nonsyndromic deafness locus (DFNB48) segregating as an autosomal recessive trait has been mapped to the long arm of chromosome 15 in bands q23-q25.1 in five large Pakistani families. The deafness phenotype in one of these five families (PKDF245) is linked to D15S1005 with a lod score of 8.6 at theta=0,and there is a critical linkage interval of approximately 7 cM on the Marshfield human genetic map, bounded by microsatellite markers D15S216 (70.73 cM) and D15S1041 (77.69 cM). MYO9A, NR2E3, BBS4, and TMC3 are among the candidate genes in the DFNB48 region. The identification of another novel nonsyndromic recessive deafness locus demonstrates the high degree of locus heterogeneity for hearing impairment, particularly in the Pakistani population. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Gent, Genet Mol Lab, NIH, Rockville, MD 20850 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Ahmad, Jamil/D-4130-2009; Nasim Khan, Shaheen/F-2135-2015; SHEIKH, RIAZUDDIN/L-2406-2015 FU NIDCD NIH HHS [Z01 DC000039-07, ZO1 DC000035-07] NR 31 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 2005 VL 116 IS 5 BP 407 EP 412 DI 10.1007/s00439-004-1247-y PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 914LZ UT WOS:000228230500012 PM 15711797 ER PT J AU Pugacheva, EM Tiwari, VK Abdullaev, Z Vostrov, AA Flanagan, PT Quitschke, WW Loukinov, DI Ohlsson, R Lobanenkov, VV AF Pugacheva, EM Tiwari, VK Abdullaev, Z Vostrov, AA Flanagan, PT Quitschke, WW Loukinov, DI Ohlsson, R Lobanenkov, VV TI Familial cases of point mutations in the XIST promoter reveal a correlation between CTCF binding and pre-emptive choices of X chromosome inactivation SO HUMAN MOLECULAR GENETICS LA English DT Article ID ENHANCER BLOCKING; CROSS-LINKING; PROTEIN CTCF; GENE; DNA; TRANSCRIPTION; INSULATOR; MOUSE; METHYLATION; SEQUENCE AB The choice mechanisms that determine the future inactive X chromosome in somatic cells of female mammals involve the regulated expression of the XIST gene. A familial C(-43)G mutation in the XIST promoter results in skewing of X chromosome inactivation (XCI) towards the inactive X chromosome of heterozygous females, whereas a C(-43)A mutation found primarily in the active X chromosome results in the opposite skewing pattern. Both mutations point to the existence of a factor that might be responsible for the skewed patterns. Here we identify this factor as CTCF, a conserved protein with a 11 Zn-finger (ZF) domain that can mediate multiple sequence-specificity and interactions between DNA-bound CTCF molecules. We show that mouse and human Xist/XIST promoters contain one homologous CTCF-binding sequence with the matching dG-contacts, which in the human XIST include the -43 position within the DNase I footprint of CTCF. While the C(-43)A mutation abrogates CTCF binding, the C(-43)G mutation results in a dramatic increase in CTCF-binding efficiency by altering ZF-usage mode required for recognition of the altered dG-contacts of the mutant site. Thus, the skewing effect of the two -43C mutations correlates with their effects on CTCF binding. Finally, CTCF interacts with the XIST/Xist promoter only in female human and mouse cells. The interpretation that this reflected a preferential interaction with the promoter of the active Xist allele was confirmed in mouse fetal placenta. These observations are in keeping with the possibility that the choice of X chromosome inactivation reflects stabilization of a higher order chromatin conformation impinging on the CTCF-XIST promoter complex. C1 NIAID, LIP, Mol Pathol Sect, NIH, Rockville, MD 20852 USA. Uppsala Univ, Dept Genet & Dev, S-75236 Uppsala, Sweden. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. RP Lobanenkov, VV (reprint author), NIAID, LIP, Mol Pathol Sect, NIH, Twinbrook I,Room 1417,MSC-8152,5640 Fisher Lane, Rockville, MD 20852 USA. EM vlobanenkov@niaid.nih.gov FU NINDS NIH HHS [NS 30994] NR 38 TC 62 Z9 65 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2005 VL 14 IS 7 BP 953 EP 965 DI 10.1093/hmg/ddi089 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 911BJ UT WOS:000227975800008 PM 15731119 ER PT J AU McChesney, R Wilcox, AJ O'Connor, JF Weinberg, CR Baird, DD Schlatterer, JP McConnaughey, DR Birken, S Canfield, RE AF McChesney, R Wilcox, AJ O'Connor, JF Weinberg, CR Baird, DD Schlatterer, JP McConnaughey, DR Birken, S Canfield, RE TI Intact HCG, free HCG beta subunit and HCG beta core fragment: longitudinal patterns in urine during early pregnancy SO HUMAN REPRODUCTION LA English DT Article DE HCG; longitudinal patterns; pregnancy; urine ID HUMAN CHORIONIC-GONADOTROPIN; PROGESTERONE METABOLITES; HYPERGLYCOSYLATED HCG; DOUBLING TIME; SERUM; IMPLANTATION; OVULATION; ASSAY; CHORIOCARCINOMA; IMMUNOASSAYS AB BACKGROUND: Detecting and monitoring early pregnancy depend on the measurement of HCG. Little is known about how production of various forms of HCG may evolve over the earliest weeks of pregnancy, particularly in naturally conceived pregnancies. METHODS: We describe the daily excretion of three urinary HCG analytes during the first 6 weeks post-conception in 37 naturally conceived pregnancies ending in singleton birth. We assayed daily first morning urine samples for intact HCG, free beta subunit and beta?core fragment, plus the combined measurement of these HCG forms. We calculated doubling times for each analyte and the inter- and intra-subject day-to-day variation. RESULTS: Intact HCG and the free beta subunit were initially the predominant forms of HCG, with the beta core fragment emerging as the predominant form in the fifth week after conception. Intact HCG and the free beta subunit showed the most day-to-day variability, and were transiently undetectable even 10 days after detection of pregnancy. The most stable estimate of doubling time was provided by the combined measurement of all these forms. CONCLUSIONS: Although intact HCG is usually regarded as the main analyte for detection and monitoring of early pregnancy, it can fluctuate markedly during early pregnancy. This variability could affect pregnancy test results based on early pregnancy urine, and may distort estimates of doubling time. Assays that combine several forms of HCG may be more reliable. C1 CUNY Brooklyn Coll, New York, NY USA. Columbia Univ, Irving Ctr Clin Res, New York, NY USA. Columbia Univ, Dept Obstet & Gynaecol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. WESTAT Corp, Durham, NC USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 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 40 TC 32 Z9 34 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2005 VL 20 IS 4 BP 928 EP 935 DI 10.1093/humrep/deh702 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 911BG UT WOS:000227975500013 PM 15665026 ER PT J AU Brinton, LA Scoccia, B Moghissi, KS Westhoff, CL Althuis, MD Lamb, EJ AF Brinton, LA Scoccia, B Moghissi, KS Westhoff, CL Althuis, MD Lamb, EJ TI Do drugs that stimulate ovulation increase the risk for endometrial stromal sarcoma? Reply SO HUMAN REPRODUCTION LA English DT Letter ID BREAST-CANCER; TAMOXIFEN THERAPY C1 NCI, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Wayne State Univ, Detroit, MI USA. Columbia Univ, New York, NY USA. Georgetown Univ, Washington, DC USA. Stanford Univ, Stanford, CA 94305 USA. RP Brinton, LA (reprint author), NCI, Bethesda, MD 20892 USA. EM Brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 9 TC 0 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2005 VL 20 IS 4 BP 1112 EP 1113 DI 10.1093/humrep/deh659 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 911BG UT WOS:000227975500043 ER PT J AU Zeng, CY Yang, ZW Wang, Z Jones, J Wang, XY Altea, J Mangrum, AJ Hopfer, U Sibley, DR Eisner, GM Felder, RA Jose, PA AF Zeng, CY Yang, ZW Wang, Z Jones, J Wang, XY Altea, J Mangrum, AJ Hopfer, U Sibley, DR Eisner, GM Felder, RA Jose, PA TI Interaction of angiotensin II type 1 and D-5 dopamine receptors in renal proximal tubule cells SO HYPERTENSION LA English DT Article DE receptors, dopamine; receptors, angiotensin II; rats, spontaneously hypertensive; normotension; kidney ID SPONTANEOUSLY HYPERTENSIVE-RATS; NA+-H+ EXCHANGER; AT(1) RECEPTOR; BLOOD-PRESSURE; GENETIC-HYPERTENSION; CONVERTING-ENZYME; NADPH OXIDASE; BLOCKADE; SYSTEM; KIDNEY AB Angiotensin II type 1 (AT(1)) receptor and D-1 and D-3 dopamine receptors directly interact in renal proximal tubule (RPT) cells from normotensive Wistar-Kyoto rats (WKY). There is indirect evidence for a D-5 and AT(1) receptor interaction in WKY and spontaneously hypertensive rats (SHR). Therefore, we sought direct evidence of an interaction between AT(1) and D-5 receptors in RPT cells. D-5 and AT(1) receptors colocalized in WKY cells. Angiotensin II decreased D-5 receptors in WKY cells in a time- and concentration-dependent manner (EC50 = 2.7 x 10(-9) M; t(1/2) = 4.9 hours), effects that were blocked by an AT(1) receptor antagonist (losartan). In SHR, angiotensin II (10(-8) M/24 hours) also decreased D-5 receptors (0.96 +/- 0.08 versus 0.72 +/- 0.08; n = 12) and to the same degree as in WKY cells (1.44 +/- 0.07 versus 0.92 +/- 0.08). However, basal D-5 receptors were decreased in SHR RPT cells (SHR 0.96 +/- 0.08; WKY 1.44 +/- 0.07; n = 12 per strain; P < 0.05) and renal brush border membranes of SHR compared with WKY (SHR 0.54 +/- 0.16 versus WKY 1.46 +/- 0.10; n = 5 per strain; P < 0.05). Angiotensin II decreased AT(1) receptor expression in WKY (1.00 +/- 0.04 versus 0.72 +/- 0.08; n +/- 8; P < 0.05) but increased it in SHR (0.96 +/- 0.04 versus 1.32 +/- 0.08; n = 8; P < 0.05). AT(1) and D-5 receptors also interacted in vivo; renal D-5 receptor protein was higher in mice lacking the AT(1A) receptor (AT(1A)-/-; 1.61 +/- 0.31; n = 6) than in wild-type littermates used as controls (AT(1A)+/+; 0.81 +/- 0.08; n = 6; P < 0.05), and renal cortical AT(1) receptor protein was higher in D-5 receptor null mice than in wild-type littermates (1.18 +/- 0.08 versus 0.84 +/- 0.07; n = 4; P < 0.05). We conclude that D-5 and AT(1) receptors interact with each other. Altered interactions between AT(1) and dopamine receptors may play a role in the pathogenesis of hypertension. C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Third Mil Med Univ, Daping Hosp, Dept Cardiol, Chongqing, Peoples R China. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Zeng, CY (reprint author), Georgetown Univ, Med Ctr, Dept Pediat, PHC-2,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM cyzeng1@hotmail.com RI Hopfer, Ulrich`/B-5463-2009 FU NHLBI NIH HHS [HL 23081, HL 62211, HL-41618, HL074940, HL68686]; NIDDK NIH HHS [DK 39308, DK52612] NR 53 TC 55 Z9 64 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 APR PY 2005 VL 45 IS 4 BP 804 EP 810 DI 10.1161/01.HYP.0000155212.33212.99 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 910DC UT WOS:000227909000060 PM 15699451 ER PT J AU Smeltz, RB Chen, J Shevach, EM AF Smeltz, RB Chen, J Shevach, EM TI Transforming growth factor-beta 1 enhances the interferon-gamma-dependent, interleukin-12-independent pathway of T helper 1 cell differentiation SO IMMUNOLOGY LA English DT Article DE IFN-gamma; T-cell differentiation; TGF-beta 1; Th1/Th2 ID GROWTH-FACTOR-BETA; CD4(+) T-CELLS; TGF-BETA; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; GATA-3 EXPRESSION; CUTTING EDGE; TH1 CELLS; ACTIVATION; IL-12 AB Transforming growth factor (TGF)-beta, a pleiotropic cytokine that has multiple effects on immune responses, has been shown to inhibit interleukin (IL)-4/GATA-3 expression as well as T helper 2 (Th2) differentiation. Consistent with these reports, we found that priming T cells from DO11.10 transgenic mice with antigen in the presence of TGF-beta inhibited GATA-3 expression and the development of IL-4-producing T cells. Unexpectedly, the inhibition of Th2 development was accompanied by a substantial increase in the number of interferon-gamma (IFN-gamma)-producing cells. T cells primed with TGF-beta secreted IFN-gamma in response to both T-cell receptor ligation and IL-12/IL-18 stimulation, and expressed high levels of T-bet and low levels of GATA-3. The TGF-beta-mediated enhancement of T helper 1 (Th1) priming was independent of IL-12 and signal transducer and activator of transcription (STAT)-4, but required endogenous IFN-gamma. TGF-beta-mediated enhancement of the IFN-gamma-dependent, IL-12-independent pathway of Th1 priming was mediated primarily by the inhibition of IL-4 produced by memory/activated T cells in the unfractionated CD4(+) responder population. Nevertheless, TGF-beta did not inhibit this pathway of Th1 differentiation when purified naive CD4(+) T cells were used as responders. These data have important implications for strategies being considered for the use of TGF-beta-producing T cells for the treatment of autoimmune disorders. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIH, Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Smeltz, RB (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 40 TC 19 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD APR PY 2005 VL 114 IS 4 BP 484 EP 492 DI 10.1111/j.1365-2567.2005.02.115.x PG 9 WC Immunology SC Immunology GA 909CN UT WOS:000227836600007 PM 15804285 ER PT J AU Sloane, AJ Raso, V Dimitrov, DS Xiao, XD Deo, S Muljadi, N Restuccia, D Turville, S Kearney, C Broder, CC Zoellner, H Cunningham, AL Bendall, L Lynch, GW AF Sloane, AJ Raso, V Dimitrov, DS Xiao, XD Deo, S Muljadi, N Restuccia, D Turville, S Kearney, C Broder, CC Zoellner, H Cunningham, AL Bendall, L Lynch, GW TI Marked structural and functional heterogeneity in CXCR4: Separation of HIV-1 and SDF-I alpha responses SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE CXCR4; glycoprotein 120; heterogeneity; SDF-1 alpha ID CHEMOKINE RECEPTOR CXCR4; IMMUNODEFICIENCY-VIRUS CORECEPTOR; 7-TRANSMEMBRANE DOMAIN RECEPTOR; PROTEIN-COUPLED RECEPTOR; CELL-SURFACE ASSOCIATION; CD4-INDEPENDENT INFECTION; MOLECULAR-CLONING; MEMBRANE-FUSION; AMINO-TERMINUS; NATIVE CD4 AB CXCR4, the chemotactic cell receptor for SDF-1 alpha, is essential for immune trafficking and HIV infection. CXCR4 is remarkably heterogeneous and the purpose of this study was to better identify the isoforms expressed by cells and compare their structure and function. We found that cells express either a predominant isoform or multiple isoforms. These were best resolved on SDS-PAGE using sucrose-gradient-fractionated, triton-insoluble, membrane extracts. We hypothesized that glycosyl modification may underpin some of this heterogeneity and that cell isoform(s) differences may underscore CXCR4's multiple cell functions. A comparison of wild-type (WT) and dual N-linked glycosylation site, N11A/N176A, mutant CXCR4 expressed in 3T3 and HEK-293 cells served to implicate variabilities in glycosylation and oligomerization in almost half of the isoforms. Immunoprecipitation of CXCR4 revealed monomer and dimer non-glycosylated forms of 34 kDa and 68 kDa from the N11A/N176A mutant, compared with glycosylated 40 kDa and 47 kDa and 73 kDa and 80 kDa forms from WT. The functional specificity of isoform action was also implicated because, despite CEMT4 cells expressing high levels of CXCR4 and 11 different isoforms, a single 83 kDa form was found to bind gp120 for HIV-IIIB infection. Furthermore, comparative studies found that in contrast to SDF-1 alpha-responsive Nalm-6 cells that expressed similar levels of a single isoform, CEMT4 cells did not show a Ca++ flux or a chemotactic response to SDF-1 alpha.. Thus, CXCR4 can differ both structurally and functionally between cells, with HIV-1 infection and chemotaxis apparently mediated by different isoforms. This separation of structure and function has implications for understanding HIV-1 entry and SDF-1 alpha responses and may indicate therapeutic possibilities. C1 Ctr Virus Res, HIV Prot Interact Lab, Westmead, NSW, Australia. Westmead Millennium Inst, Westmead, NSW, Australia. Natl Ctr HIV Virol Res Australia, Westmead, NSW, Australia. Univ Sydney, Westmead, NSW 2145, Australia. Westmead Inst Canc Res, Westmead, NSW, Australia. Westmead Hosp, Sch Dent, Cellular & Mol Pathol Res Unit, Dept Oral Pathol & Oral Med, Westmead, NSW 2145, Australia. Boston Biomed Res Inst, Watertown, MA USA. Harvard Univ, Sch Med, Watertown, MA USA. Natl Canc Inst, Prot Interact Lab, NIH, Frederick, MD USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Lynch, GW (reprint author), Australian Red Cross Blood Serv, Endeavour Operat unit, POB 98, Camperdown, NSW 1450, Australia. EM Garry_Lynch@optusnet.com.au RI Cunningham, Tony/B-7011-2013; Restuccia, David/D-7114-2012; Endnote, Wicr/E-2042-2013 OI Restuccia, David/0000-0001-7131-8065; NR 63 TC 38 Z9 39 U1 1 U2 3 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD APR PY 2005 VL 83 IS 2 BP 129 EP 143 DI 10.1111/j.1440-1711.2004.01304.x PG 15 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 910SU UT WOS:000227953300004 PM 15748209 ER PT J AU Kottilil, S Jackson, JO Polis, MA AF Kottilil, S Jackson, JO Polis, MA TI Hepatitis B & hepatitis C in HIV-infection SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Review DE HBV; HCV; HIV; highly active antiretroviral therapy (HAART) ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; CONTAINING ANTIRETROVIRAL THERAPY; LIVER FIBROSIS PROGRESSION; ADEFOVIR DIPIVOXIL THERAPY; E-ANTIGEN SEROCONVERSION; DYNAMICS IN-VIVO; COMBINATION THERAPY; RANDOMIZED-TRIAL; INTERFERON-ALPHA AB Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are the three most common chronic viral infections seen in the world. All three viruses share modes of transmission and hence co-exist in the same host at significantly high rates. HIV-induced immunosuppression has deleterious effects on the natural history, pathophysiology, diagnosis, therapeutic responses to hepatitis viruses. Responses to HBV vaccination are impaired in persons with HIV infection. Co-infection with the hepatitis viruses and HIV is likely to become a major health care catastrophe in the coming years. This review discusses the current trends in the understanding of the biology of co-infection and implications for treating these viruses effectively. C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, Bldg 10,Room 11N204,9000 Wisconsin Ave, Bethesda, MD 20892 USA. EM Skottilil@niaid.nih.gov OI Polis, Michael/0000-0002-9151-2268 NR 174 TC 10 Z9 10 U1 1 U2 1 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD APR PY 2005 VL 121 IS 4 BP 424 EP 450 PG 27 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 924VG UT WOS:000229008200020 PM 15817955 ER PT J AU Virok, DP Nelson, DE Whitmire, WM Crane, DD Goheen, MM Caldwell, HD AF Virok, DP Nelson, DE Whitmire, WM Crane, DD Goheen, MM Caldwell, HD TI Chlamydial infection induces pathobiotype-specific protein tyrosine phosphorylation in epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; HOST-CELLS; GENOME SEQUENCE; HELA-CELLS; IN-VITRO; TRACHOMATIS; ATTACHMENT; PNEUMONIAE; ACTIVATION; PSITTACI AB Members of the genus Chlamydia are strict obligate intracellular pathogens that exhibit marked differences in host range and tissue tropism despite sharing a remarkable level of genomic synteny. These pathobiotype differences among chiamydiae are also mirrored in their early interactions with cultured mammalian host cells. Chlamydial attachment and entry is known to trigger protein tyrosine phosphorylation. In this study, we examined the kinetics and pattern of protein tyrosine phosphorylation induced by infection with a comprehensive collection of chlamydial strains exhibiting diversity in host, tissue, and disease tropisms. We report new findings showing that protein tyrosine phosphorylation patterns induced by infection directly correlate with the pathobiotype of the infecting organism. Patterns of protein tyrosine phosphorylation were induced following early infection that unambiguously categorized chlamydial pathobiotypes into four distinct groups: (i) Chlamydia trachomatis trachoma biovars (serovars A to H), (ii) C. trachomatis lymphogranuloma venereurn biovars (serovars L1 to L3), (iii) C muridarum, and (iv) C. pneumoniae and C. caviae. Notably, chlamydia-infected murine and human epithelial cells exhibited the same protein tyrosine phosphorylation patterns; this is indirect evidence suggesting that the phosphorylated protein(s) is of chlamydial origin. If our hypothesis is correct, these heretofore-uncharacterized proteins may represent a novel class of bacterial molecules that influence pathogen-host range or tissue tropism. C1 NIAID, Rocky Mt Lab, Lab Intracellular Paraisites, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Rocky Mt Lab, Lab Intracellular Paraisites, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov NR 28 TC 12 Z9 14 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 APR PY 2005 VL 73 IS 4 BP 1939 EP 1946 DI 10.1128/IAI.4.1939-1946.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 911BB UT WOS:000227975000004 PM 15784533 ER PT J AU Kerepesi, LA Keiser, PB Nolan, TJ Schad, GA Abraham, D Nutman, TB AF Kerepesi, LA Keiser, PB Nolan, TJ Schad, GA Abraham, D Nutman, TB TI DNA immunization with Na+-K(+)ATPase (Sseat-6) induces protective immunity to larval Strongyloides stercoralis in mice SO INFECTION AND IMMUNITY LA English DT Article ID RECOMBINANT ANTIGEN VACCINE; ONCHOCERCA-VOLVULUS; CAENORHABDITIS-ELEGANS; SCHISTOSOMA-MANSONI; HAEMONCHUS-CONTORTUS; BALB/CBYJ MICE; INFECTION; GALECTINS; PROTEIN; GENE AB Strongyloides stercoralis causes chronic asymptomatic infections which can be maintained in the human host for many decades. Identification and treatment of S. stercoralis-infected individuals is required because immunosuppression can lead to fatal hyperinfection. In this study, human immunoglobulin G (IgG) that had previously been shown to transfer protective immunity to mice was used to identify potential protective antigens. Three antigens or genes from S. stercoralis larvae were identified as tropomyosin (Sstmy-1), Na+-K(+)ATPase (Sseat-6), and LEC-5 (Sslec-5). The genes were cloned into plasmids for DNA immunization, and mice were immunized intradermally with the three plasmids individually in combination with a plasmid containing marine granulocyte-macrophage colony-stimulating factor. Only Na+-K(+)ATPase induced a significant reduction in larval survival after DNA immunization. Immunization with a combination of all three plasmids, including Na+-K(+)ATPase, did not induce protective immunity. Serum from mice immunized with DNA encoding Na+-K(+)ATPase was transferred to naive mice and resulted in partial protective immunity. Therefore, DNA immunization with Na+-K(+)ATPase induces protective immunity in mice, and it is the first identified vaccine candidate against infection with larval S. stercoralis. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov RI Nolan, Thomas/A-1053-2007; OI Nolan, Thomas/0000-0002-6860-7947 FU NIAID NIH HHS [R01 AI 22662, R01 AI 47189, R01 AI022662, R01 AI047189] NR 58 TC 13 Z9 13 U1 1 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 APR PY 2005 VL 73 IS 4 BP 2298 EP 2305 DI 10.1128/IAI.73.4.2298-2305.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 911BB UT WOS:000227975000045 PM 15784574 ER PT J AU Engdahl, B Tambs, K Borchgrevink, HM Hoffman, HJ AF Engdahl, B Tambs, K Borchgrevink, HM Hoffman, HJ TI Screened and unscreened hearing threshold levels for the adult population: Results from the Nord-Trondelag Hearing Loss Study SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE audiometry; age; sex; sensorineural hearing loss; noise-induced hearing loss; presbyacusis; epidemiology; screening ID NOISE; AGE AB This paper presents normative data of hearing threshold levels of a population screened with various criteria, as compared to unscreened population data. Computer-controlled pure-tone audiometry was administered to the adult population in Nord-Trondelag County, Norway, during 1995-1997. The 51 975 participants also provided questionnaire information about occupational and leisure noise exposure, previous car infections, and head injury. While screening had little effect on the median hearing threshold levels of young adults, there was a substantial effect when screening men above 40 years of age for a history of noise exposure. Screening for known ear-related disorders and diseases resulted in small effects on the mean hearing threshold levels. The median hearing thresholds of both the screened and the unscreened sample exceeded the age and sex specific thresholds specified by the ISO 7029. C1 Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. Univ Clin Oslo, Rikshosp, Oslo, Norway. NIDCD, NIH, Bethesda, MD USA. RP Engdahl, B (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. EM bo.engdahl@fhi.no FU NIDCD NIH HHS [N01-DC-6-2104] NR 25 TC 48 Z9 50 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD APR PY 2005 VL 44 IS 4 BP 213 EP 230 DI 10.1080/14992020500057731 PG 18 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 940XS UT WOS:000230179800004 PM 16011050 ER PT J AU Winslow, JT AF Winslow, JT TI Neuropeptides and non-human primate social deficits associated with pathogenic rearing experience SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE autism; disorders; social deficits ID MONKEYS MACACA-MULATTA; CORTICOTROPIN-RELEASING-FACTOR; RHESUS-MONKEYS; CEREBROSPINAL-FLUID; OXYTOCIN RECEPTORS; MATERNAL-CARE; GLUCOCORTICOID-RECEPTORS; RECRUITMENT SCREAMS; PIGTAIL MACAQUES; PLASMA-CORTISOL AB There is a persuasive evidence that autism is highly heritable and likely to be substantially determined by polygenic mechanisms. Nevertheless, some intriguing findings in children raised in conditions of extreme social deprivation suggest that an autistic-like syndrome may occur as a consequence of environmental conditions. A particularly close model of this human syndrome has been studied in rhesus monkeys for almost half a century. Monkeys reared in pathogenic rearing conditions manifest considerable deficits in social interaction and increased self-directed behaviors. We have been interested in the possibility that disruptions in normal social development in non-human primates might be expressed in neuropeptide systems which have emerged in rodent studies as important candidates for a unique social biology. In recent studies, we have described persistently reduced CSF OT levels in male rhesus monkeys with significant social deficits. We also found that OT levels were positively related to the expression of affiliative social behaviors. Alterations were also detected in both CRH and AVP receptor binding patterns in limbic structures likely to influence social and emotional development. Taken together, these data suggest that abnormal rearing influences the development of brain systems critical to normal social and emotional competence in rhesus monkeys and may contribute to the development of autistic-like symptomatology associated with pathogenic rearing histories. (C) 2004 ISDN. Published by Elsevier Ltd. All rights reserved. C1 NIMH, Nonhuman Primate Neurobiol Core, Intramural Res Program, Bethesda, MD 20892 USA. RP Winslow, JT (reprint author), NIMH, Nonhuman Primate Neurobiol Core, Intramural Res Program, Bldg NIHAC 110,Room 121,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jameswinslow@mail.nih.gov FU NIMH NIH HHS [MH57704, MH58922] NR 83 TC 34 Z9 36 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD APR-MAY PY 2005 VL 23 IS 2-3 BP 245 EP 251 DI 10.1016/j.ijdevneu.2004.03.003 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 910PL UT WOS:000227943900011 PM 15749249 ER PT J AU Althuis, MD Dozier, JM Anderson, WF Devesa, SS Brinton, LA AF Althuis, MD Dozier, JM Anderson, WF Devesa, SS Brinton, LA TI Global trends in breast cancer incidence and mortality 1973-1997 SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast cancer; incidence; mortality; time-trends; international ID UNITED-STATES; RISK-FACTORS; SCREENING PRACTICES; AGE-INCIDENCE; HONG-KONG; WOMEN; JAPAN; EXPLANATION; MENOPAUSE; COUNTRIES AB Background Worldwide, breast cancer is the most common cancer and is the leading cause of cancer death among women. Methods To describe global trends, we compared age-adjusted incidence and mortality rates over three decades (fro 1973-77 to 1993-97) and across several continents. Results Both breast cancer incidence and mortality rates varied 4-fold by geographic location between countries with the highest and lowest rates. Recent (1993-1997) incidence rates ranged from 27/100000 in Asian countries to 97/100 000 among US white women. Overall, North American and northern European countries hall the highest incidence rates of breast cancer; intermediate levels were reported in Western Europe, Oceania, Scandinavia, and Israel; and Eastern Europe, South and Latin America, and Asia had the lowest levels. Breast cancer incidence rose 30-40% from the 1970s to the 1990s in most countries, with the most marked increases among women aged &GE; 50 years. Mortality from breast cancer paralleled incidence: it was highest in the countries with the highest incidence rates (between 17/100 000 and 27/100 000), lowest in Latin America and Asia (7-14/100 000), and rose most rapidly in countries with the lowest rates. Conclusions Breast cancer incidence and mortality rates remain highest in developed countries compared with developing countries, as a result of differential use of screening mammograms and disparities in lifestyle and hereditary factors. Future studies assessing the combined contributions of both environmental and hereditary factors may provide explanations for worldwide differences in incidence and mortality rates. C1 NCI, Hormone & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Gastrointestinal & Others Canc Res Grp, Div Canc Prevent, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Brinton, LA (reprint author), NCI, Hormone & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Exceut Blvd,EPS MSC 7234, Rockville, MD 20852 USA. EM brintonl@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 40 TC 255 Z9 281 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2005 VL 34 IS 2 BP 405 EP 412 DI 10.1093/ije/dyh414 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 924KY UT WOS:000228978900031 PM 15737977 ER PT J AU Abnet, CC Qiao, YL Dawsey, SM Dong, ZW Taylor, PR Mark, SD AF Abnet, CC Qiao, YL Dawsey, SM Dong, ZW Taylor, PR Mark, SD TI Tooth loss is associated with increased risk of total death and death from upper gastrointestinal cancer, heart disease, and stroke in a Chinese population-based cohort SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE death; gastrointestinal neoplasms; heart diseases; cerebrovascular accident; tooth loss; cohort studies; China ID REPUBLIC-OF-CHINA; NUTRITION INTERVENTION TRIALS; PERIODONTAL-DISEASE; GASTRIC-CANCER; CARDIOVASCULAR-DISEASE; ESOPHAGEAL CANCER; EPIDEMIOLOGY; SUPPLEMENTATION; NITROSAMINES; MORTALITY AB Background Tooth loss has previously been associated with a higher risk of cancer, heart disease, and stroke, but :he role of confounding by smoking remains an issue. Methods We conducted a cohort study including 29 584 healthy, rural Chinese adults who were participants in a chemoprevention trial from 1986 through 1991 and who have been followed-up through 2001. We categorized tooth loss for each subject as less than or equal to or greater than the median number of teeth lost for other subjects of the same age at baseline. Mortality outcomes were categorized as follows: total death (n = 9362), upper gastrointestinal (GI) cancer death (n = 2625), other cancer death (n = 514), heart disease death (n = 1932), and fatal stroke (n = 2866). Results Individuals with greater than the age-specific median number of teeth lost had statistically significant 13% increased risk of total death [95% confidence interval (CI) 9-18%], 35% increased risk of upper GI cancer death (95% CI 14-59%), 28% increased risk of heart disease death (95% CI 17-40%), and 12% increased risk of stroke death (95% CI 2-23%), but no significantly increased risk of death from cancer at other sites. These elevated risks were present in male smokers, male non-smokers, and females, nearly all never-smokers. Conclusions In this Asian population. tooth loss significantly increased the risk of total death and death from upper (;I cancer, heart disease, and stroke. These associations were not limited to tobacco smokers. C1 NCI, Canc Prevent Studies Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100037, Peoples R China. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Abnet, CC (reprint author), 6116 Execut Blvd,Room 705, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 30 TC 116 Z9 122 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2005 VL 34 IS 2 BP 467 EP 474 DI 10.1093/ije/dyh375 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 924KY UT WOS:000228978900040 PM 15659476 ER PT J AU Poole, C Peters, U Il'yasova, D Arab, L AF Poole, C Peters, U Il'yasova, D Arab, L TI Black tea and cardiovascular disease - Authors' response SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Epidemiol Publ Hlth Sci, Winston Salem, NC 27109 USA. Amgen Inc, Global Epidemiol, Thousand Oaks, CA USA. RP Poole, C (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2005 VL 34 IS 2 BP 483 EP 483 DI 10.1093/ije/dyh212 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 924KY UT WOS:000228978900047 ER PT J AU Breilh, J Branco, JC Castleman, BI Cherniack, M Christianti, DC Cicolella, A Cifuentes, E Clapp, R Cole, DC Corn, M De Ben, S Diaz, R Egilman, D Finkelstein, Y Franco, G Frank, AL Friedman, L Gassert, TH Gochfeld, M Greenberg, M Hansen, ES Hay, A Hogstedt, C Huff, J Joshi, TK Kriebel, D Laborde, A LaDou, J Levenstein, C Levin, SM Loewenson, R Mikheev, M Montenegro, R Naidoo, M Ozonoff, D Partanen, T Pendito, RI Povey, G Richter, ED Robbins, A Correa, HR Rosenman, KD Samuels, SW Santana, VS Schwartz, BS Siqueira, CE Soskolne, CL Spiegel, J Stephens, C Tajik, M Takaro, TK Teitelbaum, DT Tickner, JA Tomatis, L Victoria, C Waltner-Toews, D Wedeen, RP Wegman, DH Wesseling, C Wing, S Yassi, A AF Breilh, J Branco, JC Castleman, BI Cherniack, M Christianti, DC Cicolella, A Cifuentes, E Clapp, R Cole, DC Corn, M De Ben, S Diaz, R Egilman, D Finkelstein, Y Franco, G Frank, AL Friedman, L Gassert, TH Gochfeld, M Greenberg, M Hansen, ES Hay, A Hogstedt, C Huff, J Joshi, TK Kriebel, D Laborde, A LaDou, J Levenstein, C Levin, SM Loewenson, R Mikheev, M Montenegro, R Naidoo, M Ozonoff, D Partanen, T Pendito, RI Povey, G Richter, ED Robbins, A Correa, HR Rosenman, KD Samuels, SW Santana, VS Schwartz, BS Siqueira, CE Soskolne, CL Spiegel, J Stephens, C Tajik, M Takaro, TK Teitelbaum, DT Tickner, JA Tomatis, L Victoria, C Waltner-Toews, D Wedeen, RP Wegman, DH Wesseling, C Wing, S Yassi, A TI Texaco and its consultants SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter ID AMAZON BASIN; OIL-FIELDS; CANCER INCIDENCE; ECUADOR C1 Hlth Res & Advisory Ctr, Quito, Ecuador. Assoc Occupat Dis & Prevent, Santos, Brazil. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. French Natl Inst Environm Risks, Verneuil En Halatte, France. Natl Publ Hlth Inst, Cuernavaca, Morelos, Mexico. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Republica, Montevideo, Uruguay. Colombian Safety Council, Bogota, Colombia. Brown Univ, Providence, RI 02912 USA. Shaare Zedek Mem Hosp, Jerusalem, Israel. Univ Modena, Sch Med, Occupat Hlth Unit, I-41100 Modena, Italy. Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Newark, NJ 07103 USA. Univ Copenhagen, Inst Publ Hlth, Copenhagen, Denmark. Univ Leeds, Leeds, W Yorkshire, England. Natl Publ Hlth Inst, Stockholm, Sweden. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Ctr Environm & Occupat Hlth, New Delhi, India. Univ Massachusetts, Sch Hlth & Environm, Amherst, MA 01003 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. Mt Sinai Sch Med, New York, NY USA. Med Acad Postgrad Studies, Dept Occupat Hlth, St Petersburg, Russia. RP Breilh, J (reprint author), Hlth Res & Advisory Ctr, Quito, Ecuador. RI Santana, Vilma/E-8086-2015; Correa-Filho, Heleno/K-6733-2012 OI Correa-Filho, Heleno/0000-0001-8056-8824 NR 12 TC 8 Z9 8 U1 0 U2 5 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD APR-JUN PY 2005 VL 11 IS 2 BP 217 EP 220 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921OX UT WOS:000228775200017 PM 15875903 ER PT J AU Rabinowitz, YS Dong, LJ Wistow, G AF Rabinowitz, YS Dong, LJ Wistow, G TI Gene expression profile studies of human keratoconus cornea for NEIBank: A novel cornea-expressed gene and the absence of transcripts for aquaporin 5 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID SEQUENCE TAG ANALYSIS; ALDEHYDE DEHYDROGENASE; EYE DEVELOPMENT; WATER CHANNELS; EPITHELIUM; CDNA; IDENTIFICATION; APOPTOSIS; BIOINFORMATICS; PROJECT AB PURPOSE. To increase the database of genes expressed in human cornea and to gain insights into the molecular basis of keratoconus ( KC). METHODS. A cDNA library was constructed from KC corneas harvested at keratoplasty and used for expressed sequence tag ( EST) analysis. Data were analyzed using grouping and identification of sequence tags ( GRIST). Expression of selected clones was examined by RT-PCR. RESULTS. A total of 7680 clones was sequenced from the 5' end. After bioinformatics analysis, 4090 clusters of clones, each potentially representing individual genes, were identified. Of these, 887 genes were represented by more than one clone. The five most abundant transcripts, represented by > 60 clones each, were for keratin-12, TGFBI (BIGH3), decorin, ALDH3, and enolase 1, all known markers for cornea. Many other markers for epithelial, stromal, and endothelial genes were also present. One cluster of six clones came from an apparently novel gene ( designated KC6) located on chromosome 18 at p12.3. RT-PCR of RNA from several human tissues detected KC6 transcripts only in cornea. In addition, no clones were observed for the usually prominent corneal epithelial cell marker aquaporin 5 ( AQP5), a water channel protein. Semi-quantitative RT-PCR confirmed that expression of AQP5 is much lower in KC cornea than in non-KC cornea. CONCLUSIONS. This analysis increases the database of genes expressed in the human cornea and provides insights into KC. KC6 is a novel gene of unknown function that shows cornea-preferred expression, whereas the suppression of transcripts for AQP5 provides the first clear evidence of a molecular defect identified in KC. C1 NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Cornea Genet Eye Inst, Los Angeles, CA 90048 USA. RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct, NIH, Bldg 7,Room 201, Bethesda, MD 20892 USA. EM graeme@helix.nih.gov NR 49 TC 59 Z9 61 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 APR PY 2005 VL 46 IS 4 BP 1239 EP 1246 DI 10.1167/iovs.04-1148 PG 8 WC Ophthalmology SC Ophthalmology GA 910DB UT WOS:000227908900018 PM 15790884 ER PT J AU Jia, G Baudendistel, KT von Tengg-Kobligk, H Heverhagen, JT Polzer, H Henry, R McAuliffe, MJ Levine, AL Rosol, TJ Knopp, MV AF Jia, G Baudendistel, KT von Tengg-Kobligk, H Heverhagen, JT Polzer, H Henry, R McAuliffe, MJ Levine, AL Rosol, TJ Knopp, MV TI Assessing prostate volume by magnetic resonance imaging - A comparison of different measurement approaches for organ volume analysis SO INVESTIGATIVE RADIOLOGY LA English DT Article DE magnetic resonance imaging; benign prostatic hyperplasia; prostate volume ID TRANSRECTAL ULTRASOUND; HYPERPLASIA; MRI; THERMOTHERAPY; ACCURACY; COIL AB Objectives: We sought to evaluate the capabilities of different magnetic resonance imaging (MRI)-based methodologies for measuring prostate volume. Materials and Methods: Twenty-four male beagles with benign prostatic hyperplasia were enrolled in a drug trial and imaged at 5 time points. A total of 120 prostate volumes were determined by MRI-based semiautomated segmentation. For planimetric assessment, 8 diameter locations were determined in the axial and coronal plane of the MRI slice with maximum extension of the prostate. Thirteen calculation models based on these diameters were determined by comparison to the reference volume and evaluated during treatment. Results: The segmented MRI prostate volume significantly correlated with post necropsy Volume. The best diameter-based model also worked very well for monitoring prostate volume of dogs under treatment. Conclusions: MRI-based segmentation is highly accurate in assessing prostate volume. Diameter-based measurements are closely correlated to the segmented prostate volume and are feasible to monitor therapy. C1 Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. NIH, CIT, Bethesda, MD 20892 USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. RP Knopp, MV (reprint author), Ohio State Univ, Dept Radiol, 646 Means Hall,1654 Upham Dr, Columbus, OH 43210 USA. EM knopp.16@osu.edu RI Rosol, Thomas/G-9585-2011; Jia, Guang/A-1275-2016; von Tengg-Kobligk, Hendrik/A-1420-2017 OI Rosol, Thomas/0000-0003-3737-1190; von Tengg-Kobligk, Hendrik/0000-0003-3207-3223 NR 19 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD APR PY 2005 VL 40 IS 4 BP 243 EP 248 DI 10.1097/01.rli.0000156312.24604.7c PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 909PR UT WOS:000227872800008 PM 15770143 ER PT J AU Colavitti, R Finkel, T AF Colavitti, R Finkel, T TI Reactive oxygen species as mediators of cellular senescence SO IUBMB LIFE LA English DT Review DE cell senescence; reactive oxygen species; telomerase ID NORMAL HUMAN FIBROBLASTS; OXIDATIVE STRESS; LIFE-SPAN; CAENORHABDITIS-ELEGANS; PREMATURE SENESCENCE; CYCLE REGULATION; GROWTH ARREST; HUMAN-CELLS; RAS; PROTEINS AB Aging has often been viewed as a random process arising from the accumulation of both genetic and epigenetic changes. Increasingly, the notion that aging is a stochastic process is being supplanted by the concept that maximum lifespan of an organism is tightly regulated. This knowledge has led to a growing overlap between classical signal transduction paradigms and the biology of aging. We review certain specific examples where these seemingly disparate disciplines intersect. In particular, we review the concept that intracellular reactive oxygen species function as signalling molecules and that oxidants play a central role as mediators of cellular senescence. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10,CRC 5-3330, Bethesda, MD 20892 USA. NR 40 TC 93 Z9 98 U1 3 U2 13 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 APR-MAY PY 2005 VL 57 IS 4-5 BP 277 EP 281 DI 10.1080/15216540500091890 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 940CD UT WOS:000230120400029 PM 16036611 ER PT J AU Tuomala, RK Watts, DH Li, D Vajaranant, M Pitt, J Hammill, H Landesman, S Zorrilla, C Thompson, B AF Tuomala, RK Watts, DH Li, D Vajaranant, M Pitt, J Hammill, H Landesman, S Zorrilla, C Thompson, B CA Women Infants Transmission Study TI Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE maternal complications; adverse pregnancy outcomes; antiretroviral therapy; pregnancy ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; PROTEASE INHIBITOR; WOMEN; HIV-1; COMBINATION; TYPE-1; PREVENTION; INFECTION AB Data from 2543 HIV-infected women were analyzed to correlate antiretroviral therapy (ART) used. during pregnancy with maternal and pregnancy outcomes. ART was analyzed according to class of agents used and according to monotherapy versus combination ART containing neither protease inhibitors (PIs) nor nonnucleoside reverse transcriptase inhibitors versus highly active ART. Timing of ART was classified according to early (recorded at or before 25-week gestation study visit) and late (recorded at 32-week gestation or delivery visit) use. Maternal outcomes assessed included hematologic, gastrointestinal, neurologic, renal, and dermatologic complications; gestational diabetes; lactic acidosis; and death. Adverse pregnancy outcomes assessed included hypertensive complications; pre-term labor or rupture of membranes; preterm delivery (PTD); low birth weight; and stillbirth. Logistic regression analyses controlling for multiple covariates revealed ART to be independently associated with few maternal complications: ART use was associated with anemia (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1-2.4), and late use of ART was associated with gestational diabetes (OR = 3.5, 95% CI: 1.2-10.1). Logistic regression analyses revealed an increase in PTD at < 37 weeks for 10 women with late use of ART not containing zidovudine (ZDV, OR = 7.9, 95% CI: 1.4-44.6) and a decrease in adverse pregnancy outcomes as follows: late use of ART containing ZDV was associated with decreased risk for stillbirth and PTD at < 37 weeks (OR = 0.06, 95% CI: 0.02-0.18; OR = 0.5, 95% CI: 0.3-0.8, respectively), and ART containing nucleoside reverse transcriptase inhibitors but not ZDV during early and late pregnancy was associated with decreased risk for PTD at < 32 weeks (OR = 0.3, 95% CI: 0.2-0.7). Benefits of ART continue to outweigh observed risks. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Columbia Presbyterian Med Ctr, Dept Pediat, New York, NY USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. SUNY, Dept Med, Brooklyn, NY USA. Univ Puerto Rico, Sch Med, Dept Obstet & Gynecol, San Juan, PR 00936 USA. RP Tuomala, RK (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM rtuomala@partners.org FU NCRR NIH HHS [RR00188, RR00645]; NIAID NIH HHS [U01 AI 34858, 1 U01 AI 50274, N01 AI 85339, U01 AI 34841]; NICHD NIH HHS [U01 HD 36117, U01 HD 41983]; NIDA NIH HHS [U01 DA 15053, U01 DA 15054] NR 32 TC 103 Z9 108 U1 0 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 APR 1 PY 2005 VL 38 IS 4 BP 449 EP 473 DI 10.1097/01.qai.0000139398.38236.4d PG 25 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 906TA UT WOS:000227665000011 PM 15764963 ER PT J AU Mbulaiteye, SM Biggar, RJ Pfeiffer, RM Bakaki, PM Gamache, C Owor, AM Katongole-Mbidde, E Ndugwa, CM Goedert, JJ Whitby, D Engels, EA AF Mbulaiteye, SM Biggar, RJ Pfeiffer, RM Bakaki, PM Gamache, C Owor, AM Katongole-Mbidde, E Ndugwa, CM Goedert, JJ Whitby, D Engels, EA TI Water, socioeconomic factors, and human herpesvirus 8 infection in Ugandan children and their mothers SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE Kaposi sarcoma; Africa; human herpesvirus 8; transmission; water source; environmental factors; socioeconomic factors; epidemiology ID HUMAN-HERPESVIRUS TYPE-8; KAPOSIS-SARCOMA; RISK-FACTORS; EAST-AFRICA; TO-CHILD; TRANSMISSION; PREVALENCE; POPULATION; ADULTS; SEROPREVALENCE AB Background: Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its distribution is uneven. Transmission occurs during childhood within families by unclear routes. Methods: We evaluated 600 Ugandan children with sickle cell disease and their mothers for factors associated with HHV-8 seropositivity in a cross-sectional study. HHV-8 serostatus was determined using an HHV-8 K8.1 glycoprotein enzyme immunoassay. Odds ratios for seropositivity were estimated using logistic regression, and factor analysis was used to identify clustering among socioeconomic variables. Results: One hundred seventeen (21%) of 561 children and 166 (34%) of 485 mothers with definite HHV-8 serostatus were seropositive. For children, seropositivity was associated with age, mother's HHV-8 serostatus (especially for children aged 6 years or younger), lower maternal education level, mother's income, and low-status father's occupation (P < 0.05 for all). Using communal standpipe or using surface water sources were both associated with seropositivity (OR 2.70, 95% CI 0.80-9.06 and 4.02, 95% CI 1.18-13.7, respectively) as compared to using private tap water. These associations remained, albeit attenuated, after adjusting for maternal education and child's age (P = 0.08). In factor analysis, low scores on environmental and family factors, which captured household and parental characteristics, respectively, were positively associated with seropositivity (P-trend < 0.05 for both). For mothers, HHV-8 seropositivity was significantly associated with water source and maternal income. Conclusions: HHV-8 infection in Ugandan children was associated with lower socioeconomic status and using surface water. Households with limited access to water may have less hygienic practices that increase risk for HHV-8 infection. C1 Sci Applicat Int Corp, NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD USA. Makerere Univ, Sch Med, Kampala, Uganda. Mulago Hosp, Kampala, Uganda. NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,EPS Room 80067, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov FU NCI NIH HHS [N02-CP-91027, N01-CO-12400] NR 28 TC 45 Z9 47 U1 0 U2 1 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 APR 1 PY 2005 VL 38 IS 4 BP 474 EP 479 DI 10.1097/01.qai.0000132495.89162.c0 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 906TA UT WOS:000227665000012 PM 15764964 ER PT J AU Marden, SF AF Marden, SF TI Technology dependence and health-related quality of life: a model SO JOURNAL OF ADVANCED NURSING LA English DT Article DE technology dependence; quality of life; illness representations; healthcare technology; nursing; technology and nursing ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC-FATIGUE-SYNDROME; ARTERY BYPASS-SURGERY; ILLNESS PERCEPTIONS; HEART-TRANSPLANTATION; SYMPTOM DISTRESS; SEX-DIFFERENCES; GENDER; REPRESENTATIONS; PREDICTORS AB Aim. This paper presents a new theoretical model to explain people's diverse responses to therapeutic health technology by characterizing the relationship between technology dependence and health-related quality of life (HRQL). Introduction. Technology dependence has been defined as reliance on a variety of devices, drugs and procedures to alleviate or remedy acute or chronic health problems. Health professionals must ensure that these technologies result in positive outcomes for those who must rely on them, while minimizing the potential for unintended consequences. Little research exists to inform health professionals about how dependency on therapeutic technology may affect patient-reported outcomes such as HRQL. Organizing frameworks to focus such research are also limited. Model. Generated from the synthesis of three theoretical frameworks and empirical research, the model proposes that attitudes towards technology dependence affect HRQL through a person's illness representations or commonsense beliefs about their illness. Symptom distress, illness history, age and gender also influence the technology dependence and HRQL relationship. Five concepts form the major components of the model: a) attitudes towards technology dependence, b) illness representation, c) symptom distress, d) HRQL and e) illness history. Conclusion. The model is proposed as a guide for clinical nursing research into the impact of a wide variety of therapeutic health care interventions on HRQL. Empirical validation of the model is needed to test its generality. C1 NIH, Nursing & Patient Care Serv Clin Ctr, Bethesda, MD USA. RP Marden, SF (reprint author), NIH, Mark Hatfield Clin Res Ctr, 2-1339,MSC 1506,10 Ctr Dr, Bethesda, MD 20892 USA. EM smarden@nih.gov NR 45 TC 12 Z9 13 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD APR PY 2005 VL 50 IS 2 BP 187 EP 195 DI 10.1111/j.1365-2648.2005.03378.x PG 9 WC Nursing SC Nursing GA 908GT UT WOS:000227776200009 PM 15788083 ER PT J AU Paul, ME Mao, C Charurat, M Serchuck, L Foca, M Hayani, K Handelsman, EL Diaz, C McIntosh, K Shearer, WT AF Paul, ME Mao, C Charurat, M Serchuck, L Foca, M Hayani, K Handelsman, EL Diaz, C McIntosh, K Shearer, WT CA Women Infants Transmission Study TI Predictors of immunologic long-term nonprogression in HIV-infected children: Implications for initiating therapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE human immunodeficiency virus; perinatal; immunologic long-term nonprogression; CD8(+) T lymphocyte ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELLS; DISEASE PROGRESSION; PROGNOSTIC VALUE; VIRAL LOAD; HIV-1-INFECTED CHILDREN; FLOW-CYTOMETRY; LYMPHOCYTE-ACTIVATION; SURVIVING CHILDREN; IMMUNE ACTIVATION AB Background: Early markers that predict immunologic long-term nonprogression in infants with perinatally acquired HIV infection might assist in subsequent antiretroviral treatment decisions. Objectives: We sought to identify early markers of immunologic long-term HIV disease nonprogression. Methods: We analyzed immunologic and virologic characteristics at I and 2 months of age in HIV-infected children who were enrolled in the Women and Infants Transmission Study and born before 1995, comparing immunologic long-term nonprogressors (ILTNPs; n = 10) with non-ILTNPs (n = 127). ILTNPs were children who survived to 8 years or older with CD4 percentages of 25% or greater and counts of 500 cells/mm(3) or more without receiving highly active antiretroviral therapy. Non-ILTNPs were defined as all other HIV-infected children. Receiver operating characteristic curve analysis was used to assess combined sensitivity and specificity for each of these characteristics and to determine potential threshold values to discriminate between ILTNPs and non-ILTNPs. Results: Characteristics in the first 2 months of life associated with ILTNP status in univariate analysis included higher CD4 percentages, lower CD8(+) percentages, lower CD8(+)HLA-DR+ percentages, and lower HIV-1 RNA PCR values. In receiver operating characteristic analysis CD8+HLA-DR+ percentage had the best combined sensitivity and specificity for discriminating between ILTNPs and non-ILTNPs. CD8(+)HLA-DR+ percentages of 5% or less predicted ILTNP status with 80% sensitivity and 80% specificity. In multivariate analysis CD8+HLA-DR+ percentage of 5% or less remained a significant predictor of ILTNP status after adjusting for CD3(+) CD4(+) percentage and HIV-1 RNA PCR value (odds ratio, 15.4; 95% CI, 1.9-124.7). Conclusion: CD8(+) HLA-DR+ T-lymphocyte percentage of less than 5% at 1 to 2 months of age might be predictive for ILTNP status but should not be used at this time to make treatment-deferral decisions. Immune activation in HIV-infected infants might herald more disease progression. Further study of the use of this subpopulation in early infancy to predict ILTNP status is warranted. C1 Baylor Coll Med, Sect Allergy & Immunol, Houston, TX USA. Childrens Hosp, Boston, MA 02115 USA. Univ Maryland, Div Epidemiol & Prevent, Inst Human Virol, Baltimore, MD 21201 USA. Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Illinois, Dept Pediat, Chicago, IL USA. SUNY Downstate, Brooklyn, NY USA. Univ Puerto Rico, San Juan, PR 00936 USA. RP Paul, ME (reprint author), Texas Childrens Hosp, 6621 Fannin St FC 330-01, Houston, TX 77030 USA. EM mepaul@texaschildrens.hospital.org FU NCRR NIH HHS [RR 00645, RR 00188]; NIAID NIH HHS [U01 AI 34858, U01 AI 34841, N01 AI 85339, 1U01 AI 50274-01]; NICHD NIH HHS [HD 36117, U01 HD 41983]; NIDA NIH HHS [U01 DA 15053, 9U01 DA 15054] NR 48 TC 30 Z9 30 U1 1 U2 5 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 APR PY 2005 VL 115 IS 4 BP 848 EP 855 DI 10.1016/j.jaci.2004.11.054 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 916GM UT WOS:000228373400028 PM 15806009 ER PT J AU Martin, JE Enama, ME Koup, RA Bailer, RT Moodie, Z Roederer, M Nabel, GJ Graham, BS AF Martin, JE Enama, ME Koup, RA Bailer, RT Moodie, Z Roederer, M Nabel, GJ Graham, BS TI VRC 004: Safety and immumogenicity of a multiclade HIV-1 DNA vaccine in healthy uninfected adults (VRC-HIVD-NA009-00-VP) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 18-22, 2005 CL San Antonio, TX SP Amer Acad Allergy Asthma Immunol C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA. NR 0 TC 4 Z9 4 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 APR PY 2005 VL 115 IS 4 BP 892 EP 892 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 916GM UT WOS:000228373400049 ER PT J AU Geller, G Francomano, CA AF Geller, G Francomano, CA TI Complementary medicine and genetic medicine: Polar disciplines or dynamic partners? SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID TRADITIONAL CHINESE MEDICINE; ALTERNATIVE MEDICINE; PUBLIC-HEALTH; HUMAN GENOME; FUTURE; CARE; PROVIDERS; SEARCH; TRENDS; DNA AB For more than a decade, a powerful movement promoting the integration of complementary and alternative medicine, (CAM) and conventional medicine has evolved. Throughout the same period, there has been a monumental shift in the biologic sciences, and in perspectives on disease, resulting from advances in genetics. It is noteworthy, and perhaps not coincidental, that these "movements" have been occurring in parallel. The simultaneous growth of complementary medicine and genetic medicine may be fueled by a deep interest in the development of "personalized" medicine. There is a prevailing view that the metaphysical visions of these two fields are in conflict. To advance discussion of this question, we describe what we believe are the common philosophies and goals of these apparently disparate fields, and why it would be advantageous for them to work together in the service of the public&PRIME; s health. C1 Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Ctr Complementary & Alternat Med, Baltimore, MD USA. NIA, Intramural Res Program, Genet Lab, Human Genet & Integrat Med Sect, Baltimore, MD 21224 USA. RP Geller, G (reprint author), Johns Hopkins Med Inst, 550 N Broadway,Suite 511, Baltimore, MD 21205 USA. EM ggeller@jhmi.edu NR 40 TC 3 Z9 3 U1 3 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD APR PY 2005 VL 11 IS 2 BP 343 EP 347 DI 10.1089/acm.2005.11.343 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 924TD UT WOS:000229002400021 PM 15865502 ER PT J AU Hogan, MC Stary, CM Balaban, RS Combs, CA AF Hogan, MC Stary, CM Balaban, RS Combs, CA TI NAD(P)H fluorescence imaging of mitochondrial metabolism in contracting Xenopus skeletal muscle fibers: effect of oxygen availability SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE oxygen uptake; exercise; oxidative phosphorylation; mitochondria; cellular respiration ID REDUCED PYRIDINE-NUCLEOTIDE; PERFUSED-RAT-LIVER; NADH FLUORESCENCE; OXIDATIVE-PHOSPHORYLATION; VENTRICULAR MYOCYTES; CARDIAC TRABECULAE; INTRACELLULAR PO2; IN-VIVO; MYOGLOBIN; HEART AB The blue autofluorescence (351 nm excitation, 450 nm emission) of single skeletal muscle fibers from Xenopus was characterized to be originating from mitochondrial NAD( P) H on the basis of morphological and functional correlations. This fluorescence signal was used to estimate the oxygen availability to isolated single Xenopus muscle fibers during work level transitions by confocal microscopy. Fibers were stimulated to generate two contractile periods that were only different in the PO2 of the solution perfusing the single fibers (PO2 of 30 or 0 - 2 Torr; pH = 7.2). During contractions, mean cellular NAD( P) H increased significantly from rest in the low PO2 condition with the core ( inner 10%) increasing to a greater extent than the periphery ( outer 10%). After the cessation of work, NAD( P) H decreased in a manner consistent with oxygen tensions sufficient to oxidize the surplus NAD( P) H. In contrast, NAD( P) H decreased significantly with work in 30 Torr PO2. However, the rate of NAD( P) H oxidation was slower and significantly increased with the cessation of work in the core of the fiber compared with the peripheral region, consistent with a remaining limitation in oxygen availability. These results suggest that the blue autofluorescence signal in Xenopus skeletal muscle fibers is from mitochondrial NAD( P) H and that the rate of NAD( P) H oxidation within the cell is influenced by extracellular PO2 even at high extracellular PO2 during the contraction cycle. These results also demonstrate that although oxygen availability influences the rate of NAD( P) H oxidation, it does not prevent NAD( P) H from being oxidized through the process of oxidative phosphorylation at the onset of contractions. C1 NHLBI, Light Microscopy Facil, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Combs, CA (reprint author), NHLBI, Light Microscopy Facil, NIH, 9000 Rockville Pike,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA. EM combsc@nhlbi.nih.gov RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Stary, Creed/0000-0001-9876-6634 FU NIAMS NIH HHS [AR-40155] NR 46 TC 19 Z9 19 U1 1 U2 4 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 APR PY 2005 VL 98 IS 4 BP 1420 EP 1426 DI 10.1152/japplphysiol.00849.2004 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 906TE UT WOS:000227665400037 PM 15591295 ER PT J AU Dahl, JL Arora, K Boshoff, HI Whiteford, DC Pacheco, SA Walsh, OJ Lau-Bonilla, D Davis, WB Garza, AG AF Dahl, JL Arora, K Boshoff, HI Whiteford, DC Pacheco, SA Walsh, OJ Lau-Bonilla, D Davis, WB Garza, AG TI The re1A homolog of Mycobacterium smegmatis affects cell appearance, viability, and gene expression SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STATIONARY-PHASE; STRINGENT RESPONSE; TUBERCULOSIS; SURVIVAL; PROTEIN; TRANSCRIPTION; PERSISTENCE; ADAPTATION; PPGPP; DKSA AB The modification of metabolic pathways to allow for a dormant lifestyle appears to be an important feature for the survival of pathogenic bacteria within their host. One regulatory mechanism for persistent Mycobacterium tuberculosis infections is the stringent response. In this study, we analyze the stringent response of a nonpathogenic, saprophytic mycobacterial species, Mycobacterium smegmatis. The use of M. smegmatis as a tool for studying the mycobacterial stringent response was demonstrated by measuring the expression of two M. tuberculosis genes, hspX and eis, in M. smegmatis in the presence and absence of rel(Msm). The stringent response plays a role in M. smegmatis cellular and colony formation that is suggestive of changes in the bacterial cell wall structure. C1 Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. NIAID, TB Sect, Rockville, MD USA. Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA. RP Dahl, JL (reprint author), Washington State Univ, Sch Mol Biosci, Sci Hall,Room 301, Pullman, WA 99164 USA. EM johndahl@wsu.edu FU NIAID NIH HHS [AI-75320] NR 38 TC 31 Z9 33 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 APR PY 2005 VL 187 IS 7 BP 2439 EP 2447 DI 10.1128/JB.187.7.2439-2447.2005 PG 9 WC Microbiology SC Microbiology GA 907VJ UT WOS:000227745800025 PM 15774887 ER PT J AU Sayeed, S Brendler, T Davis, M Reaves, L Austin, S AF Sayeed, S Brendler, T Davis, M Reaves, L Austin, S TI Surprising dependence on postsegregational killing of host cells for maintenance of the large virulence plasmid of Shigella flexneri SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; INVASION GENES; SYSTEM; EXPRESSION; STABILITY; PATHWAY AB Low-copy-number plasmids all encode multiple systems to ensure their propagation, including replication, partition (active segregation), and postsegregational killing (PSK) systems. PSK systems kill those rare cells that lose the plasmid due to replication or segregation errors. PSK systems should not be used as the principle means of maintaining the plasmid. The metabolic cost of killing the many cured cells that would arise from random plasmid segregation is far too high. Here we describe an interesting exception to this rule. Maintenance of the large virulence plasmid of Shigella flexneri is highly dependent on one of its PSK systems, mvp, at 37 degrees C, the temperature experienced during pathogenesis. At 37 degrees C, the plasmid is very unstable and mvp efficiently kills the resulting cured bacterial cells. This imposes a major growth disadvantage on the virulent bacterial population. The systems that normally ensure accurate plasmid replication and segregation are attenuated or overridden at 37 degrees C. At 30 degrees C, a temperature encountered by Shigella in the outside environment, the maintenance systems function normally and the plasmid is no longer dependent on mvp. We discuss why the virulent pathogen tolerates this self-destructive method of propagation at the temperature of infection. C1 NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA. Cent Connecticut State Univ, Dept Biol Sci, New Britain, CT 06050 USA. RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA. EM austin@ncifcrf.gov NR 21 TC 9 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2005 VL 187 IS 8 BP 2768 EP 2773 DI 10.1128/JB.187.8.2768-2773.2005 PG 6 WC Microbiology SC Microbiology GA 914DH UT WOS:000228204700023 PM 15805523 ER PT J AU Xu, M Zhou, YN Goldstein, BP Jin, DJ AF Xu, M Zhou, YN Goldstein, BP Jin, DJ TI Cross-resistance of Escherichia coli RNA polymerases conferring rifarnpin resistance to different antibiotics SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RIFAMPICIN-RESISTANT; BETA-SUBUNIT; MYCOBACTERIUM-TUBERCULOSIS; RPOB MUTATIONS; STAPHYLOCOCCUS-AUREUS; IN-VITRO; MUTANTS; INHIBITION; GENE; TRANSCRIPTION AB In this study we further defined the rifampin-binding sites in Escherichia coli RNA polymerase (RNAP) and determined the relationship between rifampin-binding sites and the binding sites of other antibiotics, including two rifamycin derivatives, rifabutin and rifapentine, and streptolydigin and sorangicin A, which are unrelated to rifampin, using a purified in vitro system. We found that there is almost a complete correlation between resistance to rifampin (Rif(r)) and reduced rifampin binding to 12 RNAPs purified from different rpoB Rifr mutants and a complete cross-resistance among the different rifamycin derivatives. Most Rif(r) RNAPs were sensitive to streptolydigin, although some exhibited weak resistance to this antibiotic. However, 5 out of the 12 Rif(r) RNAPs were partially resistant to sorangicin A, and one was completely cross-resistant to sorangicin A, indicating that the binding site(s) for these two antibiotics overlaps. Both rifampin and sorangicin A inhibited the transition step between transcription initiation and elongation; however, longer abortive initiation products were produced in the presence of the latter, indicating that the binding site for sorangicin A is within the rifampin-binding site. Competition experiments of different antibiotics with 3 H-labeled rifampin for binding to wild-type RNAP further confirmed that the binding sites for rifampin, rifabutin, rifapentine, and sorangicin A are shared, whereas the binding sites for rifampin and streptolydigin are distinct. Because Rif(r) mutations are highly conserved in eubacteria, our results indicate that this set of Rif(r) mutant RNAPs can be used to screen for new antibiotics that will inhibit the growth of Rif(r) pathogenic bacteria. C1 NCI, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Lepetit Res Ctr, Varese, Italy. RP Jin, DJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, NIH, NIH Bldg 469,Room 127,POB B, Frederick, MD 21702 USA. EM djjin@helix.nih.gov NR 42 TC 33 Z9 36 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 APR PY 2005 VL 187 IS 8 BP 2783 EP 2792 DI 10.1128/JB.187.8.2783-2792.2005 PG 10 WC Microbiology SC Microbiology GA 914DH UT WOS:000228204700025 PM 15805525 ER PT J AU Piszczek, G Rozycki, J Singh, SK Ginsburg, A Maurizi, MR AF Piszczek, G Rozycki, J Singh, SK Ginsburg, A Maurizi, MR TI The molecular chaperone, ClpA, has a single high affinity peptide binding site per hexamer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATP-DEPENDENT PROTEASES; ESCHERICHIA-COLI; SUBSTRATE-RECOGNITION; CRYSTAL-STRUCTURE; HSP100 CHAPERONE; QUALITY-CONTROL; AAA+ ATPASE; PROTEIN; DEGRADATION; TRANSLOCATION AB Substrate recognition by Clp chaperones is dependent on interactions with motifs composed of specific peptide sequences. We studied the binding of short motif-bearing peptides to ClpA, the chaperone component of the ATP-dependent ClpAP protease of Escherichia coli in the presence of ATP gamma S and Mg2+ at pH 7.5. Binding was measured by isothermal titration calorimetry (ITC) using the peptide, AANDENYALAA, which corresponds to the SsrA degradation motif found at the C terminus of abnormal nascent polypeptides in vivo. One SsrA peptide was bound per hexamer of ClpA with an association constant (K-A) of 5 x 10(6) M-1. Binding was also assayed by changes in fluorescence of an N-terminal dansylated SsrA peptide, which bound with the same stoichiometry of one per ClpA hexamer (K-A similar to 1 x 10(7) M-1). Similar results were obtained when ATP was substituted for ATP gamma S at 6 degrees C. Two additional peptides, derived from the phage P1 RepA protein and the E. coli HemA protein, which bear different substrate motifs, were competitive inhibitors of SsrA binding and bound to ClpA hexamers with K-A' > 3 x 10(7) M-1. DNS-SsrA bound with only slightly reduced affinity to deletion mutants of ClpA missing either the N-terminal domain or the C-terminal nucleotide-binding domain, indicating that the binding site for SsrA lies within the N-terminal nucleotide-binding domain. Because only one protein at a time can be unfolded and translocated by ClpA hexamers, restricting the number of peptides initially bound should avoid nonproductive binding of substrates and aggregation of partially processed proteins. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piszczek, G (reprint author), NHLBI, Biochem Lab, NIH, 50 S Dr,Bldg 50,Rm 2341, Bethesda, MD 20892 USA. EM grzegorz_piszczek@nih.gov NR 51 TC 20 Z9 20 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 APR 1 PY 2005 VL 280 IS 13 BP 12221 EP 12230 DI 10.1074/jbc.M411733200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000020 PM 15657062 ER PT J AU Kobrinsky, E Tiwari, S Maltsev, VA Harry, JB Lakatta, E Abernethy, DR Soldatov, NM AF Kobrinsky, E Tiwari, S Maltsev, VA Harry, JB Lakatta, E Abernethy, DR Soldatov, NM TI Differential role of the alpha(1C) subunit tails in regulation of the Ca(v)1.2 channels by membrane potential ss subunits, and Ca2+ ions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GATED CALCIUM-CHANNELS; PROTEIN-KINASE-C; BETA-SUBUNIT; SPLICE VARIANTS; MOLECULAR DETERMINANTS; ENDOPLASMIC-RETICULUM; ALPHA(2)DELTA SUBUNIT; VENTRICULAR MYOCYTES; CALMODULIN-BINDING; MODULATION AB Voltage-gated Ca(v)1.2 channels are composed of the pore-forming alpha(1C) and auxiliary beta and alpha(2)delta subunits. Voltage-dependent conformational rearrangements of the alpha(1C) subunit C-tail have been implicated in Ca2+ signal transduction. In contrast, the alpha(1C) N-tail demonstrates limited voltage-gated mobility. We have asked whether these properties are critical for the channel function. Here we report that transient anchoring of the alpha(1C) subunit C-tail in the plasma membrane inhibits Ca2+-dependent and slow voltage-dependent inactivation. Both alpha(2)delta and beta subunits remain essential for the functional channel. In contrast, if alpha(1C) subunits are expressed with alpha(2)delta but in the absence of a beta subunit, plasma membrane anchoring of the alpha(1C) N terminus or its deletion inhibit both voltage- and Ca2+-dependent inactivation of the current. The following findings all corroborate the importance of the alpha(1C) N-tail/beta interaction: (i) coexpression of beta restores inactivation properties, (ii) release of the alpha(1C) N terminus inhibits the beta-deficient channel, and (iii) voltage-gated mobility of the alpha(1C) N-tail vis a vis the plasma membrane is increased in the beta-deficient ( silent) channel. Together, these data argue that both the alpha(1C) N- and C-tails have important but different roles in the voltage- and Ca2+-dependent inactivation, as well as beta subunit modulation of the channel. The alpha(1C) N-tail may have a role in the channel trafficking and is a target of the beta subunit modulation. The beta subunit facilitates voltage gating by competing with the N- tail and constraining its voltage- dependent rearrangements. Thus, cross-talk between the alpha(1C) C and N termini, beta subunit, and the cytoplasmic pore region confers the multifactorial regulation of Cav1.2 channels. C1 NIA, Clin Invest Lab, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), NIA, Clin Invest Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM soldatovN@grc.nia.nih.gov NR 43 TC 43 Z9 45 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 APR 1 PY 2005 VL 280 IS 13 BP 12474 EP 12485 DI 10.1074/jbc.M412140200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000051 PM 15671035 ER PT J AU Wang, T Hu, YC Dong, SZ Fan, M Tamae, D Ozeki, M Gao, Q Gius, D Li, JJ AF Wang, T Hu, YC Dong, SZ Fan, M Tamae, D Ozeki, M Gao, Q Gius, D Li, JJ TI Co-activation of ERK, NF-kappa B, and GADD45 beta in response to ionizing radiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; SUPEROXIDE-DISMUTASE GENE; FREE-RADICAL SCAVENGERS; NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTORS; STRESS RESPONSES; INHIBITOR PD98059; INDUCED APOPTOSIS; GENOTOXIC STRESS; FAMILY PROTEINS AB NF-kappa B has been well documented to play a critical role in signaling cell stress reactions. The extracellular signal-regulated kinase (ERK) regulates cell proliferation and survival. GADD45 beta is a primary cell cycle element responsive to NF-kappa B activation in anti-apoptotic responses. The present study provides evidence demonstrating that NK-kappa B, ERK and GADD45 beta are co-activated by ionizing radiation (IR) in a pattern of mutually dependence to increase cell survival. Stress conditions generated in human breast cancer MCF-7 cells by the administration of a single exposure of 5 Gy IR resulted in the activation of ERK but not p38 or JNK, along with an enhancement of the NF-kappa B transactivation and GADD45 beta expression. Overexpression of dominant negative Erk (DN-Erk) or pre-exposure to ERK inhibitor PD98059 inhibited NF-kappa B. Transfection of dominant negative mutant I kappa B that blocks NF-kappa B nuclear translocation, inhibited ERK activity and GADD45 beta expression and increased cell radiosensitivity. Interaction of p65 and ERK was visualized in living MCF-7 cells by bimolecular fluorescence complementation analysis. Antisense inhibition of GADD45 beta strikingly blocked IR-induced NF-kappa B and ERK but not p38 and JNK. Overall, these results demonstrate a possibility that NF-kappa B, ERK, and GADD45 beta are able to coordinate in a loop-like signaling network to defend cells against the cytotoxicity induced by ionizing radiation. C1 Purdue Univ, Sch Hlth Sci, Div Mol Radiobiol, W Lafayette, IN 47907 USA. Beckman Res Inst, Div Radiat Oncol, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Bio Rad Labs Inc, Life Sci Grp, San Ramon, CA 94583 USA. NCI, Ctr Canc Res, Radiat Oncol Sci Program, Mol Radiat Oncol,NIH, Bethesda, MD 20892 USA. Purdue Univ, Sch Hlth Sci, Div Mol Radiobiol, W Lafayette, IN 47907 USA. RP Li, JJ (reprint author), Purdue Univ, Sch Hlth Sci, Div Mol Radiobiol, 1279 Civil Engn Blvd,550 Stadium Mall Dr, W Lafayette, IN 47907 USA. EM jjli@purdue.edu FU NCI NIH HHS [R01 CA101990] NR 72 TC 52 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 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 1 PY 2005 VL 280 IS 13 BP 12593 EP 12601 DI 10.1074/jbc.M410982200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000064 PM 15642734 ER PT J AU Hoodbhoy, T Joshi, S Boja, ES Williams, SA Stanley, P Dean, J AF Hoodbhoy, T Joshi, S Boja, ES Williams, SA Stanley, P Dean, J TI Human sperm do not bind to rat zonae pellucidae despite the presence of four homologous glycoproteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-ACETYLGLUCOSAMINYLTRANSFERASE-I; MOLECULAR-CLONING; CORE 2; STRUCTURAL-CHARACTERIZATION; MASS-SPECTROMETRY; GENOME SEQUENCE; EGG RECOGNITION; KNOCKOUT MICE; MOUSE OOCYTES; O-GLYCANS AB The specificity of sperm-egg recognition in mammals is mediated primarily by the zona pellucida surrounding ovulated eggs. Mouse sperm are quite promiscuous and bind to human eggs, but human spermatozoa will not bind to mouse eggs. The mouse zona pellucida contains three glycoproteins, ZP1, ZP2, and ZP3, which are conserved in rat and human. The recent observation that human zonae pellucidae contain a fourth protein raises the possibility that the presence of four zona proteins will support human sperm binding. Using mass spectrometry, four proteins that are similar in size and share 62-70% amino acid identity with human ZP1, ZP2, ZP3, and ZP4/ZPB were detected in rat zonae pellucidae. However, although mouse and rat spermatozoa bind to eggs from each rodent, human sperm bind to neither, and the presence of human follicular fluid did not alter the specificity of sperm binding. In addition, mutant mouse eggs lacking hybrid/complex N-glycans or deficient in Core 2 O-glycans were no more able to support human sperm binding than normal mouse eggs. These data suggest that the presence of four zona proteins are not sufficient to support human sperm binding to rodent eggs and that additional determinants must be responsible for taxon-specific fertilization among mammals. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. RP Hoodbhoy, T (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Rm 3128, Bethesda, MD 20892 USA. EM tanyah@intra.niddk.nih.gov OI Stanley, Pamela/0000-0001-5704-3747 NR 54 TC 56 Z9 62 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 APR 1 PY 2005 VL 280 IS 13 BP 12721 EP 12731 DI 10.1074/jbc.M413569200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000079 PM 15677449 ER PT J AU LIn, XN Varnai, P Csordas, G Balla, A Nagai, T Miyawaki, A Balla, T Hajnoczky, G AF LIn, XN Varnai, P Csordas, G Balla, A Nagai, T Miyawaki, A Balla, T Hajnoczky, G TI Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; CATALYTICALLY INACTIVE PROTEIN; ENDOPLASMIC-RETICULUM; RYANODINE RECEPTORS; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; MEMBRANE LOCALIZATION; FLUORESCENT PROTEIN; PLASMA-MEMBRANE; CA2+; OSCILLATIONS AB Cytosolic Ca2+ ([Ca2+](c)) signals triggered by many agonists are established through the inositol 1,4,5-trisphosphate (IP3) messenger pathway. This pathway is believed to use Ca2+-dependent local interactions among IP3 receptors (IP3R) and other Ca2+ channels leading to coordinated Ca2+ release from the endoplasmic reticulum throughout the cell and coupling Ca2+ entry and mitochondrial Ca2+ uptake to Ca2+ release. To evaluate the role of IP3 in the local control mechanisms that support the propagation of [Ca2+](c) waves, storeoperated Ca2+ entry, and mitochondrial Ca2+ uptake, we used two IP3-binding proteins (IP3BP): 1) the PH domain of the phospholipase C-like protein, p130 (p130PH); and 2) the ligand-binding domain of the human type-IIP3R (IP3R224-605). As expected, p130PH-GFP and GFP-IP3R224-605 behave as effective mobile cytosolic IP3 buffers. In COS-7 cells, the expression of IP3BPs had no effect on store-operated Ca2+ entry. However, the IP3-linked [Ca2+] c signal appeared as a regenerative wave and IP3BPs slowed down the wave propagation. Most importantly, IP3BPs largely inhibited the mitochondrial [Ca2+] signal and decreased the relationship between the [Ca2+](c) and mitochondrial [Ca2+] signals, indicating disconnection of the mitochondria from the [Ca2+](c) signal. These data suggest that IP3 elevations are important to regulate the local interactions among IP3Rs during propagation of [Ca2+](c) waves and that the IP3-dependent synchronization of Ca2+ release events is crucial for the coupling between Ca2+ release and mitochondrial Ca2+ uptake. C1 Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1444 Budapest, Hungary. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RIKEN, Brain Sci Inst, Adv Technol Dev Ctr, Lab Cell Funct & Dynam, Wako, Saitama 3510198, Japan. RP Hajnoczky, G (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Rm 253 JAH, Philadelphia, PA 19107 USA. EM Gyorgy.Hajnoczky@jefferson.edu RI Miyawaki, Atsushi/K-3569-2014; OI Miyawaki, Atsushi/0000-0002-2329-3235; Balla, Andras/0000-0002-6450-2793; Balla, Tamas/0000-0002-9077-3335 NR 49 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 1 PY 2005 VL 280 IS 13 BP 12820 EP 12832 DI 10.1074/jbc.M411591200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000090 PM 15644334 ER PT J AU Gangisetty, O Jones, CE Bhagwat, M Nossal, NG AF Gangisetty, O Jones, CE Bhagwat, M Nossal, NG TI Maturation of bacteriophage T4 lagging strand fragments depends on interaction of T4 RNase H with T4 32 protein rather than the T4 gene 45 clamp SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-POLYMERASE-DELTA; PROTEIN-PROTEIN INTERACTIONS; FLAP ENDONUCLEASE-1; OKAZAKI FRAGMENT; ESCHERICHIA-COLI; SLIDING-CLAMP; SACCHAROMYCES-CEREVISIAE; BINDING PROTEIN; PROCESSIVITY-CLAMP; REPLICATION FORK AB In the bacteriophage T4 DNA replication system, T4 RNase H removes the RNA primers and some adjacent DNA before the lagging strand fragments are ligated. This 5 '-nuclease has strong structural and functional similarity to the FEN1 nuclease family. We have shown previously that T4 32 protein binds DNA behind the nuclease and increases its processivity. Here we show that T4 RNase H with a C-terminal deletion (residues 278-305) retains its exonuclease activity but is no longer affected by 32 protein. T4 gene 45 replication clamp stimulates T4 RNase H on nicked or gapped substrates, where it can be loaded behind the nuclease, but does not increase its processivity. An N-terminal deletion (residues 2-10) of a conserved clamp interaction motif eliminates stimulation by the clamp. In the crystal structure of T4 RNase H, the binding sites for the clamp at the N terminus and for 32 protein at the C terminus are located close together, away from the catalytic site of the enzyme. By using mutant T4 RNase H with deletions in the binding site for either the clamp or 32 protein, we show that it is the interaction of T4 RNase H with 32 protein, rather than the clamp, that most affects the maturation of lagging strand fragments in the T4 replication system in vitro and T4 phage production in vivo. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nossal, NG (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 2A19, Bethesda, MD 20892 USA. EM ngn@helix.nih.gov NR 62 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 1 PY 2005 VL 280 IS 13 BP 12876 EP 12887 DI 10.1074/jbc.M414025200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000096 PM 15659404 ER PT J AU Bandyopadhyay, BC Swaim, WD Liu, XB Redman, RS Patterson, RL Ambudkar, IS AF Bandyopadhyay, BC Swaim, WD Liu, XB Redman, RS Patterson, RL Ambudkar, IS TI Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells - Role in apical Ca2+ influx SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR POTENTIAL CHANNELS; SIGNALING COMPLEX; TRPC3 CHANNELS; GLAND-CELLS; PROTEIN; ENTRY; TRISPHOSPHATE; TRANSDUCTION; ORGANIZATION; ASSOCIATION AB Receptor-coupled [Ca2+](i) increase is initiated in the apical region of epithelial cells and has been associated with apically localized Ca2+-signaling proteins. However, localization of Ca2+ channels that are regulated by such Ca2+-signaling events has not yet been established. This study examines the localization of TRPC channels in polarized epithelial cells and demonstrates a role for TRPC3 in apical Ca2+ uptake. Endogenously and exogenously expressed TRPC3 was localized apically in polarized Madin-Darby canine kidney cells (MDCK) and salivary gland epithelial cells. In contrast, TRPC1 was localized basolaterally, whereas TRPC6 was detected in both locations. Localization of G alpha(q/11), inositol 1,4,5-trisphosphate receptor-3, and phospholipase C beta 1 and -beta 2 was also predominantly apical. TRPC3 co-immunoprecipitated with endogenous TRPC6, phospholipase C beta s, G alpha(q/11), inositol 1,4,5-trisphosphate receptor-3, and syntaxin 3 but not with TRPC1. Furthermore, 1-oleoyl-2-acetyl-sn-glycerol (OAG)-stimulated apical Ca-45(2+) uptake was higher in TRPC3-MDCK cells compared with control (MDCK) cells. Bradykinin-stimulated apical Ca-45(2+) uptake and transepithelial Ca-45(2+) flux were also higher in TRPC3-expressing cells. Consistent with this, OAG induced [Ca2+](i) increase in the apical, but not basal, region of TRPC3-MDCK cells that was blocked by EGTA addition to the apical medium. Most importantly, (i) TRPC3 was detected in the apical region of rat submandibular gland ducts, whereas TRPC6 was present in apical as well as basolateral regions of ducts and acini; and (ii) OAG stimulated Ca2+ influx into dispersed ductal cells. These data demonstrate functional localization of TRPC3/TRPC6 channels in the apical region of polarized epithelial cells. In salivary gland ducts this could contribute to the regulation of salivary [Ca2+] and secretion. C1 NIDCR, Gene Therapy & Therapeut Branch, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Oral Pathol Res Lab, Washington, DC 20422 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. RP Ambudkar, IS (reprint author), NIDCR, Gene Therapy & Therapeut Branch, Secretory Physiol Sect, NIH, Bldg 10,Rm N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov NR 41 TC 61 Z9 67 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 APR 1 PY 2005 VL 280 IS 13 BP 12908 EP 12916 DI 10.1074/jbc.M410013200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000100 PM 15623527 ER PT J AU Wen, J Huang, SM Pack, SD Yu, XB Brandt, SJ Noguchi, CT AF Wen, J Huang, SM Pack, SD Yu, XB Brandt, SJ Noguchi, CT TI Tal1/SCL binding to pericentromeric DNA represses transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE H3 METHYLATION; LOCUS-CONTROL REGION; LOOP-HELIX PROTEINS; BETA-GLOBIN LOCUS; HEMATOPOIETIC-CELLS; GENE-EXPRESSION; NUCLEAR-MATRIX; TARGET GENE; CHROMATIN; HETEROCHROMATIN AB Tal1/SCL is a basic helix-loop-helix transcription factor critical for normal hematopoiesis. To understand the mechanisms underlying transcriptional regulation by Tal1/SCL, we combined an in vitro DNA binding strategy and an in vivo chromatin immunoprecipitation analysis to search for Tal1/SCL target regions in K562 erythroleukemia cells. A 0.4-kb genomic DNA clone containing two Tal1/SCL binding E-boxes and GATA- and SATB1-binding motifs (EEGS) was identified that localized to the pericentromeric region with high homology to satellite 2 DNA. Pericentric DNA is related to heterochromatin and gene inactivation. We found that Tal1/SCL could complex with the histone H3 lysine 9 (H3K9)-specific methyltransferase Suv39H1. Binding of Tal1/SCL to EEGS chromatin correlated with hypermethylation of H3K9 and the association of heterochromatin protein HP1 to this region. In Rep4 reporter gene assays, EEGS affected repression in a manner dependent on the expression level of Tal1/SCL that was accompanied by increased H3K9 methylation in chromatin associated with EEGS and a linked promoter. A specific histone deacetylase inhibitor, trichostatin A, relieved Tal1/SCL-mediated repression by EEGS. In addition, SATB1 bound EEGS chromatin and promoted Tal1/SCL EEGS-dependent repression. We expand the list of potential interacting partners for Tal1/SCL by demonstrating direct associations of Tal1/SCL with SATB1 and with Suv39H1. These results reveal a novel mechanism of action for Tal1/SCL and implicate heterochromatin-like silencing via a cis-acting binding motif for transcriptional repression. C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 USA. Tennessee Valley Vet Affairs Healthcare Syst, Nashville, TN 37232 USA. RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,Rm 9N307,10 Ctr,MSC 1822, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov NR 63 TC 15 Z9 15 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 APR 1 PY 2005 VL 280 IS 13 BP 12956 EP 12966 DI 10.1074/jbc.M412721200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910HP UT WOS:000227922000105 PM 15677454 ER PT J AU Hartel, FW de Coronado, S Dionne, R Fragoso, G Golbeck, J AF Hartel, FW de Coronado, S Dionne, R Fragoso, G Golbeck, J TI Modeling a description logic vocabulary for cancer research SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE biomedical vocabulary; ontology development; cancer research; OWL; description logic; T-Box model AB The National Cancer Institute has developed the NCI Thesaurus, a biomedical vocabulary for cancer research. covering terminology across a wide range of cancer research domains. A major design goal of the NCI Thesaurus is to facilitate translational research. We describe: the features of Ontylog, a description logic used to build NCI Thesaurus; our methodology for enhancing the terminology through collaboration between ontologists and domain experts, and for addressing certain real world challenges arising in modeling the Thesaurus; and finally, we describe the conversion of NCI Thesaurus from Ontylog into Web Ontology Language Lite. Ontylog has proven well suited for constructing big biomedical vocabularies. We have capitalized on the Ontylog constructs Kind and Role in the collaboration process described in this paper to facilitate communication between ontologists and domain experts. The artifacts and processes developed by NCI for collaboration may be useful in other biomedical terminology development efforts. Published by Elsevier Inc. C1 NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. Apelon Inc, Ridgefield, CT USA. Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. RP de Coronado, S (reprint author), NCI, Ctr Bioinformat, 6116 Execut Blvd,Suite 403, Bethesda, MD 20892 USA. EM decorons@mail.nih.gov RI Lavbic, Dejan/G-1405-2010 OI Lavbic, Dejan/0000-0003-2390-4160 NR 25 TC 48 Z9 47 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 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2005 VL 38 IS 2 BP 114 EP 129 DI 10.1016/j.jbi.2004.09.001 PG 16 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 915OO UT WOS:000228313800003 PM 15797001 ER PT J AU Lee, D Vogeli, B Pervushin, K AF Lee, D Vogeli, B Pervushin, K TI Detection of C ' C-alpha correlations in proteins using a new time- and sensitivity-optimal experiment SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE 13-carbon observation; chemical shift correlation; residual dipolar coupling; scalar coupling; sensitivity enhancement ID TRIPLE-RESONANCE EXPERIMENTS; ORDER-SELECTIVE TRANSFER; NMR-SPECTROSCOPY; SPIN SYSTEMS; COUPLING-CONSTANTS; BIOLOGICAL MACROMOLECULES; ASSIGNMENT; C-13; HETERONUCLEAR; TROSY AB Sensitivity- and time-optimal experiment, called COCAINE (CO-CA In- and aNtiphase spectra with sensitivity Enhancement), is proposed to correlate chemical shifts of C-13' and C-13(α) stop spins in proteins. A comparison of the sensitivity and duration of the experiment with the corresponding theoretical unitary bounds shows that the COCAINE experiment achieves maximum possible transfer efficiency in the shortest possible time, and in this sense the sequence is optimal. Compared to the standard HSQC, the COCAINE experiment delivers a 2.7-fold gain in sensitivity. This newly proposed experiment can be used for assignment of backbone resonances in large deuterated proteins effectively bridging C-13' and C-13(α) stop resonances in adjacent amino acids. Due to the spin-state selection employed, the COCAINE experiment can also be used for efficient measurements of one-bond couplings (e.g. scalar and residual dipolar couplings) in any two-spin system (e.g. the N/H in the backbone of protein). C1 ETH Honggerberg, Chem Phys Lab, HCI, CH-8093 Zurich, Switzerland. NCI, NIH, Frederick, MD 21702 USA. RP Lee, D (reprint author), ETH Honggerberg, Chem Phys Lab, HCI, CH-8093 Zurich, Switzerland. EM dhlee@ncifcrf.gov; kope@phys.chem.ethz.ch RI Lee, Donghan/B-6893-2011; OI Lee, Donghan/0000-0002-6530-8060; Lee, Donghan/0000-0002-3971-986X NR 35 TC 30 Z9 30 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 2005 VL 31 IS 4 BP 273 EP 278 DI 10.1007/s10858-005-2361-4 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 931SK UT WOS:000229505400001 PM 15928994 ER PT J AU McGrath, CF Pattabiraman, N Kellogg, GE Lemcke, T Kunick, C Sausville, EA Zaharevitz, DW Gussio, R AF McGrath, CF Pattabiraman, N Kellogg, GE Lemcke, T Kunick, C Sausville, EA Zaharevitz, DW Gussio, R TI Homology model of the CDK1/cyclin B complex SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article DE homology modeling; structure-based drug design; molecular mechanics; hydropathic analysis; docking; protein 3D QSAR; cyclin dependent kinase inhibitors; paullones ID CYCLIN-DEPENDENT KINASES; CHEMICAL INHIBITORS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; INK4 INHIBITORS; ROSCOVITINE; ACTIVATION; PROTEINS; SEARCH; DESIGN AB We describe a refined homology model of a CDK1/cyclin B complex that was previously used for the structure-based optimization of the Paullone class of inhibitors. The preliminary model was formed from the homologous regions of the deposited CDK2/cyclin A crystal structure. Further refinement of the CDK1/cyclin B complex was accomplished using molecular mechanics and hydropathic analysis with a protocol of constraints and local geometry searches. For the most part, our CKD1/cyclin B homology model is very similar to the high resolution CDK2/cyclin A crystal structure regarding secondary and tertiary features. However, minor discrepancies between the two kinase structures suggest the possibility that ligand design may be specifically tuned for either CDK1 or CDK2. Our examination of the CDK1/cyclin B model includes a comparison with the CDK2/cyclin A crystal structure in the PSTAIRE interface region, connecting portions to the ATP binding domain, as well as the ATP binding site itself. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21702 USA. Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Virginia Commonwealth Univ, Sch Pharm, Inst Struct Biol & Drug Discovery, Dept Med Chem, Richmond, VA 23298 USA. Univ Hamburg, Inst Pharm, Abt Pharmazeut Chem, D-20146 Hamburg, Germany. RP McGrath, CF (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21702 USA. EM mcgratb@ncifcrf.gov RI Kellogg, Glen/A-8008-2011 FU NCI NIH HHS [N01-CO-12400] NR 29 TC 21 Z9 21 U1 2 U2 3 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD APR PY 2005 VL 22 IS 5 BP 493 EP 502 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 904NJ UT WOS:000227504700001 PM 15702922 ER PT J AU Schwartz, AV Sellmeyer, DE Strotmeyer, ES Tylavsky, FA Feingold, KR Resnick, HE Shorr, RI Nevitt, MC Black, DM Cauley, JA Cummings, SR Harris, TB AF Schwartz, AV Sellmeyer, DE Strotmeyer, ES Tylavsky, FA Feingold, KR Resnick, HE Shorr, RI Nevitt, MC Black, DM Cauley, JA Cummings, SR Harris, TB CA Health ABC Study TI Diabetes and bone loss at the hip in older black and white adults SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MN SP Amer Soc Bone & Mineral Res DE diabetes mellitus; BMD; longitudinal studies; female; male; race ID MINERAL DENSITY; RISK-FACTORS; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; FRACTURE RISK; MELLITUS; OSTEOPOROSIS; TYPE-1; MASS; MEN AB Type 2 diabetes may be associated with elevated fracture risk, but the impact on bone loss is unknown. Analysis of 4-year change in hip BMD data from a cohort of white and black well-functioning men and women 70-79 years of age found that white women with diabetes had more rapid bone loss at the femoral neck than those with normal glucose metabolism. C1 Univ Calif San Francisco, Prevent Sci Grp, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Endocrinol, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. MedStar Res Inst, Dept Epidemiol, Hyattsville, MD USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Schwartz, AV (reprint author), Univ Calif San Francisco, Prevent Sci Grp, Dept Epidemiol & Biostat, 74 New Montgomery St,Suite 600, San Francisco, CA 94143 USA. EM aschwartz@psg.ucsf.edu RI Strotmeyer, Elsa/F-3015-2014; Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Strotmeyer, Elsa/0000-0002-4093-6036 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 51 TC 76 Z9 93 U1 1 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 APR PY 2005 VL 20 IS 4 BP 596 EP 603 DI 10.1359/JBMR.041219 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 907TT UT WOS:000227741600007 PM 15765178 ER PT J AU Sakamoto, A Chen, M Kobayashi, T Kronenberg, HM Weinstein, LS AF Sakamoto, A Chen, M Kobayashi, T Kronenberg, HM Weinstein, LS TI Chondrocyte-specific knockout of the G protein G(s)alpha leads to epiphyseal and growth plate abnormalities and ectopic chondrocyte formation and growth plate abnormalities and ectopic chondrocyte formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE animal models (rodent); PTH/PTH-related peptide; pseudohypoparathyroidism; growth plate; hedgehog ID HORMONE-RELATED PEPTIDE; XL-ALPHA-S; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; PTH/PTHRP RECEPTOR; BONE-FORMATION; IN-VIVO; DIFFERENTIATION; CARTILAGE; GENE AB G(s)alpha is a ubiquitously expressed G protein alpha-subunit that couples receptors to adenylyl cyclase. Mice with chondrocyte-specific ablation of the G,,a gene had severe epiphyseal and growth plate abnormalities and ectopic cartilage formation within the metaphyseal region of the tibia. These results show that G(s)alpha negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTH-rP receptor in growth plate chondrocytes. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov FU NIDDK NIH HHS [DK58819] NR 31 TC 58 Z9 60 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2005 VL 20 IS 4 BP 663 EP 671 DI 10.1359/JBMR.041210 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 907TT UT WOS:000227741600015 PM 15765186 ER PT J AU Syed, MA Peters, DC Rashid, H Arai, AE AF Syed, MA Peters, DC Rashid, H Arai, AE TI Pulmonary vein imaging: comparison of 3D magnetic resonance angiography with 2D cine MRI for characterizing anatomy and size SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE pulmonary vein; magnetic resonance imaging; magnetic resonance angiography; atrial fibrillation ID RADIOFREQUENCY CATHETER ABLATION; PAROXYSMAL ATRIAL-FIBRILLATION; VASCULATURE; INITIATION; EMBOLISM AB Pulmonary vein imaging is integral for planning atrial fibrillation ablation procedures. We tested the feasibility of quantifying pulmonary vein ostial diameter using two-dimensional cine cardiac magnetic resonance (2D cine CMR) and three-dimensional magnetic resonance angiography (3D MRA). Nine patients with a history of atrial fibrillation and 20 normal volunteers underwent 2D cine CMR and contrast-enhanced 3D MRA of pulmonary veins on a 1.5 T scanner. Pulmonary vein ostial diameters were measured and pulmonary vein vessel border sharpness was graded qualitatively. Both techniques provided excellent pulmonary vein imaging; however, 3D MRA was faster to perform. The average difference between the systolic and diastolic pulmonary vein diameter was 2.5 mm (23.2%, p < 0.0001) in normal volunteers and 2.2 mm ( 16.9%, p < 0.0001) in atrial fibrillation patients. The ostial diameter measurements by 3D MRA were significantly larger than on 2D cine CMR. Additionally, the pulmonary vein borders appeared sharper with 2D cine CMR compared to 3D MRA. In conclusion, the 2D images can resolve differences in diameter across the cardiac cycle, while the 3D images provide high quality anatomical depiction but blur borders due to pulsatile motion. We suggest a protocol combining 2D cine CMR and 3D MRA for comprehensive evaluation of pulmonary veins. C1 NHLBI, Cardiac Energet Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Div Cardiol, Washington, DC 20007 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, US Dept HHS, NIH, 10 Ctr dr,MSC 1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM araia@nih.gov NR 18 TC 17 Z9 17 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PD APR PY 2005 VL 7 IS 2 BP 355 EP 360 DI 10.1081/JCMR-200053458 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 920MO UT WOS:000228695000003 PM 15881514 ER PT J AU Magnus, T Rao, MS AF Magnus, T Rao, MS TI Neural stem cells in inflammatory CNS diseases: mechanisms and therapy SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Review DE matrix metalloproteinases (MMPs); angiogenesis; tumor angiogenesis; MMP inhibitors; extracellular matrix remodeling; tissue inhibitors of metalloproteinases (TIMPs); thrombospondins ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS LESIONS; OLIGODENDROCYTE PRECURSOR CELLS; TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHONDROITIN-SULFATE PROTEOGLYCAN; ADULT SPINAL-CORD; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MONOCLONAL-ANTIBODY TREATMENT; CEREBELLAR GRANULE CELLS AB Autoimmune inflammatory diseases of the central nervous system (CNS) are highly complex in their interaction of different cell populations. The main therapy focus in the last years has been the inhibition of the immune system. Recent progress has shown that endogenous as well as transplanted neural stem cells might positively influence the outcome of such diseases. In this review, we discuss the current concept of the underlying pathogenesis with a specific focus on local CNS cells and potential treatment options. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Magnus, T (reprint author), NIA, Neurosci Lab, 333 Cassell Dr, Baltimore, MD 21224 USA. EM magnust@mail.nih.gov NR 158 TC 21 Z9 28 U1 0 U2 1 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 APR-JUN PY 2005 VL 9 IS 2 BP 303 EP 319 DI 10.1111/j.1582-4934.2005.tb00357.x PG 17 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 945VH UT WOS:000230529900007 PM 15963251 ER PT J AU Nagineni, CN Kutty, V Detrick, A Hooks, JJ AF Nagineni, CN Kutty, V Detrick, A Hooks, JJ TI Expression of PDGF and their receptors ion human retinal pigment epithelial cells and fibroblasts: Regulation by TGF-beta SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; GROWTH-FACTOR; MACULAR DEGENERATION; EPIRETINAL MEMBRANES; IN-VIVO; GENE-EXPRESSION; MESSENGER-RNA; RISK-FACTORS; VITREORETINOPATHY; PATHOGENESIS AB Platelet derived growth factors (PDGF) are known to be associated with vitreo retinal disorders such as proliferative vitreo-retinopathy(PVR). We have studied the expression of PDGF and their receptors in human retinal piginentepithelial cells(HRPE) and choroid fibroblasts (HCHF), and the regulation of PDGF and its receptors by various cytokines and growth factors. RT-PCR analyses showed enhanced expression of PDGF-A and PDGF-beta mRNA in HRPE treated with TGF-beta, but not with other cytokines. A minimal increase was observed in PDGF-A rnRNA in TGF-beta treated HCHF cells. PDGF-Ralpha mRNA, which was expressed prominently in HCHF and at very low levels in HRPE, was not affected by any of the agents. PDGF-Rbeta was not detectable in either HRPE or HCHF. HRPE secreted PDGF-AA and AB constitutively, and this secretion was significantly enhanced by TGF-beta. In contrast, HCHF cultures did not secrete detectable levels of any of the three isoforms of PDGF (AA, AB, 1313). All three human recombinant PDGF isoforms enhanced HCHF cell proliferation significantly, while only a minimal increase was observed in HRPE. PDGF isoforms also induced HCHF cell elongation and promoted migration of HCHF in an in vitro Wound assay. The results presented in this study demonstrate that TGF-beta activated RPE cells produce PDGF that may act on fibroblasts and other mesenchyme derived cells which express PDGF receptors. These studies indicate that the promotion of the proliferation and migration of mesenchymal cells by RPE cell derived PDGF may facilitate the formation of fibrovascular tissues associated with PVR. Publislied 2004 Wiley-Liss, Inc. C1 NEI, NIH, Immunol & Virol Sect, Immunol Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, NIH, Immunol & Virol Sect, Immunol Lab, Bldg 10,Room 6N 228, Bethesda, MD 20892 USA. EM hooksj@nei.nih.gov NR 55 TC 33 Z9 39 U1 0 U2 2 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 APR PY 2005 VL 203 IS 1 BP 35 EP 43 DI 10.1002/jcp.20213 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 903GO UT WOS:000227414000005 PM 15368539 ER PT J AU Stramer, BM Austin, JS Roberts, AB Fini, ME AF Stramer, BM Austin, JS Roberts, AB Fini, ME TI Selective reduction of fibrotic markers in repairing corneas of mice deficient in Smad3 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BRONCHIAL EPITHELIAL-CELLS; MUSCLE ACTIN EXPRESSION; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; TARGETED DISRUPTION; IN-VITRO; FIBROBLASTS; MYOFIBROBLASTS; FIBRONECTIN AB The cytokine transforming growth factor-P (TGF-beta) is a key mediator of fibrosis in all organs. Expression of fibrotic markers in repairing cutaneous wounds is reduced in mice lacking Smad, a downstream cytoplasmic mediator of TGF-beta signaling (Ashcroft et al., 1999, Nat Cell Biol 1(5):260-266). This is correlated with a reduction in inflammation, and thus in the blood elements thought to be a significant source of TGF-beta at the wound site, the principle form being TGF-beta]. Since the major cellular source of TGF-beta in corneal wounds is the epithelium, and the principal isoform is TGF-beta2, we investigated whether Smad3 deficiency has similar antifibrotic effects on corneal repair. In contrast to the situation of cutaneous repair, expression of the fibrotic marker, fibronectin, was equivalent in corneal repair tissue of Smad3-/- mice as compared to their +/- littermates, even though expression of a second fibrotic marker not previously examined in cutaneous wounds, a-smooth muscle (sm) actin, was reduced. Also unlike in cutaneous wounds, the inflammatory response was unaffected. These differences between corneal and cutaneous repair correlated with the lack of apparent change in the levels of corneal TGF-beta2. There was a significant reduction of alpha-sm actin expression in stromal cell cultures established from Smad3-/- mice as compared to their +/- littermates, but the rate of cell proliferation stimulated by TGF-beta, as well as expression of fibronectin, was unaffected. Therefore, a deficiency in Smad3 has different effects on corneal and cutaneous repair, probably due to the difference in cellular source and principal isoform of the TGF-beta involved. J. Cell. Physiol. 203: 226-232, 2005. (C) 2004 Wiley-Liss, Inc. C1 Univ Miami, Sch Med, Bascom Palmer Eye Inst, Evelyn F & William L McKnight Vis Res Ctr, Miami, FL 33101 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Fini, ME (reprint author), Univ Miami, Sch Med, Bascom Palmer Eye Inst, Evelyn F & William L McKnight Vis Res Ctr, POB 016880, Miami, FL 33101 USA. EM efini@med.miami.edu FU NEI NIH HHS [EY13078, EY14801, EY09828] NR 40 TC 20 Z9 23 U1 0 U2 0 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 APR PY 2005 VL 203 IS 1 BP 226 EP 232 DI 10.1002/jcp.20215 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 903GO UT WOS:000227414000026 PM 15521071 ER PT J AU Eisenhofer, G Goldstein, DS Sullivan, P Csako, G Brouwers, FM Lai, EW Adams, KT Pacak, K AF Eisenhofer, G Goldstein, DS Sullivan, P Csako, G Brouwers, FM Lai, EW Adams, KT Pacak, K TI Biochemical and clinical manifestations of dopamine-producing paragangliomas: Utility of plasma methoxytyramine SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SECRETING PHEOCHROMOCYTOMA; GLOMUS-JUGULARE; CATECHOLAMINES; METANEPHRINES; DIAGNOSIS; NOREPINEPHRINE; MUTATIONS; EXCRETION; TUMOR AB Measurements of plasma-free normetanephrine and metanephrine provide a sensitive test for diagnosis of pheochromocytoma but may fail to detect tumors that produce predominantly dopamine. Such tumors are extremely rare, usually found as extraadrenal paragangliomas. This report describes measurements of plasma concentrations of free methoxytyramine, the O-methylated metabolite of dopamine, in 120 patients with catecholamine-producing tumors, including nine with extraadrenal paragangliomas secreting predominantly dopamine. In seven of these nine patients, tumors were found incidentally or secondary to the space-occupying complications of the lesions. Plasma concentrations of free methoxytyramine and dopamine were increased in all nine patients, including two with normal plasma and urinary normetanephrine and metanephrine and normal urinary outputs of dopamine. Relative increases above normal for plasma methoxytyramine (104-fold) and dopamine (56-fold) were much greater ( P < 0.001) than those for urinary dopamine (3-fold). Insensitivity of the latter for identification of dopamine-secreting tumors was due to dependence of the urinary amine on renal extraction and decarboxylation of circulating 3,4-dihydroxyphenylalanine. Measurements of plasma-free methoxytyramine, in addition to normetanephrine and metanephrine, are unlikely to improve diagnosis of pheochromocytomas in hypertensive patients with symptoms of catecholamine excess but may be useful in selected patients for identification of tumors that produce predominantly dopamine. C1 NINDS, Clin Neurocardiol Sect, Dept Lab Med, Clin Ctr,NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), NINDS, Clin Neurocardiol Sect, Dept Lab Med, Clin Ctr,NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov NR 30 TC 96 Z9 101 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2005 VL 90 IS 4 BP 2068 EP 2075 DI 10.1210/jc.2004-2025 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914BG UT WOS:000228198900024 PM 15644397 ER PT J AU Freeman, LEB Dennis, LK Lynch, CE Lowe, JB Clarke, WR AF Freeman, LEB Dennis, LK Lynch, CE Lowe, JB Clarke, WR TI Test-retest of self-reported exposure to artificial tanning devices, self-tanning creams, and sun sensitivity showed consistency SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE reliability; melanoma; case-control study; sunburn; sunlamp ID CUTANEOUS MALIGNANT-MELANOMA; REPRODUCIBILITY; HISTORY; RISK AB Objective: Exposure to ultraviolet radiation has consistently been linked to an increased risk of melanoma. Epidemiologic studies are susceptible to measurement error, which can distort the magnitude of observed effects. Although the reliability of self-report of many sun exposure factors has been previously described in several studies, self-report of use of artificial tanning devices and self-tanning creams has been less well characterized. Study Design and Methods: A mailed survey was re-administered 2-4 weeks after completion of the initial survey to 76 randomly selected participants in a case-control study of melanoma. Cases and controls were individuals diagnosed in 1999 and 2000 who were ascertained from the Iowa Cancer Registry in 2002. We assessed the consistency of self-reported use of sunlamps and self-tanning creams, sun sensitivity, and history of sunburns. Results: There was substantial reliability in reporting the use of sunlamps or self-tanning creams (cases: Kappa (K) = 1.0 for both exposures; controls: K = 0.71 and 0.87, respectively). K estimates of 0.62-0.78 were found for overall reliability of several sun sensitivity factors. Conclusion: Overall, the survey instrument demonstrated substantial reproducibility for factors related to the use of sunlamps or tanning beds, self-tanning creams, and sun sensitivity factors. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. Univ Iowa, Coll Publ Hlth, Dept Community & Behav Hlth, Iowa City, IA 52242 USA. Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA 52242 USA. RP Freeman, LEB (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,Suite 511,MSC 7240, Bethesda, MD 20892 USA. EM freemala@mail.nih.gov OI Lowe, John/0000-0003-1222-2295 NR 10 TC 21 Z9 21 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 APR PY 2005 VL 58 IS 4 BP 430 EP 432 DI 10.1016/j.jclinepi.2004.09.004 PG 3 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 912CR UT WOS:000228055200015 ER PT J AU Chrousos, GP Kino, T AF Chrousos, GP Kino, T TI Ikaros transcription factors: flying between stress and inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID EXPRESSION; GENE AB The hypothalamic-pituitary-adrenal axis (a major component of the stress system) and the immune system contribute to the maintenance of homeostasis at rest and during stress. Because of their essential roles for the survival of self and species, the activities of these systems have evolutionarily developed in parallel and are intertwined at many levels. In this issue of the JCI, Ezzat et al. demonstrate that Ikaros, a differentiation factor of leukocyte lineage, also influences the maturation of the fetal pituitary corticotroph and, hence, the secretion of adrenocorticotropic hormone before and after birth (see the related article beginning on page 1021). These results indicate that Ikaros is an ontogenetic and phylogenetic integrator of the stress and immune systems and that abnormalities in its function may produce endocrine and/or immune pathologies. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Dept Pediat 1, Athens, Greece. RP Kino, T (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,Clin Res Ctr,Room 1-3140,10 Ctr Dr,MSC110, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov NR 15 TC 11 Z9 12 U1 0 U2 1 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 APR PY 2005 VL 115 IS 4 BP 844 EP 848 DI 10.1172/JCI200524886 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913IU UT WOS:000228145700015 PM 15841175 ER PT J AU Hakim, FT Memon, SA Cepeda, R Jones, EC Chow, CK Kasten-Sportes, C Odom, J Vance, BA Christensen, BL Mackall, CL Gress, RE AF Hakim, FT Memon, SA Cepeda, R Jones, EC Chow, CK Kasten-Sportes, C Odom, J Vance, BA Christensen, BL Mackall, CL Gress, RE TI Age-dependent incidence, time course, and consequences of thymic renewal in adults SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; T-CELLS; IMMUNE RECONSTITUTION; DRIVEN PROLIFERATION; INFECTED PATIENTS; CENTRAL MEMORY; IN-VIVO; REPERTOIRE AB Homeostatic regulation of T cells involves an ongoing balance of new T cell generation, peripheral expansion, and turnover. The recovery of T cells when this balance is disrupted provides insight into the mechanisms that govern homeostasis. In a long-term, single cohort study, we assessed the role of thymic function after autologous transplant in adults, correlating serial computed tomography imaging of thymic size with concurrent measurements of peripheral CD4(+)T cell populations. We established the age-dependent incidence, time course, and duration of thymic enlargement in adults and demonstrated that these changes were correlated with peripheral recovery of naive CD45RA(+)CD62L(+) and signal-joint TCR rearrangement excision circle-bearing CD4(+) populations with broad TCR diversity. Furthermore, we demonstrated that renewed thymopoiesis was critical for the restoration of peripheral CD4(+)T cell populations. This recovery encompassed the recovery of normal CD4+ T cell numbers, a low ratio of effector to central memory cells, and a broad repertoire of TCR V beta diversity among these memory cells. These data define the timeline and consequences of renewal of adult thymopoietic activity at levels able to quantitatively restore peripheral T cell populations. They further suggest that structural thymic regrowth serves as a basis for the regeneration of peripheral T cell populations. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hakim, FT (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM fhakim@helix.nih.gov RI Memon, Sarfraz/E-1198-2013 NR 60 TC 200 Z9 204 U1 0 U2 5 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 APR PY 2005 VL 115 IS 4 BP 930 EP 939 DI 10.1172/JCI22492 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 913IU UT WOS:000228145700024 PM 15776111 ER PT J AU Kleinerman, RA Tucker, MA Tarone, RE Abramson, DH Seddon, JM Stovall, M Li, FP Fraumeni, JF AF Kleinerman, RA Tucker, MA Tarone, RE Abramson, DH Seddon, JM Stovall, M Li, FP Fraumeni, JF TI Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: An extended follow-up SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEREDITARY RETINOBLASTOMA; BILATERAL RETINOBLASTOMA; NONOCULAR TUMORS; CHILDHOOD-CANCER; RADIATION; NEOPLASMS; SARCOMAS AB Purpose Many children diagnosed with retinoblastoma (Rb) survive into adulthood and are prone to subsequent cancers, particularly hereditary patients, who have germline Rb-1 mutations. We have extended the follow-up of a large cohort of Rb patients for 7 more years to provide new information on the risk of additional cancers after radiotherapy in long-term survivors. Patients and Methods We analyzed the risk of new cancers through 2000 in 1,601 Rb survivors, diagnosed from 1914 to 1984, at two US medical centers. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cancers after hereditary and nonhereditary Rb to the expected number from the Connecticut Tumor Registry. The cumulative incidence of a new cancer after hereditary and nonhereditary Rb and radiotherapy was calculated with adjustment for competing risk of death. Results Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% Cl, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% Cl, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% Cl, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% Cl, 31% to 41 %) for hereditary and 5.7% (95% Cl, 2.4% to 11 %) for nonhereditary patients. Conclusion Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Int Epidemiol Inst, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Dana Farber Canc Inst, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS 7044,6120 Execut Ser, Rockville, MD 20852 USA. EM Kleinerr@mail.nih.gov RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N02-CP-81121] NR 29 TC 201 Z9 205 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 APR 1 PY 2005 VL 23 IS 10 BP 2272 EP 2279 DI 10.1200/JCO.2005.05.054 PG 8 WC Oncology SC Oncology GA 914XA UT WOS:000228260200021 PM 15800318 ER PT J AU Dudley, ME Wunderlich, JR Yang, JC Sherry, RM Topalian, SL Restifo, NP Royal, RE Kammula, U White, DE Mavroukakis, SA Rogers, LJ Gracia, GJ Jones, SA Mangiameli, DP Pelletier, MM Gea-Banacloche, J Robinson, MR Berman, DM Filie, AC Abati, A Rosenberg, SA AF Dudley, ME Wunderlich, JR Yang, JC Sherry, RM Topalian, SL Restifo, NP Royal, RE Kammula, U White, DE Mavroukakis, SA Rogers, LJ Gracia, GJ Jones, SA Mangiameli, DP Pelletier, MM Gea-Banacloche, J Robinson, MR Berman, DM Filie, AC Abati, A Rosenberg, SA TI Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; T-CELLS; IN-VIVO; ANTIGEN; REGRESSION; INTERLEUKIN-2; CANCER; IMMUNOTHERAPY; AUTOIMMUNITY AB Purpose We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL) -2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m(2)). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51 %) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 +/- 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol & Transplantat Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC 3-3940,10 Ctr Dr MSC 1201, Bethesda, MD 20892 USA. EM sar@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 33 TC 958 Z9 990 U1 3 U2 35 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 APR 1 PY 2005 VL 23 IS 10 BP 2346 EP 2357 DI 10.1200/JCO.2005.00.240 PG 12 WC Oncology SC Oncology GA 914XA UT WOS:000228260200029 PM 15800326 ER PT J AU Fuse, E Kuwabara, T Sparreboom, A Sausville, EA Figg, WD AF Fuse, E Kuwabara, T Sparreboom, A Sausville, EA Figg, WD TI Review of UCN-01 development: A lesson in the importance of clinical pharmacology SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review DE UCN-01; drug development; anticancer drug; pharmacology ID PROTEIN-KINASE-C; CANCER-CELL-LINES; ALPHA(1)-ACID GLYCOPROTEIN; ANTICANCER DRUG; 7-HYDROXYSTAUROSPORINE UCN-01; ALTERED PHARMACOKINETICS; SELECTIVE INHIBITOR; CHECKPOINT FUNCTION; A431 CELLS; PHASE-I AB UCN-01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmocologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimination half-life was unusually long (> 200 hours). The unbound fraction in human plasma was also much smaller than that in dogs, rats and mice, as was the binding of UCN-01 to human alpha-1 acid glycoprotein much stronger than that to human serum albumin orhumany gamma-glolobulin. The association constants for alpha-1 acid glycoprotein and human plasma were approximately 8 x 10(8)(mol/L)(-1), indicating extremely high affinity. In this review article, the authors discuss the pharmacologic features of UGN-01 across species and provide a perspective on how this information could be applied prospectively to the future development of this agent. C1 NCI, Bethesda, MD 20892 USA. Kyowa Hakko Kogyo Co Ltd, Pharmacokinet Res Labs, Pharmaceut Res Inst, Shizuoka, Japan. RP Figg, WD (reprint author), NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 28 TC 76 Z9 78 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2005 VL 45 IS 4 BP 394 EP 403 DI 10.1177/0091270005274549 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 907SL UT WOS:000227738200005 PM 15778420 ER PT J AU Hasler, G Buysse, DJ Gamma, A Ajdacic, V Eich, D Rossler, W Angst, J AF Hasler, G Buysse, DJ Gamma, A Ajdacic, V Eich, D Rossler, W Angst, J TI Excessive daytime sleepiness in young adults: A 20-year prospective community study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHOLOGICAL STATUS; GENDER-DIFFERENCES; NOCTURNAL SLEEP; INSOMNIA; DISORDERS; POPULATION; PREVALENCE; WORKERS; HABITS; DISTURBANCES AB Objective: Excessive daytime sleepiness (EDS) is a symptom with high clinical and public health importance because of its association with increased risk for accidents, decreased productivity, and impaired quality of life. Little information is available regarding the longitudinal course or clinical correlates of EDS. The aim of this study was to explore associations between self-reported EDS, sleep disorder symptoms, major depression, and anxiety in a longitudinal community study of young adults. Method: A prospective single-age community study of young adults (Zurich Cohort Study) was conducted from 1978 through 1999. Information was derived from 6 interviews administered when participants (N = 591) were ages 20, 22, 27, 29, 34, and 40 years. Trained health professionals administered a semistructured interview for health habits and psychiatric and medical conditions. The presence of either or both of 2 symptoms-accidentally falling asleep or excessive need for sleep during the day was used to establish the presence of EDS. Results: EDS was a common complaint among the study participants, with increasing prevalence with age. Cross-sectionally, EDS was associated with insomnia symptoms, nocturnal hypersonmia, anxiety disorders, somatization, and reduced quality of life. Longitudinally, impaired sleep quality, waking up too early, and anxiety were associated with later EDS. Conversely, EDS was not significantly associated with later anxiety or depressive disorders. Conclusions: Insomnia symptoms and anxiety are associated with the subsequent occurrence of EDS. Although these findings do not demonstrate causality, insomnia and anxiety disorders are prevalent and treatable conditions, and our results may have important clinical implications for the prevention and treatment of EDS. Whether the results of this study are limited to populations with elevated levels of psychopathology remains to be tested. C1 NIMH, NIH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. Univ Zurich, Hosp Psychiat, Zurich, Switzerland. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Hasler, G (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, Intramural Res Program, 15K N Dr,Room 200,MSC 2670, Bethesda, MD 20892 USA. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Ajdacic-Gross, Vladeta/0000-0002-7032-9237 NR 55 TC 42 Z9 43 U1 2 U2 2 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 APR PY 2005 VL 66 IS 4 BP 521 EP 529 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 917TF UT WOS:000228491400016 PM 15816796 ER PT J AU Labayru, C Eiros, JM Hernandez, B de Lejarazu, RO Torres, AR AF Labayru, C Eiros, JM Hernandez, B de Lejarazu, RO Torres, AR TI RNA extraction prior to HIV-1 resistance detection using Line Probe Assay (LiPA): comparison of three methods SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV; resistance; LiPA; RNA extraction ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 DRUG-RESISTANCE; SOCIETY-USA PANEL; REVERSE-TRANSCRIPTASE; ANTIRETROVIRAL THERAPY; GENOTYPIC RESISTANCE; PLASMA SAMPLES; VIRAL LOAD; MUTATIONS; RECOMMENDATIONS AB Background: Genotyping testing has been accepted as a guidance in the therapeutic management of Human Immunodeficiency virus 1 (HIV-1). However, optimization of the available routine techniques for such purpose has not been fulfilled. Objective: To evaluate the use of three RNA extraction methods in order to be applied in the genotypic HIV-1 resistance testing by LiPA. Study design: Comparative prospective study of three HIV-1 RNA extraction methods. Forty-eight plasma samples were tested for the determination of viral load (VL) by means of Cobas Amplicor HIV-1 Monitor (TM) (Roche Diagnostics. Branchburg, NJ, USA), preserving the obtained RNA extracts. RNA was also extracted using two other techniques: "SV Total RNA Isolation System" (Promega Corporation. Madison, WI, USA) and "QIAamp Viral RNA" (QIAGEN Inc., Valencia, CA, USA). The three RNA extracts were processed in parallel for the detection of HIV resistance by LiPA, and bands were recorded comparatively. Results: Results obtained by Roche extraction method were superior, followed by those of Qiagen and Promega, in the several studied parameters. First, proportion of amplified samples (75.0% by Promega versus 95.8 by Qiagen and 97.9% by Roche for LiPA RT and 97.7% by Promega versus 100.0% by Roche and Qiagen for LiPA P); second, percentage of combined mutations patterns, and third, differences in band intensity. Thus, for LiPA RT 51.4% and 54.3% of the samples showed greater intensity after Roche and Qiagen extractions, respectively. These percentages dropped to 12.8 and 19.1 for LiPA P. Conclusions: The outcome obtained by LiPA after RNA extraction by Roche methodology was remarkably superior to those of Promega. and Qiagen. LiPA technique needs further optimization, especially the sample amplification phase of LiPA RT. (c) 2004 Elsevier B.V. All rights reserved. C1 Hosp Gen Yague, Microbiol Serv, Burgos 09005, Spain. Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid 28220, Spain. Univ Hosp Valladolid Spain, Microbiol Serv, Valladolid 74005, Spain. NCI, Ctr Clin, Bethesda, MD 20892 USA. RP Eiros, JM (reprint author), Fac Med, 6th Floor,Avda Ramon & Cajal S-N, Valladolid 47005, Spain. EM eiros@med.uva.es NR 44 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD APR PY 2005 VL 32 IS 4 BP 265 EP 271 DI 10.1016/j.jcv.2004.08.007 PG 7 WC Virology SC Virology GA 916XZ UT WOS:000228421400001 PM 15780803 ER PT J AU Kearns, DN Weiss, SJ Schindler, CW Panlilio, LV AF Kearns, DN Weiss, SJ Schindler, CW Panlilio, LV TI Conditioned inhibition of cocaine seeking in rats SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIOR PROCESSES LA English DT Article ID COMPOUNDING DISCRIMINATIVE STIMULI; DRUG-SEEKING; ADDICTION; BEHAVIOR; CONSEQUENCES; ASSOCIATIONS; EXTINCTION; EXCITATION; RESPONSES AB Despite its potential relevance to the treatment of drug abuse, conditioned inhibition of drug seeking has not been systematically investigated before. In this study, rats could self-administer cocaine by lever pressing whenever a click or tone was present. Responding was not reinforced when a light was present. The light was presented simultaneously with the click (i.e., in an excitatory context) in 1 group, but the light was always presented alone in another group. When it was later presented in compound with the tone, the light was a highly effective conditioned inhibitor, suppressing cocaine seeking by 92% in the former group and by 74% in the latter. These results suggest ways to improve cue-oriented behavioral treatments for drug abuse. C1 American Univ, Dept Psychol, Washington, DC 20016 USA. NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. RP Kearns, DN (reprint author), American Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM dk0085a@american.edu FU NIDA NIH HHS [DA-08651] NR 35 TC 18 Z9 19 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0097-7403 J9 J EXP PSYCHOL ANIM B JI J. Exp. Psychol.-Anim. Behav. Process. PD APR PY 2005 VL 31 IS 2 BP 247 EP 253 DI 10.1037/0097-7403.31.2.247 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA 920FN UT WOS:000228674900011 PM 15839780 ER PT J AU Li, LN Yang, L Kotin, RM AF Li, LN Yang, L Kotin, RM TI The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression SO JOURNAL OF GENE MEDICINE LA English DT Article DE DNA minor groove binding agents; recombinant adeno-associated virus; bisbenzimidazole dye; gene expression; kinetics; gene therapy ID 33342 INDUCES APOPTOSIS; BC3H-1 MYOCYTES; 33342-INDUCED APOPTOSIS; TOPOISOMERASE-I; GENE-EXPRESSION; CELL-CULTURES; HL-60 CELLS; VECTORS; TRANSDUCTION; PROTEIN AB Background Recombinant adeno-associated viruses (rAAV) are commonly used in pre-clinical and clinical gene transfer studies. However, the relatively slow kinetics of rAAV transgene expression complicates in vitro and in vivo experiments. Methods 293 and COS-1 cells were transduced with rAAV2-EGFP, rAAV1-EGFP, or rAAV5-EGFP. The rAAV-EGFP expression was analyzed in the presence of Hoechst 33 258 or 33 342 as a function of time and concentration by flow cytometry and fluorescent microscope. Effects of Hoechst on cell cycle populations were determined by flow cytometry. Enhanced green fluorescent protein (EGFP) expression plasmids with or without AAV inverted terminal repeats (ITR) were constructed and gene expression by transient transfection was compared in the presence of Hoechst. Results We found that Hoechst 33 258 and 33 342 increase both the level and the population of EGFP gene expressing cells, transduced by several different serotypes of rAAV-EGFP. The augmentation of rAAV-EGFP expression occurs in different cell types in a concentration-dependent manner. In addition, the Hoechst 33 258 or 33 342 mediated enhancement of rAAV gene expression correlated with an increase of cells in S phase and G2/M phases of the cell cycle. Finally, gene expression from transfected ITR-containing plasmid DNA was also enhanced by Hoechst dyes. Conclusions Our results revealed that two different, although related, DNA-binding drugs, Hoechst 33 258 and 33 342, accelerate the kinetics of rAAV transgene expression. These findings may provide the basis for more sensitive assessment of rAAV biological activity and also extend the applications of rAAV for in vivo gene transfer. Published in 2004 John Wiley C Sons, Ltd. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10,Rm 7D05,10 Ctr Dr, Bethesda, MD 20892 USA. EM kotinr@nhlbi.nih.gov RI kotin, robert/B-8954-2008 NR 25 TC 4 Z9 4 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD APR PY 2005 VL 7 IS 4 BP 420 EP 431 DI 10.1002/jgm.681 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 917UC UT WOS:000228493700004 PM 15538728 ER PT J AU Kok, MR Voutetakis, A Yamano, S Wang, JH Cotrim, A Katano, H Bossis, I Chiorini, JA Tran, SD Tak, PP Baum, BJ AF Kok, MR Voutetakis, A Yamano, S Wang, JH Cotrim, A Katano, H Bossis, I Chiorini, JA Tran, SD Tak, PP Baum, BJ TI Immune responses following salivary gland administration of recombinant adeno-associated virus serotype 2 vectors SO JOURNAL OF GENE MEDICINE LA English DT Article DE rAAV2; immune response; gene transfer; salivary glands; readministration ID MEDIATED GENE-TRANSFER; IMMUNOCOMPETENT MICE; SJOGRENS-SYNDROME; MAMMALIAN BRAIN; VIRAL VECTORS; MOUSE LUNG; ADENOVIRUS; TRANSDUCTION; EXPRESSION; INDUCTION AB Background Gene transfer to salivary glands (SGs) can be accomplished in a minimally invasive manner, resulting in stable, long-term secretion of the transgene product. Therefore, SGs provide a novel target site for several potentially useful clinical gene therapeutics applications. Previous studies have indicated that intravenous, intramuscular and intranasal administration of recombinant adeno-associated virus serotype 2 (rAAV2) vectors induce host immune responses. There are no reported studies on immune responsiveness of rAAV2 vector administration to SGs. Material and methods Vectors were administered by retrograde infusion to the SGs of Balb/c mice in various combinations. Thereafter, transgene expression was determined, and evaluations of host innate and adaptive immune responsiveness performed over a 56-day period. Results Histological examination of SGs from vector-treated mice showed no significant changes in appearance from controls, including the frequency of activated macrophage detection. There were also no differences in salivary flow rates among experimental groups. In vitro stimulation of splenocytes from mice administered rAAV2 showed elevated interferon-gamma levels in culture media. Significant titers of neutralizing antibodies to rAAV2 were detected in serum of mice following rAAV2 vector administration. While SGs could be transduced with low doses of vector it was not possible to repeat the administration and detect transduction with the same serotype at low doses. However, repeat administration was possible with an alternative serotype (rAAV4). Conclusions Following a single administration of rAAV2 vectors to SGs there is no significant innate immune response. However, rAAV2 vector administration to SGs results in both cellular and humoral immune responses. The latter may interfere with the efficacy of repeated rAAV2 vector administration. Copyright (c) 2004 John Wiley C Sons, Ltd. C1 Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. RP Kok, MR (reprint author), Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, Meibergdreef 9,Room F4-218, NL-1105 AZ Amsterdam, Netherlands. EM m.r.kok@amc.uva.nl OI Yamano, Seiichi/0000-0003-2056-4359 NR 32 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD APR PY 2005 VL 7 IS 4 BP 432 EP 441 DI 10.1021/jgm.678 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 917UC UT WOS:000228493700005 PM 15515118 ER PT J AU Mccarthy, EP Pencina, MJ Bourland, AC Kelly-Hayes, M Bums, RB Murabito, JM AF Mccarthy, EP Pencina, MJ Bourland, AC Kelly-Hayes, M Bums, RB Murabito, JM TI Cause and place of death: The Framingham Heart Study experience. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 54 EP 54 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000103 ER PT J AU Mccarthy, EP Pencina, MJ Oberacker, EJ Kelly-Hayes, M Burns, RB Murabito, JM AF Mccarthy, EP Pencina, MJ Oberacker, EJ Kelly-Hayes, M Burns, RB Murabito, JM TI Healthcare preferences among community-dwelling elders: The Framingham Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 56 EP 56 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000111 ER PT J AU Sudore, R Schillinger, D Satterfield, S Harris, TB Mehta, K Simonsick, E Newman, A Rosano, C Rooks, R Rubin, S Ayonayon, H Yaffe, K AF Sudore, R Schillinger, D Satterfield, S Harris, TB Mehta, K Simonsick, E Newman, A Rosano, C Rooks, R Rubin, S Ayonayon, H Yaffe, K TI Limited literacy is associated with mortality in the elderly: The health, aging, and body composition study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN USA. NIH, Chevy Chase, MD USA. NIA, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Kent State Univ, Kent, OH 44242 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 57 EP 57 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000115 ER PT J AU Vidula, H Mcdermott, MM Liu, K Zheng, J Ferrucci, L Guralnik, JM Greenland, P Green, D Criqui, MH Schneider, J Tian, L AF Vidula, H Mcdermott, MM Liu, K Zheng, J Ferrucci, L Guralnik, JM Greenland, P Green, D Criqui, MH Schneider, J Tian, L TI Inflammatory blood markers predict mortality in patients with peripheral arterial disease. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Northwestern Univ, Chicago, IL 60611 USA. NIA, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 57 EP 57 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000114 ER PT J AU Golin, CE Arora, N Bowling, M Strigo, T Rimer, B AF Golin, CE Arora, N Bowling, M Strigo, T Rimer, B TI When do I tell my doctor what I saw on the Internet? The interaction between doctor communication style and cancer patients' self-efficacy to communicate SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ N Carolina, Chapel Hill, NC USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 74 EP 74 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000173 ER PT J AU Ginsburg, M Goold, SD Danis, M AF Ginsburg, M Goold, SD Danis, M TI Adults with disabilities prioritize their medical benefit options SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Michigan, Ann Arbor, MI 48109 USA. Sacramento Healthcare Decis, Rancho Cordova, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 107 EP 108 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831000284 ER PT J AU Fu, SS Willenbring, ML Nelson, DB Nugent, S Joseph, AM AF Fu, SS Willenbring, ML Nelson, DB Nugent, S Joseph, AM TI Ethnic differences in the timing of smoking cessation for patients in alcohol dependence treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Minnesota, Minneapolis, MN USA. NIH, Rockville, MD USA. VA Med Ctr, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 176 EP 176 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001133 ER PT J AU Chwastiak, LA Goulet, J Bryant, KJ Conigliaro, J Crystal, S Day, NL Fiellin, DA O'Connor, P Rimland, D Rodriguez-Barradas, M Justice, AC AF Chwastiak, LA Goulet, J Bryant, KJ Conigliaro, J Crystal, S Day, NL Fiellin, DA O'Connor, P Rimland, D Rodriguez-Barradas, M Justice, AC TI Prescribing patterns of opioid pain medications and benzodiazepines among HIV plus and HIV-patients in the national VA system. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Yale Univ, New Haven, CT USA. NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Emory Univ, Decatur, GA 30033 USA. Baylor Coll Med, Houston, TX 77030 USA. RI Day, Nancy/H-3171-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 179 EP 179 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001143 ER PT J AU Rodond, N Vittinghoff, E Cornuz, J Butler, J Ding, J Satterfield, S Newman, A Harris, TB Hulley, SB Bauer, DC AF Rodond, N Vittinghoff, E Cornuz, J Butler, J Ding, J Satterfield, S Newman, A Harris, TB Hulley, SB Bauer, DC TI Aspirin use for the primary prevention of coronary heart disease in a biracial cohort of older adults. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Lausanne Hosp, Lausanne, Switzerland. Vanderbilt Univ, Nashville, TN USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIH, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 SU 1 BP 197 EP 197 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922IQ UT WOS:000228831001205 ER PT J AU Silberberg, SD Chang, TH Swartz, KJ AF Silberberg, SD Chang, TH Swartz, KJ TI Secondary structure and gating rearrangements of transmembrane segments in rat P2X(4) receptor channels SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE purinergic receptors; point mutation; scanning mutagenesis; oocytes; ligand-gated channel ID SHAKER K+ CHANNEL; GATED ION CHANNELS; TRYPTOPHAN SCANNING MUTAGENESIS; VOLTAGE-SENSING DOMAINS; POTASSIUM CHANNEL; ACETYLCHOLINE-RECEPTOR; ELECTROSTATIC INTERACTIONS; MEMBRANE-PROTEINS; CRYSTAL-STRUCTURE; HELICAL STRUCTURE AB P2X receptors are cation selective channels that are activated by extracellular nucleotides. These channels are likely formed by three identical or related subunits, each having two transmembrane segments ( TM1 and TM2). To identify regions that undergo rearrangement during gating and to probe their secondary structure, we performed tryptophan scanning mutagenesis on the two putative TMs of the rat P2X 4 receptor channel. Mutant channels were expressed in Xenopus oocytes, concentration-response relationships constructed for ATP, and the EC50 estimated by fitting the Hill equation to the data. Of the 22 mutations in TM1 and 24 in TM2, all but one in TM1 and seven in TM2 result in functional channels. Interestingly, the majority of the functional mutants display an increased sensitivity to ATP, and in general these perturbations are more pronounced for TM2 when compared with TM1. For TM1 and for the outer half of TM2, the perturbations are consistent with these regions adopting alpha-helical secondary structures. In addition, the greatest perturbations in the gating equilibrium occur for mutations near the outer ends of both TM1 and TM2. Surface biotinylation experiments reveal that all the nonfunctional mutants traffic to the surface membrane at levels comparable to the WT channel, suggesting that these mutations likely disrupt ion conduction or gating. Taken together, these results suggest that the outer parts of TM1 and TM2 are helical and that they move during activation. The observation that the majority of nonconducting mutations are clustered toward the inner end of TM2 suggests a critical functional role for this region. C1 Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Silberberg, SD (reprint author), Ben Gurion Univ Negev, Dept Life Sci, POB 653, IL-84105 Beer Sheva, Israel. EM silberbs@ninds.nih.gov FU Intramural NIH HHS [ZIA NS003018-03] NR 67 TC 55 Z9 56 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD APR PY 2005 VL 125 IS 4 BP 347 EP 359 DI 10.1085/jgp.200409221 PG 13 WC Physiology SC Physiology GA 913WX UT WOS:000228187400001 PM 15795310 ER PT J AU Barth, H Ulsenheimer, A Pape, GR Diepolder, HM Hoffmann, M Neumann-Haefelin, C Thimme, R Henneke, P Klein, R Paranhos-Baccala, G Depla, E Liang, TJ Blum, HE Baumert, TF AF Barth, H Ulsenheimer, A Pape, GR Diepolder, HM Hoffmann, M Neumann-Haefelin, C Thimme, R Henneke, P Klein, R Paranhos-Baccala, G Depla, E Liang, TJ Blum, HE Baumert, TF TI Uptake and cross-presentation of hepatitis C virus-like particles by human dendritic cells SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 Univ Freiburg, Dept Med 2, Freiburg, Germany. Univ Munich, Klinikum Grosshadern, Dept Med 2, D-8000 Munich, Germany. Univ Freiburg, Childrens Hosp, Freiburg, Germany. Univ Tubingen, Dept Med 2, Tubingen, Germany. CNRS, CERVI, IFR127, UMR2714, Lyon, France. Innogent NV, Ghent, Belgium. NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RI Neumann-Haefelin, Christoph/E-5550-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 BP 22 EP 22 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000050 ER PT J AU Martin, J Piguet, AC Schmidt, K Lee, JS Thorgeirsson, SS Dufour, JF AF Martin, J Piguet, AC Schmidt, K Lee, JS Thorgeirsson, SS Dufour, JF TI Hint2 is a pro-apoptotic tumor suppressor gene downregulated in a subclass of human hepatocellular carcinoma SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 Univ Bern, Inst Clin Pharmacol, Bern, Switzerland. Natl Canc Inst, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 MA 351 BP 130 EP 130 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000352 ER PT J AU Baumert, TF Yang, C Schurmann, R Kock, J Ziegler, C Grullich, C Nassal, M Liang, TJ Blum, HE von Weizsacker, F AF Baumert, TF Yang, C Schurmann, R Kock, J Ziegler, C Grullich, C Nassal, M Liang, TJ Blum, HE von Weizsacker, F TI Hepatitis B virus mutations associated with fulminant hepatitis induce apoptosis in primary tupaia hepatocytes SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 Univ Freiburg, Dept Med 2, Freiburg, Germany. Univ Freiburg, Dept Med 1, Freiburg, Germany. NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 MA 389 BP 143 EP 143 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000390 ER PT J AU Feldmann, G Nattermann, J Banasch, B Nischalke, HD Ahlenstiel, G Kuntzen, T Schulz, M Woitas, R Teschendorf, C Schmiegel, W Sauerbruch, T Spengler, U AF Feldmann, G Nattermann, J Banasch, B Nischalke, HD Ahlenstiel, G Kuntzen, T Schulz, M Woitas, R Teschendorf, C Schmiegel, W Sauerbruch, T Spengler, U TI Induction of interleukin-6 by HCV core protein in patients with HCV-associated cryoglobulinemia and B-cell non-Hodgkin's lymphoma SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 Univ Bonn, Dept Internal Med 1, Bonn, Germany. Natl Inst Hlth, Liver Dis Sect, Bethesda, MD USA. Ruhr Univ Bochum, Dept Internal Med, Bochum, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 MA 429 BP 157 EP 157 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000430 ER PT J AU Lempicki, R Yang, J McLaughlin, M Koratich, C Wu, L Rehm, C Masur, H Polis, MA Kottilil, S AF Lempicki, R Yang, J McLaughlin, M Koratich, C Wu, L Rehm, C Masur, H Polis, MA Kottilil, S TI Gene expression profiles in HCV/HIV coinfection: Class prediction analyses prior to treatment predicts outcome of HCV therapy among HIV co-infected individuals SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 13-17, 2005 CL Paris, FRANCE C1 NCI, SAIC, NIH, DHHS, Frederick, MD 21701 USA. DHHS, CCMD, CC, NIH, Frederick, MD 21701 USA. NIAID, LIR, NIH, DHHS, Frederick, MD 21701 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2005 VL 42 SU 2 MA 571 BP 208 EP 208 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925AN UT WOS:000229024000571 ER PT J AU Fedorova, OV Kolodkin, NI Agalakova, NI Namikas, AR Bzhelyansky, A St-Louis, J Lakatta, EG Bagrov, AY AF Fedorova, OV Kolodkin, NI Agalakova, NI Namikas, AR Bzhelyansky, A St-Louis, J Lakatta, EG Bagrov, AY TI Antibody to marinobufagenin lowers blood pressure in pregnant rats on a high NaCl intake SO JOURNAL OF HYPERTENSION LA English DT Article DE bufanolides; dietary sodium; marinobufagenin; Na(+)-K(+)-exchanging ATPase; pre-eclampsia; pregnancy; rats; transmembrane electrolyte transport ID DIGITALIS-LIKE FACTORS; HIGH-SALT DIET; SODIUM-PUMP; ENDOGENOUS DIGITALIS; VOLUME EXPANSION; NA/K-ATPASE; OUABAIN; HYPERTENSION; LIGAND; BUFODIENOLIDE AB Objective The pathogenesis of pre-eclampsia (PE), a major cause of maternal and fetal mortality, is not fully understood. Digitalis-like sodium pump ligands (SPLs) are believed to be implicated in PE, as illustrated by clinical observations that DIGIBIND, a digoxin antibody that binds SPLs, lowers blood pressure (BP) in PE. We recently reported that plasma levels of marinobufagenin (MBG), a vasoconstrictor SPL, are increased four-fold in patients with PE. In the present study, we tested whether a polyclonal antibody to MBG can lower BP in rats with pregnancy-associated hypertension. Methods Systolic BP (SBP), 24-h renal excretion of MBG and endogenous ouabain (EO), and sodium pump activity in the thoracic aortae were measured in virgin and pregnant Sprague-Dawley rats without and with NaCl supplementation (drinking 1.8% NaCl solution). Results NaCl supplementation of virgin rats stimulated renal excretion of MBG by 60%, but not that of EO, and did not change the BP. Compared with virgin rats, the last week of pregnancy in non-NaCl-loaded rats was associated with a decrease in SBP (106 +/- 2 versus 117 +/- 2 mmHg); a moderate increase in renal excretion of MBG (97.6 +/- 4.9 versus 57.4 +/- 7.0 pmoles/24 h) and EO (36.2 +/- 4.3 versus 24.1 +/- 3.2 pmoles/24 h). NaCl-loaded pregnant rats exhibited elevation in SBP (139 +/- 3 mmHg; P < 0.01 versus non-NaCl-loaded pregnant rats), in renal excretion of MBG (160.0 +/- 17.5 pmoles/24 h; P < 0.01 versus non-NaCl-loaded pregnant rats), but not in EO, and showed fetal growth retardation. Administration of the anti-MBG antibody to NaCl-loaded pregnant rats lowered SBP (111 +/- 2 mmHg; P < 0.01) and increased aortic sodium pump activity (144 +/- 3 versus 113 +/- 5 nmol Rb-86/g per min; P < 0.01 versus non-NaCl-loaded pregnant rats). Conclusions These observations provide evidence that MBG contributes to BP elevation in pregnant rats rendered hypertensive by NaCl supplementation. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Montreal, Hop St Justine, Res Ctr, Montreal, PQ H3C 3J7, Canada. Univ Montreal, Fac Med, Dept Obstet & Gynecol, Montreal, PQ H3C 3J7, Canada. IM Sechenov Evolut Physiol & Biochem Inst, St Petersburg 194223, Russia. State Inst Highly Pure Biopreperat, St Petersburg, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bagrova@grc.nia.nih.gov RI Bzhelyansky, Anton/J-8302-2014 OI Bzhelyansky, Anton/0000-0001-6184-9284 NR 34 TC 44 Z9 44 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD APR PY 2005 VL 23 IS 4 BP 835 EP 842 DI 10.1097/01.hjh.0000163153.27954.33 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 914PP UT WOS:000228240300024 PM 15775789 ER PT J AU Munitic, I Ryan, PE Ashwell, JD AF Munitic, I Ryan, PE Ashwell, JD TI T cells in G(1) provide a memory-like response to secondary stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PEPTIDE-MHC COMPLEXES; IN-VIVO; IMMUNOLOGICAL SYNAPSE; ANTIGENIC-STIMULATION; FLOW-CYTOMETRY; LYMPHOCYTE-ACTIVATION; EFFECTOR FUNCTIONS; CLONAL EXPANSION; DOWN-MODULATION; DENDRITIC CELLS AB The commitment of naive T cells to proliferate is a function of the strength and duration of stimuli mediated by the TCR and coreceptors. Ranges of 2-20 h of stimulation have been reported as necessary in vitro. Whether T cells actually experience uninterrupted stimulation for such long periods under physiological conditions is controversial. Here we ask whether commitment to proliferate requires continuous stimulation, or can T cells integrate intermittent periods of stimulation. T cells were stimulated for two short-term (subthreshold) periods (5-7 h) either sequentially or separated by an interval of rest. Naive lymph node T cells were able to integrate interrupted stimulation, even when the duration of rest was as long as 2 days. Furthermore, when short-term-stimulated T cells were separated by density, three populations were observed: low density blasts, intermediate density G, cells, and high density G,, cells. Low density cells progressed to division without further stimulation, whereas G, and G, cells remained undivided. However, after a period of rest, a second subthreshold stimulation caused the G, but not the G,, fraction to quickly proceed through the cell cycle. We conclude that noncycling T cells in the G, phase of the cell cycle remain in a state of readiness for prolonged periods of time, and may represent a population of memory-like effectors capable of responding rapidly to antigenic challenge. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 37,Room 3002,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 69 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2005 VL 174 IS 7 BP 4010 EP 4018 PG 9 WC Immunology SC Immunology GA 911KD UT WOS:000228000100027 PM 15778358 ER PT J AU Li, Y Zhi, W Wareski, P Weng, NP AF Li, Y Zhi, W Wareski, P Weng, NP TI IL-15 activates telomerase and minimizes telomere loss and may preserve the replicative life span of memory CD8(+) T cells in vitiro SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; IN-VIVO; LYMPHOCYTE DEVELOPMENT; REGULATED EXPRESSION; HUMAN-DISEASE; LENGTH; INTERLEUKIN-15; PROLIFERATION; HOMEOSTASIS; INDUCTION AB The preservation of the replicative life span of memory CD8(+) T cells is vital for long-term immune protection. Although IL-15 plays a key role in the homeostasis of memory CD8(+) T cells, it is unknown whether IL-15 regulates the replicative life span of memory CD8(+) T cells. In this study, we report an analysis of telomerase expression and telomere length in human memory phenotype CD8(+) T cells maintained by IL-15 in vitro. We demonstrate that IL-15 is capable of activating telomerase in memory CD8(+) T cells via Jak3 and PI3K signaling pathways..;urthermore, IL-15 induces a sustained level of telomerase activity over long periods of time, and in turn minimizes telomere loss ii memory CD8(+) T cells after substantial cell divisions. These findings suggest that IL-15 activates stable telomerase expression art I compensates telomere loss in memory phenotype CD8(+) T cells, and that telornerase may play anJimportant role in memory CD8(+) T cell homeostasis. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM wengn@grc.nia.nih.gov NR 37 TC 39 Z9 43 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2005 VL 174 IS 7 BP 4019 EP 4024 PG 6 WC Immunology SC Immunology GA 911KD UT WOS:000228000100028 PM 15778359 ER PT J AU Feng, CG Jankovic, D Kullberg, M Cheever, A Scanga, CA Hieny, S Caspar, P Yap, GS Sher, A AF Feng, CG Jankovic, D Kullberg, M Cheever, A Scanga, CA Hieny, S Caspar, P Yap, GS Sher, A TI Maintenance of pulmonary Th1 effector function in chronic tuberculosis requires persistent IL-12 production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; IFN-GAMMA; IN-VIVO; IMMUNE-RESPONSE; AUTOIMMUNE INFLAMMATION; ACTIVE TUBERCULOSIS; LATENT TUBERCULOSIS; TOXOPLASMA-GONDII; INTERFERON-GAMMA AB The mechanisms that prevent reactivation of latent Mycobacterium tuberculosis infection in asymptomatic individuals are poorly understood. Although IL-12 is critical for the induction of IFN-gamma-dependent host control of M. tuberculosis, the requirement for the cytokine in the maintenance of host resistance and pulmonary Th1 effector function has not yet been formally examined. In this study, we reconstituted IL-12p40-deficient mice with IL-12 during the first 4 wk of infection and then assessed the effects of cytokine withdrawal. Although IL-12 administration initially resulted in restricted mycobacterial growth and prolonged survival, the reconstituted animals eventually succumbed to infection. This breakdown in bacterial control was accompanied by a marked reduction in the numbers of IFN-gamma-producing CD4(+) T cells in lungs. Moreover, whereas CD4(+) T cells isolated from chronically infected wild-type mice expanded and transferred long-term protection to M. tuberculosis-challenged RAG(-/-) mice, they failed to do so in IL-12p40-deficient RAG(-/-) recipients and were clearly reduced in frequency within pulmonary granulomas in the latter animals. These studies establish that continuous IL-12 production is necessary for maintenance of the pulmonary Th1 cells required for host control. of persistent M. tuberculosis infection and suggest that breakdown of this mechanism could be a contributing factor in reactivated disease. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Rockville, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. RP Feng, CG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Room 6148,Bldg 50,50 South Dr, Bethesda, MD 20892 USA. EM cfeng@niaid.nih.gov NR 63 TC 76 Z9 86 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2005 VL 174 IS 7 BP 4185 EP 4192 PG 8 WC Immunology SC Immunology GA 911KD UT WOS:000228000100048 PM 15778379 ER PT J AU Park, JM Terabe, M Sakai, Y Munasinghe, J Forni, G Morris, JC Berzofsky, JA AF Park, JM Terabe, M Sakai, Y Munasinghe, J Forni, G Morris, JC Berzofsky, JA TI Early role of CD4(+) Th1 cells and antibodies in HER-2 adenovirus vaccine protection against autochthonous mammary carcinomas SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSGENIC BALB/C MICE; HUMAN-BREAST-CANCER; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; RECOMBINANT ADENOVIRUSES; DNA VACCINATION; OVARIAN-CANCER; TUMOR-GROWTH; CARCINOGENESIS; PREVENTION AB HER-2 is an oncogenic tumor-associated Ag that is overexpressed in several human tumors including breast and ovarian cancer. The efficacy and mechanism of a HER-2-expressing recombinant adenoviral vaccine to protect against tumorigenesis was examined using HER-2 transgenic (BALB-neuT) mice, which develop spontaneous breast tumors in all 10 mammary glands, and also using a transplantable mouse tumor model. Vaccination beginning at 6-8 wk of age (through 19 wk of age) prevented development of spontaneous mammary tumors even after 50 wk, whereas the animals in the control groups had tumors in all mammary glands by 25 wk. Such long-term protection after the last boost has not been achieved previously in this transgenic mouse in which the oncogene is continuously spawning tumorigenesis. Using beta(2)-microglobulin-knockout, IFN-gamma-knockout, and B cell-deficient mice, CD4(+) and CD8(+) cell depletion, and Ab transfer studies, we show that induction of anti-HER-2/neu Abs are both necessary and sufficient for protection, and the IgG2a isotype is most effective. In contrast, CD8(+) T cells are not necessary at all, and CD4(+) T cells are necessary for only 36-48 It after immunization to provide help for B cells but not as effector cells. Equal protection in immunized mice deficient in Fc gamma RI/III excluded an FcR-mediated mechanism. Anti-HER-2 serum not only inhibited growth of mammary tumor cell lines expressing HER-2 in vitro but also protected mice from tumors in vivo, suggesting a direct action of Ab on the tumor cells. Such a vaccine may provide Ab-mediated protection against HER-2-expressing breast cancers in humans. C1 NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Canc Gene Therapy Sect, Metab Branch, Bethesda, MD 20892 USA. Natl Natl Inst Neurol Disorders & Stroke, Mouse Imaging Facil, Bethesda, MD 20892 USA. Univ Turin, Dept Clin & Biol Sci, Orbassano, Italy. RP Berzofsky, JA (reprint author), NCI, Vaccine Branch, Ctr Canc Res, Bldg 10,Room 6B-04, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov NR 36 TC 62 Z9 64 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2005 VL 174 IS 7 BP 4228 EP 4236 PG 9 WC Immunology SC Immunology GA 911KD UT WOS:000228000100054 PM 15778385 ER PT J AU Jones, KS Akel, S Petrow-Sadowski, C Huang, Y Bertolette, DC Ruscetti, FW AF Jones, KS Akel, S Petrow-Sadowski, C Huang, Y Bertolette, DC Ruscetti, FW TI Induction of human T cell leukemia virus type I receptors on quiescent naive T lymphocytes by TGF-beta(1,2) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; TGF-BETA; PERIPHERAL-BLOOD; HTLV-I; ENVELOPE GLYCOPROTEIN; POTENTIAL MECHANISM; SYNCYTIUM FORMATION; HIV-1 INFECTION; DENDRITIC CELLS; DOWN-REGULATION AB The retrovirus human T cell leukemia virus (HTLV) type I (HTLV-I) is primarily transmitted by breast-feeding or sexual contact, by cell-to-cell contact between T cells. TGF-beta, which has been shown to enhance transmission of HTLV-I in vitro, is found at high levels in breast milk and semen. In this study, the ability of TGF-beta to regulate expression of molecules involved in HTLV-1 binding and entry was examined. Previous studies using a soluble form of the HTLV-1 envelope protein SU have shown that quiescent human T cells do not express cell surface molecules that specifically bind SU. After T cell activation, HTLV SU binding proteins are rapidly induced. In this study, we report that TGF-beta induces expression of proteins that bind soluble HTLV SU and HTLV virions on naive CD4(+) T lymphocytes. The induction of these proteins occurred without cell cycle entry or expression of activation markers, involved TGF-beta-induced intracellular signaling, and required de novo transcription and translation. Treatment of naive CD4+ T lymphocytes with TGF-beta induced expression of GLUT-1, which has recently been reported to function as a receptor for HTLV. Treatment of a TGF-beta-sensitive human myeloid cell line increased the titer of both HTLV-I- and HTLV-II-pseudotyped viruses. Although earlier studies suggested that HTLV SU binding proteins might be an early marker of T cell activation and/or cell proliferation, we report in this study that TGF-beta induces binding of HTLV virions and expression of glucose transporter type 1 in primary CD4(+) T lymphocytes that remain quiescent. C1 NCI, Bas Res Program, Sci Applicat Int Corp Frederick Inc, Ft Detrick, MD 21702 USA. NCI, Expt Immunol Lab, Ft Detrick, MD 21702 USA. Hashemite Univ, Dept Med Lab Sci, Zarqa, Jordan. RP Jones, KS (reprint author), NCI, Bas Res Program, Sci Applicat Int Corp Frederick Inc, Bldg 567,Room 253, Ft Detrick, MD 21702 USA. EM jonesk@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 72 TC 25 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2005 VL 174 IS 7 BP 4262 EP 4270 PG 9 WC Immunology SC Immunology GA 911KD UT WOS:000228000100058 PM 15778389 ER PT J AU Zhao, YB Zheng, ZL Robbins, PF Khong, HT Rosenberg, SA Morgan, RA AF Zhao, YB Zheng, ZL Robbins, PF Khong, HT Rosenberg, SA Morgan, RA TI Primary human lymphocytes transduced with NY-ESO-1 antigen-specific TCR genes recognize and kill diverse human tunior cell lines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CYTOTOXIC T-LYMPHOCYTES; MHC CLASS-I; RETROVIRAL VECTORS; CYTOKINE PRODUCTION; ANTIBODY-RESPONSES; ADOPTIVE TRANSFER; IMMUNE-RESPONSES; DONOR LEUKOCYTES; TRANSFER THERAPY AB cDNAs encoding TIER alpha- and beta-chains specific for HLA-A2-restricted cancer-testis Ag NY-ESO-1 were cloned using a 5'RACE method from RNA isolated from a CTL generated by in vitro stimulation of PBMC with modified NY-ESO-1-specific peptide (p157-165. 9V). Functionality of the cloned TCR was confirmed by RNA electroporation of primary PBL. cDNA for these a- and beta-chains were used to construct a murine stem cell virus-based retroviral vector, and high titer packaging cell lines were generated. Gene transfer efficiency in primary T lymphocytes of up to 60% was obtained without selection using a method of precoating retroviral vertors onto culture plates. Both CD4(+) and CD8(+) T cells could be transduced at the same efficiency. High avidity Ag recognition was demonstrated by coculture of transduced lymphocytes with target cells pulsed with low levels of peptide (< 20 pM). TCR-transduced CD4 T cells, when cocultured with NY-ESO-1 peptide pulsed T2 cells, could produce IFN-gamma, GMCSF, IL-4, and IL-10, suggesting CD8-independent, HLA-A2-restricted TCR activation. The transduced lymphocytes could efficiently recognize and kill HLA-A2- and NY-ESO-1-positive melanoma cell lines in a 4-h Cr-51 release assay. Finally, transduced T cells could efficiently recognize NY-ESO-1-positive nonmelanoma tumor cell lines. These results strongly support the idea that redirection of normal T cell specificity by TCR gene transfer can have potential applications in tumor adoptive inimunotherapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 6N110,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 41 TC 117 Z9 125 U1 2 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2005 VL 174 IS 7 BP 4415 EP 4423 PG 9 WC Immunology SC Immunology GA 911KD UT WOS:000228000100076 PM 15778407 ER PT J AU Karron, RA Wright, PF Belshe, RB Thumar, B Casey, R Newman, F Polack, FP Randolph, VB Deatly, A Hackell, J Gruber, W Murphy, BR Collins, PL AF Karron, RA Wright, PF Belshe, RB Thumar, B Casey, R Newman, F Polack, FP Randolph, VB Deatly, A Hackell, J Gruber, W Murphy, BR Collins, PL TI Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th International Symposium on Respiratory Viral Infections CY MAR, 2004 CL Sanibel Isl, FL SP Natl Inst Hlth, Wyeth Vaccines Res ID INFLUENZA-A VIRUS; SERONEGATIVE CHIMPANZEES; TEMPERATURE SENSITIVITY; INACTIVATED VACCINE; REVERSE GENETICS; YOUNG-CHILDREN; RSV VACCINE; IN-VITRO; SH GENE; MUTATIONS AB Background. Recombination technology can be used to create live attenuated respiratory syncytial virus (RSV) vaccines that contain combinations of known attenuating mutations. Methods. Two live attenuated, recombinantly derived RSV vaccine candidates, rA2cp248/404DeltaSH and rA2cp248/404/1030DeltaSH, were evaluated in 31 adults and in 95 children greater than or equal to6 months old. rA2cp248/404/1030DeltaSH was subsequently evaluated in 44 infants 1 - 2 months old. These vaccine candidates share 4 attenuating genetic elements and differ only in a missense mutation ( 1030) in the polymerase gene. Results. Both vaccines were highly attenuated in adults and RSV-seropositive children and were well tolerated and immunogenic in RSV-seronegative children. Compared with that of rA2cp248/404DeltaSH, replication of rA2cp248/404/1030DeltaSH was restricted in RSV-seronegative children (mean peak titer, 10(4.3) vs. 10(2.)5 plaque-forming units [pfu]/mL), indicating that the 1030 mutation had a potent attenuating effect. Although rA2cp248/404/ 1030DeltaSH was well tolerated in infants, only 44% of infants who received two 10(5.3)-pfu doses of vaccine had detectable antibody responses. However, replication after administration of the second dose was highly restricted, indicating that protective immunity was induced. At least 4 of 5 attenuating genetic elements were retained in recovered vaccine viruses. Conclusions. rA2cp248/404/1030DeltaSH is the first RSV vaccine candidate to be sufficiently attenuated in young infants. Additional studies are needed to determine whether rA2cp248/404/1030DeltaSH can induce protective immunity against wild-type RSV. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. St Louis Univ, Hlth Sci Ctr, Div Infect Dis, St Louis, MO 63103 USA. Wyeth Vaccines Res, Pearl River, NY USA. Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Nashville, TN USA. RP Karron, RA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Hampton House 117,624 N Broadway, Baltimore, MD 21205 USA. EM rkarron@jhsph.edu FU NIAID NIH HHS [N01-AI-15444] NR 39 TC 148 Z9 157 U1 2 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2005 VL 191 IS 7 BP 1093 EP 1104 DI 10.1086/427813 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 903IB UT WOS:000227418200012 PM 15747245 ER PT J AU Watts, DH Fazarri, M Minkoff, H Hillier, SL Sha, B Glesby, M Levine, AM Burk, R Palefsky, JM Moxley, M Ahdieh-Grant, L Strickler, HD AF Watts, DH Fazarri, M Minkoff, H Hillier, SL Sha, B Glesby, M Levine, AM Burk, R Palefsky, JM Moxley, M Ahdieh-Grant, L Strickler, HD TI Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CERVICAL INTRAEPITHELIAL NEOPLASIA; VAGINAL MICROBIAL-FLORA; HERPES-SIMPLEX VIRUS-2; CHLAMYDIA-TRACHOMATIS; INTERAGENCY HIV; TRICHOMONAS-VAGINALIS; UNINFECTED WOMEN; TRACT INFECTIONS; ASSOCIATION AB Background. Whether the natural history of human papillomavirus (HPV) infection is affected by bacterial vaginosis (BV) or Trichomonas vaginalis ( TV) infection has not been adequately investigated in prospective studies. Methods. Human immunodeficiency virus 1 (HIV-1) - infected (n = 1763) and high-risk HIV-1-uninfected (n = 493) women were assessed semiannually for BV (by Nugent's criteria), TV infection (by wet mount), type-specific HPV ( by polymerase chain reaction with MY09/MY11/HMB01HPV primers), and squamous intraepithelial lesions (SIL) ( by cytological examination). Sexual history was obtained from patient report at each visit. Risk factors for prevalent and incident HPV infection and SIL were evaluated by use of multivariate models. Results. BV was associated with both prevalent and incident HPV infection but not with duration of HPV infection or incidence of SIL. TV infection was associated with incident HPV infection and with decreased duration and lower prevalence of HPV infection. TV infection had no association with development of SIL. Effects of BV and TV infection were similar in HIV-1-infected and high-risk HIV-1-uninfected women. HIV-1 infection and low CD4(+) lymphocyte count were strongly associated with HPV infection and development of SIL. Conclusions. BV and TV infection may increase the risk of acquisition ( or reactivation) of HPV infection, as is consistent with hypotheses that the local cervicovaginal milieu plays a role in susceptibility to HPV infection. The finding that BV did not affect persistence of HPV infection and that TV infection may shorten the duration of HPV infection helps explain the lack of effect that BV and TV infection have on development of SIL. C1 NICHHD, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Maimonides Hosp, Brooklyn, NY 11219 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Los Angeles, CA USA. Georgetown Univ, Washington, DC USA. RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, 6100 Execut Blvd,Rm 4B11,MSC 7510, Bethesda, MD 20892 USA. EM hw59i@nih.gov FU NCI NIH HHS [R01 CA85178-01]; NCRR NIH HHS [M01 RR00079]; NIAID NIH HHS [U01-AI-42590, N01-AI-35161, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-35004, U01-AI34994]; NICHD NIH HHS [U01-HD-32632] NR 54 TC 86 Z9 89 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2005 VL 191 IS 7 BP 1129 EP 1139 DI 10.1086/427777 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 903IB UT WOS:000227418200016 PM 15747249 ER PT J AU Gil-Lamaignere, C Simitsopoulou, M Roilides, E Maloukou, A Winn, RM Walsh, TJ AF Gil-Lamaignere, C Simitsopoulou, M Roilides, E Maloukou, A Winn, RM Walsh, TJ TI Interferon-gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important Zygomycetes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 15th Congress of the International-Society-for-Human-and-Animal-Mycology CY MAY 29, 2003 CL San Antonio, TX SP Int Soc Human & Anim Mycol ID OPPORTUNISTIC FUNGAL PATHOGENS; RHIZOPUS-ORYZAE HYPHAE; MHC CLASS-II; HUMAN-NEUTROPHILS; ASPERGILLUS-FUMIGATUS; ANTIFUNGAL ACTIVITY; CANDIDA-ALBICANS; AMPHOTERICIN-B; IN-VITRO; GM-CSF AB Zygomycetes cause serious invasive infections, predominantly in immunocompromised and diabetic patients with poor prognoses and limited therapeutic options. We compared the antifungal function of human polymorphonuclear leukocytes (PMNLs) against hyphae of Rhizopus oryzae and R. microsporus, the most frequently isolated zygomycetes, with that against the less frequently isolated Absidia corymbifera. We then evaluated the effects of interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF), alone or combined, on PMNL antifungal function against these zygomycetes. Both PMNL oxidative burst in response to hyphae and PMNL-induced hyphal damage were significantly lower in response to Rhizopus species than in response to A. corymbifera. Incubation of PMNLs with IFN-gamma and GM-CSF alone or combined for 22 h increased the PMNL-induced hyphal damage of all 3 species. The treatment of PMNLs with the combination of IFN-gamma and GM-CSF significantly increased the release of tumor necrosis factor-alpha in response to R. microsporus and A. corymbifera hyphae. IFN-gamma significantly reduced interleukin-8 release in response to all zygomycetes. Although Rhizopus species demonstrate a decreased susceptibility to the antifungal activity of human PMNLs, in comparison with A. corymbifera, IFN-gamma and GM-CSF augment the hyphal damage of all 3 zygomycetes, suggesting a role for IFN-gamma and GM-CSF in the management of invasive zygomycosis. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54006 Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 59 TC 83 Z9 87 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2005 VL 191 IS 7 BP 1180 EP 1187 DI 10.1086/428503 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 903IB UT WOS:000227418200022 PM 15747255 ER PT J AU Gow, AJ Payson, AP Bonaventura, J AF Gow, AJ Payson, AP Bonaventura, J TI Invertebrate hemoglobins and nitric oxide: How heme pocket structure controls reactivity SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE invertebrates; nitric oxide; hemoglobin ID OXYGEN-AVID HEMOGLOBIN; ESCHERICHIA-COLI; ASCARIS HEMOGLOBIN; NITROSATIVE STRESS; CARBON-MONOXIDE; OXIDATIVE STRESS; LIGAND-BINDING; ARABIDOPSIS-THALIANA; HUMAN NEUROGLOBIN; DAPHNIA-MAGNA AB Hemoglobins (Hbs), generally defined as 5 or 6 coordinate heme proteins whose primary function is oxygen transport, are now recognized to occur in virtually all phyla of living organisms. Historically, study of their function focused on oxygen as a reversibly bound ligand of the ferrous form of the protein. Other diatomic ligands like carbon monoxide and nitric oxide were considered "non-physiological" but useful probes of structure-function relationships in Hbs. This investigatory landscape changed dramatically in the 1980s when nitric oxide was discovered to activate a heme protein, cyclic guanylate cyclase. Later, its activation was likened to Perutz' description of Hb's allosteric properties being triggered by a ligand-dependent "out-of-plane/into-plane" movement of the heme iron. In 1996, a functional role for nitric oxide in human and mammalian Hbs was demonstrated and since that time, the interest in NO as a physiologically relevant Hb ligand has greatly increased. Concomitantly, non-oxygen binding properties of Hbs have challenged the view that Hbs arose for their oxygen storage and transport properties. In this focused review we discuss some invertebrate Hbs' functionally significant reactions with nitric oxide and how strategic positioning of a few residues in the heme pocket plays an large role in the interplay of diatomic ligands to ferrous and ferric heme iron in these proteins. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Puerto Rico, Prot Res Ctr, Ctr Biomed Res Excellence, NIH, Mayaguez, PR 00681 USA. Univ Penn, Childrens Hosp Philadelphia, Stokes Res Inst, Philadelphia, PA 19104 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. RP Payson, AP (reprint author), Univ Puerto Rico, Prot Res Ctr, Ctr Biomed Res Excellence, NIH, Box 9255, Mayaguez, PR 00681 USA. EM alexpayson@yahoo.com; joeb@duke.edu RI Gow, Andrew/N-8566-2013 OI Gow, Andrew/0000-0003-0876-5158 FU NCRR NIH HHS [5P20 RR 016439] NR 77 TC 9 Z9 10 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR PY 2005 VL 99 IS 4 BP 903 EP 911 DI 10.1016/j.jinorgbio.2004.12.001 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 919IH UT WOS:000228611200003 PM 15811507 ER PT J AU Udey, MC AF Udey, MC TI Gone fishin' in 2005 - Insights into the inner workings of dendritic cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; GENERATION; ANTIGEN; IDENTIFICATION; ALPHA C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 BP VI EP VII DI 10.1111/j.0022-202X.2005.23666.x PG 2 WC Dermatology SC Dermatology GA 908GY UT WOS:000227776700001 PM 15816821 ER PT J AU Schieke, SM Ruwiedel, K Gers-Barlag, H Grether-Beck, S Krutmann, J AF Schieke, SM Ruwiedel, K Gers-Barlag, H Grether-Beck, S Krutmann, J TI Molecular crosstalk of the ultraviolet A and ultraviolet B signaling responses at the level of mitogen-activated protein kinases SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID DOWN-REGULATION; SINGLET OXYGEN; UVA RADIATION; RECEPTOR; IRRADIATION; INDUCTION; PATHWAY; MOUSE C1 Heinrich Heine Univ gGmbH, IUF, D-40225 Dusseldorf, Germany. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Beiersdorf AG, Hamburg, Germany. RP Krutmann, J (reprint author), Heinrich Heine Univ gGmbH, IUF, Hennekamp 50, D-40225 Dusseldorf, Germany. EM krutmann@rz.uni-duesseldorf.de NR 12 TC 17 Z9 19 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 BP 857 EP 859 DI 10.1111/j.0022-202X.2005.23671.x PG 3 WC Dermatology SC Dermatology GA 908GY UT WOS:000227776700026 PM 15816846 ER PT J AU Aho, S Kalinin, A Aho, M Casciola-Rosen, L Rosen, A Uitto, J AF Aho, S Kalinin, A Aho, M Casciola-Rosen, L Rosen, A Uitto, J TI Specific cleavage of periplakin by granzyme B SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Unilever Res & Dev, Skin Biosci, Edgewater, NJ USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NIAMS, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 409 BP A69 EP A69 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900409 ER PT J AU Arbiser, JL Kau, T Konar, M Ramachandran, R Silver, PA Bain, J Cohen, P Gray, A Whitmire, D Tseng, P Chen, C Furness, S Bowen, PJ AF Arbiser, JL Kau, T Konar, M Ramachandran, R Silver, PA Bain, J Cohen, P Gray, A Whitmire, D Tseng, P Chen, C Furness, S Bowen, PJ TI Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphoinositol-3 kinase SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27412 USA. Sch Life Sci, Div Signal Transduct Therapy, Dundee, Scotland. Univ Georgia, Dept Chem, Athens, GA 30602 USA. NCI, Pathol Lab, Rockville, MD USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 005 BP A1 EP A1 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900006 ER PT J AU Beer, JZ Yamaguchi, Y Tadokoro, T Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Hearing, VJ AF Beer, JZ Yamaguchi, Y Tadokoro, T Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Hearing, VJ TI UV-induced redistribution of epidermal melanin in different races - a defensive response? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Beiersdorf AG, Skin Res, Res & Dev, Hamburg, Germany. RI Yamaguchi, Yuji/B-9312-2008 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 808 BP A135 EP A135 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901350 ER PT J AU Cardones, AR Sugaya, M Blauvelt, A Hwang, ST AF Cardones, AR Sugaya, M Blauvelt, A Hwang, ST TI Oncostatin M increases CCL21 expression by human primary endothelial cells in vitro and in marine skin in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 OHSU, Dept Dermatol, Portland, OR USA. NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 012 BP A2 EP A2 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900013 ER PT J AU DiGiovanna, JJ Liang, C Schmidt, D Morris, A Schiffmann, R Kraemer, KH AF DiGiovanna, JJ Liang, C Schmidt, D Morris, A Schiffmann, R Kraemer, KH TI Trichothindystrophy: diagnosis and spectrum of clinical phenotypes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Basic Res Lab, Bethesda, MD 20892 USA. Brown Med Sch, Providence, RI USA. NINDS, Bethesda, MD 20892 USA. HHMI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 464 BP A78 EP A78 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901008 ER PT J AU Ermilov, A Roessler, E Wang, A Grachtchouk, M Dlugosz, A Muenke, M AF Ermilov, A Roessler, E Wang, A Grachtchouk, M Dlugosz, A Muenke, M TI Full-length human GL12 contains a previously undescribed transcriptional repressor domain SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Michigan, Ann Arbor, MI 48109 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 151 BP A26 EP A26 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900151 ER PT J AU Grachtchouk, M Liu, J Hutchin, M Wang, A Glick, AB Dlugosz, A AF Grachtchouk, M Liu, J Hutchin, M Wang, A Glick, AB Dlugosz, A TI Hedgehog signaling and sebocyte development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Michigan, Ann Arbor, MI 48109 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 648 BP A108 EP A108 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901192 ER PT J AU Guzman, EA Tuchinda, C He, H Croxen, A Neville, J Hornyak, TJ Strickland, FM AF Guzman, EA Tuchinda, C He, H Croxen, A Neville, J Hornyak, TJ Strickland, FM TI Regulation of UV-induced apoptosis in melanocytes by MITF SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Bethesda, MD 20892 USA. Henry Ford Hlth Syst, Dermatol, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 872 BP A146 EP A146 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901415 ER PT J AU He, Y Huang, J Block, ML Hong, J Chignell, CF AF He, Y Huang, J Block, ML Hong, J Chignell, CF TI Role of phagocyte oxidase in UVA-induced oxidative stress and apoptosis in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIEHS, LPC, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 814 BP A136 EP A136 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901356 ER PT J AU Hebert, J Chang, C Cheng, K Khaimskiy, Y Kopelovich, L Bickers, DR Wakabayashi, Y Balmain, A Epstein, EH AF Hebert, J Chang, C Cheng, K Khaimskiy, Y Kopelovich, L Bickers, DR Wakabayashi, Y Balmain, A Epstein, EH TI Basal cell carcinoma in Ptch1+/- exposed to ionizing radiation - effects of genetic background SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 130 BP A22 EP A22 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900131 ER PT J AU Hoashi, T Vieira, WD Hearing, VJ AF Hoashi, T Vieira, WD Hearing, VJ TI HMB45 antibody reacts with the internal repeat domain of the human melanosomal matrix protein Pmel17/gp100 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 857 BP A143 EP A143 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901396 ER PT J AU Hutchin, ME Liu, J Wang, A Grachtchouk, M Wei, L Waldinger, J Glick, AB Dlugosz, A AF Hutchin, ME Liu, J Wang, A Grachtchouk, M Wei, L Waldinger, J Glick, AB Dlugosz, A TI Hedgehog signal transduction in hair follicle epithelium is essential for proper epithelial-mesenchymal interactions and post-natal hair morphogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Michigan, Ann Arbor, MI 48109 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 650 BP A109 EP A109 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901196 ER PT J AU Hwang, J Morasso, MI AF Hwang, J Morasso, MI TI Analysis of Dlx3 gene expression in lacZ knock-in mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 594 BP A99 EP A99 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901138 ER PT J AU Imoto, K Slor, H Orgal, S Khan, SG Oh, KS Busch, DB Nadem, C Ueda, T Gadoth, N Jaspers, NJ Kraemer, KH AF Imoto, K Slor, H Orgal, S Khan, SG Oh, KS Busch, DB Nadem, C Ueda, T Gadoth, N Jaspers, NJ Kraemer, KH TI Xeroderma pigmentosum group F patients with late onset neurological disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Basic Res Lab, Bethesda, MD 20892 USA. Tel Aviv Med Sch, Tel Aviv, Israel. Erasmus Univ, Rotterdam, Netherlands. AFIP, Washington, DC USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 466 BP A78 EP A78 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901011 ER PT J AU Jaber, S Cowen, E Haworth, L Booher, S Berman, D Rosenberg, S Hwang, S AF Jaber, S Cowen, E Haworth, L Booher, S Berman, D Rosenberg, S Hwang, S TI A CD4 T cell predominant dermatitis in stage IV melanoma patients treated with anti-CTLA-4 monoclonal antibody as a single agent. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 220 BP A37 EP A37 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900220 ER PT J AU Kakinuma, T Nadiminti, H Murakami, T Perez, B Hwang, ST AF Kakinuma, T Nadiminti, H Murakami, T Perez, B Hwang, ST TI Control and implications of non-tumor forming B16 murine melanoma cells in skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 838 BP A140 EP A140 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901380 ER PT J AU Kalinin, O Hwang, M Morasso, MI AF Kalinin, O Hwang, M Morasso, MI TI Expression pattern of the novel calcium-binding proteins, Scarf and Scarf2, during development and epidermal differentiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 593 BP A99 EP A99 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901135 ER PT J AU Khan, SG LEhmann, AR Imoto, K Oh, KS Clarkson, S Nemeth, AH Downes, SM Talbot, K Nadem, C Kraemer, KH AF Khan, SG LEhmann, AR Imoto, K Oh, KS Clarkson, S Nemeth, AH Downes, SM Talbot, K Nadem, C Kraemer, KH TI An A to G change at a splice donor site of the XPG DNA repair gene is associated with neurologic disease in two adult brothers SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Basic Res Lab, Bethesda, MD 20892 USA. Univ Sussex, Brighton, E Sussex, England. Univ Med Ctr, Geneva, Switzerland. Univ Oxford, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 484 BP A81 EP A81 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901029 ER PT J AU Kim, AL Zhu, Y Tang, X Han, L Kopelovich, L Athar, M Bickers, DR AF Kim, AL Zhu, Y Tang, X Han, L Kopelovich, L Athar, M Bickers, DR TI Rescue of mutant p53 by CP-31398 suppresses the induction of squamous cell carcinomas (SCCs) by ultraviolet B (UVB) radiation in SKH-l hairless mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Columbia Univ, Med Ctr, New York, NY USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 APR PY 2005 VL 124 IS 4 SU S MA 145 BP A25 EP A25 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900146 ER PT J AU Kim, B Miyagawa, F Katz, SI AF Kim, B Miyagawa, F Katz, SI TI Induction of a graft-versus-host-like skin disease by intradermal injection of CD8+ T cell receptor (OT-1) transgenic T cells into keratin 14-ovalbumin-expressing transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Dermatol Branch, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 677 BP A113 EP A113 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901219 ER PT J AU Koochek, A Suh, KS Crutchley, JM Dumont, RA Yuspa, SH AF Koochek, A Suh, KS Crutchley, JM Dumont, RA Yuspa, SH TI CLIC4, a proapoptotic chloride channel protein, has potential as a novel molecular target for tumor therapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 141 BP A24 EP A24 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900142 ER PT J AU Lopez, S Verbeek, S Sunderkoetter, C Knop, J Udey, MC von Stebut, E AF Lopez, S Verbeek, S Sunderkoetter, C Knop, J Udey, MC von Stebut, E TI Phagocytosis of L-major by dendritic cells (DC) is mediated by Fc gamma RI (CD64) and Fc gamma RIII (CD16) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. Leiden Univ, Med Ctr, Leiden, Netherlands. Univ Ulm, Dept Dermatol, Ulm, Germany. NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 748 BP A125 EP A125 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901290 ER PT J AU Miyagawa, F Katz, SI AF Miyagawa, F Katz, SI TI Identification of CD3(+)CD4(-)CD8(-) T cells as potential regulatory cells in experimental graft vs host disease (GvHD). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 661 BP A111 EP A111 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901205 ER PT J AU Moelle, K Lopez, S Steinbrink, K Knop, J Udey, MC von Stebut, E AF Moelle, K Lopez, S Steinbrink, K Knop, J Udey, MC von Stebut, E TI Impaired dendritic cell-mediated T cell-priming results in delayed lesion involution in L-major infected B-cell deficient mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 758 BP A127 EP A127 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901301 ER PT J AU Nadiminiti, H Lee, C Kakinuma, T Cardones, AR Zhang, H Perez, B Hwang, ST AF Nadiminiti, H Lee, C Kakinuma, T Cardones, AR Zhang, H Perez, B Hwang, ST TI CXCR4 enhances human and murine melanoma cell experimental lung metastasis and adhesion to microvascular endothelial cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RI Lee, Chih-Hung /B-4081-2010 NR 0 TC 1 Z9 1 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 APR PY 2005 VL 124 IS 4 SU S MA 837 BP A140 EP A140 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901377 ER PT J AU Nadiminti, H Kakinuma, T Goldberg, S Perez, B Zhuang, Z Barrett, J Hwang, ST AF Nadiminti, H Kakinuma, T Goldberg, S Perez, B Zhuang, Z Barrett, J Hwang, ST TI A model of human melanoma tumor latency demonstrates spontaneous changes (upon delayed tumor formation) in the endogenous expression of known and novel genes that regulate cancer progression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NINDS, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 120 BP A20 EP A20 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900121 ER PT J AU Nakanishi, G Kim, Y Iwatsuki, K Jetten, A AF Nakanishi, G Kim, Y Iwatsuki, K Jetten, A TI The Kruppel zinc-finger protein Gli-similar 1: its expression and function in skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Okayama Univ, Sch Med, Dept Dermatol, Okayama 700, Japan. NIEHS, Cell Biol Sect, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 533 BP A89 EP A89 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901075 ER PT J AU Oh, K Schmidt, D Kraemer, KH AF Oh, K Schmidt, D Kraemer, KH TI A new xeroderma pigmentosum group E kindred with a R273H mutation in the DDB2 gene has features mimicking XP variant cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIH, Basic Res Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 APR PY 2005 VL 124 IS 4 SU S MA 485 BP A81 EP A81 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901027 ER PT J AU Ohyama, M Terunuma, A Tock, CL Radonovich, M Brady, JN Vogel, JC AF Ohyama, M Terunuma, A Tock, CL Radonovich, M Brady, JN Vogel, JC TI Differential expression of cell surface markers on bulge and non-bulge cells in human anagen hair follicle SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 643 BP A108 EP A108 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901187 ER PT J AU Radoja, N Blumenberg, M Morasso, MI AF Radoja, N Blumenberg, M Morasso, MI TI Dlx3 inhibits the proliferation of normal and transformed human keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. NYU, Sch Med, Dept Dermatol, New York, NY USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NYU, Sch Med, Inst Canc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 461 BP A77 EP A77 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901003 ER PT J AU Segre, J Xi, Z Patel, S McGaughey, D Seo, E AF Segre, J Xi, Z Patel, S McGaughey, D Seo, E TI Klf4 and glucocorticoid receptor coordinately activate genes involved in establishing the epidermal permeability barrier SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NHGRI, GMBBB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 518 BP A87 EP A87 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901064 ER PT J AU Seo, E Patel, S Bugge, TH Segre, JA AF Seo, E Patel, S Bugge, TH Segre, JA TI Identification of genes response to loss of epidermal barrier SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 508 BP A85 EP A85 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901053 ER PT J AU Sugaya, M Root, M Blauvelt, A AF Sugaya, M Root, M Blauvelt, A TI C34, a membrane fusion inhibitor, blocks HIV infection of human Langerhans cells (LC) and LC-mediated transfer of virus to T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Oregon Hlth & Sci Univ, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 750 BP A125 EP A125 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901291 ER PT J AU Tada, Y Riedl, E Lowenthal, MS Liotta, LA Briner, D Crouch, EC Udey, MC AF Tada, Y Riedl, E Lowenthal, MS Liotta, LA Briner, D Crouch, EC Udey, MC TI Identification of endogenous Langerin ligands in marine skin extracellular matrix SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 656 BP A110 EP A110 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901202 ER PT J AU Takahashi, K Yamaguchi, Y Hoashi, T Hearing, VJ AF Takahashi, K Yamaguchi, Y Hoashi, T Hearing, VJ TI Melanin content and DNA damage in normal human skin in response to chronic ultraviolet radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RI Yamaguchi, Yuji/B-9312-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 800 BP A134 EP A134 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901343 ER PT J AU Takeuchi, S Takeuchi, F Katz, SI AF Takeuchi, S Takeuchi, F Katz, SI TI Collared mice: a model to assess the effects of scratching SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 718 BP A120 EP A120 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901261 ER PT J AU Tang, X Kim, AL Huaijie, Z Kopelovich, L Athar, M Bickers, DR AF Tang, X Kim, AL Huaijie, Z Kopelovich, L Athar, M Bickers, DR TI Budesonide, a corticosteroid, and bexarotene, a retinoid X receptor-selective ligand, synergistically inhibit ultraviolet B-induced squamous cell carcinomas (SCCs) in SKH-1 hairless mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Columbia Univ, Med Ctr, New York, NY USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 147 BP A25 EP A25 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900148 ER PT J AU Terunuma, A Udey, MC Vogel, JC AF Terunuma, A Udey, MC Vogel, JC TI An anatomically correct in vivo competitive repopulation assay to evaluate human keratinocyte stem cell candidates SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 437 BP A73 EP A73 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900437 ER PT J AU Terunuma, A Blonder, J Kapoor V Telford, WG Conrads, TP Veenstra, TD Vogel, JC AF Terunuma, A Blonder, J Kapoor, V Telford, WG Conrads, TP Veenstra, TD Vogel, JC TI A quantitative LC-MS/MS analysis for the proteomic characterization of the membrane fraction from human keratinocyte label-retaining cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 436 BP A73 EP A73 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900436 ER PT J AU Voscopoulos, CJ Wolf, R Lewerenz, V Cataisson, C Walz, M Ruzicka, T Yuspa, SH AF Voscopoulos, CJ Wolf, R Lewerenz, V Cataisson, C Walz, M Ruzicka, T Yuspa, SH TI Identification of the mouse ortholog of the human S100A7/15 subfamily from murine skin and its regulation by calcium and PKC SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Ctr Canc, LCCTP, NIH, Bethesda, MD USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 415 BP A70 EP A70 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900415 ER PT J AU Wang, J Crooks, D Takeuchi, F Li, S Pacheco-Rodriguez, G Moss, J Darling, TN AF Wang, J Crooks, D Takeuchi, F Li, S Pacheco-Rodriguez, G Moss, J Darling, TN TI Neoplastic cells purified from tuberous sclerosis skin tumors show loss of tuberin function through biallelic mutations in TSC2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 111 BP A19 EP A19 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900112 ER PT J AU Yamaguchi, Y Takahashi, K Zmudzka, BZ Kornhauser, A Miller, SA Tadokoro, T Berens, W Itami, S Katayama, I Beer, JZ Hearing, VJ AF Yamaguchi, Y Takahashi, K Zmudzka, BZ Kornhauser, A Miller, SA Tadokoro, T Berens, W Itami, S Katayama, I Beer, JZ Hearing, VJ TI Melanin in the upper epidermis not only protects against UV-induced DNA damage but also facilitates apoptosis in its vicinity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. Osaka Univ, Grad Sch Med, Suita, Osaka, Japan. RI Yamaguchi, Yuji/B-9312-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 830 BP A139 EP A139 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901373 ER PT J AU Zhang, D Beyer, LA Kabara, L Halsey, K Raphael, Y Dolan, DF Hornyak, TJ AF Zhang, D Beyer, LA Kabara, L Halsey, K Raphael, Y Dolan, DF Hornyak, TJ TI Hearing dysfunction and loss of strial melanocytes in Mitf(Mi-wh)/+ mice, a model for human Waardenburg and Tietz syndromes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Kresge Hearing Res Inst, Dept Otolaryngol, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 862 BP A144 EP A144 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901404 ER PT J AU Zhu, Y Kopelovich, L Athar, M Kim, AL Bickers, DR AF Zhu, Y Kopelovich, L Athar, M Kim, AL Bickers, DR TI Resveratrol-mediated modulation of NF kappa B activity by SIRT1 in human epidermoid carcinoma (A431) cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 Columbia Univ, Med Ctr, New York, NY USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 584 BP A98 EP A98 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901130 ER PT J AU Arepally, A Karmarkar, PV Weiss, C Rodriguez, ER Lederman, RJ Atalar, E AF Arepally, A Karmarkar, PV Weiss, C Rodriguez, ER Lederman, RJ Atalar, E TI Magnetic resonance image-guided trans-septal puncture in a swine heart SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE interventional; magnetic resonance imaging; trans-septal catheterization; cardiac; MR guided ID REAL-TIME; CORONARY CATHETERIZATION; ABLATION; VISUALIZATION; MRI AB Purpose: To test the feasibility of performing magnetic resonance M-guided bans septal punctures in the swine heart. Materials and Methods: All procedures were performed in a 1.5-T MR scanner. A novel, active MR intravascular needle system was utilized for needle tracking and septal punctures. Trans-septal punctures were performed in five swine using electrocardiogram (ECG)-gated high resolution and non-ECG-gated, real-time MR imaging techniques. The intravascular needle was advanced over a guidewire from the femoral vein. Once the needle was in proper position, trans-septal punctures were made. Results: Active tracking of the needle traversing the septum was possible. The location of the catheter tip was confirmed using real time gradient recalled echo (GRE). After a confirmatory ventriculogram with gadolinium-DTPA, a 0.014-inch guidewire was advanced into the left atrium and left ventricle. All punctures were made with no change in cardiac rhythm or rate; postmortem analysis was performed on all animals and demonstrated that 18/19 (95%) punctures were directly through the fossa ovalis. Conclusion: : Using only MR guidance and a novel active intravascular needle system, we were able to repeatedly puncture the fossa ovalis in a swine heart from a trans-femoral approach, with direct visualization of all components, including the needle, the atria, the fossa ovalis, and the surrounding vasculature. C1 Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA. NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Arepally, A (reprint author), Johns Hopkins Univ Hosp, Blalock 545,600N Wolfe St, Baltimore, MD 21287 USA. EM aarepal@jhmi.edu RI Atalar, Ergin/D-3184-2012; OI Atalar, Ergin/0000-0002-6874-6103; lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL005062-05]; PHS HHS [R01 57483] NR 13 TC 21 Z9 21 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2005 VL 21 IS 4 BP 463 EP 467 DI 10.1002/jmri.20262 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911UD UT WOS:000228029900020 PM 15779027 ER PT J AU Li, TQ Kim, DH Moseley, ME AF Li, TQ Kim, DH Moseley, ME TI High-resolution diffusion-weighted imaging with interleaved variable-density spiral acquisitions SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion-weighted imaging; self-navigator; motion correction; interleaved variable-density spiral acquisiton; high-resolution MRI ID PROPELLER MRI; WHITE-MATTER; HUMAN BRAIN; ARTIFACTS; TRACKING; MOTION AB Purpose: To develop a multishot magnetic resonance imaging (MRI) pulse sequence and reconstruction algorithm for diffusion-weighted imaging (DWI) in the brain with sub-millimeter in-plane resolution. Materials and Methods: A self-navigated multishot acquisition technique based on variable-density spiral k-space trajectory design was implemented on clinical MRI scanners. The image reconstruction algorithm takes advantage of the oversampling of the center k-space and uses the densely sampled central portion of the k-space data for both imaging reconstruction and motion correction. The developed DWI technique was tested in an agar gel phantom and three healthy volunteers. Results: Motions result in phase and k-space shifts in the DWI data acquired using multishot spiral acquisitions. With the two-dimensional self-navigator correction, diffusion-weighted images with a resolution of 0.9 x 0.9 x 3 mm(3) were successfully obtained using different interleaves ranging from 8-32. The measured apparent diffusion coefficient (ADC) in the homogenous gel phantom was (1.66 +/- 0.09) x 10(-3) mm(2)/second, which was in a good agreement with the reported literature values. Conclusion: The self-navigated multishot variable-density spiral acquisition provides a time efficient approach to acquire high resolution provides a time efficient approach to acquire high resolution diffusion-weighted images on a clinical scanner. The reconstruction algorithm based on motion correction in the k-space data is robust, and measured ADC values are accurate and reproducible. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Radiol, Radiol Sci Lab, Stanford, CA 94305 USA. RP Li, TQ (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Room 10-B1D720, Bethesda, MD 20892 USA. EM litie@ninds.nih.gov RI Kim, Dong-Hyun/G-5096-2012; OI Li, Tieqiang/0000-0002-6636-8938; Li, Tie-Qiang/0000-0002-4866-5904 FU NIMH NIH HHS [MH063455-01A1R01] NR 26 TC 17 Z9 17 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2005 VL 21 IS 4 BP 468 EP 475 DI 10.1002/jmri.20287 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911UD UT WOS:000228029900021 PM 15779030 ER PT J AU Richani, K Soto, E Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, S Kim, YM Hong, JS Mazor, M AF Richani, K Soto, E Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, S Kim, YM Hong, JS Mazor, M TI Normal pregnancy is characterized by systemic activation of the complement system SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE complement system; anaphylatoxins; innate immunity; pregnancy; C3a; C4a; C5a ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; REGULATORY PROTEINS; C5A RECEPTOR; ANAPHYLATOXIN LEVELS; HUMAN TROPHOBLAST; SERUM COMPLEMENT; OXYGEN RADICALS; 5TH COMPONENT; PREECLAMPSIA; BLOOD AB Background. The complement system, a major component of innate immunity, has recently been implicated in the mechanisms of fetal loss and placental inflammation in the anti-phospholipid antibody syndrome. Inhibition of complement has been proposed as an absolute requirement for normal pregnancy. Yet, pregnancy is characterized by a generalized activation of the innate immune system. This study was conducted to determine whether or not normal pregnancy is associated with complement activation in the maternal circulation. Methods. Anaphylatoxins (C3a, C4a and C5a) were determined in the plasma of normal pregnant ( 20 - 42 wks; n = 134) and non-pregnant women ( n = 40). These complement split products ( C3a, C4a and C5a) were measured using specific immunoassays. Non-parametric statistics were used for analysis. Results. 1) The median plasma concentrations of C3a, C4a and C5a were significantly higher in normal pregnant women than in non-pregnant women ( all p<0.001); 2) the concentration of C3a, C4a and C5a did not change with gestational age ( p>0.05); and 3) the median plasma concentration of C3a had a positive correlation with the plasma C4a and C5a concentrations ( r = 0.36, p<0.001 and r = 0.35, p<0.001, respectively). Conclusion. 1) Normal human pregnancy is associated with evidence of complement activation, as determined by higher concentrations of the anaphylatoxins C3a, C4a and C5a in the maternal circulation; and 2) we propose that physiologic activation of the complement system during pregnancy is a compensatory mechanism aimed at protecting the host against infection. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU NICHD NIH HHS [Z01 HD002400-14] NR 61 TC 60 Z9 64 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2005 VL 17 IS 4 BP 239 EP 245 DI 10.1080/14767050500072722 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 947SP UT WOS:000230667000001 PM 16147832 ER PT J AU Soto, E Richani, K Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, S Kim, YM Hong, JS Goncalves, L Mazor, M AF Soto, E Richani, K Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, S Kim, YM Hong, JS Goncalves, L Mazor, M TI Increased concentration of the complement split product C5a in acute pyelonephritis during pregnancy SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE pregnancy; complement system; anaphylatoxins; acute pyelonephritis; innate immunity; C3a; C4a; C5a ID RESPIRATORY-DISTRESS SYNDROME; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; TUMOR-NECROSIS-FACTOR; HUMAN-NEUTROPHILS; ANAPHYLATOXIN RECEPTOR; ANTI-C5A ANTIBODIES; MONONUCLEAR-CELLS; EPITHELIAL-CELLS; SEPTIC PRIMATES; ACTIVATION AB Objective. Pregnant women with acute pyelonephritis develop acute respiratory distress syndrome ( ARDS) more frequently than non-pregnant women. The reasons for this remain unknown. The complement system is a complex set of self-assembling proteins that have been implicated in the pathophysiology of ARDS and sepsis. The purpose of this study was to determine if activation of the complement system occurs in pregnant women with acute pyelonephritis. Methods. A cross-sectional study was conducted to determine the plasma concentrations of C3a, C4a and C5a (i.e., complement split products) in pregnant patients with acute pyelonephritis (n = 38) and normal pregnant women ( n = 38). The complement split products C3a, C4a and C5a were measured using ELISA. Data were analyzed using non-parametric statistics. Results. 1) The median plasma concentration of C5a in pregnant patients with acute pyelonephritis was significantly higher than that in normal pregnant women ( p<0.001); 2) there was no statistical difference in the median plasma concentration of C3a and C4a between the two groups ( p>0.05); and 3) concentrations of C3a, C4a and C5a were not different among patients with acute pyelonephritis with and without bacteremia. Conclusions. 1) Pyelonephritis in pregnant women is associated with an increased plasma concentration of C5a, but not C3a and C4a; and 2) an excess of C5a can predispose pregnant women to develop ARDS and multi-organ failure in pyelonephritis. This finding may have clinical implications since blocking C5a improves ARDS in experimental sepsis. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU NICHD NIH HHS [Z01 HD002400-14] NR 65 TC 19 Z9 19 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2005 VL 17 IS 4 BP 247 EP 252 DI 10.1080/14767050500072805 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 947SP UT WOS:000230667000002 PM 16147833 ER PT J AU Correa-Cerro, LS Wassif, CA Waye, JS Krakowiak, PA Cozma, D Dobson, NR Levin, SW Anadiotis, G Steiner, RD Krajewska-Walasek, M Nowaczyk, MJM Porter, FD AF Correa-Cerro, LS Wassif, CA Waye, JS Krakowiak, PA Cozma, D Dobson, NR Levin, SW Anadiotis, G Steiner, RD Krajewska-Walasek, M Nowaczyk, MJM Porter, FD TI DHCR7 nonsense mutations and characterisation of mRNA nonsense mediated decay in Smith-Lemli-Opitz syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID PREMATURE STOP MUTATIONS; 7-DEHYDROCHOLESTEROL REDUCTASE GENE; CHOLESTEROL-BIOSYNTHESIS; CARRIER FREQUENCY; CYSTIC-FIBROSIS; CFTR FUNCTION; PHENOTYPE; DIAGNOSIS; DISEASE; PLASMA C1 NICHD, Heritable Disorders Branch, NIH, DHHS,Unit Mol Dysmorphol, Bethesda, MD 20892 USA. McMaster Univ, Dept Pathol & Mol Med & Pediat, Hamilton, ON, Canada. Natl Naval Med Res Inst, Dept Pediat, Bethesda, MD USA. Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. Legacy Childrens Hosp, Portland, OR USA. Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Child Dev Rehabil Ctr, Dept Pediat, Portland, OR USA. Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Child Dev Rehabil Ctr, Dept Mol & Med Genet, Portland, OR USA. Childrens Mem Hlth Inst, Dept Med Genet, Warsaw, Poland. RP Porter, FD (reprint author), NICHD, Heritable Disorders Branch, NIH, DHHS,Unit Mol Dysmorphol, Bld 10,Rm 9S241,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov OI Steiner, Robert/0000-0003-4177-4590; Wassif, Christopher/0000-0002-2524-1420 NR 37 TC 21 Z9 22 U1 0 U2 5 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 APR PY 2005 VL 42 IS 4 BP 350 EP 357 DI 10.1136/jmg.2004.022749 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 912JV UT WOS:000228074900010 PM 15805162 ER PT J AU Ghildyal, R Dagher, H Donninger, H de Silva, D Li, X Freezer, NJ Wilson, JW Bardin, PG AF Ghildyal, R Dagher, H Donninger, H de Silva, D Li, X Freezer, NJ Wilson, JW Bardin, PG TI Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE rhinovirus; primary fibroblasts; ENA-78; VEGF ID BRONCHIAL EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; IN-SITU HYBRIDIZATION; RESPIRATORY-INFECTIONS; ASTHMATIC-PATIENTS; REPLICATION; DEXAMETHASONE; INFLAMMATION; STIMULATION; CORTICOSTEROIDS AB The events linking rhinovirus (RV) infection to airway symptoms are poorly understood. The virus initially infects airway epithelium followed by a vigorous inflammatory response that may entail spread of RV from epithelium to other cells in the airway wall. However, RV has fastidious growth characteristics and to date reproductive infection of primary cells other than human airway epithelium has not been confirmed. Airway fibroblasts are adjacent to and in contact with epithelial cells, play a key role in innate immune responses, and may participate in the evolution of inflammation. To investigate fibroblast actions, we first determined whether RV could infect and replicate in primary culture human lung fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung tissue, and virus infection with replication was demonstrated by a combination of techniques. RT-PCR was used to show an increase in RV transcription; confocal microscopy demonstrated colocalization of the replicative form of RV genome (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from the culture supernatant of infected fibroblasts. Functional consequences of RV infection were next examined. RV infection of fibroblasts was followed by an increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and protein. The permeability factor vascular endothelial growth factor (VEGF) was also induced over a similar time course. These data suggest that interactions between RV and human fibroblasts are feasible, may coordinate neutrophil chemoattraction with enhanced vascular permeability and that fibroblasts may contribute to inflammatory responses following RV infections. C1 Monash Univ, Monash Med Ctr, Dept Resp Med Med & Surg, Melbourne, Vic 3004, Australia. Monash Univ, Monash Inflammatory Dis, Melbourne, Vic 3004, Australia. NCI, NIH, Rockville, MD USA. Alfred Hosp, Melbourne, Vic, Australia. RP Bardin, PG (reprint author), Monash Med Ctr, Dept Resp & Sleep Med, 246 Clayton Rd, Clayton, Vic 3168, Australia. EM p.bardin@southernhealth.org.au RI Dagher, Hayat/D-7990-2013 OI Dagher, Hayat/0000-0002-0260-5594 NR 39 TC 37 Z9 38 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD APR PY 2005 VL 75 IS 4 BP 608 EP 615 DI 10.1002/jmv.20315 PG 8 WC Virology SC Virology GA 904OC UT WOS:000227506600017 PM 15714497 ER PT J AU Resnik, DB AF Resnik, DB TI The patient's duty to adhere to prescribed treatment: An ethical analysis SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE contracts; non-adherence; noncompliance; patient's duties; physician-patient relationship ID NONCOMPLIANT PATIENT; PHYSICIAN; CARE; ISSUES AB This article examines the ethical basis for the patient's duty to adhere to the physician's treatment prescriptions. The article argues that patients have a moral duty to adhere to the physician's treatment prescriptions, once they have accepted treatment. Since patients still retain the right to refuse medical treatment, their duty to adhere to treatment prescriptions is a prima facie duty, which can be overridden by their other ethical duties. However, patients do not have the right to refuse to adhere to treatment prescriptions if their non-adherence poses a significant threat to other people. This paper also discusses the use of written agreements between physicians and patients as a strategy for promoting patient adherence. C1 E Carolina Univ, Greenville, NC USA. RP Resnik, DB (reprint author), NIEHS, NIH, POB 12233,Mail Drop NH-06, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov NR 40 TC 10 Z9 10 U1 2 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD APR PY 2005 VL 30 IS 2 BP 167 EP 188 DI 10.1080/03605310590926849 PG 22 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 924BZ UT WOS:000228955000004 PM 16025851 ER PT J AU McCarthy, J McLeod, CJ Minners, J Essop, MF Ping, PP Sack, MN AF McCarthy, J McLeod, CJ Minners, J Essop, MF Ping, PP Sack, MN TI PKC is an element of activation augments cardiac mitochondrial respiratory post-anoxic reserve - a putative mechanism in PKC is an element of cardioprotection SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE protein kinase C; cardiac protection; mitochondrial respiratory function ID SIGNALING MODULES; EPSILON; PROTECTION; PHOSPHORYLATION; PERMEABILITY; METABOLISM; ISCHEMIA; PROTEINS; HEART AB Modest cardiac-overexpression of constitutively active PKC epsilon (aPKC epsilon) in transgenic mice evokes cardioprotection against ischemia. As aPKC epsilon interacts with mitochondrial respiratory-chain proteins we hypothesized that aPKC epsilon Modulates respiration to induce cardioprotection. Using isolated cardiac mitochondria wild-type and aPKC epsilon mice display similar basal mitochondrial respiration, rate of ATP synthesis and adenosine nucleotide translocase (ANT) functional content. Conversely, the aPKC epsilon mitochondria exhibit modest hyperpolarization of their inner mitochondrial membrane potential (Delta Psi(m)) compared to wild-type mitochondrial by flow cytometry. To assess whether this hyperpolarization engenders resilience to simulated ischemia, anoxia-reoxygenation experiments were per-formed. Mitochondria were exposed to 45 min anoxia followed by reoxygenation. At reoxygenation, aPKC epsilon mitochondria recovered ADP-dependent respiration to 44 +/- 3% of baseline compared to 28 +/- 2% in WT controls (P = 0.03) in parallel with enhanced ATP synthesis. This preservation in oxidative phosphorylation is coupled to greater ANT functional content [42% > concentration of atractyloside for inhibition in the aPKC epsilon mitochondria vs. WT control (P < 0.0001)], retention of mitochondrial cytochrome c and conservation of Delta Psi(m). These data demonstrate that mitochondria from PKC epsilon activated mice are intrinsically resilient to anoxia-reoxygenation compared to WT controls. This resilience is in part due to enhanced recovery of oxidative phosphorylation coupled to maintained ANT activity. As maintenance of ATP is a prerequisite for cellular viability we conclude that PKC epsilon activation augmented mitochondrial respiratory capacity in response to anoxia-reoxygenation may contribute to the PKC epsilon cardioprotective program. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Cape Town, Sch Med, Hatter Inst Cardiol Res, ZA-7925 Cape Town, South Africa. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA USA. RP Sack, MN (reprint author), NHLBI, NIH, Bldg 10,CRC, Bethesda, MD 20892 USA. EM SackM@nhlbi.nih.gov NR 19 TC 28 Z9 28 U1 0 U2 3 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 APR PY 2005 VL 38 IS 4 BP 697 EP 700 DI 10.1016/j.yjmcc.2005.02.010 PG 4 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 917UT UT WOS:000228495400022 PM 15808847 ER PT J AU Buscaglia, M Kubelka, J Eaton, WA Hofrichter, J AF Buscaglia, M Kubelka, J Eaton, WA Hofrichter, J TI Determination of ultrafast protein folding rates from loop formation dynamics SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding; contact rate; triplet state quenching; unfolded state; villin headpiece subdomain ID INTRAMOLECULAR CONTACT FORMATION; VILLIN HEADPIECE SUBDOMAIN; AMINO-ACIDS; SPEED LIMIT; TIME-SCALE; SIMULATIONS; POLYPEPTIDES; PEPTIDES; STATE; FLEXIBILITY AB Quenching of the triplet state of tryptophan by contact with cysteine can be used to measure the kinetics of loop formation in unfolded proteins. Here we show that cysteine quenching dynamics also provide a novel method for measuring folding rates when the exchange between folded and unfolded states is faster than the unquenched triplet lifetime (similar to 100 mu s). We use this technique to investigate folding/unfolding kinetics of the 35 residue headpiece subdomain of the protein villin, which contains a single tryptophan residue and was engineered to contain a cysteine residue at the N terminus. At intermediate concentrations of denaturant the time-course of the triplet decay consists of two relaxations, the rates and amplitudes of which reveal the fast kinetics for folding and unfolding of this protein. The folding rates extracted using a simple kinetic model are close to those reported previously from laser-induced temperature-jump experiments that employ the change in tryptophan fluorescence as a probe. However, the results differ significantly from those reported from dynamic NMR line shape analysis on a variant with methionine at the N terminus, an issue that remains to be resolved. The analysis of the triplet quenching kinetics also shows that the quenching rates in the unfolded state increase with decreasing denaturant concentration, indicating a compaction of the unfolded protein. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hofrichter, J (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM jim@sunder.niddk.nih.gov RI Buscaglia, Marco/C-2435-2008 OI Buscaglia, Marco/0000-0001-5010-0278 NR 34 TC 53 Z9 54 U1 2 U2 9 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 APR 1 PY 2005 VL 347 IS 3 BP 657 EP 664 DI 10.1016/j.jmb.2005.01.057 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908KC UT WOS:000227784900014 PM 15755457 ER PT J AU Kinyamu, HK Chen, J Archer, TK AF Kinyamu, HK Chen, J Archer, TK TI Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Review ID RNA-POLYMERASE-II; HUMAN ESTROGEN-RECEPTOR; BREAST-CANCER CELLS; HUMAN PROGESTERONE-RECEPTORS; STEROID-HORMONE RECEPTOR; DNA-REPAIR ENZYME; GLUCOCORTICOID-RECEPTOR; HISTONE H3; ANDROGEN RECEPTOR; COP9 SIGNALOSOME AB Over 25 years ago, eukaryotic cells were shown to contain a highly specific system for the selective degradation of short-lived proteins, this system is known as the ubiquitin-proteasome pathway. In this pathway, proteins are targeted for degradation by covalent modification by a small highly conserved protein named ubiquitin. Ubiquitin-mediated degradation of regulatory proteins plays an important role in numerous cell processes, including cell cycle progression, signal transduction and transcriptional regulation. Recent experiments have shown that the ubiquitin-proteasome pathway is also involved in nuclear hormone receptor (NR)-mediated transcriptional regulation. The idea that the ubiquitin-proteasome pathway is involved in NR-mediated transcription is strengthened by experiments showing that ubiquitin-proteasome components are recruited to NR target gene promoters. However, it is not clear how these components modulate NR-mediated chromatin remodeling and gene expression. In this review, we postulate the role of the ubiquitin-proteasome pathway on NR-mediated chromatin remodeling and gene regulation based on the current knowledge from studies implicating the pathway in chromatin structure modifications that are applicable to NR function. Since evidence from this laboratory, using the glucocorticoid receptor responsive mouse mammary tumor virus (MMTV) promoter organized as chromatin, suggest that the ubiquitin-proteasome system may be involved in the elongation phase of transcription, we particularly concentrate on chromatin modifications associated with the elongation phase. C1 Natl Inst Environm Hlth Sci, Chromat & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Chromat & Gene Express Sect, Mol Carcinogenesis Lab, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov NR 190 TC 70 Z9 71 U1 0 U2 3 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD APR PY 2005 VL 34 IS 2 BP 281 EP 297 DI 10.1677/jme.1.01680 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 918XV UT WOS:000228583800002 PM 15821097 ER PT J AU Liu, D Zhang, Z Teng, CT AF Liu, D Zhang, Z Teng, CT TI Estrogen-related receptor-gamma and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha regulate estrogen-related receptor-alpha gene expression via a conserved multi-hormone response element SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID INDEPENDENT TRANSCRIPTIONAL ACTIVATION; ORPHAN NUCLEAR RECEPTORS; HUMAN LACTOFERRIN GENE; ERR-ALPHA; ALLOSTERIC MODULATION; PROMOTER; BETA; BINDING; LIGAND; PGC-1 AB The expression of estrogen-related receptor-a (ERR alpha) is stimulated by estrogen in selective tissues. Recently, a correlation between ERR alpha. expression and the induction of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. (PGC-1 alpha) in the liver of fasting animals and in cold-stressed brown-fat tissues and skeletal muscle was shown. To explore the molecular mechanisms of ERR alpha regulation by diverse signals, the promoter of the human ERR alpha. gene was cloned and characterized. Mutation and deletion analyses revealed that a 53 bp region containing repeated core element AGGTCA motifs of the ERRa gene serves as a multi-hormone response element (MHRE) for several nuclear receptors in transient co-transfection studies of human endometrial carcinoma (HEC-1B) cells. Among the nuclear receptors tested, ERR gamma bound to and robustly stimulated the transcription of reporters containing at least two AGGTCA motifs. Ectopic expression of PGC-1 alpha in HEC-1B cells strongly activated the reporter containing the MHRE, presumably via the endogenous nuclear receptor binding to the element. Reducing the endogenous level of ERR gamma by small interfering RNA, and increasing the ERR gamma level by ectopic expression, substantially decreased and increased respectively the transactivation capability of PGC-1 alpha. The activation function 2 domain of the ERR gamma and the L2 and L3 motifs of PGC-1 alpha were essential to transactivate the MHRE. Additionally, PGG-1 alpha increases the amount of endogenous ERR gamma bound to the MHRE region as determined by a chromatin immunoprecipitation assay. The present study demonstrates that the MHRE of the ERR alpha. gene is a target for ERR gamma transactivation, which is enhanced by PGC-1 alpha. C1 Natl Inst Environm Hlth Sci, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), Natl Inst Environm Hlth Sci, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM teng@niehs.nih.gov NR 61 TC 35 Z9 36 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD APR PY 2005 VL 34 IS 2 BP 473 EP 487 DI 10.1677/jme.1.01586 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 918XV UT WOS:000228583800016 PM 15821111 ER PT J AU Wu, YR Fung, HC Lee-Chen, GJ Gwinn-Hardy, K Ro, LS Chen, ST Hsieh-Li, HM Lin, HY Lin, CY Li, SN Chen, CM AF Wu, YR Fung, HC Lee-Chen, GJ Gwinn-Hardy, K Ro, LS Chen, ST Hsieh-Li, HM Lin, HY Lin, CY Li, SN Chen, CM TI Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE SCA17; CAG expansion; Parkinsons disease; Alzheimers disease ID SPINOCEREBELLAR ATAXIA TYPE-2; CAG TRINUCLEOTIDE REPEAT; EXPANDED POLYGLUTAMINE; REDUCED PENETRANCE; CLINICAL-DIAGNOSIS; SCA17 LOCUS; EXPANSION; GENE; PARKINSONISM; FEATURES AB Trinucleotide repeat (TNR) expansion in the gene for TATA binding protein (TBP) has recently been described as causal for spinocerebellar ataxia type 17. The normal number of repeats has been considered to be 42 or less. An intermediate range with reduced penetrance has been assumed to be 43-47 CAA/CAG repeats. We examined this gene in 30 patients with autosomal-dominant cerebellar ataxia (ADCA), 35 patients with sporadic ataxia, 11 patients with Huntington's disease (HD), 351 patients with idiopathic Parkinson's disease (PD), 105 patients with Alzheimer's disease (AD), and 291 controls with no history of neurodegenerative disease. Three patients (one with sporadic PD and two with AD) carrying more than 42 TNRs in the TBP gene were identified. This reveals that the phenotype associated with CAG/CAA expansion in the TBP gene may be heterogeneous. C1 Chang Gung Mem Hosp, Dept Neurol 2, Taipei 10591, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan. NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. RP Wu, YR (reprint author), Chang Gung Mem Hosp, Dept Neurol 2, 199 Tung Hwa N Rd, Taipei 10591, Taiwan. EM cmchen@adm.cgmh.org.tw RI Gwinn, Katrina/C-2508-2009; OI Gwinn, Katrina/0000-0002-8277-651X NR 33 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD APR PY 2005 VL 112 IS 4 BP 539 EP 546 DI 10.1007/s00702-004-0197-9 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 910BW UT WOS:000227905400006 PM 15365789 ER PT J AU d'Hellencourt, CL Harry, GJ AF d'Hellencourt, CL Harry, GJ TI Molecular profiles of mRNA levels in laser capture microdissected murine hippocampal regions differentially responsive to TMT-induced cell death SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE microglia; hippocampus; trimethyltin ID NECROSIS-FACTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-C; GENE-EXPRESSION; MICROARRAY ANALYSIS; NEURONAL SURVIVAL; TRIMETHYLTIN INTOXICATION; STATUS EPILEPTICUS; MOUSE HIPPOCAMPUS; GLIAL-CELLS AB Using a chemical-induced model of dentate granule (DG) cell death, cDNA microarray analysis was used to identify gene profiles from the laser-captured microdissected (LCM) hippocampal DG cell region versus the CA pyramidal cell layer ( CA) from 21-day-old male CD1 mice injected with trimethyltin hydroxide (TMT; 3.0 mg/kg, i.p.). At 6 h post-TMT, lectin + microglia displaying a reactive morphology were in contact with active caspase 3+ neurons. By 18 h, amoeboid microglia and signs of phagocytosis, and a mild astrocytic response were present in the DG. There was no evidence of IgG extravasation in the hippocampus, or cell death and glial reactivity in the CA. Atlas 1.2K Clontech array detected 115 genes changed in the hippocampus with TMT and included genes associated with immediate-early responses, calcium homeostasis, cellular signaling, cell cycle, immunomodulation and DNA repair. Early responses localized to LCM DG samples consisted of elevations in inflammatory factors such as tumor necrosis factor-alpha and receptors, as well as MIP1 alpha, CD14, CD18, and a decrease in factors associated with calcium buffering. By 18 h, in the DG, changes occurred in transcripts associated with apoptosis, cell adhesion, DNA repair, cell proliferation and growth. In the CA, a differential level of elevation was seen in CD86 antigen, zinc finger protein 38 and DNA damage inducible transcript 3. A significant number of genes was decreased at these early time points in both hippocampal regions. C1 Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Mol Toxicol Lab, NIH,Natl Inst Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Mol Toxicol Lab, NIH,Natl Inst Hlth & Human Serv, POB 12233,MD C104, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov NR 63 TC 22 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2005 VL 93 IS 1 BP 206 EP 220 DI 10.1111/j.1471-4159.2004.03017.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 904XZ UT WOS:000227533200021 ER PT J AU Greggio, E Bergantino, E Carter, D Ahmad, R Costin, GE Hearing, VJ Clarimon, J Singleton, A Eerola, J Hellstrom, O Tienari, PJ Miller, DW Beilina, A Bubacco, L Cookson, MR AF Greggio, E Bergantino, E Carter, D Ahmad, R Costin, GE Hearing, VJ Clarimon, J Singleton, A Eerola, J Hellstrom, O Tienari, PJ Miller, DW Beilina, A Bubacco, L Cookson, MR TI Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; genetics; neuromelanin; Parkinson's disease; tyrosinase ID HUMAN SUBSTANTIA-NIGRA; ALPHA-SYNUCLEIN; MELANOSOME BIOGENESIS; ENDOPLASMIC-RETICULUM; MAMMALIAN TYROSINASE; TYR GENE; NEUROMELANIN; NEURONS; CELLS; TRANSPORT AB Tyrosinase is a key enzyme in the synthesis of melanin in skin and hair and has also been proposed to contribute to the formation of neuromelanin (NM). The presence of NM, which is biochemically similar to melanin in peripheral tissues, identifies groups of neurons susceptible in Parkinson's disease (PD). Whether tyrosinase is beneficial or detrimental to neurons is unclear; whilst the enzyme activity of tyrosinase generates dopamine-quinones and other oxidizing compounds, NM may form a sink for such radical species. In the present study, we demonstrated that tyrosinase is expressed at low levels in the human brain. We found that mRNA, protein and enzyme activity are all present but at barely detectable levels. In cell culture systems, expression of tyrosinase increases neuronal susceptibility to oxidizing conditions, including dopamine itself. We related these in vitro observations to the human disease by assessing whether there was any genetic association between the gene encoding tyrosinase and idiopathic PD. We found neither genotypic or haplotypic association with three polymorphic markers of the gene. This argues against a strong genetic association between tyrosinase and PD, although the observed contribution to cellular toxicity suggests that a biochemical association is likely. C1 Univ Padua, Inst Biol, Dept Biol, I-35121 Padua, Italy. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. NCI, Pigment Cell Biol Sect, Bethesda, MD 20892 USA. Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. Univ Helsinki, Biomedicum Helsinki, Program Neurosci, Helsinki, Finland. Seinojaki Cent Hosp, Dept Neurol, Seinajoki, Finland. RP Greggio, E (reprint author), Univ Padua, Inst Biol, Dept Biol, Via Ugo Bassi 58B, I-35121 Padua, Italy. EM elisa@cribi.unipd.it RI Singleton, Andrew/C-3010-2009; Tienari, Pentti/A-4893-2012; Bubacco, Luigi/B-5602-2012; Greggio, Elisa/H-6119-2013; OI Greggio, Elisa/0000-0002-8172-3598; Clarimon, Jordi/0000-0002-6824-6942; Bubacco, Luigi/0000-0001-7927-9208 NR 46 TC 50 Z9 52 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2005 VL 93 IS 1 BP 246 EP 256 DI 10.1111/j.1471-4159.2005.03019.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 904XZ UT WOS:000227533200024 PM 15773923 ER PT J AU Luo, YQ Cai, JL Xue, HP Miura, T Rao, MS AF Luo, YQ Cai, JL Xue, HP Miura, T Rao, MS TI Functional SDF1 alpha/CXCR4 signaling in the developing spinal cord SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE chemotaxis; extracellular signal-regulated kinase activation; gene expression; migration; neural progenitors ID ETS TRANSCRIPTION FACTORS; CELL-DERIVED FACTOR-1; NEUROEPITHELIAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR; GROWTH-FACTOR; NEURONAL PRECURSORS; PROGENITOR CELLS; GRANULE CELLS; NEURAL-TUBE AB Stromal cell-derived factor (SDF1) and its cognate receptor CXCR4 have been shown to play a central role in the development of the cerebellum, hippocampus, and neocortex. However, little is known about the functions of SDF1/CXCR4 in early spinal cord progenitor cell differentiation. Here, we show that a functional SDF1 alpha/CXCR4 signaling pathway is present in developing spinal cord cells (a spliced variant of SDF1). RT-PCR analysis of SDF1 alpha and CXCR4 showed that they were present in E10.5 neural tube and their expression increased as neuroepithelial cells differentiated into more committed spinal cord progenitors. Stimulation of the more differentiated progenitors (E14.5) with SDF1 alpha resulted in rapid activation of the extracellular signal-regulated kinase (ERK)1/2. This SDF1 alpha-induced ERK activity was dose dependent and could be inhibited by pre-treatment of the cells with either pertussis toxin, an inactivator of G-protein-coupled receptors, or PD98059, a MEK1 inhibitor. Concomitant with ERK activation, SDF1 alpha also activated the downstream transcription factor Ets, a substrate for ERK phosphorylation. Further, downstream activation of genes associated with cell survival, differentiation and migration was assessed using a G-protein-coupled receptor pathway-focused microarray. We found that 23 genes, including PDK1, Egr-1, Grm5, and E-selectin, were up-regulated by SDF1 alpha. Furthermore, SDF1 alpha induced chemotaxis in both neural and glial progenitors in in vitro migration assays. Pre-treatment of the cells with either pertussis toxin or PD98059 completely inhibited SDF1 alpha-induced chemotaxis. Thus, our data suggest that SDF1 alpha may function through a CXCR4/ERK/Ets-linked signalling pathway in spinal cord neural development to modulate migration of progenitor cells. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Rao, MS (reprint author), Rm 4064,333 Cassell Dr, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov NR 49 TC 34 Z9 40 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2005 VL 93 IS 2 BP 452 EP 462 DI 10.1111/j.1471-4159.2005.03049.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 911PS UT WOS:000228017300020 PM 15816868 ER PT J AU Wei, FY Tomizawa, K Ohshima, T Asada, A Saito, T Nguyen, C Bibb, JA Ishiguro, K Kulkarni, AB Pant, HC Mikoshiba, K Matsui, H Hisanaga, S AF Wei, FY Tomizawa, K Ohshima, T Asada, A Saito, T Nguyen, C Bibb, JA Ishiguro, K Kulkarni, AB Pant, HC Mikoshiba, K Matsui, H Hisanaga, S TI Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calmodulin; cyclin-dependent kinase 5; proteasome; glutamate; N-methyl-D-aspartate; long-term potentiation ID SYNAPTIC VESICLE ENDOCYTOSIS; NEURONAL-SPECIFIC ACTIVATOR; NEURITE OUTGROWTH; CORTICAL-NEURONS; PHOSPHORYLATION; P25; RECEPTORS; SUBUNIT; CLEAVAGE; CALPAIN AB Although the roles of cyclin-dependent kinase 5 (Cdk5) in neurodevelopment and neurodegeneration have been studied extensively, regulation of Cdk5 activity has remained largely unexplored. We report here that glutamate, acting via NMDA or kainate receptors, can induce a transient Ca2+/calmodulin-dependent activation of Cdk5 that results in enhanced autophosphorylation and proteasome-dependent degradation of a Cdk5 activator p35, and thus ultimately down-regulation of Cdk5 activity. The relevance of this regulation to synaptic plasticity was examined in hippocampal slices using theta burst stimulation. p35(-/-) mice exhibited a lower threshold for induction of long-term potentiation. Thus excitatory glutamatergic neurotransmission regulates Cdk5 activity through p35 degradation, and this pathway may contribute to plasticity. C1 Tokyo Metropolitan Univ, Grad Sch Sci, Dept Sci Biol, Hachioji, Tokyo 1920397, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Physiol, Okayama, Japan. Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama, Japan. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Mitsubishi Kagaku Inst Life Sci, Tokyo, Japan. NINDS, Funct Genom Unit, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NINDS, Lab Neurochem, NIH, Bethesda, MD USA. RP Hisanaga, S (reprint author), Tokyo Metropolitan Univ, Grad Sch Sci, Dept Sci Biol, Hachioji, Tokyo 1920397, Japan. EM hisanaga-shinichi@c.metro-u.ac.jp RI Tomizawa, Kazuhito/F-2405-2015; Mikoshiba, Katsuhiko/N-7943-2015 OI Tomizawa, Kazuhito/0000-0002-5663-2627; NR 51 TC 59 Z9 63 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2005 VL 93 IS 2 BP 502 EP 512 DI 10.1111/j.1471-4159.2005.03058.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 911PS UT WOS:000228017300025 PM 15816873 ER PT J AU Bryceson, YT Foster, JA Kuppusamy, SP Herkenham, M Long, EO AF Bryceson, YT Foster, JA Kuppusamy, SP Herkenham, M Long, EO TI Expression of a killer cell receptor-like gene in plastic regions of the central nervous system SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE dentate gyros; MHC class I; NK cell receptor; olfactory bulb; plasticity ID PRIMARY SENSORY NEURONS; NEURAL STEM-CELLS; INFECTION IN-VIVO; INHIBITORY RECEPTORS; CUTTING EDGE; T-CELLS; MHC; IMMUNE; RAT; NK AB A property common to the immune system and the nervous system is regulation by a highly complex and adaptable network of cellular interactions. Major histocompatibility complex (MHC) class I molecules, which are ligands of antigen-specific receptors on CD8 T cells and of inhibitory receptors on natural killer cells, have an important and surprising role in the control of activity-dependent neuronal plasticity in the central nervous system (CNS). While expression of MHC class I molecules in neurons has been reported, corresponding immune receptors have not been identified in the CNS. Here we show selective expression of a gene related to killer cell immunoglobulin-like receptor (KIR) genes in subregions of the mouse brain where synaptic plasticity and neurogenesis occur, including olfactory bulbs, rostral migratory stream and dentate gyrus of hippocampus. These results suggest new functions for KIR-like molecules in the CNS. Published by Elsevier B.V. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM herkenh@mail.nih.gov; eLong@niaid.nih.gov RI Long, Eric/G-5475-2011; OI Long, Eric/0000-0002-7793-3728; Herkenham, Miles/0000-0003-2228-4238; Bryceson, Yenan/0000-0002-7783-9934 NR 41 TC 29 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR PY 2005 VL 161 IS 1-2 BP 177 EP 182 DI 10.1016/j.jneuroim.2004.11.018 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 911KS UT WOS:000228001700020 PM 15748957 ER PT J AU Zhu, DM Wu, X Strauss, KI Lipsky, RH Qureshi, Z Terhakopian, A Novelli, A Banaudha, K Marini, AM AF Zhu, DM Wu, X Strauss, KI Lipsky, RH Qureshi, Z Terhakopian, A Novelli, A Banaudha, K Marini, AM TI N-methyl-D-aspartate and TrkB receptors protect neurons against glutamate excitotoxicity through an extracellular signal-regulated kinase pathway SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE NMDA; cerebellar granule cells; TrkB receptors; MAPK; Akt; BDNF; excitotoxicity; glutamate; Bcl-2; Bcl-X-L; Bax ID CEREBELLAR GRANULE NEURONS; FOCAL CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; RAT DENTATE GYRUS; FACTOR-KAPPA-B; NEUROTROPHIC FACTOR; CELL-DEATH; PHOSPHATIDYLINOSITOL 3-KINASE; NERVOUS-SYSTEM; MAP KINASE AB N-Methyl-D-aspartate (NMDA) at a subtoxic concentration (100 mu M) promotes neuronal survival against glutamate-mediated excitotoxicity via a brain-derived neurotrophic factor (BDNF) autocrine loop in cultured cerebellar granule cells. The signal transduction mechanism(s) underlying NMDA neuroprotection, however, remains elusive. The mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways alter gene expression and are involved in synaptic plasticity and neuronal survival. This study tested whether neuroprotective activation of NMDA receptors, together with TrkB receptors, coactivated the MAPK or PI3-K pathways to protect rat cerebellar neurons. NMDA receptor activation caused a concentration- and time-dependent activation of MAPK lasting 24 hr. This activation was blocked by the NMDA receptor antagonist MK-801 but was attenuated only partially by the tyrosine kinase inhibitor k252a, suggesting that activation of both NMDA and TrkB receptors are required for maximal neuro protection. The MAPK kinase (MEK) inhibitor U0126 (10 mu M) partially blocked NMDA neuroprotection, whereas LY294002, a selective inhibitor of the PI3-K pathway, did not affect the neuroprotective activity of NMDA. Glutamate excitotoxicity decreased bcl-2, bcl-X-L, and bax mRNA levels. NMDA increases Bcl-2 and Bcl-X-L protein levels and decreases Bax protein levels . NMDA and TrkB receptor activation thus converge on the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway to protect neurons against glutamate-mediated excitotoxicity. By increasing antiapoptotic proteins of the Bcl-2 family, NMDA receptor activation may also promote neuronal survival by preventing apoptosis. (c) 2005 Wiley-Liss, Inc. C1 Uniformed Serv Univ Hlth Sci, Dept Neurol, Dept Neurol & Neurosci, Bethesda, MD 20814 USA. Univ Cincinnati, Coll Med, Dept Neurosurg, Cincinnati, OH 45267 USA. Univ Oviedo, Fac Psychol, Dept Psychol, Oviedo, Spain. NIAAA, Neurogenet Lab, NIH, Rockville, MD USA. RP Marini, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, Dept Neurol & Neurosci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM amarini@usuhs.mil RI Novelli, Antonello/P-7476-2015; OI Novelli, Antonello/0000-0002-0129-8350; Lipsky, Robert/0000-0001-7753-1473 FU NINDS NIH HHS [R01 NS038654] NR 76 TC 53 Z9 61 U1 0 U2 6 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 APR 1 PY 2005 VL 80 IS 1 BP 104 EP 113 DI 10.1002/jnr.20422 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 914CW UT WOS:000228203400011 PM 15744743 ER PT J AU Dunson, DB Taylor, JA AF Dunson, DB Taylor, JA TI Approximate Bayesian inference for quantiles SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE comet assay; nonparametric; median regression; order constraints; prior elicitation; quantile regression; single-cell electrophoresis; substitution likelihood ID REGRESSION; LIKELIHOOD AB Suppose data consist of a random sample from a distribution function F-gamma, which is unknown, and that interest focuses on inferences on theta, a vector of quantiles of F-gamma. When the likelihood function is not fully specified, a posterior density cannot be calculated and Bayesian inference is difficult. This article considers an approach which relies on a substitution likelihood characterized by a vector of quantiles. Properties of the substitution likelihood are investigated, strategies for prior elicitation are presented, and a general framework is proposed for quantile regression modeling. Posterior computation proceeds via a Metropolis algorithm that utilizes a normal approximation to the posterior. Results from a simulation study are presented, and the methods are illustrated through application to data from a genotoxicity experiment. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 19 TC 37 Z9 37 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1048-5252 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PD APR-MAY PY 2005 VL 17 IS 3 BP 385 EP 400 DI 10.1080/10485250500039049 PG 16 WC Statistics & Probability SC Mathematics GA 915JG UT WOS:000228299900008 ER PT J AU Sakata, SF Okumura, S Matsuda, K Horikawa, Y Maeda, M Kawasaki, K Chou, JY Tamaki, N AF Sakata, SF Okumura, S Matsuda, K Horikawa, Y Maeda, M Kawasaki, K Chou, JY Tamaki, N TI Effect of fasting on methionine adenosyltransferase expression and the methionine cycle in the mouse liver SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY LA English DT Article DE methionine adenosyltransferase; adenosylmethionine; fasting; methylation; glutathione ID S-ADENOSYLMETHIONINE SYNTHETASE; DNA METHYLATION; RAT-LIVER; DEFICIENCY; GENE; ADENOSYLHOMOCYSTEINE; HYPOMETHYLATION; PURIFICATION; METABOLISM; HOMOCYSTEINE AB The effect of fasting on mouse liver methionine adenosyltransferase (MAT I/III) expression and the regulation of methionine metabolism were investigated. The mRNA level, protein level, and activity of MAT I/III were increased by fasting for 10 or 16 h. In spite of the increase of MAT I/III activity, S-adenosylmethionine, the product of methionine due to MAT I/III, decreased. S-Adenosylhomocysteine, which is made from S-adenosylmethionine by its coupling to methyltransfcrase, increased as a result of fasting for 16 h. These results suggest that the total methylation reactions using S-adenosylmethionine are stimulated in the fasting mouse liver. However, the DNA methylation level was not changed by fasting for 16 h. Glutathione, which is made by the transsulfuration pathway from homocysteine, decreased due to fasting. Regulation of supplementation of S-adenosylmethionine may occur in the fasting mouse because MAT I/III activity increases and the flow to glutathione is decreased. C1 Kobe Gakuin Univ, Fac Nutr, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, Fac Pharm, Kobe, Hyogo 6512180, Japan. NICHHD, Bethesda, MD USA. RP Sakata, SF (reprint author), Kobe Gakuin Univ, Fac Nutr, Kobe, Hyogo 6512180, Japan. EM sakata@nutr.kobegakuin.ac.jp NR 38 TC 3 Z9 4 U1 0 U2 0 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN SN 0301-4800 J9 J NUTR SCI VITAMINOL JI J. Nutr. Sci. Vitaminol. PD APR PY 2005 VL 51 IS 2 BP 118 EP 123 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 926FR UT WOS:000229109100011 PM 16022199 ER PT J AU Zhang, YW Cantor, KP Lynch, CF Zhu, Y Zheng, TZ AF Zhang, YW Cantor, KP Lynch, CF Zhu, Y Zheng, TZ TI Occupation and risk of pancreatic cancer: A population-based case-control study in Iowa SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID K-RAS MUTATIONS; METALWORKING FLUIDS; PLANT WORKERS; FOLLOW-UP; MORTALITY; EXPOSURE; VALIDITY; HYDROCARBONS; VALIDATION; ETIOLOGY AB Objective: Previous epidemiological studies have inconsistently linked various occupations and industries to pancreatic cancer risk. Methods: We analyzed data from a population-based case-control study conducted in Iowa involving 376 histologically confirmed incident pancreatic cancer cases and 2434 control subjects. Results: A significantly increased risk was observed among men who worked in the following industries: chemical and allied products, transportation, and elementary and secondary schools. Increased risks also were observed in men who were employed as truck drivers; railroad brake, signal, and switch operators; purchasing agents and buyers; teachers; insurance a significantly increased agents; and retail supervisors. Among women, risk of pancreatic cancer was found for employment in furniture and home furnishing stores, and a borderline significantly increased risk textile sewing machine operators and tenders. Conclusions: among text Working in several occupations and industries was associated with an increased risk of pancreatic cancer in this study, and these associations warrant further investigation. C1 Yale Univ, Sch Publ Hlth, New Haven, CT USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. RP Zheng, TZ (reprint author), 60 Coll St,Room 442, New Haven, CT 06520 USA. EM tongzhang.zheng@yale.edu NR 48 TC 6 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2005 VL 47 IS 4 BP 392 EP 398 DI 10.1097/01.jom.0000158707.88801.f5 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 915UN UT WOS:000228336900008 PM 15824631 ER PT J AU Green, RS Gold, EB Samuels, SJ Dosemeci, M AF Green, RS Gold, EB Samuels, SJ Dosemeci, M TI The relation of occupational organic solvent exposure to symptom reporting in a sample of white and chinese midlife women SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID MENOPAUSAL SYMPTOMS; MENSTRUAL DISORDERS; HONG-KONG; WORKERS; HEALTH; POPULATION; EXPERIENCE; TOLUENE; MATRIX; RISK AB Objective: This study examined the relation of occupational solvent exposure to menopausal and other symptoms in midlife women. Methods: We conducted a cross-sectional study of 480 Chinese and 494 white women, aged 40-55 years, in Northern California. Levels of exposure to organic solvents (none, low, medium, or high) were assigned to each current job using a job-exposure matrix. Results: A lower proportion of women with low occupational organic solvent exposure reported hot flashes or night sweats than working women with no solvent exposure (adjusted prevalence odds ratio [APOR] 0.48, 95% confidence interval [CI] = 0.19-1.21). A greater Proportion of women with high solvent exposure reported forgetfulness than women with no exposure (APOR = 2.51, 95% CI = 1.12-5.63). Conclusions: Some symptom reporting in midlife women was related to their occupational organic solvent exposure. C1 Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA 94612 USA. Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. SUNY Albany, Sch Publ Hlth, Dept Epidemiol, Rensselaer, NY USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Green, RS (reprint author), Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, 1515 Clay St,16th Floor, Oakland, CA 94612 USA. EM sgreen@oehha.ca.gov FU NIA NIH HHS [U01 AG012531, U01 AG012546, U01 AG012554, U01 AG012535, U01 AG012539, U01 AG012505]; NINR NIH HHS [U01 NR04061] NR 46 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2005 VL 47 IS 4 BP 410 EP 423 DI 10.1097/01.jom.0000158709.64716.06 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 915UN UT WOS:000228336900010 PM 15824633 ER PT J AU Engel, PS Tsvaygboym, KP Bachilo, S Smith, WB Jiang, JJ Chignell, CF Motten, AG AF Engel, PS Tsvaygboym, KP Bachilo, S Smith, WB Jiang, JJ Chignell, CF Motten, AG TI Photorearrangement of alpha-azoxy ketones and triplet sensitization of azoxy compounds SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ELECTRON-SPIN-RESONANCE; NUCLEAR MAGNETIC-RESONANCE; ARYL-ALKYL KETONES; DIAZENE N-OXIDES; PHOTOLYTIC ISOMERIZATION; ANTIFUNGAL AGENT; HALO COMPOUNDS; BOND FORMATION; RADICALS; PHOTOCHEMISTRY AB Although some aspects of azoxy group radical chemistry have been investigated,(1) unhindered alpha-azoxy radicals remain poorly understood. Here we report the generation of alpha-azoxy radicals under mild conditions by irradiation of alpha-azoxy ketones 4a,b. These compounds undergo a-cleavage to yield radicals 5a,b, whose oxygen atom then recombines with benzoyl radicals to produce presumed intermediate 15. Formal Claisen rearrangement gives alpha-benzoyloxyazo compounds 8a,b, which are themselves photolabile, leading to both radical and ionic decomposition. The ESR spectrum of 5a was simulated to extract the isotropic hyperfine splitting constants, which showed its resonance stabilization energy to be exceptionally large. Azoxy compounds have been found for the first time to be good quenchers of triplet excited acetophenone, the main sensitized photoreaction of 7Z in benzene being deoxygenation. While this reaction has been reported previously, it was always in hydrogen atom donating solvents, where chemical sensitization occurred. The principal direct irradiation product of 4bZ and model azoxyalkane 7Z is the E isomer, whose thermal reversion to Z is much faster than that of previously studied analogues. C1 Rice Univ, Dept Chem, Houston, TX 77005 USA. Texas Christian Univ, Dept Chem, Ft Worth, TX 76129 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Rice Univ, Dept Chem, POB 1892, Houston, TX 77005 USA. EM engel@rice.edu NR 76 TC 1 Z9 1 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 1 PY 2005 VL 70 IS 7 BP 2598 EP 2605 DI 10.1021/jo040274v PG 8 WC Chemistry, Organic SC Chemistry GA 910JU UT WOS:000227928200023 PM 15787549 ER PT J AU Stoffel, EC Ulibarri, CM Folk, JE Rice, KC Craft, RM AF Stoffel, EC Ulibarri, CM Folk, JE Rice, KC Craft, RM TI Gonadal hormone modulation of mu, kappa, and delta opioid antinociception in male and female rats SO JOURNAL OF PAIN LA English DT Article DE testosterone; estradiol; progesterone; pain; analgesia; sex differences ID VENTROLATERAL PERIAQUEDUCTAL GRAY; MORPHINE-INDUCED ANTINOCICEPTION; SEX-RELATED DIFFERENCES; INDUCED ANALGESIA; RECEPTOR; GONADECTOMY; BEHAVIOR; STEROIDS; PROGESTERONE; NOCICEPTION AB Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectornized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50 degrees C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. in females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat. Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. (c) 2005 by the American Pain Society. C1 Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. Washington State Univ, Dept Vet & Comparat Anat Pharmacol & Physiol, Pullman, WA 99164 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Craft, RM (reprint author), Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. EM craft@wsu.edu FU NIDA NIH HHS [DA10284, R29 DA010284-05] NR 52 TC 65 Z9 69 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2005 VL 6 IS 4 BP 261 EP 274 DI 10.1016/j.jpain.2004.12.006 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 926JZ UT WOS:000229120800008 PM 15820914 ER PT J AU Stephens, MC Baldassano, RN York, A Widemann, B Pitney, TC Jayaprakash, T Adamson, PC AF Stephens, MC Baldassano, RN York, A Widemann, B Pitney, TC Jayaprakash, T Adamson, PC TI The bioavailability of oral methotrexate in children with inflammatory bowel disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE methotrexate; bioavailability; inflammatory bowel disease; Crohn disease; ulcerative colitis ID REFRACTORY CROHNS-DISEASE; ISRAELI MULTICENTER TRIAL; LOW-DOSE METHOTREXATE; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; ULCERATIVE-COLITIS; PHARMACOKINETICS; REMISSION; EFFICACY; MAINTENANCE AB Objectives: Methotrexate is used to treat patients with inflammatory bowel disease. Although no available pharmacologic data support the assumption that the bioavailability of methotrexate is diminished in patients with inflammatory bowel disease, most such patients receive methotrexate parenterally. Methods: The oral bioavailability of methotrexate was determined in 11 pediatric patients being treated with methotrexate for inflammatory bowel disease. Serial plasma methotrexate concentrations were determined after equal subcutaneous and oral doses of methotrexate. Results: The mean bioavailability of methotrexate in patients with inflammatory bowel disease was 84% +/- 38%. Interpatient variability in drug exposure was similar after oral and subcutaneous administration. Conclusions: The bioavailability of methotrexate in patients with inflammatory bowel disease is no different from that observed in other disease states. Subcutaneous administration of methotrexate does not appear to decrease the interpatient variability in drug exposure. There is no sound pharmacologic basis for favoring administration of methotrexate via the subcutaneous route for patients with inflammatory bowel disease. (c) 2005 Lippincott Williams C Wilkins. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Clin Pharmacol & Therapeut,Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Ctr Pediat IBD,Dept Pediat, Philadelphia, PA 19104 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Adamson, PC (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Clin Pharmacol & Therapeut,Dept Pediat, 3615 Civ Ctr Blvd,ARC 916, Philadelphia, PA 19104 USA. EM adamsonp@mail.med.upenn.edu FU NCRR NIH HHS [M01RR000240]; NICHD NIH HHS [U10 HD37255]; NIDDK NIH HHS [T-32DK07066] NR 36 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD APR PY 2005 VL 40 IS 4 BP 445 EP 449 DI 10.1097/01.MPG.0000157588.27125.50 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 912KZ UT WOS:000228078400009 PM 15795592 ER PT J AU Malozowski, S AF Malozowski, S TI Treatment of adolescents with gynecomastia SO JOURNAL OF PEDIATRICS LA English DT Letter C1 NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Malozowski, S (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2005 VL 146 IS 4 BP 576 EP 576 DI 10.1016/j.jpeds.2004.10.041 PG 1 WC Pediatrics SC Pediatrics GA 916VJ UT WOS:000228414200031 PM 15812473 ER PT J AU King, JE Weiss, A Farmer, KH AF King, JE Weiss, A Farmer, KH TI A chimpanzee (Pan troglodytes) analogue of cross-national generalization of personality structure: Zoological parks and an African sanctuary SO JOURNAL OF PERSONALITY LA English DT Article ID 5-FACTOR MODEL; LIFE-SPAN; CULTURES; DOMINANCE; CONSERVATION; NUMBER AB Six personality factors, including five resembling the human Big Five, had previously been identified in a separate group of zoo-housed chimpanzees. Comparability of chimpanzee personality factor structure was examined in two highly contrasting habitats: zoos and a large African sanctuary. Questionnaires for the zoo chimpanzees were in English, while most for the chimpanzees in the sanctuary were in French. Differences between the two settings were sufficiently extensive to make them analogous to cross-national human personality studies. Internal consistencies for five of the six factors did not differ between the two samples. The patterns of correlations between the unit-weighted factors were also similar for the two samples. Data from these two samples were pooled and factor analyzed. The resulting factor structure was then rotated to the factor structure described in the original study of chimpanzee personality. Dominance, Extraversion, Dependability, and Agreeableness had high congruences. Emotionality and Openness did not, but the items that had the highest loadings were consistent with the factors' definitions. Finally, sex and age effects for all factors generalized across habitats. C1 Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Natl Inst Aging, Baltimore, MD USA. Univ Stirling, Stirling FK9 4LA, Scotland. RP King, JE (reprint author), Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. EM kingj@u.arizona.edu NR 45 TC 54 Z9 55 U1 2 U2 9 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0022-3506 J9 J PERS JI J. Pers. PD APR PY 2005 VL 73 IS 2 BP 389 EP 410 DI 10.1111/j.1467-6494.2005.00313.x PG 22 WC Psychology, Social SC Psychology GA 902IX UT WOS:000227349400004 PM 15745435 ER PT J AU Jia, L Tomaszewski, JE Noker, PE Gorman, GS Glaze, E Protopopova, M AF Jia, L Tomaszewski, JE Noker, PE Gorman, GS Glaze, E Protopopova, M TI Simultaneous estimation of pharmacokinetic properties in mice of three anti-tubercular ethambutol analogs obtained from combinatorial lead optimization SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE anti-tubercular drug; ethambutol; pharmacokinetic screening; cassette dosing ID MYCOBACTERIUM-TUBERCULOSIS; IN-VIVO; IDENTIFICATION; PREDICTION; DRUGS AB Integrating combinatorial lead optimization of [1,2]-diamine core structure based on ethambutol with high-throughput screening has led us to focus on three promising analogs (SQ37, SQ59 and SQ109) as potential anti-tubercular drug candidates from thousands of synthesized diamine analogs for further characterization of their biopharmaceutical and pharmacokinetic properties by using liquid chromatography/tandem mass spectrometry (LC/MS/MS) and cassette dosing for pharmacokinetic screening. Simultaneous separation of the three analogs was achieved on reversed phase HPLC using a gradient mobile phase composed of MeOH/CH3COONH4 (5 mM)/trifluoroacetic acid: 80/20/0.1 (v/v/v). After extraction with acetonitrile from biomatrices, samples were analyzed on the LC/MS/MS system in the positive mode using an electrospray ion source. The retention time for the analogs ranged from 3.70 to 4.48 min. Incubation of SQ37 with plasma at 37 degrees C for 6 h resulted in its degradation in human and rat plasma (20-35%), but no significant degradation was observed in mouse and dog plasma. SQ59 was relatively stable in the plasma of the four species. SQ109 was degraded in human and dog plasma (30-40%), but stable in mouse and rat plasma during the 6 h incubation. A rapid multiple pharmacokinetic screening was taken by cassette dosing of the three analogs to mice and simultaneous analysis of their plasma concentrations. The analogs showed large Vd(ss) ranging from 11,300 (SQ37),12,800 (SQ109) to 63,900 ml/kg (SQ59). The clearance ranged from 3240 (SQ109), 3530 (SQ37) and 8043 ml/kg/h (SQ59). The elimination t(1/2) ranged from 4.4 to 21.1 h dependent on the routes. The oral bioavailability was 5.1 (SQ59), 20.1 (SQ37) and 7.8% (SQ109), respectively. Both SQ37 and SQ109 possess good pharmacokinetic properties. Published by Elsevier B.V. C1 NCI, Dev Therapeut Program, EPN, NIH, Rockville, MD 20852 USA. So Res Inst, Birmingham, AL 35255 USA. Sequella Inc, Rockville, MD 20849 USA. RP Jia, L (reprint author), NCI, Dev Therapeut Program, EPN, NIH, Rm 8042,6130 Execut Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov NR 17 TC 25 Z9 27 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 1 PY 2005 VL 37 IS 4 BP 793 EP 799 DI 10.1016/j.jpba.2004.11.036 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 921SA UT WOS:000228783800023 PM 15797803 ER PT J AU Lee, SJ Bell, DA Coulter, SJ Ghanayem, B Goldstein, JA AF Lee, SJ Bell, DA Coulter, SJ Ghanayem, B Goldstein, JA TI Recombinant CYP3A4*17 is defective in metabolizing the hypertensive drug nifedipine, and the CYP3A4*17 allele may occur on the same chromosome as CYP3A5*3, representing a new putative defective CYP3A haplotype SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; CYTOCHROME-P450 3A4; ESCHERICHIA-COLI; LIVER-MICROSOMES; IN-VITRO; EXPRESSION; TACROLIMUS; PURIFICATION; CYCLOSPORINE; POPULATIONS AB Genetic variation in CYP3A activity may influence the rate of the metabolism and elimination of CYP3A substrates in humans. We previously reported four new CYP3A4 coding variants in three different racial groups. In the present study, we examined metabolism of nifedipine by the recombinant forms of these allelic variants. Metabolism of nifedipine by the L293P (CYP3A4*18), M445T (CYP3A4*3), and P467S (CYP3A4*19) allelic variants was not significantly different from wild- type CYP3A4*1. However, F189S (CYP3A4*17) exhibited a 99% decrease in both V-max and CLmax of nifedipine compared with CYP3A4*1. Of 72 racially diverse individuals, CYP3A4*17 was identified in 1 of 24 Caucasian samples [1: 5 Eastern European (Adygei ethnic group)]. Genotyping of an extended set of 276 genomic DNAs of Caucasians (100 from the Coriell Repository and an additional 176 from the United States) for CYP3A4*17 detected no additional individuals containing the CYP3A4*17 allele. However, additional genotyping of four more Adygei samples available from Coriell detected an additional individual carrying the CYP3A4*17 allele. New specific polymerase chain reaction-restriction fragment length polymorphism genotyping procedures were developed for the major splice variant of CYP3A5 (CYP3A5*3) and CYP3A4*17. Genotyping revealed that the two individuals carrying CYP3A4*17 were either homozygous or heterozygous for the more frequent CYP3A5*3 allele, suggesting that the two alleles may exist on the same chromosome as a new putative CYP3A poor metabolizer haplotype. We predict that individuals who are homozygous for defective alleles of both of these genes would metabolize CYP3A substrates poorly. The new genetic tests will be useful in future clinical studies to investigate genotype/phenotype associations. C1 NIEHS, Human Metab Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Genom Sect, Lab Computat Biol & Risk Assessment, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Metab & Exposure Markers Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Human Metab Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012; OI Coulter, Sherry/0000-0002-2732-3470 NR 33 TC 42 Z9 50 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2005 VL 313 IS 1 BP 302 EP 309 DI 10.1124/jpet.104.078758 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 907QM UT WOS:000227733000035 PM 15634941 ER PT J AU Rieg, T Steigele, H Schnermann, J Richter, K Osswald, H Vallon, V AF Rieg, T Steigele, H Schnermann, J Richter, K Osswald, H Vallon, V TI Requirement of intact adenosine a1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID A(1) RECEPTOR ANTAGONIST; TUBULOGLOMERULAR FEEDBACK; GLUCOSE-TRANSPORT; TUBULAR FUNCTION; MICE LACKING; CYCLIC-AMP; ADENOSINE; RAT; PHOSPHATE; EXCRETION AB Although the diuretic and natriuretic effects of the methylxanthines caffeine and theophylline are well established, the mechanisms responsible for these effects are unclear and may be related to inhibition of phosphodiesterases and/or antagonism of adenosine receptors. With regard to the latter, pharmacological blockade of A(1) receptors can induce diuresis and natriuresis by inhibition of proximal tubular reabsorption. To elucidate the role of the A(1) receptor in renal actions of methylxanthines, experiments were performed in A(1) receptor knockout (A(1)R-/-) and littermate wild-type (A(1)R+/+) mice. Urinary excretion was determined in awake mice in metabolic cages over 3 h in response to theophylline (as theophylline(2)/ethylenediamine, 45 mg/kg), caffeine (45 mg/kg), or vehicle (0.9 ml/30 g b.wt. of 0.85% NaCl) given by oral gavage. Theophylline and caffeine elicited a diuresis and natriuresis (in absolute terms and related to urinary creatinine excretion) in A(1)R+/+ but not in A(1)R-/- mice. In a second series, the renal effect of intravenous application of theophylline (30 mg/kg) was determined in clearance experiments under anesthesia. This study revealed that the blunted diuretic and natriuretic effect of theophylline in A(1)R-/- mice was not due to different responses in blood pressure or glomerular filtration rate. The data indicate that an intact A(1) receptor is necessary for caffeine- and theophylline-induced inhibition of renal reabsorption causing diuresis and natriuresis. This is consistent with the assumption that A(1) receptor blockade mediates these effects. C1 Univ Calif San Diego, Dept Med, San Diego, CA 92161 USA. Univ Tubingen, Inst Pharmacol & Toxicol, Tubingen, Germany. NIDDK, NIH, Bethesda, MD USA. Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92161 USA. VASDHS, San Diego, CA 92161 USA. RP Vallon, V (reprint author), Univ Calif San Diego, Dept Med, 3350 La Jolla Village Dr 9151, San Diego, CA 92161 USA. EM vvallon@ucsd.edu NR 41 TC 49 Z9 50 U1 7 U2 19 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2005 VL 313 IS 1 BP 403 EP 409 DI 10.1124/jpet.104.080432 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 907QM UT WOS:000227733000047 PM 15590766 ER PT J AU Tryoen-Toth, P Decaillot, FM Filliol, D Befort, K Lazarus, LH Schiller, PW Schmidhammer, H Kieffer, BL AF Tryoen-Toth, P Decaillot, FM Filliol, D Befort, K Lazarus, LH Schiller, PW Schmidhammer, H Kieffer, BL TI Inverse agonism and neutral antagonism at wild-type and constitutively active mutant delta opioid receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BIOLOGICAL EVALUATION; ACTIVATION; BINDING; PEPTIDES; LIGAND; POTENT; TIPP; MU; 14-ALKOXYMORPHINANS AB The delta opioid receptor modulates nociceptive and emotional behaviors. This receptor has been shown to exhibit measurable spontaneous activity. Progress in understanding the biological relevance of this activity has been slow, partly due to limited characterization of compounds with intrinsic negative activity. Here, we have used constitutively active mutant (CAM) delta receptors in two different functional assays, guanosine 5'-O-(3-thio)triphosphate binding and a reporter gene assay, to test potential inverse agonism of 15 delta opioid compounds, originally described as antagonists. These include the classical antagonists naloxone, naltrindole, 7-benzylidene-naltrexone, and naltriben, a new set of naltrindole derivatives, H-Tyr-Tic-Phe-Phe-OH (TIPP) and H-Tyr-Tic Psi[CH2N]Cha-Phe-OH[TICP(Psi)], as well as three 2',6'-dimethyltyrosine-1,2,3,4-tetrahydroquinoline-3-carboxylate (Dmt-Tic) peptides. A reference agonist, SNC 80 [(+)-4-[(alpha)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide], and inverse agonist, ICI 174864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu), were also included. In a screen using wild-type and CAM M262T delta receptors, naltrindole (NTI) and close derivatives were mostly inactive, and TIPP behaved as an agonist, whereas Dmt-Tic-OH and N,N(CH3)(2)-Dmt-Tic-NH2 showed inverse agonism. The two latter compounds showed negative activity across 27 CAM receptors, suggesting that this activity was independent from the activation mechanism. These two compounds also exhibited nanomolar potencies in dose-response experiments performed on wild-type, M262T, Y308H, and C328R CAM receptors. TICP(Psi) exhibited strong inverse agonism at the Y308H receptor. We conclude that the stable N,N(CH3)(2)-Dmt-Tic-NH2 compound represents a useful tool to explore the spontaneous activity of delta receptors, and NTI and novel derivatives behave as neutral antagonists. C1 Univ Strasbourg 1, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, F-67404 Illkirch Graffenstaden, France. CUNY Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA. Natl Inst Environm Hlth Sci, Med Chem Grp, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC USA. Clin Res Inst Montreal, Lab Chem Biol & Peptide Res, Montreal, PQ H2W 1R7, Canada. Univ Innsbruck, Inst Pharm, Dept Pharmaceut Chem, A-6020 Innsbruck, Austria. RP Kieffer, BL (reprint author), Univ Strasbourg 1, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, 1 Rue Laurent Fries,BP 1042, F-67404 Illkirch Graffenstaden, France. EM briki@igbmc.u-strasbg.fr FU NIDA NIH HHS [DA05010, P50 DA005010] NR 39 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2005 VL 313 IS 1 BP 410 EP 421 DI 10.1124/jpet.104.077321 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 907QM UT WOS:000227733000048 PM 15590769 ER EF